Begomovirus (family Geminiviridae), with potential recombination hot- and cold-spots also having been identified. Nevertheless, because very little is understood about either the biochemical predispositions of different genomic regions to recombine or what makes some recombinants more viable than others, the sources of the evolutionary and biochemical forces shaping distinctive recombination patterns observed in nature remain obscure. Here we present a detailed analysis of unique recombination events detectable in the DNA-A and DNA-A-like genome components of bipartite and monopartite begomoviruses. We demonstrate both that recombination breakpoint hot- and cold-spots are conserved between the two groups of viruses, and that patterns of sequence exchange amongst the genomes are obviously non-random. Using a computational technique designed to predict structural perturbations in chimaeric proteins, we demonstrate that observed recombination events tend to be less disruptive than sets of simulated ones. Purifying selection acting against natural recombinants expressing improperly folded chimaeric proteins is therefore a major determinant of natural recombination patterns in begomoviruses.With the development of reliable recombination detection tools and an increasing number of available genome sequences, many studies have reported evidence of recombination in a wide range of virus genera. Recombination is apparently a major mechanism in virus evolution, allowing viruses to evolve more quickly by providing immediate direct access to many more areas of a sequence space than are accessible by mutation alone. Recombination has been widely described amongst the insect-transmitted plant viruses in the genus  The exchange of genetic material between different virus species, called inter-species recombination, has the potential to generate, within a single genome replication cycle, an almost unimaginable number of genetically distinct virus strains, including many that might cause deadly new human, animal, or plant diseases. Many fear that inter-species recombination could provide viruses with quick access to evolutionary innovations such as broader host ranges, altered tissue tropisms, or increased severities. However, mounting evidence suggests that recombination is not an unconstrained process and that most inter-species recombinants that occur in nature are probably defective. It is suspected that networks of coevolved interactions between different parts of virus genomes and their encoded proteins must be kept intact for newly formed inter-species recombinants to have any chance of out-competing their parents. One category of coevolved interaction is that between contacting amino acids within the 3-D structures of folded proteins. Here we examine the distributions of recombination events across the genomes of a group of rampantly recombining plant viruses and find very good evidence that this class of interaction tends to be preserved amongst recombinant sequences sampled from nature. This indicates that selection against misfolded proteins strongly influences the survival of natural recombinants. Besides its vital cellular role in maintaining and repairing broken DNA molecules ,2, recomIn virology, two recombinational processes can be distinguished: genome reassortment and true recombination. Genome reassortment, also called pseudo-recombination, involves the exchange of intact genome components between viruses with multipartite genomes to yield viruses whose genomes are comprised of new combinations of components. True recombination, on the other hand, involves the exchange of genetic material between individual genomic molecules. The rearrangement of genetic information mediated by both true recombination and pseudo-recombination must yield fully functional and reasonably fit genomes for these processes to be easily detectable in nature. However, analysis of the functionality of recombinant genes ,9 and thWhile full accounts of experimentally verified intra-genome interactions are currently unavailable for any virus species, potential amino acid interactions within folded proteins can be inferred with reasonable accuracy given high resolution protein structural data. In the past five years, protein engineers have made substantial progress in the development of computational methods capable of accurately inferring degrees of recombination-induced fold disruption in experimentally generated chimaeras of proteins with known structures ,14,15. Arep) gene encoding a protein for which a high resolution crystal structure is available. In this paper we describe an expanded analysis of recombination amongst begomoviruses. We identify sets of unambiguously unique recombination events detectable in publicly available monopartite begomovirus DNA-A-like sequences and bipartite begomovirus DNA-A sequences. We then determine the distribution of recombination breakpoints across the analysed sequences and confirm the recombination hot- and cold-spots identified previously. We use a method called SCHEMA  (AY795983), ToLCYTV-[Dem] (AJ865341), and TYLCSV (X61153). The Protein Data Bank (http://www.pdb.org/) ID number for TYLCSV N-terminal region structure is 1L2M.The National Center for Biotechnology Information (


The principles and design of a Hadamard transform UV absorbance detector for liquid chromatography are outlined, and some spectra of aromatic compounds passing through its flow cell are presented. This approach could be valuable in providing alow-cost multi-wavelength detection method for liquid chromatography.


The occurrence of biliary stricutures in allografts following liver transplantation correlateswith the duration of preservation time. The correlation between preservation timeand biliary strictures suggests that anoxic or reperfusion injury of the bile duct epitheliumcauses stricture formation. However, the relative susceptibility of bile duct cells to anoxicor reoxygenation injury is unknown. Our aims were to determine the vulnerability of ratliver bile duct cells to anoxic and reoxygenation injury and to compare the results withhepatocytes. During anoxia, bile duct epithelial cells were significantly more resistant tocell killing than hepatocytes. Rates of cellular proteolysis were also 2.5-fold lower in bileduct cells than in hepatocytes during anoxia. In contrast to anoxia, reoxygenation ofanoxic cells increased cell killing of bile duct cells but improved viability of hepatocytes.The rate of toxic oxygen species formation by bile duct cells was 5-fold greater than inhepatocytes during reoxygenation. In addition, basal levels of glutathione are lower in bileduct cells than in hepatocytes. These data suggests that bile duct cells are more susceptibleto reoxygenation injury than to anoxia. These studies support the hypothesis thatreoxygenation injury during liver preservation leads to bile duct injury during livertransplantation.


Long term complications of laparoscopic cholecystectomy are uncommon. However, as experience with this procedure accumulates, sporadic reports of non-biliary complication have been published. We report a case of abdominal wall sinus formation secondary to gallbladder perforation and stone spillage occurring during laparoscopic cholecystectomy.


Ichthyosis uteri is a rare condition in which the entire surface of the endometrium is replaced by stratified squamous epithelium. Though the condition often is considered as benign, anaplastic and dysplastic changes have been reported. We describe herein a rare case of low-grade squamous cell carcinoma of endometrium associated with extensive ichthyosis uteri with dysplasia. The cervix showed moderate to severe dysplastic changes while the right fallopian tube showed extensive squamous metaplasia with dysplastic changes. We conclude that squamous cell carcinoma could develop into pre-existing ichthyosis uteri. A 65-year-old multi-gravida presented with complaints of abdominal pain and postmenopausal bleeding per vagina for seven months. Her past medical history was insignificant with no history of tuberculosis, inflammatory conditions of the uterus or iatrogenically introduced substances in uterus. She had attained menopause about 15 years back.Gynecological examination revealed atrophic ectocervix flushed with vagina. The vagina appeared normal. Uterus was bulky of around 12 weeks and adnexae were unremarkable. Colposcopy showed schiller's unstained areas on anterior lip of cervix. Ultrasound abdomen showed endometrial thickness of 2.6 cms. and fluid in the endometrial cavity. Ectocervical biopsy showed strips of moderate to severe dysplastic stratified squamous epithelium. Endometrial curetting revealed strips of stratified squamous epithelium showing moderate dysplastic changes. No normal endometrium was seen. The pyometra was drained, following which the patient underwent type-II radical hysterectomy. The procedure was well tolerated and the postoperative period was uneventful.The hysterectomy specimen revealed thickened and widened endometrial cavity with gray white nodule in the sub-adjacent myometrium. The cervix showed no obvious growth. The cut-section of the right fallopian tube showed thickened mucosa. Both the ovaries did not show any gross abnormality.The sections revealed entire endometrium replaced by stratified squamous epithelium showing areas of heavy keratinization, koilocytic changes, nuclear hyperchromasia and moderate increase in nuclear-cytoplasmic ratio indicating low grade dysplastic changes in underlying ichthyosis uteri Fig . ExtensiZeller coined the term "ichthyosis uteri" in the year 1885 to describe a condition of extensive squamous metaplasia of the surface endometrium following iatrogenically introduced caustic substances such as formalin or iodine [Ichthyosis is considered as benign condition. However, anaplastic and dysplastic changes have been reported by some authors -3. TheseBesides the dysplastic or anaplastic changes, a case of malignant degeneration has also been reported in ichthyosis uteri . This caIn summary, we describe a case of low-grade squamous cell carcinoma of endometrium developing in pre-existing extensive ichthyosis uteri with dysplasia. Though considered as benign condition, based on the present case report and that of Heckeroth et al , the posThe author(s) declare that they have no competing interests.KM, UM, VS drafted the manuscript. TR revised the draft critically for intellectual content. All authors read and approved the final manuscript.


This was performed under fresh (resting) conditions and after incubation for 6 h without (unstimulated) and with (stimulated) Escherichia coli endotoxin. The malignant groups showed higher mTF levels than each of the three controls for resting  unstimulated  and stimulated cells . Similarly, the benign inflammatory groups had higher mTF levels than controls for resting , unstimulated  and stimulated cells . There was no significant difference between malignant and benign inflammatory groups in each organ. mTF levels showed an increase corresponding to that of histological tumour progression and were higher in non-surviving patients. In conclusion, mTF levels are raised in malignant and inflammatory disease compared to controls and patients with non-inflammatory conditions. Stimulated cells give better discrimination between the groups and may be of value in identifying high risk individuals. mTF levels showed an association with tumour grade or stage and the patients' survival time. © 1999 Cancer Research CampaignMonocytes express tissue factor (mTF) in several conditions including cancer where levels may be valuable in assessing tumour presence and progression. Using a two-stage kinetic chromogenic assay (KCA), mTF levels were measured in controls [normal subjects (


Brassica genome structure and systematically relate it to the Arabidopsismodel. Hitherto, our view of the co-linearities between these closely related genomeshad been largely inferred from comparative RFLP data, necessitating substantialinterpolation and expert interpretation. Sequencing of the Brassica rapa genomeby the Multinational Brassica Genome Project will, however, enable an entirelycomputational approach to this problem. Meanwhile we have been developingdatabases and bioinformatics tools to support our work in Brassica comparativegenomics, including a recently completed draft physical map of B. rapa integratedwith anchor probes derived from the Arabidopsis genome sequence. We are alsoexploring new ways to display the emerging Brassica–Arabidopsis sequence homologydata. We have mapped all publicly available Brassica sequences in silico to theArabidopsis TIGR v5 genome sequence and published this in the ATIDB databasethat uses Generic Genome Browser (GBrowse). This in silico approach potentiallyidentifies all paralogous sequences and so we colour-code the significance of themappings and offer an integrated, real-time multiple alignment tool to partition theminto paralogous groups. The MySQL database driving GBrowse can also be directlyinterrogated, using the powerful API offered by the Perl Bio∷DB∷GFF methods,facilitating a wide range of data-mining possibilities.Recent advances, such as the availability of extensive genome survey sequence (GSS)data and draft physical maps, are radically transforming the means by which wecan dissect


A case report is presented of intra-mural gallbladder carcinoma discovered incidentally after laparoscopic cholecystectomy who subsequently developed abdominal wall recurrence at the epigastric exit port, and axillary lymph node metastases. Possible preventative steps for tumour dissemination and a management plan if incidental carcinoma is diagnosed is discussed. The use of a non-porous retrieval bag, early recognition of the carcinoma and excision of the exit wound are advocated.


