Biomedical subjects
Publications and source records attributed to S Singh.
True synovial based hemangiomas are rare lesions and should be differentiated from mass lesions especially pigmented villonodular synovitis. A case of 4 years old male child, presenting with recurrent painful swelling, is described in the present article. The differential diagnosis is also discussed.
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Secretory carcinoma is the currently preferred designation for a unique neoplasm earlier thought to be exclusive to the adolescent/pre-menarchal breast. The neoplasm has a predilection for juveniles and young adults (< 30 years of age), becoming progressive less common with advancing age. This report is of one such instance in a 52 year old female, rare occurrence in the elderly (> 50 years of age), with only five earlier cases on record in the English literature.
PURPOSE: To study and compare the efficacy of supratarsal injection of dexamethasone sodium phosphate, triamcinolone acetonide and hydrocortisone sodium succinate in treating refractory vernal keratoconjunctivitis (VKC). METHODS: Prospective randomized, double-masked, case control trial, including 90 eyes of 45 patients with refractory VKC. Both eyes of each patient were randomly assigned to receive supratarsal injection of one of three compounds under study: dexamethasone sodium phosphate (2 mg), triamcinolone acetonide (10.5 mg), and hydrocortisone sodium succinate (50 mg). RESULTS: All the three drugs were equally effective with no statistically significant difference in the time of resolution of cobblestone papillae, lid oedema, conjunctival discharge and chemosis, Tranta's dots and shield ulcers. There was no statistically significant difference in the severity and rate of recurrence of disease following supratarsal injection of all the three drugs. But recurrence of disease to same severity was seen within 6 months of injection in all cases irrespective of compounds used. CONCLUSION: Supratarsal injection of corticosteroids is very effective for temporary suppression of severe inflammation associated with VKC.
This report describes the extent and severity of retinopathy of prematurity (ROP) in a large maternity unit. The screening of 79 preterm babies showed that ophthalmic examinations should become an important part of neonatal care.
Immobilized artificial-membrane chromatography is a potential in vitro technique for determining lipophilicity and studying drug transport and membrane interactions. It is reproducible, efficient and simple. Several other and newer applications of immobilized stationary-phase liquid chromatography have been reported, including the purification of membrane proteins, the synthesis of biomolecules and the simultaneous determination of enzyme activity and enantioselectivity. This article describes the immobilized artificial-membrane concept and provides an overview of the applications, advantages and limitations, in general, of immobilized stationary-phase chromatography.
OBJECTIVE: The aim of this paper is to examine the factors that vocational trainers regard as important in a 'good' dentist and to assess whether they think recent graduates were achieving these factors. DESIGN: The study was based on a statistical analysis of returns from a postal questionnaire. SETTING: Postal questionnaires were sent to all vocational advisors in England who then sent them on to a number of their vocational trainers. MATERIALS AND METHODS: The questionnaire was analysed using various statistical techniques including factor analysis. Analysis was undertaken to determine whether student or trainer characteristics influenced the trainer's responses. RESULTS: The vocational trainers judged that the group of skills that contribute to technical ability are the most important component in making a 'good' dentist. However, the most important single skill is communication with patients, closely followed by diagnostic skills and communication with the dental team. The areas where trainees are most likely to fall short in terms of actual as compared to desired performance are in areas of technical ability. CONCLUSION: Overall, recent trainees scored rather well when compared with an idealised good dentist. However, it is clear that more evaluation of vocational training is needed. Recent studies, including this one have looked at several different aspects of vocational training. However, the time seems ripe for a full-scale prospective evaluation.
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BACKGROUND: This double-blind, multicenter, placebo-controlled study determined the efficacy and safety of dofetilide in converting atrial fibrillation (AF) or atrial flutter (AFl) to sinus rhythm (SR) and maintaining SR for 1 year. METHODS AND RESULTS: Patients with AF or AFl (n=325) were randomized to 125, 250, or 500 microgram dofetilide or placebo twice daily. Dosages were adjusted for QTc response and, after 105 patients were enrolled, for calculated creatinine clearance (Cl(Cr)). Pharmacological cardioversion rates for 125, 250, and 500 microgram dofetilide were 6.1%, 9.8%, and 29.9%, respectively, versus 1.2% for placebo (250 and 500 microgram versus placebo; P=0.015 and P<0.001, respectively). Seventy percent of pharmacological cardioversions with dofetilide were achieved in 24 hours and 91% in 36 hours. For the 250 patients who successfully cardioverted pharmacologically or electrically, the probability of remaining in SR at 1 year was 0.40, 0.37, 0.58 for 125, 250, and 500 microgram dofetilide, respectively, and 0.25 for placebo (500 microgram versus placebo, P=0.001). Two cases of torsade de pointes occurred, 1 on day 2 and the other on day 3 (0.8% of all patients given active drug); 1 sudden cardiac death, classified as proarrhythmic, occurred on day 8 (0.4% of all patients given active drug). CONCLUSIONS: Dofetilide, a new class III antiarrhythmic agent, is moderately effective in cardioverting AF or AFl to SR and significantly effective in maintaining SR for 1 year. In-hospital initiation and dosage adjustment based on QTc and Cl(Cr) are necessary to minimize a small but nonnegligible proarrhythmic risk.
