Biomedical subjects
Publications and source records attributed to K Singh.
Molluscicidal property of Azadirachta indica A. Juss (neem) against the snails Lymnaea acuminata and Indoplanorbis exustus was studied. It was observed that the molluscicidal activity of the leaf, bark, cake, neem oil and the neem-based pesticides, achook and nimbecidine, was both time- and dose-dependent. The toxic effect of pure azadirachtin against both the snails was greater than the synthetic molluscicides.
The 3D structures of alpha-crystallin, a major eye lens protein, and related small heat shock proteins are unresolved. It has been assumed that alpha-crystallin is primarily a beta-sheet globular protein similar to alpha-crystallin (Siezen and Argos, Biochim. Biophys. Acta, 1983, 748, 56-67) containing sequence repeats in its two domains (Wistow, FEBS Lett. 1985, 181, 1-6). Positional flexibility of amino acid residues and far UV-circular dichroism spectroscopy were used to investigate structural relationships among these proteins. The utility of flexibility plots for predicting protein structure is demonstrated by the excellent correlation of these plots with the known 3D X-ray structures of beta/gamma-crystallins. Similar analyses of alpha-crystallin subunits, alpha A and alpha B, and human heat shock protein 27 show that the C-terminal domains and connecting segments of these proteins are very similar while the N-terminal domains have significant structural differences. Unlike beta/gamma-crystallins, both Hsp27 and alpha-crystallin subunits are asymmetrical with highly flexible C-terminal domains. Flexibility is considered essential for protein functional activity. Therefore, the C-terminal region may play an active role in alpha-crystallin and small heat shock protein function. Differences in flexibility profiles and estimated secondary structure distribution in alpha-crystallin by three recent/updated algorithms from far UV-CD spectra support our predicted 3D structure and the concept that alpha-crystallin and members of beta/gamma superfamily are structurally dissimilar.
Nitric oxide (NO) acts as an autocrine- and paracrine-acting signaling autacoid that, among other functions, has been shown to regulate cardiac contractile responsiveness to beta-adrenergic and muscarinic cholinergic agonists. Nitric oxide (NO) is formed by the oxidation of one of two equivalent guanidino nitrogens in L-arginine by O2 to form NO and L-citrulline. This reaction is catalyzed by a family of enzymes termed NO synthases. Three distinct isoforms of NOS have been identified, each the product of a separate gene. Cellular constituents of cardiac muscle, including ventricular myocytes as well as microvascular endothelial cells, have been shown to express the "endothelial constitutive" isoform of NO synthase (ecNOS or NOS3) in vivo, and both cell types also express the NO synthase isoform induced by specific inflammatory cytokines (iNOS or NOS2) in vivo and in vitro. While NO-dependent intracellular signalling in cardiac myocytes clearly involves the activation of guanylate cyclase and downstream signalling by cGMP, there is accumulating evidence that non-cGMP-dependent regulatory signalling events are also initiated by NO. In addition, decreased contractile responsiveness of cardiac myocytes to beta-adrenergic agonists, following induction of NOS2 by inflammatory cytokines, requires the presence of insulin and the co-induction of enzymes responsible for production of tetrahydrobiopterin, a NOS co-factor. Inappropriate or excessive production of NO by cardiac myocytes and by microvascular endothelial cells likely contributes to the cardiac contractile dysfunction characteristic of the systemic inflammatory response syndrome and cardiac allograft rejection.