Novel antiangiogenic agents currently being developed may ultimately be more effective against solid tumours and less toxic than cytotoxic chemotherapy. As a result of the early clinical trials of angiogenesis inhibitors, investigators are beginning to appreciate the complexity of targeting angiogenesis and the realisation that developing clinically useful antiangiogenic therapy will be more challenging than originally thought. It is now apparent that new methods and surrogate markers to assess these agents' biological activity are crucial for their successful development. This review summarises the currently available clinical data on the development of surrogate markers of angiogenesis inhibitors. Many anPreclinical studies suggested that angiogenesis inhibitors are cytostatic (growth-delaying) rather than cytotoxic. Traditionally, the maximum tolerated dose of a cytotoxic agent (determined by its dose-limiting toxicity) provided an estimation of the active dose range for subsequent clinical studies  that are recruited from the bone marrow during tumour neovascularisation  after initiation of treatment might provide an early indication of antiangiogenic activity before clinically demonstrable reductions in tumour size. Elevated levels of angiogenic growth factors, proteases, and endothelial adhesion molecules have been detected in sera of patients with malignant disease  and the basement membrane during angiogenesis include the family of matrix metalloproteinases (MMPs) . Proteolvs those with stable disease  of action of the angiogenesis inhibitor or the disease under study. In a Phase I study of tetrathiomolybdate  can provide early proof of whether the biologic agent has successfully reached its hypothesised target. Some of the most compelling studies involved quantitative analysis by laser scanning cytometry (LSC) . In contrast, preclinical studies suggested that these small molecules had great potential, as they induced significant levels of apoptosis in endothelial cells, consequently inhibiting tumour growth  . In addition, LSC-mediated analysis of additional surrogate markers hypothesised to be effected by endostatin including nuclear hypoxia-inducible factor-1α and endothelial cell Bcl-2 levels peaked at similar doses of endostatin but failed to reach statistical significance. Importantly, two patients treated at intermediate doses of endostatin had minor antitumour responses  and tumour metabolism [18F](FDG-fluorodeoxyglucose) 28 and 56 days after endostatin therapy . Importantly, the 95% confidence interval identified for blood flow overlapped the OBD (250 mgm2d) determined from the tumour biopsy studies. Thus, integration of surrogate marker data along with imaging studies was crucial for assessing the OBD of recombinant human endostatin.Routine radiographic imaging techniques  are useful for conventional measurement of disease and evaluating the effect of a biologic agent on tumour size  after initiation of therapy may provide an assessment of optimal antivascular activity. Indeed, LSC-mediated analysis of apoptosis in tumour cells 48 h after initiation of treatment has proven useful for predicting clinical response to cytotoxic therapies in breast cancer (


Epidemiologic evidence has recently identified an association between an endemic outbreak of pleural and peritoneal mesothelioma in the Urgup region of Turkey and exposure to zeolite fibres. This malignancy is usually associated with exposure to asbestos dusts whose mineralogical characteristics differ from those of zeolites. The present study further defines the in vitro biologic activity of erionite, a common zeolite fibre found in the Urgup region of Turkey. Both erionite and crocidolite asbestos fibres were clastogenic in synchronous Chinese hamster ovary (CHO) fibroblasts. Both fibres also altered CHO ploidy. Erionite, unlike crocidolite or Min-U-Sil quartz, caused a slight increase in sister chromatid exchanges in synchronous CHO cells. Neither erionite nor crocidolite was mutagenic in a human lymphoblastoid cell line. Erionite fibres thus produced in vitro cytogenic changes similar to those caused by asbestiform mineral dusts and, like asbestos fibres, did not induce mutations in human lymphoblastoid cells.


We have addressed the question whether the epithelial stroma in the thymus is derivedfrom a common stem cell or whether cortical and medullary epithelial cells are derived fromdifferent embryonic stem cells emerging, for example, from endoderm and ectoderm. By theuse of rapidly expanding cultures of thymic epithelial cells (TEC) from 14 to 16 day-oldmurine fetuses and by specific antibodies against cortical and medullary epithelium,respectively, we were able to demonstrate a small subpopulation of double-labeled TEC inthe cultures. These cells were not present in TEC cultures initiated from thymuses ofneonatal mice. Double-labeled TEC were also found in tissue sections from fetal thymuses.These findings may indicate that TEC populations of the cortex and the medulla are derivedfrom a common stem cell, with potential for differentiation toward both cortical andmedullary TEC.


The heterogeneity evident among home care clients highlights the need for greater understanding of the clinical and social determinants of multi-dimensional health-related quality of life (HRQL) indices and of potential sex-differences in these determinants. We examined the relative contribution of social and clinical factors to HRQL among older home care clients and explored whether any of the observed associations varied by sex.The Canadian-US sample included 514 clients. Self-reported HRQL was measured during in-home interviews (2002-04) using the Health Utilities Index Mark 2 (HUI2). Data on clients' sociodemographic, health and clinical characteristics were obtained with the Minimum Data Set for Home Care. The relative associations between clients' characteristics and HUI2 scores were examined using multivariable linear regression models.Women had a significantly lower mean HUI2 score than men . Clients with distressed caregivers and poor self-rated health exhibited significantly lower HRQL scores after adjustment for a comprehensive list of clinical conditions. Several other factors remained statistically significant  or clinically important  correlates of lower HUI2 scores in adjusted analyses. These associations generally did not vary significantly by sex.For females and males, HRQL scores were negatively associated with conditions predictive or indicative of disability and with markers of psychosocial stress. Despite sex differences in the prevalence of social and clinical factors likely to affect HRQL, few varied significantly by sex in their relative impact on HUI2 scores. Further exploration of differences in the relative importance of clinical and psychosocial well-being  to HRQL among female and male clients may help guide the development of sex-specific strategies for risk screening and care management. Health-related quality of life (HRQL) represents an important construct in understanding the health status and outcomes of older home care clients  and ultiarthritis, heart failure, stroke, chronic obstructive pulmonary disease (COPD), urinary incontinence and mental health disorders. Despite some suggestion of sex differences in the strength of the associations between selected chronic diseases and HRQL indices ), cognitive and emotional status from MDS-HC items, we chose not to present the adjusted models including these scales because of interpretation difficulties due to collinearity between these measures (and other correlates of interest) and the single attributes comprising the HUI2 [As illustrated by the multivariable linear regression results, the strongest associations with overall HUI2 scores were observed for high caregiver stress and poor self-rated health. Several other factors remained statistically significant  or clinically important  correlates of lower HUI2 scores in the adjusted analyses  displayed clinically important lower HUI2 scores. Some caution is warranted in the interpretation of the sex-differences observed for pressure ulcers and urinary tract infections given the relative low occurrence of these conditions and missing data (for pressure ulcers). A clinically important difference in HUI2 scores was observed for male  clients reporting feelings of loneliness. None of the two-way interaction terms with sex were found to be statistically significant at p < 0.05 in the full model.and social factors to multi-dimensional HRQL indices such as the HUI2. Even less consideration has been paid to potential sex-differences in the relative importance of selected associations. In addition to highlighting the relative importance of the above disability-related conditions we found statistically significant and clinically important decrements in clients’ HRQL associated with poor selfrated health, urinary infections and caregiver distress . Clients’ HUI2 scores varied little with age, marital status, or the presence of several common disease diagnoses. HUI2 scores were clinically reduced for those with self-reported loneliness, congestive heart failure and pressure ulcers. Generally, the observed associations were not significantly modified by sex; however, the magnitude of score differences associated with selected factors  did vary between females and males. Older home care clients often show considerable variability in physical, cognitive and social indices of vulnerability. The relative frailty of our client sample is reflected by their significantly lower overall mean HUI2 scores  compared with published age-specific HUI2 norms  . The lowThe relatively weak associations between individual disease diagnoses and clients' HRQL have also been reported by others ,7,37 andIn interpreting the relatively strong impact of poor self-rated health and caregiver distress on the HRQL of female and male clients it is important to acknowledge that these factors may serve as proxy measures for poorer clinical and functional status. Yet, both remained significantly associated with lower HUI2 scores after adjusting for clients' clinical and functional status including additional MDS-HC measures of ADL and cognitive impairment. Consequently, a broader interpretation might suggest that both factors provide unique information about clients' psychosocial well-being  relevant to their overall HRQL ,39. AddiWidowhood and reported loneliness, although significantly more common among women, were not significantly associated with lower HRQL. Self-reported loneliness did, however, show a clinically important association with lower HUI2 scores among male clients. Others have reported weak to no associations between both marital status and living arrangements  and HRQL in older populations ,21,22. AOur cross-sectional study precludes any clear discussion of the causal nature of selected observed associations . The absence of longitudinal data also limits our ability to detect and comment on relevant changes in clients' HRQL precipitated by expected fluctuations in their clinical and health conditions . ConsistWith our relatively select and small sample, some caution is warranted in generalizing our findings to other older populations and care settings including those in rural areas, in long-term care institutions and with moderate to severe cognitive impairment. Our relatively small number of male clients may also explain the relative absence of significant sex differences. As with other commonly used HRQL measures the HUI2 is particularly sensitive to physical impairment . Also, iAs expected, we observed important decrements in clients' HRQL for common health conditions predictive or indicative of disability, including arthritis, mental health disorders and incontinence. For both females and males, HUI2 scores varied little with the presence of several other prevalent clinical diagnoses. Most of the observed variation in clients' HRQL scores was accounted for by two factors, poor self-rated health and caregiver distress. Although the direction of these associations are unclear, both factors may serve as important markers of psychosocial frailty and increased risk for poor client outcomes including future declines in HRQL. Despite sex differences in the prevalence of social and clinical factors likely to affect HRQL, most did not vary significantly by sex in their relative impact on HUI2 scores. However, our findings highlight several areas worthy of further investigation with larger samples, including possible sex differences in the relative importance of arthritis, incontinence, mental health and self-reported loneliness. Further demonstration of a differential impact of these factors among female and male clients may assist in the identification of appropriate sex-specific strategies for risk screening and care management of vulnerable seniors in community care settings.DHF has a proprietary interest in Health Utilities Incorporated, Dundas, Ontario, Canada. HUInc. distributes copyrighted Health Utilities Index (HUI) materials and provides methodological advice on the use of HUI. All other authors declare that they have no competing interests.CJM developed the initial study, supervised data collection, directed data analyses and wrote and edited the manuscript. JK conducted the primary analyses. JW assisted with study design and implementation, data preparation and analyses. JZ assisted with data preparation and analyses. DBH assisted with study development and implementation. DHF assisted with study design and implementation. WW co-led the development of the initial study, supervised data collection and assisted with data analyses. All authors made meaningful contributions during the editing of the manuscript and approved the final version.