The hHus1 and several hRad proteins are involved in the control of DNA integrity checkpoints, although the mechanisms underlying these processes are unknown. Using a yeast two-hybrid system to detect protein-protein interactions, we found that human proliferating cell nuclear antigen (PCNA), a protein known to function in both DNA replication and repair, interacts with the human checkpoint-related protein Hus1 (hHus1). In human skin fibroblast cells, exposure to ionizing radiation of hydroxyurea triggers translocation of hHus1 from the cytosol to the nucleus, where it associates with PCNA as well as another checkpoint protein, hRad9. This nuclear translocation and the complex formation or hHus1 with PCNA and hRad9 correlate closely with changes in cell cycle distribution in response to radiation exposure. These results suggest that this multi-protein complex may be important for coordinating cell-cycle progression, DNA replication and repair of damaged DNA.
Tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) levels are elevated among patients with human immunodeficiency virus (HIV) infection. TNF-alpha is known to lower NO production. In this study we used a TNF-alpha inhibitor, pentoxiphylline, to treat patients with HIV infection who were free of opportunistic infections and see if NO production was altered with this drug. NO production was determined by spectrophotometric analysis using nitrite and citrulline as surrogate markers and TNF-alpha levels were determined by ELISA before and after 4 weeks of the treatment. Nineteen patients (ten males, mean age 36.6+/-5.2 years) and 16 age and sex matched healthy controls were studied. Mean CD4 counts of patients were 206.5 mm(3). Nitrite level among patients at recruitment was 99.7+/-26.5 nmol/ml (range 50-167 nmol/ml) and was significantly higher than 46.4+/-16.2 nmol/ml; the value of healthy controls (P<0.05). Patient levels declined significantly to 44. 2+/-19.7 nmol/ml (range 10-106.6 nmol/ml) following 4 weeks of therapy (P<0.01). Citrulline level at recruitment was 810.8+/-425.8 nmol/ml (range 366.6-1888.7 nmol/ml), which was significantly higher than 488.6+/-224.5 nmol/ml, the level of controls (P<0.01). There was a statistically significant decrease in these levels among patients to 533.6+/-299.5 nmol/ml (range 250-163.4 nmol/ml) after 4 weeks of therapy (P<0.01). TNF-alpha levels showed a significant decline in the OD values from 0.34+/-0.22 at the start of therapy to 0.24+/-0.18 (P<0.05). We conclude that the use of pentoxiphylline is associated with decrease in TNF-alpha levels and NO production.
Sulfate conjugation by sulfotransferase enzymes is an important pathway for the detoxication of xenobiotics and endogenous compounds. The large surface area of the gastrointestinal tract exposes the body to a range of potential toxins, and hence local metabolism is likely to be important. The ability of different regions of the gut to sulfate micromolar concentrations of simple phenols and catecholamines has been determined throughout the gut using 4-nitrophenol and dopamine as standard substrates. The pattern of sulfation of both compounds was similar, with activity highest in the small bowel >right colon >left colon >rectum >stomach >esophagus. High concentrations of sulfotransferases in the reservoir areas of the right and left colon indicate possible importance in detoxication by sulfation and also perhaps in activating mutagens in the same areas. Nutritional factors, such as a high-fat diet may, however, alter sulfotransferase activity.
Twenty four patients of Takayasu arteritis (TA) aged less than 18 years were studied over a period of 20 years (1978-98). There were 4 males and 20 females with a male:female ratio of 1:5. The mean age of presentation was 14 years and the disease had a mean onset of time 4+/-1.5 months prior to admission to the hospital. Hypertension was the commonest mode of presentation seen in 83% of patients. 16% patients had congestive heart failure. Left ventricular hypertrophy was present in 54% patients. Angiographic findings showed that abdominal aorta was the commonest segment of aorta that was involved (71% cases). Renal artery was involved in 75% cases. Treatment modalities included antihypertensive drugs in 19 patients, antitubercular drugs in 7 patients and steroids in 7 patients. Renal angioplasty was performed in 2 patients with excellent results. On follow up 2 patients died. The causes of mortality were renal failure and heart failure in one patient each. The clinical profile of young patients with TA is similar to that of adults with this disease.