STUDY OBJECTIVE: Abortion legislation in Singapore has gone through dramatic changes in the past 25 years. In this paper, we studied the effect of abortion legislation on abortion trends in Singapore. SETTING AND PARTICIPANTS: The Ministry of Health, Singapore, collects data on all abortions performed in Singapore. These data have been analyzed and are presented in this paper. RESULTS: The liberalization of abortion legislation resulted in a dramatic increase in the number of abortions performed beginning in 1974. The rate peaked at 23,512 abortions in 1985, and in fact, 35% of all pregnancies were terminated in 1985. The introduction of mandatory abortion counseling in 1986 resulted in a decline in the number of abortions to 16,476 in 1993 with only 24.6% of pregnancies being terminated. The teenage abortion rate was 0.2 per 1000 female teenagers under 20 years of age in 1970. With the liberalization of abortions, the rate reached a peak of 13.7 per 1000 female teenagers in 1985. In 1993, the teenage abortion rate was 9.5%. The proportion of nulliparous women seeking abortion has increased phenomenally from 0.5% in 1976 to 40.6% in 1993. Close to 95% of the women seeking abortions in 1993 did so for social reasons, 3.7% for medical reasons, and 2.0% for failed contraception (Table 3). CONCLUSION: Mandatory abortion counseling and a change in the government policy which now encourages Singaporeans to have more children if they can afford it, have resulted in a decrease in the number of abortions being performed. The problems of teenage abortions, nulliparous abortions, and repeated abortions need to be further addressed.
Secondary trisomics and telotrisomics representing the 12 chromosomes of rice were isolated from the progenies of primary trisomics. A large population of each primary trisomic was grown. Plants showing variation in gross morphology compared to the primary trisomics and disomic sibs were selected and analyzed cytologically at diakinesis and pachytene. Secondary trisomics for both arms of chromosomes 1, 2, 6, 7 and 11 and for one arm of chromosomes 4, 5, 8, 9 and 12 were identified. Telotrisomics for short arm of chromosomes 1, 8, 9 and 10 and for long arms of chromosomes 2, 3 and 5 were isolated. These secondary and telotrisomics were characterized morphologically and for breeding behavior. Secondary trisomics 2n + 1S.1S, 2n + 1L.1L, 2n + 2S.2S, 2n + 2L.2L, 2n + 6S.6S, 2n + 6L.6L and 2n + 7L.7L are highly sterile, and 2n + 1L.1L, 2n + 2L.2L and 2n + 7L.7L do not set any seed even upon backcrossing. Telotrisomics are fertile and vigorous. Genetic segregation of 43 marker genes was studied in the F2 or backcross progenies. On the basis of segregation data, these genes were delimited to specific chromosome arms. Correct orientation of 10 linkage groups was determined and centromere positions on nine linkage groups were approximated. A revised linkage map of rice is presented.
Esophagocutaneous fistula due to tuberculosis is a distinctly rare entity, with only two cases reported over the past 25 years. We report this unusual complication in an 85-year-old, human immunodeficiency virus-negative man and review the relevant literature.
Primary sclerosing cholangitis (PSC) is considered to be rare in India. The aim of the present study was to investigate the incidence, clinical profile and outcome of PSC seen in a tertiary care centre. Over a period of 10 years (July, 1984-June, 1994) 18 patients of PSC were diagnosed at cholangiography (14 patients by endoscopic retrograde cholangiopancreatography, two patients by percutaneous transhepatic cholangiography and two patients by both methods). The presence of secondary causes, such as choledocholithiasis, biliary tract surgery, congenital biliary tract anomalies, cholangiocarcinoma and pancreatic diseases, were excluded. These patients were evaluated retrospectively with respect to their clinical presentation, radiological findings, presence of associated idiopathic ulcerative colitis (IUC), treatment instituted and outcome. The mean (+/- s.d.) age at diagnosis of PSC was 39.0 (+/- 16.1) years with a male:female ratio of 1.57:1. Nine (50%) patients had associated IUC. The diagnosis of the IUC preceded that of PSC in all but one case. Fifteen (83.3%) patients had cholestatic jaundice at presentation, while three (16.7%) patients had asymptomatic rise of alkaline phosphatase. Three (16.7%) patients had recurrent cholangitis and five (27.8%) patients developed portal hypertension during the course of the disease. At cholangiography, intrahepatic radicles were involved in all and extrahepatic radicles in 12 (66.6%) cases. Patients were managed with steroids (n = 7), colchicine (n = 3), ursodeoxycholic acid (UDCA; n = 2) and methotrexate (n = 1), along with symptomatic measures. Mean duration of follow up available in 11 (61%) patients was 20.1 months (range: 1 month-8 years). Four (36.4%) patients died. Steroids and colchicine did not have any effect while the one patient on UDCA and one on methotrexate showed improvement. In conclusion, in India PSC does not seem to be a rare entity. Its clinical profile and outcome are somewhat similar to those seen in Western countries.