Ralstonia  metallidurans (Rme) is better able to withstandhigh concentrations of heavy metals than any other well-studied organism. This factrenders it a potential agent of bioremediation as well as an ideal model organism forunderstanding metal resistance phenotypes. We have analysed the genome of Rmefor genes encoding homologues of established and putative transport proteins; 13%of all genes in Rme encode such homologues. Nearly one-third of the transportersidentified (32%) appear to function in inorganic ion transport with three-quartersof these acting on cations. Transporters specific for amino acids outnumber sugartransporters nearly 3 : 1, and this fact plus the large number of uptake systems fororganic acids indicates the heterotrophic preferences of these bacteria. Putative drugefflux pumps comprise 10% of the encoded transporters, but numerous efflux pumpsfor heavy metals, metabolites and macromolecules were also identified. The resultspresented should facilitate genetic manipulation and mechanistic studies of transportin this remarkable bacterium.


Occurrence of bioprosthetic valve thrombosis less than a year after replacement is very uncommon. Here, we describe a case of a 57 year old male, who presented 10 months after receiving a bioprosthetic mitral valve replacement with a two week history of dyspnea on exertion, worsening orthopnea and decreased exercise tolerance. Echocardiography revealed severe mitral regurgitation (MR), thrombosis of the posterior mitral leaflet, left atrial (LA) mural thrombus and a depressed left ventricular ejection fraction of twenty-five percent. Given severe clot burden and decompensated heart failure (New York Heart Association - NYHA class III) repeat sternotomy was done to replace the bioprosthetic mitral valve and remove LA mural thrombus. MR was resolved postoperatively. This brief report further reviews promoting factors, established guidelines and management strategies of bioprosthetic valve thrombosis. Bioprosthetic mitral valves are advantageous over mechanical valves as their incidence of thrombosis, pannus formation and embolic events are significantly lower. This disparity in thromboembolic events as compared to mechanical valves avoids a need for chronic anticoagulation in many patients receiving bioprosthetic valve replacement . HoweverA 57 year old male with a past medical history of chronic atrial fibrillation, a depressed ejection fraction of 25%, and severe MR underwent mitral valve replacement with a bioprosthetic Mosaic valve  and a complete left and right sided MAZE procedure. Post operative transthoracic echocardiogram (TTE) showed a competent mitral valve tissue prosthesis and the patient was discharged on warfarin. Anticoagulation was discontinued three months after valve replacement and the patient remained in sinus rhythm on electrocardiography.Ten months following mitral valve replacement, the patient presented with a two week history of progressive dyspnea on exertion, orthopnea and weight gain. TTE revealed severe mitral valve stenosis and mitral regurgitation, with a mean gradient of 8.5 mmhg (max. gradient -- 25.5 mmhg) across the mitral valve, and restricted motion of mitral leaflets. On transesophageal echocardiogram (TEE), a mitral mass was observed on the posterior leaflet along with mural thrombus in a dilated left atrium measuring 4.90 cm in diameter figure . EjectioIntraoperatively, mural clot was debrided from the free and posterior left atrial walls. The mitral bioprosthesis was incompetent with pannus growing on the posterior leaflet. This valve was excised and replaced with a 25 mm On-X mechanical valve  that functioned without leakage after placement. Postoperatively, the patient had improved exercise tolerance and was discharged on indefinite warfarin therapy.Clinically significant bioprosthetic valve thrombosis is considered uncommon, however, its incidence on routine echocardiographic surveillance is reported as high as six percent . Specifi2 score is greater or equal to 2 [Although freedom from long term anticoagulation is a feature of bioprosthetic valve replacement, this case calls for a brief review of current anticoagulation guidelines following bioprosthetic valve replacement and a radioablative MAZE procedure. The 2008 American Heart Association (AHA) and American College of Cardiology (ACC) guidelines state that high risk patients with any of the following risk factors including atrial fibrillation, LV dysfunction with EF < 30%, recurrent thromboembolic events or a hypercoagulable condition meet a class I indication for indefinite anticoagulation . To reduual to 2 . These gThis case also calls for frequent post operative echocardiographic monitoring in non- anticoagulated patients with risk factors promoting valve thrombosis. The 2007 European Society of Cardiology (ESC) guidelines  recommenAccording to the 2007 ESC guidelines , once vaManagement of non-obstructive prosthetic valve thrombosis depends on the occurrence of thromboembolism (TE) and thrombus size . InitialIn the present case, obstructive valve thrombosis, large clot burden and critical illness made surgical replacement a reasonable and successful treatment option.Bioprosthetic mitral valve thrombosis is an under recognized complication in high risk patients that leads to rapid valve incompetence. Post-operatively, patients must be stratified in high or low risk categories, and anticoagulation should be maintained indefinitely for high risk patients. If anticoagulation is not maintained for individualized reasons then a semi-annual TTE within the first year and annually thereafter may detect subclinical bioprosthetic valve thrombosis in asymptomatic patients.Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-n-Chief of this journal.OML discloses that he has served as a consultant and received research grants from Medtronic Corporation and On-X Life Technologies. The rest of the authors declare that they do not have any competing interests.OS: Resident physician, provided pre-operative care and primary author.BRW: Cardiologist, provided pre-operative care and advice during the manuscript writing process.MK: Assisted in writing and preparing manuscript.OL: Cardiothoracic Surgeon, performed the bioprosthetic valve repair and provided advice during the manuscript writing process.All authors have read and approve the final manuscript.


Hemangiomas and venous lymphatic malformations are the two most common orbital vascular lesions seen in pediatric patients. Orbital venous-lymphatic malformations (OVLMs) (previously referred to as ′lymphangiomas′) are uncommon, benign cystic type I vascular malformations.OVLMs may remain clinically unapparent or might manifest in childhood with slowly progressive proptosis, periorbital swelling and displacement of globe. These malformations usually enlarge slowly. Spontaneous intraorbital hemorrhage or venous thrombosis may cause sudden acute proptosis, severe pain, compressive optic neuropathy or loss of vision, when intervention is indicated . Orbital2A 20-year-old girl presented with left-sided progressive painless orbital proptosis since birth . On examSystemic corticosteroids have been used as an adjuvant treatment to surgery, although their role is controversial. The diffuse form of orbital lymphangioma is well known for its difficult surgical treatment and frequent recurrences. Small, repeated excisions may be required. Surgical debulking with carbon dioxide laser through a lateral orbitotomy combined with three-wall orbital decompression is a preferred surgical technique and may be a useful alternative treatment in patients with severe proptosis.Ultrasonography of OVLMs show high amplitude echoes with a very wide separation due to large encapsulated fluid lakes. On CT scan, these are poorly defined slightly enhancing lesions that cross anatomic boundaries, such as the conal fascia and orbital septum. Areas of hemorrhage cause cyst-like masses with rim enhancement. In the last decade, role of MRI has been emphasized in the literature as it has the capability to precisely delineate and characterize these lesions. It is reWe conclude that imaging plays a crucial role in diagnosis of OVLMs and intracranial associations. However, atypical characteristics may be seen in a few pediatric patients and excision biopsy may be indicated to facilitate diagnosis.


Heterotransplantation of a human colonic neoplasm with classical morphologic characteristics of a carcinoid was sucessful in the cheek pouches of unconditioned, adult golden hamsters after a short sojourn in cell-impermeable chambers in rats. Although no mucin-secreting cells were detected in the donor carcinoid, the cheek pouch transplants exclusively exhibited mucinsecreting tumour cells of signet-ring type consistent with adenocarcinoma. This transplantable tumour, designated GW-77, has retained this appearance as well as expansive growth characteristics in xenogeneic hosts for a period of 4 years.These findings represent strong biological evidence consonant with views, based upon morphological findings, advocating a histogenetic relationship between colonic carcinoid and adenocarcinoma. It is believed that colonic adenocarcinoma has a selective advantage over carcinoid for serial propagation in an alien environment, indicating the less differentiated nature of its cellular components. Since the donor carcinoid cells failed to exhibit argentaffin reactions, these conclusions may be limited only to the nonreactive forms of carcinoid.