Properties of an endo-beta-xylanase produced by a locally isolated Thermomyces lanuginosus strain SSBP was compared to seven other T. lanuginosus strains isolated from different geographical regions. Strain SSBP produced the highest xylanase activity of 59600 nkat ml(-1) when cultivated on corn cobs (maize) medium, whereas the seven other strains produced xylanase activities ranging from 6000 to 32000 nkat ml(-1). No cellulase activity was produced by the strains. Despite the variability in the production of xylanase, little difference in the other characteristics of the strains could be found. The optimal temperature and pH for xylanase production by the strains was either 40 or 50 degrees C and between pH 6 and 7, respectively. Optimal xylanase activity of the strains was observed at 70 degrees C and at pH 6 or 6.5. Culture supernatant analysis by SDS-PAGE and isoelectric focusing PAGE of all strains revealed the presence of a single 24.7 kDa and pI 3.9 xylanase. Phylogenetic analysis by PCR amplification and sequencing of the internal transcribed spacer of nuclear rRNA repeat units and 5.8S rDNA revealed no strain diversity. However, random amplified polymorphic DNA analysis pointed to greater diversity and with one primer (5'-GCCCGACGCG-3'), a relationship was established between xylanase levels and the RAPD pattern.
We report the synthesis of the single enantiomers of permanently charged dihydropyridine derivatives (DHPs with alkyl linker lengths of two and eight carbon atoms) and their activities on cardiac and neuronal L-type calcium channels. Permanently charged chiral 1,4-dihydropyridines and methyl (omega)-trimethylalkylammonium) 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate iodides were synthesized in high optical purities from (R)-(-) and (S)-(+)-1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)-3-+ ++pyridinecarboxylic acid, obtained by resolution of racemic 1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)-3-pyridi necarboxylic acid. Competition binding experiments with radioligand [3H]-(+)-PN200-110 and the block of whole cell barium currents through L-type calcium channels in GH4C1 cells show that the compounds with the eight-carbon alkyl linker optimally block the L-type Ca2+ channels, and that the S-enantiomer is more potent than the R-enantiomer.
The human herpesvirus 8 (HHV8/KSHV), along with certain other herpesviruses, encodes a gene with cyclin homology. Although the functional significance of the encoded cyclin is not clear at present, various lines of evidence propose a role for this cyclin in latently infected cells and possibly in the induction of tumors that arise in HHV8-infected individuals. We provide evidence here that the cyclin protein is expressed in HHV8 positive primary effusion lymphoma (PEL)-derived cell lines and that its level of expression varies greatly between different lines. Our analysis indicates that the level of cyclin protein expression in different PEL cell lines may correlate with the level of transcript expression during latency but not in cells induced to undergo lytic replication. In highly expressing BC-3 cells the cyclin is complexed with cdk6, cdk4, cdk2, and cdk5 under both latent and lytic conditions, although subtle changes in the level of cdk association are seen after induction of the lytic cycle. Altogether our findings support the notion that the cyclin is a latency-associated gene product expressed in PEL tumor cells. They furthermore indicate that after lytic cycle induction, the level of cyclin transcript expression may not be a reliable indicator for the level of cyclin protein expression.
PAX6 is required for proper development of the eye, central nervous system, and nose. PAX6 has two DNA binding domains, a glycine-rich region that links the two DNA binding domains, and a transactivation domain. There is evidence that the different DNA binding domains of PAX6 have different target genes. However, it is not clear if the two DNA binding domains function independently. We have studied the effect of structural changes in the paired domain on the function of PAX6 mediated through its homeodomain. The R26G and I87R mutations have been reported in different human patients with clinically different phenotypes and are in the N- and the C-terminal halves of the paired domain, respectively. Surprisingly, we found that the I87R mutant protein not only lost the transactivation function but also failed to bind DNA by either of its DNA binding domains. In contrast, the R26G mutant protein lost DNA binding through its paired domain but had greater DNA binding and transactivation than wild-type PAX6 on homeodomain binding sites. Like R26G, the 5a isoform showed higher DNA binding than wild-type PAX6. This study demonstrates that the two subdomains of the paired domain influence the function of the homeodomain differentially and also provides an explanation for the difference in phenotypes associated with these mutations.
Resveratrol (3,4',5-trihydroxy stilbene) is a phytoalexin and a polyphenolic compound present in human dietary material such as peanuts, mulberries, grapes and red wine. It is widely considered to possess cardiovascular protective properties and has also been shown to be chemopreventive against various stages of chemically induced carcinogenesis. It has recently been shown that resveratrol induces strand breakage in DNA in the presence of copper ions. In this paper, we have shown that resveratrol catalyzes the reduction of Cu(II) to Cu(I), which is accompanied by the formation of 'oxidized product(s)' of resveratrol, which in turn also appear to catalyze the reduction of Cu(II). Strand scission by the resveratrol-Cu(II) system was found to be biologically active as assayed by bacteriophage inactivation. The results are discussed in relation to the putative chemopreventive mechanism of resveratrol.