First examples of peptidomimetic inhibitors of interleukin-1 beta converting enzyme.
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Biomedical subjects
Publications and source records attributed to A Saha.
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BACKGROUND: Dural lesions incurred during endonasal sinus surgery must be repaired surgically because of the risk of potentially fatal late meningitis. DESIGN: Retrospective survey. SETTING: Ear, nose, and throat department of a university teaching hospital. PATIENTS: Consecutive sample of 47 patients who had undergone duraplasty for repair of a dural lesion that occurred as a complication of endonasal sinus surgery. Forty-two patients were interviewed after an average postoperative period of more than 5 years. INTERVENTION: Endonasal duraplasty, external duraplasty (fronto-orbital or transfrontal extradural approach) by underlay or onlay technique. MAIN OUTCOME MEASURES: Fluorescein test (intrathecal administration of fluorescein sodium and subsequent nasal endoscopy), subjective complaints, history of meningitis, cerebrospinal fluid rhinorrhea, or hyposmia. RESULTS: There were 44 endonasal and 3 external duraplasties (2 by the fronto-orbital and 1 by the transfrontal extradural approach); the underlay technique was used in 25 and the onlay technique in 22. The fluorescein test, performed in 43% (20/47) of the patients was negative in all cases. Twenty-six percent of the patients had had 1 or more episodes of bacterial sinusitis without meningitis. Duraplasty was clinically intact in 100%. Postoperative olfactory disturbances were reported in 17%. CONCLUSIONS: Duraplasty can be performed satisfactorily by the endonasal route, thus avoiding the disadvantages of the fronto-orbital approach (visible scar, risk of damage to the supraorbital nerve, and removal of bone from the floor of the frontal sinus with a tendency to stenosis of the nasofrontal duct and subsequent mucocele). Allogeneic connective tissue in combination with fibrin glue has proved suitable as a graft material.
Two-hundred-and-seventeen children admitted with diarrhoea and 204 unmatched controls hospitalized during the 2-year period from November 1990 to October 1992 were included in this prospective study. Their stool samples were subjected to microscopy, cultures, ELISA for rotavirus and electron microscopy. Human rotavirus (HRV) was detected in 68 (31 per cent) of the stool samples in the study group and 12 (6 per cent) in the control group. There was an increased incidence in the cooler months of the year; typically, most of the affected infants and children presented with vomiting and respiratory symptoms, and had mild to moderate dehydration. Biochemical profile showed normal or hyponatraemia and normokalaemia. A more detailed community-based study of diarrhoeal diseases in Oman is to follow this pilot study.
The reactions of OH and eaq- adducts of cytosine, cytidine and deoxycytidine in the presence of Cu(II) ions have been studied by product analysis and pulse radiolysis. The product analysis studies show that the degradation of the base is enhanced in N2O-saturated conditions in the presence of Cu(II) ions and the major radiolytic products are Cu(I), cytosine glycols and 5(6)-hydroxycytosine. It is also interesting to note that the yields of Cu(I) are equivalent to cytosine degradation yields, which suggests that the interaction of the OH adducts with Cu(II) ions restricts the radical recombination reactions (known to be the major physicochemical repair process) which partly regenerate the parent cytosine. The rate constants of the reactions of cytosine OH adducts with Cu(II) ions determined by pulse radiolysis lie between 10(7) and 10(8) dm3 mol-1 s-1. The growth in the transient absorption spectra of cytosine OH adducts in the range 330-400 nm, observed in the presence of copper(II) ions in free and complexed state, suggests formation of copper radical adduct which decays by water insertion at the copper-carbon bond to give glycol as the major product. Such copper radical adduct formation was also observed in the case of cytidine and deoxycytidine. The protonated electron adducts (at the hetero atoms) of cytosine, cytidine and deoxycytidine transfer electrons to the Cu(II) ions with rate constants of 10(8) and 10(9) dm3 mol-1 s-1. Here no adduct formation is observed. The steady-state results show that such electron transfer reactions regenerate the parent molecules themselves. Hence such electron transfer reactions do not contribute to enhanced base degradation in the presence of copper ions.