Several pathogens of humans and domestic animals depend on hematophagous arthropods to transmit them from one vertebrate reservoir host to another and maintain them in an environment. These pathogens use antigenic variation to prolong their circulation in the blood and thus increase the likelihood of transmission. By convergent evolution, bacterial and protozoal vector-borne pathogens have acquired similar genetic mechanisms for successful antigenic variation. Borrelia spp. and Anaplasma marginale (among bacteria) and African trypanosomes, Plasmodium falciparum, and Babesia bovis (among parasites) are examples of pathogens using these mechanisms. Antigenic variation poses a challenge in the development of vaccines against vector-borne pathogens.


Effects of neonatal androgenization or neonatal ovariectomy in female rats on endocrine functions and mammary tumourigenesis are examined. Pituitary gonadotrophin contents (both LH and FSH) are significantly lower in neonatally androgenized rats (TT) and significantly increased in neonatally ovariectomized rats (NO) when compared with controls of the same age. Plasma and pituitary prolactin levels are higher in TT rats than in the control rats of the same age, but the difference is not significant. Mammary tumours developing in TT rats after DMBA treatment are predominantly fibroadenomata, and lactogenesis in TT rats occurs almost entirely in those receiving DMBA treatment. Neonatal ovariectomy in female rats protects against subsequent induction of mammary cnacer by DMBA. The relationship between neonatal modification of endocrine functions and mammary tumourigenesis is discussed.


Myopotential oversensing in implantable defibrillators causing inhibition of pacing and inappropriate therapies is well described. Current literature is dominated by reports of diaphragmatic muscle as the source of such far-field oversensing. Those reporting pectoral muscle sources were invariably due to unipolar sensing circuits, incorrect DF-1 connections or inappropriate programming. We report an interesting case of pectoral muscle myopotential oversensing causing inhibition of bradycardia pacing leading to presyncope and syncope. Oversensing of skeletal muscle myopotentials is well described -3 and isA 60 year old female with hypertrophic cardiomyopathy had originally presented with syncope and documented ventricular tachycardia. A dual chamber cardioverter-defibrillator (Guidant VENTAK 1861) was implanted in June 2003 and an integrated bipolar right ventricular defibrillator lead was used (Guidant SN 0158). Electrogram amplitudes, pacing and defibrillation thresholds at the time of implantation were normal.After the procedure, the patient was without symptoms for two years. Device interrogation during routine follow-up demonstrated low levels of noise on ventricular electrograms. There were no appropriate or inappropriate therapies although three therapies were diverted.In Feb 2006 the patient developed persistent atrial fibrillation. Pharmacological attempts to maintain sinus rhythm were unsuccessful, she declined a left atrial ablation procedure and in May 2007 the patient underwent atrio-ventricular (AV) node ablation for ventricular rate control and was rendered pacemaker dependant. One month after AV node ablation the patient attended the cardiac device clinic complaining of recurrent episodes of dizziness and syncope during certain physical activities such as showering or washing dishes. At this time pacing thresholds, electrogram amplitudes and impedances were normal. A chest X-ray showed no radiographic evidence of loss of lead integrity.Device interrogation revealed 16 diverted therapies in the VF zone. One such episode is shown in At interrogation, these potentials were not reproducible with the usual provocative manoeuvres such as rapid, deep respiration and generator agitation, but were reproducible with isometric upper limb exercise  and resulted in pacing inhibition and dizziness.Our immediate management was to reduce the sensitivity to the minimum programmable setting. This was deemed safe as a short term measure as VF detection at minimal sensitivity was confirmed at defibrillation threshold testing at implantation. We advised the patient to avoid driving and provocative manoeuvres. The patient was admitted electively for re-operation. At procedure the existing lead connections to the generator were found to be secure and appropriate. Invasive lead tests were satisfactory. We elected to leave the integrated lead in situ and implant a new dedicated bipolar pacing lead (Medtronic 5076) for ventricular sensing and pacing. The new pace/sense lead was connected to the ventricular IS-1 socket on the existing device and the old integrated defibrillator lead remained connected via the DF-1 sockets. The defibrillator lead IS-1 terminal was capped and secured within the prepectoral pocket.  Subsequently, the patient's symptoms resolved and no further myopotentials were recordable.The case highlights a problem specific to integrated bipolar lead technology, that is, far-field myopotential oversensing due to distance between the lead tip and distal defibrillator coil.This patient only became symptomatic when rendered pacing dependant after AV node ablation when upper body muscular movement caused pacing inhibition through myopotential oversensing. Fortunately, this consistently caused dizziness or syncope which stopped physical activity thus terminating myopotential oversensing. As a result, therapies were always diverted and pacing resumed. It is therefore curious that no inappropriate therapies were delivered prior to AV node ablation. This may simply be explained by a dynamic ventricular sensing threshold facility available in most defibrillators, in this case, automatic gain control see . FollowiAtrial and T-wave oversensing, which have also been reported with integrated bipolar leads are usually easily overcome with re-programming. True myopotential oversensing however, invariably requires re-operation. Our solution in this case was to introduce a separate dedicated bipolar pace/sense lead and retain the integrated lead for defibrillation. An alternative solution would have been to replace the lead with a dedicated bipolar defibrillator lead and either extract the integrated lead or leave it redundant  .The alternative to re-operation is to reduce ventricular lead sensitivity to exclude unwanted potentials. This particular device had three sensitivity settings - "nominal", "less" and "least". Although implant testing is done at "least" sensitivity, VF re-induction at "least" sensitivity to confirm VF sensing would have been a reasonable approach (though not without risk) as changes in sensing may have occurred with lead maturation. In this case, we employed this strategy only as an interim, particularly as "least" sensitivity would not have guaranteed a resolution to myopotential oversensing, because it could not be confidently reproduced in the setting of the device clinic as myopotential interference may change with patient position and activity.With dedicated bipolar (quadripolar) defibrillator leads available, the use of integrated leads may be questioned. Quadripolar leads are, however, not without problems. Increased pacing thresholds and sensing latency causing ventricular pseudofusion and unnecessary ventricular pacing are not uncommon . More prProgress in lead technology has not paralleled the rapid advances in generator design and technology. Newer quadripolar constructions with active fixation are gaining merit but longevity data is still anticipated. Hence, to date lead choice remains at the discretion of the implanter rather than guided by evidence.


Leucocyte interactions with the cremaster muscle microcirculation in vivo were investigated in response to culture medium conditioned with different cell types in 25 adult male Swiss mice. Animals were divided into five groups. Three groups received ex vivo fluorescently labelled lymphokine activated killer (LAK) cells systemically and had either tumour (murine melanoma K1735)-conditioned medium (TCM), fibroblast (murine 3T3)-conditioned medium (FCM) or fresh culture medium administered topically to the cremaster muscle. In the two remaining groups, the host leucocytes were labelled fluorescently by systemic administration of acridine red, and either TCM or FCM was applied topically to the cremaster muscle. There was an immediate but transient increase in the frequency of rolling and adherent LAK cells, and a subsequent (90-120 min later) increase in rolling and adherent host leucocytes, demonstrating temporal differences in the response to topical administration of TCM. These increases in contact with the vascular endothelium occurred in all vessel types, venules, arterioles and capillaries, with the greatest response observed in the venules. The FCM and normal culture medium did not affect the distribution and localization of either LAK cells or host leucocytes. These data suggest that there are one or more soluble tumour-specific chemoattractants for leucocytes present in the conditioned medium. The mouse cremaster muscle microcirculation is therefore a useful model to investigate the mechanism of leucocyte-endothelium interactions in tumour biology.


The patient had exertional chest pain and dyspnea prompting referral for cardiac evaluation. These symptoms were reproduced during intravenous adenosine infusion, and simultaneous first-pass perfusion imaging showed a significant subendocardial defect; both symptoms and perfusion deficit were absent at rest. Epicardial coronaries were free of disease by invasive angiography; together, these findings support the notion of impaired myocardial perfusion reserve in FA.We present the first  This report describes myocardial perfusion reserve abnormality in Freidreich's ataxia (FA), a heritable disorder whose major manifestations are neurological and myocardial disease. In more than 90% of cases, this autosomal recessive condition results from excess of DNA triplet repeats (GAA) in the first intron at the end of exon 1 leading to suppression of FRDA (frataxin) gene expression. Around 5% of patients have a point mutation in the frataxin gene; both forms result in a deficiency of the protein frataxin that is located in the inner mitochondrial membrane, neitherA 26 year-old nonsmoking Middle Eastern woman presented for evaluation of exertional chest pain and shortness of breath. The past medical history was notable for genotype-proven Friedreich's ataxia (FA) diagnosed at age 19 that had produced ambulatory limitation with frequent falls due to her ataxia. Genotyping showed 846GAA repeats  consistent with FA. Family history revealed extensive affected members and carriers  with a 12-channel phased array coil. Resting steady-state free precession cine imaging showed normal left ventricular (LV) size and systolic function, with LV end-systolic volume 21 cc/mBased on the reproduction of chest pain with adenosine stress and accompanying perfusion abnormality, she was referred for invasive coronary angiography. This showed angiographically normal epicardial coronary arteries Figure  and normIn summary, we identified impaired microcirculatory reserve in FA using CMR that occurred in the absence of epicardial coronary artery disease. Friedreich's ataxia is a neurodegenerative condition frequently accompanied by cardiomyopathy due to a mutation in the gene frataxin, resulting in intra-mitochondrial accumulation of iron. The predilection for neuromuscular and myocardial involvement in FA reflects the high energy demands of both systems.et al. using positron emission tomography; their work suggested that compensation for impaired energetics in FA occurs by increasing myocardial oxygen consumption rather than myocardial blood flow, though this study was conducted under resting conditions only[Prior magnetic resonance-based evaluation of FA cardiomyopathy has focused on cardiac magnetic resonance spectroscopy  or quantions only.The detection of subendocardial perfusion abnormality afforded by adenosine CMR is similar to that described in other conditions such as syndrome X and coarctation of the aorta,7, thougThe author(s) declare that they have no competing interests.


