Trace amounts of enhancing factor/phospholipase A<SUB>2</SUB> in mouse peritoneal exudate cells

Enhancing factor (EF), a mouse phospholipase A2 (PLA2), has been purified from the small intestines, based on its ability to increase the binding of epidermal growth factor in a radioreceptor assay. EF/PLA2 was found to be localized predominantly in the Paneth cells in the small intestines. Whether mouse intestinal EF/PLA2 is identical/similar to mouse secretory PLA2 was to be determined. Phospholipases are known to play a crucial role in the process of inflammation. This paper reports the presence of trace amounts of EF/PLA2 in the peritoneal exudate cells. Western blot analysis of the acid extracts showed the presence of a 14 kDa immunologically cross-reactive protein. RT-PCR analysis using EF specific primers amplified a ~700 bp product which was further confirmed to be EF-specific by nested PCR analysis and sequencing. Presence of EF in the peritoneal exudate cells could be a unique mode of transport of growth factor modulator to the site of injury to aid in regeneration/cell proliferation of damaged tissue

Prognosis of operable squamous cell carcinoma of the esophagus. Relationship with clinicopathologic features and DNA ploidy

Background: Reports on the influence of various prognostic factors in carcinoma of the esophagus are conflicting. The prognostic value of a set of clinicopathologic factors and DNA ploidy were examined in 74 patients with surgically resected squamous cell carcinoma of the lower and middle third of the esophagus. Methods: All patients had surgery performed in a single thoracic surgical unit at the Tata Memorial Hospital between January, 1984 and December, 1987. The clinicopathologic factors studied were (1) gross residual disease at operation; (2) morphology of the tumor; (3) depth of microscopic invasion; (4) lymph node involvement; (5) histologic grade; (6) vascular and lymphatic embolism; and (7) sex. DNA ploidy and S-phase fraction (SpF) were determined by flow cytometry on archival tissues extracted from paraffin blocks. Ploidy status could be determined successfully in all 74 tumors, whereas SpF could be assessed only in 25. Results: Of the various prognostic factors examined with the Cox stepwise regression model, residual disease (P = 0.000), depth of invasion (P = 0.047), and lymph node status (P = 0.077) were found to be correlated with overall survival. Conclusions: DNA ploidy was not related to prognosis. The overall survival of this group of patients at 36 months was 28%, and median survival was 18 months

Evaluation of prescribing pattern of drugs use in patients of coronary artery disease at a tertiary care hospital

Background: Coronary artery disease (CAD) is a major cause responsible for mortality more in younger age group than in elderly. Studies have reported underuse of four evidence based medicines namely aspirin, β-blockers, angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB), and statins in patients with CAD, particularly in developing countries. Therefore, this study was planned to analyse the prescriptions of patients with CAD to determine the appropriateness of the prescriptions.Methods: After obtaining the Institutional ethics committee permission, a cross sectional observational study was conducted at a tertiary care hospital. Total 150 patients were enrolled from the outpatient department, wards and intensive care unit of medicine department. Total 150 patients’ prescriptions presenting with varied category of CAD were screened and analysed.Results: The most common categories of CAD encountered was ST segment elevated myocardial infarction (N=50, 33%) followed by chronic stable angina (N=29, 20%). Among the drugs prescribed, antiplatelet drugs were prescribed to 135 (90%), hypolipidemics to 134 (89%), nitrates to 114 (76%), beta blockers to 97 (65%), ACE inhibitors to 94 (64%), anticoagulants to 60 (40%) and miscellaneous drugs to 52 (35%), patients. Of 68 (45%) patients with type 2 diabetes mellitus, 15 (22%) were prescribed only metoprolol and others were given ACE-I or ARBs.Conclusions: Among four evidence based drugs, use of 3 drugs, antiplatelets, beta blockers and hypolipidemics was apparent in 90% of prescriptions. Use of ACE inhibitors and ARBs was observed in type 2 diabetic patients with CAD, reflecting rational prescribing behavior of clinicians