OBJECTIVE: To determine the level of correlation between mother and machine detected episodes and clusters of fetal movements and their association with fetal heart rate acceleration. METHODOLOGY: An observational study conducted on health pregnant women between 29-40 weeks gestation who were admitted in spurious labour to the Department of Obstetrics and Gynaecology, National University Hospital, Republic of Singapore. A continuous record of fetal heart rate and fetal movement was obtained using the fetal actocardiograph. Fetal movements felt by mother were also noted. If a continuous series of fetal movements were perceived over a period of 15 secs or more it was termed clusters of fetal movement. The presence or absence of acceleration in relation to these movements were noted. RESULTS: There was a highly significant correlation between mother and machine in detection of clusters of fetal movements (r = 0.77, p < 0.001); for episodes of fetal movements, the correlation was weaker (r = 0.23, p < 0.05). All clusters of fetal movements perceived by the mother were recorded by the machine and were associated with fetal heart rate accelerations. Two or more accelerations within 3 minutes of the fetal movements were seen with 87.8% of clusters felt by mother compared with 66.7% detected by the machine (p = 0.01). In the 2,263 minutes of recording in 42 women, a cluster of fetal movements was felt at least every 25 minutes by the mother. CONCLUSION: Maternal perception of 1 or 2 clusters of fetal movements in 30 to 60 minutes may be as reliable as a non-stress test in reassuring good health. It would be less time consuming than the traditional count to 10 fetal movement chart and a more reliable indicator of fetal health than counting episodes of fetal movements. Thus, our study suggests that clusters rather than episodes of fetal movements should be considered for evaluating fetal health based on fetal movements.
The study was aimed to determine the role of endoscopic retrograde cholangiopancreatography (ERCP) in patients with postcholecystectomy symptoms in respect to interval of presentation following cholecystectomy. 170 patients with postcholecystectomy symptoms and negative upper gastrointestinal endoscopy were evaluated using ERCP. One hundred and seventeen (75%) out of 156 patients with successful ERCP had one or more abnormalities seen at ERCP. Bile duct stones (55 patients), benign strictures of bile duct (27 patients) were the common lesions detected. A significantly higher (p < 0.001) positive diagnosis was possible at ERCP in patients presenting with jaundice (100%) as compared to those without jaundice (61.8%). Spectrum of causes among patients presenting in early post-operative period (< 1 month) was somewhat different from those presenting later. Bile duct ligature and biliary fistula were the predominant causes in the former group, while stones and benign strictures were commoner in the patients presenting late. Endoscopic sphincterotomy and stone removal was performed successfully in 25 out of 30 patients in whom it was attempted. ERCP was found to be a very useful procedure in the management of postcholecystectomy symptoms. Spectrum of underlying disease was different in patients presenting before 1 month following cholecystectomy as compared to those presenting later.
BACKGROUND: Colonic tuberculosis is common in developing countries. However, its diagnosis is difficult. Nevertheless, colonoscopy and biopsy examination have shown promising results. METHODS: We evaluated the clinical spectrum and colonoscopic features of 62 patients with colonic tuberculosis. RESULTS: Abdominal pain, fever, anorexia, weight loss, and change in bowel habit were seen in more than 50% of the patients. Massive rectal bleeding was frequently (13%) observed. Colonoscopy revealed strictures in 17, deformed ileocecal valve in 34, ulcers in 52, nodules in 49, polypoidal lesions in three, and fibrous bands in five patients. Segmental tuberculosis, lesions mimicking carcinoma, and multiple site involvement were observed in 19%, 20%, and 50% of the patients, respectively. Histopathologically, well formed granulomas were seen in 27, collections of epithelioid cells in 18, and chronic, nonspecific inflammatory changes in 17 of the cases. Acid-fast bacilli could not be isolated from any of the patients. All of the patients responded to the anti-tubercular treatment. Follow-up colonoscopy in 22 patients demonstrated regression of lesions. CONCLUSIONS: Colonic tuberculosis is common in India. Our findings indicate that colonoscopy is useful for its diagnosis. However, histopathology many not always be helpful. Therefore, in a given clinical and colonosopic setting, a therapeutic trial may be indicated.