Whole-blood caeruloplasmin measured by electron spin resonance was studied in 41 patients with chronic lymphocytic leukaemia. The levels were above normal at all stages of the disease, rose with increasing clinical involvement, and were higher in progressive than inactive disease. Whole-blood iron transferrin levels were more variable, and were significantly raised only in patients with marrow failure.


Patients with advanced idiopathic pulmonary artery hypertension have often a chronic pericardial effusion. It is the result of increased transudation and impaired re-absorption due to elevated venous pressure. These patients have pre-existent symptoms and signs of chronic right heart failure. High degree of suspicion is required to detect of development of an atypical form of tamponade with isolated compression of left heart chambers as shown in present case report. Transthoracic echocardiography provides a rapid access to the correct diagnosis, a prompt relief of symptoms following the ultrasound guided pericardiocentesis and important diagnostic tool for regular follow up of patients thereafter as shown in our case report. Circumferential pericardial effusion typically results in biventricular tamponade and equalization of intracardiac and pericardial pressure during diastole. In classic subacute tamponade the rising of pericardial pressure causes a progressive collapse of right atrium and ventricle preventing venous return to the right atrium. Symptoms and signs referable to increased filling pressure and diminished cardiac output ensue. Patients presents with dyspnea, orthopnea, peripheral edema, fatigability, hepatic engorgement. The three principal features: jugular venous distention, soft or absent heart sounds and hypotension (Beck's triad), tachycardia and pulsus paradoxus are present. However, tamponade may involve the right or left heart. While isolated left ventricular tamponade can occur as a postoperative complication form localized posterior pericardial effusions or hematoma, circumferential pericardial effusions leading to left heart tamponade are rare .We present a clinical course and echocardiographic examination in a patient with idiopathic pulmonary artery hypertension (IPAH) and chronic pericardial effusion who developed a subacute isolated left heart tamponade.A 57-year-old patient with IPAH and a previously known chronic pericardial effusion presented in an outpatient clinic with symptoms of dyspnea on exertion, in the last days even at rest, ortopnea and leg edema. During the past few months he was in good physical condition. He was on therapy with sildenafil, amlodipine, acenocoumarol and had a combination inhaler containing fluticasone propionate and salmeterol xinafoate. The clinical examination showed distended jugular veins, leg edema and an accentuated second heart sound. A chest radiogram showed an enlarged heart shadow. The echocardiographic examination showed a dilated right atrium and ventricle Figure  with redAfter the normalisation of the haemosthasis with fresh frozen plasma echocardiographicly guided pericardiocentesis using a parsternal approach was performed. Immediately after removal of 250 ml of yellow fluid the patient became normopnoic. There was still 1.5 cm large pericardial effusion behind the left ventricular posterior wall without left heart collapse  were negative. Rheumatic markers , angiotensin-convertyng enzyme and tumor markers  were all in normal range. The function of the thyroid gland was normal.Patients with cor pulmonale and circumferential pericardial effusion develop an atypical form of cadiac tamponade with isolated left heart compression. Pre-existing pulmonary arterial hypertension can modify the classic presentation. Symptoms and signs of right heart failure could already be present, so a high index of suspicion for tamponade is required in every worsening of right heart failure symptoms. When the pericardial pressure starts to increase in a patent with cor pulmonale, elevated pressure in right heart chambers prevent right atrial and ventricular compression, but while the pericardial pressure rises to the point to exceed left chambers pressure, this results first in diastolic collapse of left atrium and later on in left ventricle collapse due to a transient reversal of the transmural pressure ,3. SignsThe most probable mechanism of accumulation of pericardial fluid in patients with IPAH is transudation and impaired re-absorption of pericardial fluid due to elevated venous hydrostatic pressure in the setting of cor pulmonale.In the setting of pulmonary arterial hypertension large hemodynamically significant pericardial effusions might be treated surgically and/or conservative and it is known that prognosis of patients with this complication is poor ,5. HowevThe right ventricle-to-right atrial pressure gradient may be difficult to estimate in the setting of severe tricuspid regurgitation, when there is a large color flow regurgitant jet. In this case, the peak velocity may not reflect the true pressure gradient.In conclusion, patients with advanced IPAH have often a chronic pericardial effusion. It is the result of increased transudation and impaired re-absorption due to elevated venous pressure. These patients have pre-existent symptoms and signs of chronic right heart failure. High degree of suspicion is required to detect of development of an atypical form of tamponade with isolated compression of left heart chambers. Transthoracic echocardiography provides a rapid access to the correct diagnosis, a prompt relief of symptoms following the ultrasound guided pericardiocentesis and important diagnostic tool for regular follow up of patients thereafter.Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.TM: carried out interpretation and drafted the manuscriptHM: carried out interpretation and drafted the manuscriptBS: treated the patient, carried out interpretation and drafted the manuscriptMP: treated the patient, made acquisition of data, carried out interpretation and drafted the manuscriptAll authors read and approved the final manuscript.Transthoracic echocardiography from apical four chamber view shows enlarged right ventricle (RV) and right atrium (RA). There is pericardial effusion (PE) compressing left ventricle (LV) and left atrium (LA).Click here for fileTransthoracic echocardiography from short-axis plane at the papillary muscle level shows enlarged right ventricle (RV) with paradoxical movement of intraventricular septum. Left ventricle is compressed by RV and pericardial effusion (PE).Click here for fileTransthoracic echocardiography from apical four chamber view shows enlarged right ventricle (RV) and tricuspid regurgitation (TR).Click here for fileTransthoracic echocardiography from apical four chamber view after pericardiocentesis. Right ventricle (RV), right atrium (RA), left ventricle (LV), left atrium (LA).Click here for file


Dear Sir,Communicable and nutritional eye diseases are declining in Oman while age-related and chronic eye diseases are on the rise. All stak2At present, there are three private hospitals with surgical eye care facilities in Oman. In addition, there are twelve private eye clinics with ophthalmologists, nearly 30 qualified contact lens practitioners, and 150 optical shops.[The private sector could assist national eye care services and contribute in policy making efforts within VISION 2020 initiative of Oman, in the following key areas:Refractive surgery and contact lens practice.Corneal transplant and collagen cross-linkage for keratoconus.Photo therapy and intravitreal management modalities for retinal diseases such as age-related macular degeneration and advanced cases of diabetic retinopathy.Individualized case management of rare eye conditions where multisystem care is needed.Low vision care to the adult population.Eye screening procedures in private schools for amblyopia and refractive error as per the recommendations of the National policies.Offering eye screening for driving licensing, insurance, and preemployment medical checkups.Provision of eye care through insurance and payment system to citizen of Oman, thereby reducing the workload of MOH institutions.Training Omani mid-level eye care people through collaboration with institutions of international standards.Keeping the ophthalmic fraternity knowledgeable through periodic meetings, where internationally renowned guest speakers could be invited.


Habitat use may lead to variation in diversity among evolutionary lineages because habitats differ in the variety of ways they allow for species to make a living. Here, we show that structural habitats contribute to differential diversification of limb and body form in dragon lizards (Agamidae). Based on phylogenetic analysis and ancestral state reconstructions for 90 species, we find that multiple lineages have independently adopted each of four habitat use types: rock-dwelling, terrestriality, semi-arboreality and arboreality. Given these reconstructions, we fit models of evolution to species’ morphological trait values and find that rock-dwelling and arboreality limit diversification relative to terrestriality and semi-arboreality. Models preferred by Akaike information criterion infer slower rates of size and shape evolution in lineages inferred to occupy rocks and trees, and model-averaged rate estimates are slowest for these habitat types. These results suggest that ground-dwelling facilitates ecomorphological differentiation and that use of trees or rocks impedes diversification. Anolis lizards , Diporiphora [size]; see In addition, our sampling of agamid species likely influenced the pattern of evolutionary rate variation we document. Our data set represents approximately one-quarter of recognized agamid species diversity, though this proportion is not uniform across the major clades. The under-sampling of species from the southwest Asian/African clade may be the most problematic with respect to our conclusions because at least two primarily terrestrial genera, Our results provide compelling evidence that habitat use shapes diversification of limb and body form in Agamidae. The pattern of variation in rates of morphological evolution suggests that terrestrial habitats promote ecological differentiation whereas diversification is slower in rocky and arboreal habitats; however, the precise mechanism by which these habitats contribute differently to diversification remains speculative. We recommend that future research investigate the extent to which functional constraints, habitat complexity or biotic interactions within habitats influence the pattern we document. For example, locomotor performance tests could be applied across a range of agamid forms to determine whether arboreal and rocky surfaces impose more stringent functional demands than terrestrial surfaces. Also, comparisons of the number of co-occurring agamid species within each habitat type could assess whether these habitats present different numbers and types of species interactions. Application of such studies to Agamidae or other animal taxa has the potential to provide further insights into how habitat contributes to differential diversification among evolutionary lineages.