S110, a novel decitabine dinucleotide, increases fetal hemoglobin levels in baboons (P. anubis)

<p>Abstract</p> <p>Background</p> <p>S110 is a novel dinucleoside analog that could have advantages over existing DNA methyltransferase (DNMT) inhibitors such as decitabine. A potential therapeutic role for S110 is to increase fetal hemoglobin (HbF) levels to treat β-hemoglobinopathies. In these experiments the effect of S110 on HbF levels in baboons and its ability to reduce DNA methylation of the γ-globin gene promoter in vivo were evaluated.</p> <p>Methods</p> <p>The effect of S110 on HbF and γ-globin promoter DNA methylation was examined in cultured human erythroid progenitors and in vivo in the baboon pre-clinical model. S110 pharmacokinetics was also examined in the baboon model.</p> <p>Results</p> <p>S110 increased HbF and reduced DNA methylation of the γ-globin promoter in human erythroid progenitors and in baboons when administered subcutaneously. Pharmacokinetic analysis was consistent with rapid conversion of S110 into the deoxycytosine analog decitabine that binds and depletes DNA.</p> <p>Conclusion</p> <p>S110 is rapidly converted into decitabine, hypomethylates DNA, and induces HbF in cultured human erythroid progenitors and the baboon pre-clinical model.</p

Cardiogenesis with a focus on vasculogenesis and angiogenesis

The initial intraembryonic vasculogenesis occurs in the cardiogenic mesoderm. Here, a cell population of proendocardial cells detaches from the mesoderm that subsequently generates the single endocardial tube by forming vascular plexuses. In the course of embryogenesis, the endocardium retains vasculogenic, angiogenic and haematopoietic potential. The coronary blood vessels that sustain the rapidly expanding myocardium develop in the course of the formation of the cardiac loop by vasculogenesis and angiogenesis from progenitor cells of the proepicardial serosa at the venous pole of the heart as well as from the endocardium and endothelial cells of the sinus venosus. Prospective coronary endothelial cells and progenitor cells of the coronary blood vessel walls (smooth muscle cells, perivascular cells) originate from different cell populations that are in close spatial as well as regulatory connection with each other. Vasculo‐ and angiogenesis of the coronary blood vessels are for a large part regulated by the epicardium and epicardium‐derived cells. Vasculogenic and angiogenic signalling pathways include the vascular endothelial growth factors, the angiopoietins and the fibroblast growth factors and their receptors

Biliary atresia

Biliary atresia (BA) is a rare disease characterised by a biliary obstruction of unknown origin that presents in the neonatal period. It is the most frequent surgical cause of cholestatic jaundice in this age group. BA occurs in approximately 1/18,000 live births in Western Europe. In the world, the reported incidence varies from 5/100,000 to 32/100,000 live births, and is highest in Asia and the Pacific region. Females are affected slightly more often than males. The common histopathological picture is one of inflammatory damage to the intra- and extrahepatic bile ducts with sclerosis and narrowing or even obliteration of the biliary tree. Untreated, this condition leads to cirrhosis and death within the first years of life. BA is not known to be a hereditary condition. No primary medical treatment is relevant for the management of BA. Once BA suspected, surgical intervention (Kasai portoenterostomy) should be performed as soon as possible as operations performed early in life is more likely to be successful. Liver transplantation may be needed later if the Kasai operation fails to restore the biliary flow or if cirrhotic complications occur. At present, approximately 90% of BA patients survive and the majority have normal quality of life

A strategy to discover new organizers identifies a putative heart organizer

Organizers are regions of the embryo that can both induce new fates and impart pattern on other regions. So far, surprisingly few organizers have been discovered, considering the number of patterned tissue types generated during development. This may be because their discovery has relied on transplantation and ablation experiments. Here we describe a new approach, using chick embryos, to discover organizers based on a common gene expression signature, and use it to uncover the anterior intestinal portal (AIP) endoderm as a putative heart organizer. We show that the AIP can induce cardiac identity from non-cardiac mesoderm and that it can pattern this by specifying ventricular and suppressing atrial regional identity. We also uncover some of the signals responsible. The method holds promise as a tool to discover other novel organizers acting during development