Effect of gamma radiation on flavocytochrome b2 in dilute aqueous solution was studied. A study of the effect of the radiolytically produced inorganic free-radical anions such as I2.-, Br2.- and (SCN)2.- on the enzyme activity indicates the involvement of cysteine and tyrosine residues in the catalytic activity of flavocytochrome b2. The changes in kinetic parameters, i.e., Michaelis-Menten constant Km and maximal velocity Vmax, due to irradiation under different conditions suggest that radiation induced enzyme inactivation is the result of destruction of active-site residues as well as modification of the substrate binding site. Fluorescence studies of unirradiated and irradiated enzyme reveal that FMN (flavin mononucleotide) is inaccessible to water radicals.
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Cytokines and thymic hormones are thought to play critical roles in the regulation of T-lymphocyte development and function. In an effort to determine the effectiveness of such agents in an immunotherapeutic strategy, we employed aged mice in a hydrocortisone treatment model to generate an immunodeficient state and to study its reconstitution. Mice were given five daily injections of a natural cytokine mixture (NCM), recombinant interleukins (rIL-1, rIL-2) or their combination, thymosin alpha 1 or fraction 5 (T alpha 1, TF5), or the combinations of NCM plus T alpha 1 and of NCM plus TF5. Spleen and thymus weights were obtained and the cellular responses to stimulation in vitro with NCM, IL-1, IL-2 and mitogens (PHA and Con A) were assayed. Both NCM and T alpha 1 in vivo treatment augmented thymocyte and splenocyte in vitro responses to both interleukins and mitogens. Neither treatments with equivalent doses of rIL-1, rIL-2 nor their combination, nor TF5 achieved similar results. Of all the treatments, only NCM plus T alpha 1 augmented spleen weight; none augmented thymus weight. Surface marker analyses of T-lymphocytes and subsets indicate that treatment of mice with NCM plus T alpha 1 increased spleen T-cell numbers of both CD4 and CD8 positive cells significantly. These data indicate that NCM and T alpha 1 alone and in combination may be therapeutically useful to restore T-lymphocyte number or function in secondary immunodeficiency.
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The obliteration of the frontal sinus via an osteoplastic approach is performed with the aim of achieving a permanent 'switching off' by final and conclusive clearing out. For this, freshly harvested abdominal fat has shown itself to be the best clinically. It is possible to demonstrate the vitality of fat transplanted into the frontal sinus without an operation, i.e. by a macroscopical and histological examination using magnetic resonance imaging (MRI). The magnetic resonance examinations were carried out on a supraconductive 0.5 T Magnet (Gyroscan T.S.II, Philips Medicine Systems, Eindhoven, Netherlands) with a quadrature (square) head spool. We produced T1-weighted spin echo images (TR: 450-550 ms; TE: 20-25 ms), T2-weighted fast spin echo images or in double-echo technique in transverse orientation (Turbo SE or TR: 2000-2500 ms; TE: 50-90 ms) and short tau inversion recovery (STIR) sequences for fat suppression (TJ: 140 ms; TR: 1400 ms; TE: 30 ms). The fat implanted into the frontal sinus of 11 patients aged 22-65 years, having undergone an osteoplastic frontal sinus operation with obliteration, was examined post-operatively by MRI. Objectives were the time-dependent distribution of portions of vital fatty or connective tissue, the eventual development of necroses or cysts as well as recurrences, inflammatory complications or re-epithelization of the frontal sinus four to 24 months post-operatively. In only six out of 11 cases was vital fatty tissue found. Fatty necrosis occurred five times, whereas in four cases a transformation into granulation tissue and in one case into connective tissue could be seen. All 11 patients were complaint-free. Long-term observations are needed to see if differences in the recurrence rate of frontal sinus disease are dependent on whether the implanted fat remains vital or necrosed and transformed.