Biliary tract abnormalities occur in about one of every three people, usually being minor and of noclinical significance.Major abnormalities, however, may present in an unusual manner and provide amajor hazard to the unsuspecting surgeon.A patient presenting with cholangitis without jaundice or abnormal liver function tests is reported.Endoscopic retrograde cholangiography failed to demonstrate any bile ducts in the right postero-lateralsegments of the liver, the “naked segment sign”. A percutaneous transhepatic cholangiogram demonstrateda stricture obstructing the right posterior segmental hepatic duct with hepatolithiasis above thestricture. At operation an anomalous vessel was found at the site of the stricture.This case highlights the unusual way in which biliary tract anomalies may present and the importanceof adequate pre-operative investigation.


Biliary tact carcinoids are extremely rare: only ten cases have been reported up to now. TheAuthors describe a successfully treated carcinoid tumour ofthe proximal bile duct and review theliterature about these rare malignancies.Despite extensive preoperative work-up, including ultrasound, CT scan and ERCP, a definitediagnosis is hardly possible prior to histologic examination of the operative or necropsyspecimen.Due to the slow-growing nature and the non-aggressive behaviour of these malignancies,surgical resection followed by biliodigestive anastomosis should be the treatment of choice.


Clinicopathologic correlation offive cases ofcystadenomas of the liver are reported. All patientswere female and radical surgical procedure, total excision or resection was performed four times,and partial excision once. In all patients the postoperative course was uneventful and they are allalive and well. Examined by conventional histological and special immuno-histochemical stainsthe tumors fulfilled diagnostic criteria for these rare cystic growths. The cyst wall was composedof three, histologically distinct layers. From the viewpoint of histogenesis and differentialdiagnosis immunohistochemical properties were analysed. CEA and EMA were demonstratedin epithelial cells and Vimentin in stromal cells.


We read with great interest the article by Xynos et al. reporting 2 cases of leishmaniasis in patients treated with biologic drugs  infections occur more frequently than clinically apparent VL cases. An estimated 10%–20% of persons with asymptomatic infections develop clinically overt VL  role in detecting Leishmania infection in this vulnerable patient population. Screening for leishmaniasis has been hampered by the lack of a standard test. Currently available serologic methods have variable sensitivities, specificities, and cross-reactivities, depending on the species being tested and the region where tests are performed. Many experts believe that serologic tests may complement other existing diagnostic tools, raising cost-efficiency concerns, especially in financially deprived countries  result indicates exposure to Variations in specificities and sensitivities limit the diagnostic potential of available diagnostic tools. The context of immunosuppression further contributes to the diagnostic complications and increases the need for additional research in leishmaniasis diagnostics.


Prion diseases are fatal neurodegenerative disorders caused by accumulation of abnormalprion protein . PrPres accumulation is also detected in lymphoidorgans after peripheral infection. Several studies suggest that follicular dendritic cells(FDC) could be the site of PrPres retention and amplification.            in situ and in vitro. When tonsillar cryosections were treated with anti-PrPantibody, the label was found on some very delicate cell extensions inside the lymphoid follicles,especially in the germinal centres. These extensions react with DRC1 antibody, used frequentlyto label FDC. Other structures labelled with anti-PrP antibody were the keratinocytes.Here we show that human follicular dendritic cells can express normal cellular prion protein(PrPc) both             To confirm the ability of FDC to synthesise PrPc, we isolated FDC by a non-enzymaticprocedure and cultured them. By cytochemistry and flow cytometry it was clearly shown thatFDC do produce PrPc.


Stroke caused by brain ischemia is the third leading cause of adult disability. Active prevention and early treatment of stroke targeting the causes and risk factors may decrease its incidence, mortality and subsequent disability. Pien Tze Huang (PZH), a Chinese medicine formula, was found to have anti-edema, anti-inflammatory and anti-thrombotic effects that can prevent brain damage. This study aims to investigate the potential mechanisms of the preventive effects of Pien Tze Huang on brain damage caused by chronic ischemia and hypertensive stroke in rats.The effects of Pien Tze Huang on brain protein expression in spontaneously hypertensive rat (SHR) and stroke prone SHR (SHRsp) were studied with 2-D gel electrophoresis and mass spectrometric analysis with a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF)/TOF tandem mass spectrometer and on brain cell death with enzyme link immunosorbent assay (ELISA) and immunostaining.2 in the electron transfer chain of mitochondria preventing reactive oxygen species (ROS) damage and possibly subsequent cell death (caspase 3 assay) as caused by chronic ischemia or hypertensive stroke to hippocampus and cerebellum.Pien Tze Huang decreased cell death in hippocampus and cerebellum caused by chronic ischemia and hypertensive stroke. Immunostaining of caspase-3 results indicated that Pien Tze Huang prevents brain cells from apoptosis caused by ischemia. Brain protein expression results suggested that Pien Tze Huang downregulated QCRPien Tze Huang showed preventive effects on limiting the damage or injury caused by chronic ischemia and hypertensive stroke in rats. The effect of Pien Tze Huang was possibly related to prevention of cell death from apoptosis or ROS/oxidative damage in mitochondria. Cerebral ischemia and stroke are the major causes of mortality and morbidity worldwide -4. In thHypertension is the most important risk factor for ischemic stroke ,2,11 whicirca 1555 AD) in China, contains musk, Calculus Bovis , Shedan  and Panax notoginseng (Tianqi or Sanqi) and is used to treat liver diseases, cancer and inflammation Click here for fileDirected acyclic graph of proteins. Expressed proteins in cerebellum. [Note: This graph should be read from top to bottom.]Click here for fileFunctional annotation by protein information resources (RIP). 3 most frequent gene ontology in hippocampus and cerebellum.Click here for file


Myocardial MIBG scintigraphy is established in the diagnosis and differential diagnosis of Parkinson's disease (PD). Numerous studies address the pathophysiological impact of myocardial MIBG scintigraphy: the myocardial MIBG uptake correlates with the clinical phenotype of PD; the background of this phenomenon is unclear. Furthermore MIBG scintigraphy enables to study the extracranial Lewy body type-degeneration. In combination with cerebral dopamine transporter imaging, MIBG scintigraphy allows to correlate cerebral and extracranial Lewy body type-degeneration in PD. The accumulation of MIBG is visualized and measured by planar whole-body scintigraphy. In clinical practice, the MIBG scintigraphy is mainly used to detect (and sometimes to treat) neuroendocrine tumours, primarily pheochromocytomas and neuroblastomas /[counts per pixel in the upper mediastium] [The myocardial MIBG scintigraphy measures the postganglionic sympathetic cardiac innervation . In the iastium] , 18. PD iastium] –13. For iastium] , age, diiastium] –24.Coronary heart disease represents an exclusion criterion for myocardial MIBG scintigraphy, since a myocardial hypoperfusion due to coronary heart disease may influence myocardial MIBG scintigraphy. 99mTc-Metoxy-Isopropyl-Isonitril (MIBI) scintigraphy can detect a local myocardial hypoperfusion . TherefoPD is diagnosed clinically. The UK Brain Bank criteria  represenPD and Lewy body dementia (LBD) share a common pathology with a Lewy body type-degeneration of the nervous system. The anatomical distribution of this Lewy body type-degeneration—in PD primarily in the basal ganglia, in LBD primarily in cortical areas—decides whether the patient shows clinical symptoms of PD or LBD. Both diseases, PD and LBD, are characterized by a remarkable Lewy body type-degeneration of postganglionic myocardial sympathetic neurons. Therefore MIBG scintigraphy discloses a pathologically reduced myocardial MIBG uptake in both PD and LBD patients , 39. MyoThere exist only small data to MIBG scintigraphy in hereditary Parkinsonism (HP): Quattrone et al.  reportedIn multiple system atrophy (MSA), the autonomic nervous system is mainly affected in its preganglionic structures, whereas postganglionic involvement of the autonomic nervous system predominates in PD . FollowiOrimo et al.  reportedSmall case series disclosed contradictory findings: Nagayama et al.  observedPatients with essential tremor (ET) reveal a normal myocardial MIBG uptake, as reported by Lee et al.  in 22 ETSince myocardial MIBG scintigraphy measures the sympathetic myocardial function, it is of interest whether myocardial MIBG uptake correlates with other autonomous functions. The autonomous nervous system can be investigated by means of several clinical tests such as orthostatic reaction, deep breathing, or Valsalva manoeuvre. During these clinical tests, the blood pressure (regulated mainly by the sympathetic nervous system), the heart rate, and variability of heart rate (regulated mainly by the parasympathetic nervous system) are measured . There aMyocardial MIBG uptake correlates with motor symptoms in PD; patients with tremor dominant PD reveal a significantly higher MIBG uptake  than patPD is characterized by a cerebral as well as extracranial Lewy body type-degeneration. The cerebral—predominantly nigrostriatal dopaminergic—Lewy body degenerations is usually visualized by cerebral SPECT of the presynaptic dopamine transporters (DAT). As mentioned above, MIBG scintigraphy quantifies exactly the extent of extracranial myocardial sympathetic Lewy body degeneration. It is unclear whether cerebral nigrostriatal dopaminergic and extracranial sympathetic Lewy body degeneration occur independently from each other or not. “Extreme” cases might be possible in whom only the cerebral nigrostriatal system but not the extracranial sympathetic system degenerates or vice versa. The intraindividual comparison between cerebral nigrostriatal DAT SPECT and myocardial MIBG scintigraphy may clarify this aspect: Spiegel et al.  and SpieMyocardial MIBG scintigraphy helps to differentiate between PD and other parkinsonian syndromes in clinically difficult cases. Furthermore, the myocardial MIBG scintigraphy allows insights into the pathophysiology of PD; myocardial MIBG uptake correlates significantly with the motor phenotype and with the nigrostriatal function (measured by DAT SPECT). These facts suggest that cerebral nigrostriatal dopaminergic degeneration and myocardial sympathetic degeneration are closely coupled in PD.