Many patients continue to have symptoms even after cholecystectomy. We studied 4 patients with postcholecystectomy problems over a period of seven years; 208 were females, males and their mean age was 41.8 years (range 14-70). Presenting symptoms were abdominal pain (217), jaundice (74), cholangitis (38) and external biliary fistula (eight). Fifteen patients also had a t-tube in situ. Endoscopic retrograde cholangiopancreatography was successfully performed in 239 patients and revealed abnormal findings in 179. These included: stones (89), strictures (53), choledochoduodenal fistula (10), choledochal cyst (three), biloma (three), ligation of bile duct (five), ascaris in bile duct (three), pancreatitis (nine), long cystic duct stump (11), and various other findings. Endoscopic sphincterotomy was carried out in 59 patients with stones. Seven patients with strictures were managed with stents. Ascaris in the bile duct of three patients was removed with the help of a Dormia basket. To conclude, stones and strictures are common postcholecystectomy problems and endoscopic retrograde cholangiopancreatography is very helpful in the diagnosis and management of postcholecystectomy patients.
AIM: To study the frequency and significance of pancreas divisum. METHODS: Retrospective analysis of all pancreatograms carried out between July 1989 and June 1994. RESULTS: The 809 pancreatograms performed included 207 in patients with pancreatitis (acute 74, chronic 133), 330 with biliary disease, 238 with obscure abdominal pain and 34 with pancreatic malignancy. Of these, 30 patients (3.7%) were diagnosed to have pancreas divisum - 26 had type I variant, one had type II variant and three had type III variant. Accessory papillary cannulation was attempted in 10 patients; 8 were successful, with dorsal ductography confirming pancreas divisum in all of them. Two of these 8 patients had changes of chronic pancreatitis in the dorsal duct. The frequency of pancreas divisum in patients with pancreatitis (19 of 207, 9.2%) was significantly higher than in patients with biliary diseases and those with obscure abdominal pain (11 of 568, 1.9%; p < 0.001). CONCLUSIONS: Pancreas divisum is not an uncommon condition in India and its frequency in patients with idiopathic pancreatitis is higher than that in patients with other abdominal conditions. It should be looked for in any case of idiopathic pancreatitis.
The effect of fenbendazole and mebendazole on the activity of some enzymes of the homogenates of swine kidney worm Stephanurus dentatus was investigated. Fenbendazole at 10(-5) M inhibited malate oxidation by 49% and 51% and oxaloacetate reduction by 33% and 40% whereas, mebendazole at 10(-5) M diminished malate oxidation by 25% and 35% and oxaloacetate reduction by 12% and 14% in male and female S. dentatus, respectively. Lactate dehydrogenase activity was inhibited by 45% and 50% in male and female worm respectively by 10(-5) M fenbendazole. Aldolase activity in both male and female S. dentatus was inhibited by 10(-5) M fenbendazole and mebendazole. Fenbendazole at 10(-5) M caused moderate inhibition of acid and alkaline phosphomonoesterases but mebendazole did not show a significant effect on these enzymes. Cholinesterase activity was not affected significantly with either compound. The possible mode of action of the two compounds is compared.