Concordance in diabetic foot ulceration : a cross-sectional study of agreement between wound swabbing and tissue sampling in infected ulcers

BACKGROUND: There is inadequate evidence to advise clinicians on the relative merits of swabbing versus tissue sampling of infected diabetic foot ulcers (DFUs). OBJECTIVES: To determine (1) concordance between culture results from wound swabs and tissue samples from the same ulcer; (2) whether or not differences in bacterial profiles from swabs and tissue samples are clinically relevant; (3) concordance between results from conventional culture versus polymerase chain reaction (PCR); and (4) prognosis for patients with an infected DFU at 12 months' follow-up. METHODS: This was a cross-sectional, multicentre study involving patients with diabetes and a foot ulcer that was deemed to be infected by their clinician. Microbiology specimens for culture were taken contemporaneously by swab and by tissue sampling from the same wound. In a substudy, specimens were also processed by PCR. A virtual 'blinded' clinical review compared the appropriateness of patients' initial antibiotic regimens based on the results of swab and tissue specimens. Patients' case notes were reviewed at 12 months to assess prognosis. RESULTS: The main study recruited 400 patients, with 247 patients in the clinical review. There were 12 patients in the PCR study and 299 patients in the prognosis study. Patients' median age was 63 years (range 26-99 years), their diabetes duration was 15 years (range 2 weeks-57 years), and their index ulcer duration was 1.8 months (range 3 days-12 years). Half of the ulcers were neuropathic and the remainder were ischaemic/neuroischaemic. Tissue results reported more than one pathogen in significantly more specimens than swabs {86.1% vs. 70.1% of patients, 15.9% difference [95% confidence interval (CI) 11.8% to 20.1%], McNemar's p-value < 0.0001}. The two sampling techniques reported a difference in the identity of pathogens for 58% of patients. The number of pathogens differed in 50.4% of patients. In the clinical review study, clinicians agreed on the need for a change in therapy for 73.3% of patients (considering swab and tissue results separately), but significantly more tissue than swab samples required a change in therapy. Compared with traditional culture, the PCR technique reported additional pathogens for both swab and tissue samples in six (50%) patients and reported the same pathogens in four (33.3%) patients and different pathogens in two (16.7%) patients. The estimated healing rate was 44.5% (95% CI 38.9% to 50.1%). At 12 months post sampling, 45 (15.1%) patients had died, 52 (17.4%) patients had a lower-extremity ipsilateral amputation and 18 (6.0%) patients had revascularisation surgery. LIMITATIONS: We did not investigate the potential impact of microbiological information on care. We cannot determine if the improved information yield from tissue sampling is attributable to sample collection, sample handling, processing or reporting. CONCLUSIONS: Tissue sampling reported both more pathogens and more organisms overall than swabbing. Both techniques missed some organisms, with tissue sampling missing fewer than swabbing. Results from tissue sampling more frequently led to a (virtual) recommended change in therapy. Long-term prognosis for patients with an infected foot ulcer was poor. FUTURE WORK: Research is needed to determine the effect of sampling/processing techniques on clinical outcomes and antibiotic stewardship. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Regulation of proteinaceous effector expression in phytopathogenic fungi

Effectors are molecules used by microbial pathogens to facilitate infection via effector-triggered susceptibility or tissue necrosis in their host. Much research has been focussed on the identification and elucidating the function of fungal effectors during plant pathogenesis. By comparison, knowledge of how phytopathogenic fungi regulate the expression of effector genes has been lagging. Several recent studies have illustrated the role of various transcription factors, chromosome-based control, effector epistasis, and mobilisation of endosomes within the fungal hyphae in regulating effector expression and virulence on the host plant. Improved knowledge of effector regulation is likely to assist in improving novel crop protection strategies