Prediction of optimal cytoreduction in patients with advanced epithelial ovarian caner preoperatively.Patients with advanced epithelial ovarian cancer who underwent surgery for the first time from Jan. to June 2008 at gynecologic oncology ward of TUMS  were eligible for this study. The possibility of predicting primary optimal cytoreduction considering multiple variables was evaluated. Variables were peritoneal carcinomatosis, serum CA125, ascites, pleural effusion, physical status and imaging findings.Univariate comparisons of patients underwent suboptimal cytoreduction carried out using Fisher's exact test for each of the potential predictors. The wilcoxon rank sum test was used to compare variables between patients with optimal versus suboptimal cytoreduction.41 patients met study inclusion criteria. Statistically significant association was noted between peritoneal carcinomatosis and suboptimal cytoreduction. There were no statistically significant differences between physical status, pleural effusion, imaging findings, serum CA125 and ascites of individuals with optimal cytoreduction compared to those with suboptimal cytoreduction.Because of small populations in our study the results are not reproducible in alternate populations. Only the patient who is most unlikely to undergo optimal cytoreduction should be offered neoadjuvant chemotherapy, unless her medical condition renders her unsuitable for primary surgery. Ovarian cancer is the leading cause of morbidity and mortality among the gynecologic cancers . EpithelIt is not possible to do primary optimal debulking for all patients, in these cases primary surgery not only dose not have any benefit but also causes morbidity . The 30-Primary debulking in patients with advanced epithelial ovarian cancer has been compared with chemotherapy and interval debulking in different studies. Equal survival has been reported in patients undergoing primary surgery compared to patients undergoing debulking surgery after taking chemotherapy by Onnes et al. . They haIn 1999, Shwartz et al. demonstrated that women who underwent cytoreductive surgery after induction chemotherapy had statistically improved overall survival compared to women who did not undergo surgery.One randRegarding that residual tumor is more than 1 cm in many patients underwent primary surgiery, considering another method in this group of patients seems necessary. Although neoadjuvant chemotherapy and interval cytoreduction sounds to be good management but its indications have not yet determined.A critical point in order to define indications of neoadjuvant chemotherapy for advanced ovarian cancer is determination of uniform selection criteria that can consistently identify patients with surgically unresectable disease without depriving others from potential advantage associated with an optimal primary resection. Several studies have been done for determining markers which can reliably predict optimal resectability -18. CT-SApproval to conduct this study was obtained from research organization of gynecologic oncology department of Tehran University of Medical Sciences(TUMS). Patients with stage 3 and stage 4 epithelial ovarian cancer underwent primary surgery between Jan. to June 2008 at gynecologic oncology ward of Vali-e-Asr hospital of TUMS were eligible for entering the study.The possibility of predicting primary optimal cytoreduction considering multiple variables was assessed in this group. Variables were peritoneal carcinomatosis, serum CA125 level, ascites, pleural effusion, physical status and imaging findings.All surgeries were performed by gynecologic oncologists of TUMS. Optimal cytoreduction was defined as ≤ 1 cm residual disease. All imagings were reported by the professors of radiology of TUMS. Considered imaging parameters included: omental extention, liver involvement, peritoneal involvement and suprarenal adenopathy. Blood samples for measuring serum CA125 levels were taken at the morning.Physical statusesof patients were defined according to physical status classification of the American society of anesthesiology. In addition we considered optimal and suboptimal cytoreduction. Residual tumor less than 1 cm after surgery was considered as optimal cytoreduction.Univariate comparisons of the percentage of patients who underwent suboptimal cytoreduction carried out using Fisher's exact test for each of the potential predictors. The wilcoxon rank sum test was used to compare variables between patients with optimal versus suboptimal cytoreduction.Forty one patients from patients who were admitted at Vali-e-Asr hospital of TUMS from Jan. to June 2008 met study inclusion criteria. Demographic and clinical data are described in table Peritoneal carcinomatosis and suboptimal cytoreduction had statistically significant assosciation. There were no statistically significant differences between physical status, pleural effusion, imaging findings, CA125 serum levels and ascites in patients with optimal cytoreduction compared to those who underwent suboptimal debulking.Table Our current study identifies intraperitoneal carcinomatosis as being the only statistically significant predictor of suboptimal cytoreduction. Table There is no statistically significant difference between pleural effusions in individuals underwent optimal cytoreduction compared to those with suboptimal cytoreduction. It seems that low number of patients caused this result because the number of patients who were suboptimally cytoreduced is in confidence interval range of those who were optimally cytoreduced.The number of patients in our study is only 41. Considering small sample size of the study, proofing these results demands larger randomized study. We used imaging findings as predictive predictors of suboptimal debulking according to previous studies which had mentioned these factors have predictive value.To date, the predictive performance of clinical parameters, serum CA-125 threshold values, and radiographic imaging criteria have not demonstrated sufficient accuracy to achieve widespread applicability ,21-24.The most common criteria cited as justification for abandoning an up-front attempt at surgical cytoreduction are ascites volume greater than 1000 ml, peritoneal carcinomatosis, parenchymal liver disease, splenic metastasis or omental extension to the spleen, porta hepatitis disease, and bulky disease involving the diaphragm one of tOne of the principle difficulties in development of any reliable predictive model of surgical outcome for patients with advanced ovarian cancer is the challenge of factors in the significant impact of each institute surgeons' philosophy, effort and ability to utilize advanced surgical techniques to achieve maximal cytoreduction, in order to omit this factor, in this study all surgeries were performed by gynecologic oncology professors of TUMS.In summary, identification of risk factors for suboptimal cytoreduction in small populations such as ours is not reproducible in alternate populations. Until prospective randomized trials have demonstrated that neoadjuvant chemotherapy followed by interval cytoreduction is equivalent in terms of survival outcomes to primary optimal cytoreduction followed by chemotherapy, extreme caution should be used when applying preoperative predictors to decide between primary surgical exploration and neoadjuvant chemotherapy in the medically fit patient. Only the patient who is most unlikely to undergo optimal cytoreduction should be offered neoadjuvant chemotherapy, unless her medical condition renders her unsuitable for primary surgery.The authors declare that they have no competing interests.AM: supervised research project, carried out operations, supervised statistics. MMM: participated in operation as first aid, collect data, drafted the manuscript, and acted as corresponding author and did the revisions. MMG: carried out operations, she was head of the department. FG: carried out operations. NB: carried out operations. SA: participated in operation as first aid.


Immature teeth with necrotic pulp and large periapical lesion are difficult to treat via conventional endodontic therapy. The role of materials such as calcium hydroxide and mineral trioxide aggregate in apexification is indispensable. This case report presents the successful healing and apexification with combined use of white mineral trioxide aggregate and demineralized freeze-dried bone allograft. Complete asepsis and three-dimensional obturation of the root canal system are essential for long-term endodontic success. In certain cases such as immature teeth, the absence of natural apical constriction creates a challenge. Therefore, one of the aims of endodontic treatment is to produce an apical barrier or stop, against which one can place a root canal filling material avoiding overextrusion. This technique is termed apexification.Clinicians have tried several materials to form apical barrier in the past. These include: calcium hydroxide paste, calcium hydroxide powder; mixed with different vehicles,–3 tricalMineral trioxide aggregate (MTA) was developed at Loma Linda University for use as a root-end filling material. MTA has 13Bio-resorbable demineralized bone matrix (DMBM) is the protein component of bone and is widely used in various clinical conditions such as periodontal defects and oral and maxillofacial bone defects. Periodontal defects grafted with demineralized bone matrix allograft showed histologic evidence of regeneration of new bone and periodontium. ConsiderThe apical matrix of some resorbable and biocompatible material is essential to control extrusion of MTA. “Modified matrix concept” for repair of perforation utilized resorbable collagen as a matrix followed by condensation of MTA. ConsiderTherefore, present case report highlights the nonsurgical management of symptomatic tooth with blunderbuss canal and large periapical radiolucency using bio-resorbable demineralized bone matrix and MTA.A 16-year-old male patient of south Indian origin reported to the department of conservative dentistry and endodontics, PMNM Dental College and Hospital, Bagalkot, Karnataka, India, with the complain of pain in right mandibular posterior teeth since 3 weeks. Careful intraoral examination revealed sinus opening in relation to the right lower second premolar. Hard tissue examination revealed the presence of “dens evaginatus” and a deep pit in right mandibular second premolar . ConcernDespite the higher success rate of apical barrier formation using calcium hydroxide, long-term follow-up is essential. Problems such as failure to control infection, recurrence of infection, and cervical root fracture may occur.18 ApexifMTA has superior biocompatibility and sealing ability and is less cytotoxic than other materials currently used in pulpal therapy. The 5-mmApexification using MTA lessens the treatment time between the patient’s first appointment and the final restoration. The importance of this approach lies in the expedient cleaning and shaping of the root canal, followed by apical seal with a material that favors regeneration. In addition, there is reduced potential for fracture of immature teeth with thin roots, because of immediate placement of bonded core within the root canal.In the present case, combination of calcium hydroxide and iodoform was used as intracanal medicament for 15 days to make the canal dry and free from infection. Use of calcium hydroxide for such a short term does not adversely affect the fracture resistance of the tooth.The demineralized bone matrix acts as an osteoconductive and possibly as an osteoinductive material.26 Hence,Decalcified freeze-dried bone allograft material has been extensively used in the management of extensive periodontal defects. Its use results in significant probing depth reduction, clinical attachment gain, and bone fill. Definite evidence exists that sites grafted with DFDBA heal with regeneration of periodontium.28 Follow‘Dens evaginatus’ or ‘evaginated odontoma’ is a developmental anomaly that occurs more often in mandibular premolars; however,This case report presents a novel approach to achieve single visit apexification of the cases with open apex and large periapical lesion. Present case also stresses the early detection and treatment of ‘dens evaginatus’ which if undetected can cause undue damage.