6-Thioguanine, a thioderivative of the nucleic acid base guanine, is a metabolic inhibitor and possesses antitumor activity. In addition, it inhibits the synthesis of nucleotides and is incorporated readily into the nucleic acid during the polymerization reaction by substituting for guanine. The biological activity of 6-thioguanine has been related to the alterations in the dimensions and energetics of a duplex DNA as a result its incorporation in place of guanine (Bugg and Thewalt 1975). With the advancement in the computer hardware technology and emergence of sophisticated molecular modeling packages, it is now possible to simulate the biological activities of different drugs. An effort has been made to explain the biological activities of thoiderivatives of nucleic acid bases. For this, semiempirical MNDO quantum chemical calculations were performed on some non-complementary (thiosubstituted) base pairs to understand the effects of substitution of sulfur for oxygen in nucleic acid bases. The base pairs considered in this study are thioguanine-cytosine (TG-C), guanine-thiocytosine (G-TC) and thioguanine-thiocytosine (TG-TC). The results obtained suggest that the replacement of guanine by thioguanine and/or replacement of cytosine by thiocytosine weakens the stability of the double helical DNA by reducing the strength of the hydrogen bonds.
Elective lymph node dissection for patients with malignant melanoma remains controversial. Sentinel lymph node sampling has been recommended to select patients who will benefit from lymphadenectomy. Vital blue dye and a gamma detecting probe have been used to identify the sentinel node. Two patients are described in whom microscopic disease was identified in the sentinel node as the sole focus of metastasis. The ability to excise the sentinel node provides accurate pathologic and staging information, is cost effective, and minimizes the morbidity associated with a routinely performed lymphadenectomy.
The mean electrical axis (MEA) of heart was evaluated in 38 patients suffering from chronic severe anemia. It was found that despite cardiomegaly the MEA of heart remains unaffected in chronic severe anemia as compared to age and sex matched control subjects.
In heart muscle, the cytokine-inducible isoform of nitric oxide synthase (NOS2) is expressed in both cardiac myocytes and microvascular endothelial cells (CMEC). mRNA levels for both NOS2 and for osteopontin, a multifunctional extracellular matrix phosphoprotein containing and RGD integrin binding domain, are increased in cardiac muscle following intraperitoneal injection of adult rats with lipopolysaccharide. In vitro, interleukin-1 beta and interferon-gamma increased osteopontin mRNA levels in CMEC as well as NOS2 expression in both CMEC and cardiac myocytes. However, osteopontin mRNA levels in heart muscle in vivo, and in cardiac myocytes and CMEC in vitro, also are increased 10-30-fold by the synthetic glucocorticoid dexamethasone, an agent that suppresses cytokine induction of NOS2 in both cell types. The hexapeptide GRGDSP, which interrupts binding of RGD-containing proteins to cell surface integrins, increased NOS2 mRNA, while a synthetic osteopontin peptide analogue decreased NOS2 mRNA and protein levels in both cytokine-pretreated cardiac myocytes and CMEC cultures. Also, transfection with a full-length antisense-osteopontin cDNA in cytokine-pretreated CMEC decreased endogenous osteopontin mRNA and increased NOS2 mRNA levels. These results suggest that osteopontin could regulate the location and extent of NOS2 induction in the heart. Increased expression of osteopontin also may be one mechanism by which glucocorticoids suppress NOS2 activity in cardiac myocytes and microvascular endothelial cells.
alpha-Crystallin, the major protein in all vertebrate lenses, functions as a chaperone. In the present analysis, an 'open' micellar structure composed of alpha A subunits is used to simulate chaperoning of partially heat denatured soluble gamma-crystallin. The interaction is both electrostatic and hydrophobic and satisfies experimental evidence for a 1:1 alpha/gamma molar ratio, a doubling of molecular mass and a minimal increase in the dimensions of the complex [J. Biol. Chem. (1994) 269, 13601-13608; Invest. Opthalmol. Vis. Sci. (1995) 36, 311-21]. These data are also in accord with Farahbaksh et al. [Biochemistry (1995) 34, 509-16]; i.e. the bound gamma-crystallin monomers are not in a central cavity, but are separated by alpha A subunits.