Biomedical subjects
Publications and source records attributed to S Singh.
The planar furan ring in the title compound (6beta-acetoxyazadirone, C(30)H(38)O(6)) is twisted with respect to the steroid D ring. The crystal structure is stabilized by C-H.O hydrogen bonds and van der Waals interactions.
The seed oil in Macadamia integrifolia contains about 30% palmitoleic acid (16:1(Delta9)) and Nerium oleander about 12% isoricinoleic acid (Delta9-hydroxy-18:1(Delta12)). It has been shown that palmitoleic acid can be produced by acyl-acyl carrier protein (ACP) desaturases and it has also been shown that fatty acid hydroxylation can occur via direct substitution of a hydrogen atom. Therefore it seemed possible that the enzymes responsible for the making of these unusual fatty acids in M. integrifolia and N. oleander were of acyl-ACP desaturase type. Extracts from developing M. integrifolia developing seeds showed a relative ratio of 16:0-ACP to 18:0-ACP desaturation that was about 13 times higher than in sunflower seeds. N. oleander seed extracts catalysed conversion of 18:0-ACP to 18:1(Delta9) but only trace amounts of Delta9-hydroxy fatty acids were formed. A total of four cDNAs were isolated from developing seeds, of both species, using a fragment isolated with PCR amplification. The M. integrifolia acyl-ACP desaturase cDNA was expressed in Escherichia coli. A partly purified fraction of the enzyme showed a 16:0-ACP to 18:0-ACP desaturation ratio about 90-fold less than that in the Macadamia extracts. Expressed N. oleander acyl-ACP desaturase cDNAs showed predominantly 18:0-ACP desaturase activity and no hydroxylase activity. Thus it is not likely that any of the four acyl-ACP desaturases cloned from M. integrifolia or N. oleander is involved in the production of unusual fatty acids.
BACKGROUND/PURPOSE: Graduates of a university surgical residency program were surveyed to identify the timing of specialty selection and the impact that studying in a research laboratory had on subsequent acceptance into a fellowship program. METHODS: Between 1975 and 1990, 86 residents completed general surgery training at UCLA Medical Center. A survey was sent to all graduates to determine the focus of their previous laboratory research and when they selected their eventual surgical specialty. Responses were received from 67 of the 86 graduates (78%). RESULTS: Forty-eight of the sixty-seven respondents (72%) took one or more years of surgical research during residency. Postresidency fellowship training was selected by 55 of 67 (82%); 50 applied to fewer than five programs; 49 of 55 (89%) received one of their top three choices. Twenty-seven of the sixty-seven residents pursued an academic career (40%). Residents who performed at least 2 years of research were more likely to become academicians (53%) than residents who did 1 year or less of research (22%). Only 39 of 67 residents (58%) had selected a specialty after 2 years of clinical training; 28 more made the selection after the third clinical year. All residents interested in cardiac surgery (n = 18) or plastic surgery (n = 4) prior to research were accepted into fellowships in those specialities, whereas only 37% of those who had an interest in other fields pursued the same specialty (P < 0.0001). Residents performing research in general surgery (n = 9), surgical oncology (n = 18), cardiac surgery (n = 14), and plastic surgery (n = 3) were more likely to practice in that specialty than those doing research in other specialty laboratories. CONCLUSIONS: General surgery residents performing research in a specialty laboratory are likely to pursue fellowship training relating to that field. Those who select a career in cardiac or plastic surgery prior to research are most likely to enter into these fields as their eventual specialty. Residents who perform 2 or more years of laboratory research publish more papers and often pursue an academic career.
Antibodies against the amino-terminal domain of the Plasmodium falciparum P0 phosphoriboprotein were detected extensively in immune people living in malaria endemic areas of India. It has been shown earlier that specific antibodies raised against the PfP0N domain (17-61 amino acid) of the PfP0 protein inhibit P. falciparum growth in vitro. To study the properties of the rest of the protein, the remaining 61-316 amino acids on the carboxy-side of the PfP0 protein were expressed as a glutathione-S-transferase fusion protein (PfP0C). Antibodies raised against PfP0C identified the 38 kDa P0 protein on a parasite Western blot analysis. An ELISA assay using both the PfP0N and PfP0C fusion proteins showed no reactivity with malaria patient sera samples, but showed extensive reactions with the immune sera. Antibodies against both the PfP0C and PfP0N domains were raised in rabbits and different inbred strains of mice. T-cells from immunized mice showed lymphoproliferation when presented with PfP0 protein domains. IgG from both anti-PfP0N and anti-PfP0C sera inhibited the growth of P. falciparum in vitro in a concentration dependent manner. The IgG did not show any significant effect on the growth of intraerythrocytic stages, but specifically inhibited re-invasion of red cells. Merozoites and sexual stages showed surface reactivity to both anti-PfP0N and anti-PfP0C antibodies in immunofluorescence assays. These properties strongly indicate PfP0 as a possible target for invasion-blocking antibodies.