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Varietal resistance of tea towards Bipolaris carbonum was tested following detached leaf inoculation technique. Among the fourteen varieties tested, three were found to be highly susceptible, while other three were resistant. Leaf exudates and diffusates collected from the resistant varieties were more fungitoxic than those from the susceptible ones. Two antifungal compounds isolated from healthy and B. carbonum-infected tea leaves exhibited clear inhibition zones at RF 0.8 and 0.65, respectively, in a chromatographic bioassay. On the basis of their color reaction on TLC and UV-spectra these were identified to be catechin and pyrocatechol. Resistant and susceptible varieties accumulated 439-510 and 187-212 micrograms/g fresh mass tissue of pyrocatechol, respectively, 2 d after inoculation with B. carbonum, while a low concentration (45-58 micrograms/g) of this compound was detected in healthy leaf tissue.
There were 63 patients of Ebstein's anomaly of tricuspid valve encountered from 1976 to 1991; 28 (44.4%) were male and 35 (55.6%) female. Their age at presentation ranged from 3 months to 51 years. Five (7.9%) patients were asymptomatic, 48 (76.2%) had class II-III exertional dyspnoea, palpitation or both. Thirty patients (47.6%) had cyanosis. Electrocardiogram showed paroxysmal atrial fibrillation in two, chronic atrial fibrillation in four (6.3%), paroxysmal supraventricular tachycardia in seven, atrial or ventricular ectopic beats in five (7.9%), 2:1 atrioventricular block in one (1.6%), complete atrioventricular block in two (3.2%) and type B WPW syndrome in nine patients (14.3%). Chest X-ray showed diminished vascularity in 22 (34.9%). Diagnosis was established by cardiac catheterization and or echocardiography. Atrialized right ventricular chamber was demonstrated in 51 (80.9%) by angiography and in 40 (63.5%) by electrophysiology. Patients were followed up for 1-172 months. Seventeen patients (26.9%) required surgery. Three patients (4.8%) died during medical follow-up, and five (7.9%) died following surgery. Survival probability for 46 medical patients was 88.9% at 172 months. Factors affecting survival were pulmonary blood flow, cyanosis, clubbing and systemic arterial oxygen saturation.
The objective of this study was to determine the long-term survival pattern and variables affecting long-term survival and complications occurring during follow-up of patients with Eisenmenger syndrome. A retrospective study of patients diagnosed with Eisenmenger syndrome were followed up. A tertiary care centre was used and it provided superspeciality services in various disciplines. The subjects included 201 patients with Eisenmenger syndrome--diagnosed by a combination of echocardiography and a peripheral arterial oxygen saturation study and/or cardiac catheterisation with or without angiocardiography--worked up and followed up for variable duration over a period of 16 years from 1976 to 1992. One hundred nine patients were females and 92 were males--age of presentation varied from 3 months to 62 years (mean +/- standard deviation 19.23 +/- 12.62 years). A total of 12 different anatomic lesions were seen--the most common three being ventricular septal defect (33.33%), aterial septal defect (29.85%), and patent ductus arteriosus (14.23%). History, physical examination, chest skiagram and electrocardiogram established only the presence of pulmonary arterial hypertension except where differential cyanosis indicating ductus was discernible or the degree of splitting of second heart sound provided some clue to the level of shunt. Contrast echocardiography, completed in 25.4% established the level of shunt in all patients. In others the diagnosis was confirmed by cardiac catheterisation. Twenty patients died during a mean follow-up period of 54.6 +/- 54.47 months. Sudden cardiac deaths (30%), congestive heart failure (25%) and haemoptysis (15%) were the most predominant causes of death. Only one patient died during puerperium.(ABSTRACT TRUNCATED AT 250 WORDS)