C. elegans and Drosophila), have contributed enormously to defining homology. The characteristics of specificity and memory and whether the antigen is pathogenic or nonpathogenic reveal considerable information on homology, thus deconstructing the more fundamentalist view. Senescence, cancer, and immunosuppression often associated with mammals that possess both innate and adaptive immunity also exist in invertebrates that only possess innate immunity. Strict definitions become blurred casting skepticism on the utility of creating rigid definitions of what innate and adaptive immunity are without considering overlaps.Adaptive immunity has often been considered the penultimate of immune capacities. That system is now being deconstructed to encompass less stringent rules that govern its initiation, actual effector activity, and ambivalent results. Expanding the repertoire of innate immunity found in all invertebrates has greatly facilitated the relaxation of convictions concerning what actually constitutes innate and adaptive immunity. Two animal models, incidentally not on the line of chordate evolution ( All multicellular animals (invertebrates and vertebrates) manage to keep self-integrity. Any attempt to answer questions concerning immune recognition must consider the universality of receptor-mediated responses. These may designate two forms: 1) rearranging clonally distributed antigen-specific receptors that distinguish between self and nonself according to classical Burnet hypothesis; and/or 2) pattern recognition receptors introduced by Janeway [ rearrang pattern With this in mind, we felt compelledto clarify and extend what seems to be the blurring or masking of certainimmunological characteristics of invertebrates and vertebrates –8. TodoAncient innate immunity-related functions like phagocytosis and cytokine production  were already developed 700 million years ago in sponges and higher aquatic invertebrates . These fundamental functions remained unaltered during phylogenesis. A major evolutionary step happened 500 million years ago when fish developed jaws accompanied by evolution of the gut associated immune system. This system was fundamental to providing the genetic material required for recombination and mutation to produce variability and diversity of proteins . This system also enabled the occurrence of a wide spectrum of antigen-presenting proteins like the major histocompatibility complex (MHC). These MHC molecules developed from a primordial molecule over 300 million years ago .A genetically colorful background is generally considered to be advantageous for species in their constant adaptation to the neighboring environment. On the other hand, for a suddenly emerging costly macroscopic function like adaptive immunity, working with clonally distributed receptors, intraspecies genetic backcrosses can make survival difficult. Therefore, in such cases, interspecies borders may help the genetic solidification of evolutionarily novel characteristics. However, drawing interspecies borders is not always easy as often seen in cases of hybridogenesis with certain invertebrate arthropods or even with vertebrate fish and amphibian species –12.In the case of invertebrate organisms, species survival is maintained at the population level,which is risky for individuals. Whenever a new pathogen takes its toll, theremaining individuals are spared because they are more resistant than others.Such differences are genetically encoded . HoweverEcological immunology is a young but increasing science that examines causes and consequences of changes in immune function in the context of evolution and of ecology. Millions of invertebrate species depend exclusively on using innate immunity, in contrast to the only 45 000 vertebrate species that employ an additional acquired immune system. Regardless of this major distinction, most studies of ecological immunology discuss only vertebrates. Nevertheless, insect immunity might be more specific and similar to vertebrate immunity than previously thought –17.An explanation to why an anticipatory immune system employing clonally distributed receptors has not developed in invertebrates may be provided by immunological ecology. Highly developed organisms tend to be large in size. Since the size of individual cells does not show significant interspecies variances, being larger means having more cells. Adaptive immunity works with a huge number of recognition molecules distributed in a clonal pattern. Therefore, only highly developed organisms can afford to run such a costly immune system; otherwise costs would always outweigh benefits. It seems that having huge and complex communities of cells not only demands a highly effective adaptive immune system, but actually provides its basic framework in order to exist , 19.Senescence and age-related research isa promising approach that discovers revolutionary data. Immunological senescence of vertebrate adaptive immunity is a process widely accepted by most immunologists. This is, however, less evident when thinking in terms of invertebrate innate immunity. However, this will likely change in the near future as there is accumulating evidence of senescence and more specifically immunological senescence in invertebrate species.Morphological features of the aging process (senescence) have been recognized for many years in invertebrates. For example, when earthworms are maintained for long periods in the laboratory, a progressive decrease in size reminiscent of degeneration and a kind of wasting syndrome occur . Congo rDrosophila melanogaster expresses increasing levels of numerous antimicrobial peptides if exposed to septic bacterial infections, but not in response to bacterial extracts [Caenorhabditis elegans ortholog of the above MRG15) in the aging process has also been demonstrated [Caenorhabditis elegans and this function seems to be evolutionarily conserved: the DAF pathway also affects aging in Drosophila melanogaster and rodents [Caenorhabditis elegans are also regulated by the TGFβ-like and the p38 MAPK pathways. The requirement of the DAF-2 cascade in regulating senescence and immunity raises molecular-level linkage of these processes [During senescence, extracts . Mortalinstrated . The DAF rodents . Innate ocesses .Cancer development has often been addressed in vertebrate species especially its relation with adaptive immunity. However, invertebrates also develop tumors in response to environmental carcinogens. Studying cancer development in species possessing innate immunity alone is a very promising field of research and may highlight adaptivelike functions present in invertebrates.Mytilus edulis homologue of vertebrate ras and p53 demonstrates extreme evolutionary conservatism in active domains, including four mutational hot spots [Mya arenaria have also been reported [Mussels are vulnerable to several environmental toxicants and carcinogens. DNA sequence alignment of the ot spots . Cases oreported –30.Drosophila offers a unique platform for the rapid identification and characterization of tumor suppressor genes, many of which have mammalian homologues. Genomewide microarray analysis of Drosophila brain tumor caused by the disfunction of the Brat tumor suppressor gene has identified over three hundred associated genes. Sixty of these sequences show homology to existing mammalian genes involved in tumor development [wts) sequence. The wts sequence was identified by the massive overgrowth of clones homozygous for wts deletion [elopment . As in deletion , 33. Sideletion .Cotesia congregata is a wasp thatinjects its eggs into the host caterpillar Manduca sexta. However, inthis particular host-parasite relation, the presence of a third partner isnecessary for successful parasitism: a bracovirus. The C. congregata bracovirus (CcBV) is injected simultaneously with the wasp eggs. Expression ofviral genes hijacks the caterpillar's immune defense responses, which favorsthe survival and development of adult parasitoid wasps [blurring of immunological functions [For those who believein the orthodox split between innate and adaptive immunities in terms of characteristics,it is perhaps difficult to accept the existence of viruses that specifically suppressthe cellular components of innate immunity. Nevertheless, as proved by experimentaldata, innate immunity-specific immunosuppressive viruses exist. id wasps , 64. Thid wasps . In inveunctions .C. elegans and Drosophila. In contrast, the lophotrochozoan systems share some distinct differences; mollusks may havemanaged immunological defense in a special manner similar to the annelidsincluding earthworms [Numerous examples have been presented of animal immune responses that may developfollowing challenge by pathogenic organisms or nonpathogenic stimuli . Here, rthworms   [Sea urchins and seastars exhibit immune responses against grafted tissues similar to those foundin vertebrates , 50. Thed Fu/HC) , 75–78.Ciona intestinalis has been sequenced, it allows for the rapid identification ofearly evolutionary roots of adaptive immunity. In the hemocytes of C. intestinalis, certain adaptive-immunity homologous ESTs have been identified including vWF-like (von Willebrandfactor-like), distant homologues of type I interferon (IFN) receptors, and C6-like(complement 6-like) elements [Since the complete genome of the urochordate elements , 80. Moelements .The emergence of adaptive immunity was not a sudden event; its far-reaching evolutionary roots are currently under investigation by modern molecular biological methods. Genomewide sequence analysis of invertebrates has focused on the genes of innate immunity including complement components, Toll-like receptors, and those involved in intracellular signal transduction of immune responses. Assessment of extracellular C-type lectins, immunoglobulin domains, intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs), and immunoreceptor tyrosine-based activation motifs (ITAMs)  suggests that activating and inhibitory receptors have an early evolutionary origin .α−1, and GM-CSF. Malagoli et al.have identified a putative helical cytokine in Drosophila melanogaster by elaborate bioinformatics transcriptomeanalysis. It is very promising that transcription from this homologue isupregulated in parallel with the known antimicobial factors defensin andcecropin A1 following Gram− or Gram+ challenge [Pacifastacus leniusculus by mass spectrometry and PCR using degenerate primers. An astakine homologue has also been identified in the shrimp Penaeus monodon. In vertebrates, PK domains direct angiogenic growth. It has been demonstratedthat injections of recombinant astakine actively influencedifferentiation and growth of hemopoietic stem cells in vivo [After decades of anticipation, the ancestors of some cytokines—soluble intercellular signaling moleculesthat form a complex network for the regulation of immunity—have recently beenidentified. In vertebrates, helical cytokines inlude IL2, IL6, INF hallenge , 84. Si in vivo .14 unique VLR receptors [It is a notable observation that even our most distant vertebrate relatives, jawless fish, have an adaptivelike immune system. It operates by means ofclonally distributed leucine-rich repeat (LRR) receptors (similar to Toll-likereceptors) using a novel mechanism of gene rearrangement other than RAG. TheseLRR modules constitute the variable lymphocyte receptors (VLRs). Computer-assistedprediction suggests a repertoire of approximately 10ceptors –89. In rceptors . Recent ceptors .blurring and the strict distinction between innate and adaptive immunitiesmight need revision  . Consequrevision .


Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Klebsiella pneumonae. The activity data show the metal complexes to be more active than the parent freeligands against one or more bacterial species.Biologically active complexes of Co(II), Ni(II), Cu(II) and Zn(II) with novel ONO, NNO andSNO donor pyrazinoylhydrazine-derived compounds have been prepared and characterized on the basis ofanalytical data and various physicochemical studies. Distorted octahedral structures for all the complexeshave been proposed. The synthesized ligands and their complexes have been screened for their antibacterialactivity against bacterial species