The thermostability of beta-xylanases produced by nine thermophilic Thermomyces lanuginosus strains in a coarse corn cob medium was assessed. The xylanase produced by T. lanuginosus strain SSBP retained 100% of its activity after 6 h at temperatures up to 65 degrees C. In comparison seven ATCC strains and the DSM 5826 strain of T. lanuginosus only retained 100% xylanase activity at temperatures up to 60 degrees C. Culture filtrates of T. lanuginosus strain SSBP grown on coarse corn cobs, oatspelts xylan, birchwood xylan, wheatbran, locust beangum, and sugar cane bagasse, retained 100% xylanase activity at temperatures up to 60 degrees C. The xylanase produced on corn cobs was the most thermostable and showed an increase of approximately 6% from 70 degrees C to 80 degrees C. The T(1/2) of all strains at 70 degrees C at pH 6.5 varied greatly from 63 min for strain ATCC 28083 to 340 min for strain SSBP. The xylanase of strain SSBP was much less thermostable at pH 5.0 and pH 12.0 with T(1/2) values of 11.5 min and 15 min, respectively at 70 degrees C. At 50 degrees C, the enzyme of T. lanuginosus strain SSBP produced on coarse corn cobs was stable within the pH range of 5.5-10.0. Furthermore, the enzyme retained total activity at 60 degrees C for over 14 days and at 65 degrees C for over 48 h. The xylanase of T. lanuginosus strain SSBP possesses thermo- and pH stability properties that may be attractive to industrial application.
Compound 73/602 (AA) is a structural analogue of vasicinone, an alkaloid present in the leaves and roots of Adhatoda vasica (Acanthaceae). It possesses potent antiallergic activity in mice, rats and guinea pigs. The pK(a) of AA was determined to be 2.87+/-0. 19 by UV spectrophotometry. The absorption kinetics of this compound were studied in-situ using a rat gut technique at pH 2.6 and 7.4. The rate of absorption at pH 2.6 (0.0288+/-0.004 min(-1)) was slightly less than at pH 7.4 (0.035+/-0.0008 min(-1)). This characteristic behavior was attributed to the low pK(a) of AA, a weekly basic compound, where nearly 35% of the compound remained in the unionized form at pH 2.6. Also, the return of compound into the mucosal lumen from the blood capillaries over a period of 2 h after administering a 2 mg dose in tail vein was less than 0.3%. Hence it was concluded that entero-enteric circulation of AA did not contribute significantly to the in-situ absorption rates. Pharmacokinetic parameters of AA were determined in male rats after administering a single 10 mg/kg intravenous dose (i.v.) and 50 mg/kg oral bolus dose. Following i.v. administration the initial decline in serum concentration was rapid with half-life of 20.2 min. After a single oral dose the concentration-time data of AA in rats was best described by a one-compartment model with equal first order absorption and apparent elimination rate constants. The half-life of the decline in serum concentration of AA following oral administration was 50.6 min, indicating absorption rate limiting disposition at the high dose given. Comparison of AUC of oral and i. v. data indicates that only about 60% of the oral dose reach the systemic circulation.
Explore the source record for details and available documents.
CONTEXT: Previous studies have shown oseltamivir, a neuraminidase inhibitor, to be effective in preventing influenza and treating experimental influenza. OBJECTIVE: To evaluate the efficacy and safety of oseltamivir in the treatment of naturally acquired influenza infection. DESIGN: Randomized, placebo-controlled, double-blind study conducted January through March 1998. SETTING: Sixty primary care and university health centers throughout the United States. PARTICIPANTS: A total of 629 healthy nonimmunized adults aged 18 to 65 years with febrile respiratory illness of no more than 36 hours' duration with temperature of 38 degrees C or more plus at least 1 respiratory symptom and 1 constitutional symptom. INTERVENTIONS: Individuals were randomized to 1 of 3 treatment groups with identical appearing pills: oral oseltamivir phosphate, 75 mg twice daily (n = 211) or 150 mg (n = 209) twice daily, or placebo (n = 209). MAIN OUTCOME MEASURES: Duration and severity of illness in individuals infected with influenza. RESULTS: Two individuals withdrew before receiving medication and were excluded from further analyses. A total of 374 individuals (59.6%) were infected with influenza. Their duration of illness was reduced by more than 30% with both oseltamivir, 75 mg twice daily (median, 71.5 hours; P < .001), and oseltamivir, 150 mg twice daily (median, 69.9 hours; P = .006), compared with placebo (median, 103.3 hours). Severity of illness was reduced by 38% (median score, 597 score-hours; P < .001) with oseltamivir, 75 mg twice daily, and by 35% (median score, 626 score-hours; P < .001) with oseltamivir, 150 mg twice daily, vs placebo (median score, 963 score-hours). Oseltamivir treatment reduced the duration of fever and oseltamivir recipients returned to usual activities 2 to 3 days earlier than placebo recipients (P < or = .05). Secondary complications such as bronchitis and sinusitis occurred in 15% of placebo recipients compared with 7% of combined oseltamivir recipients (P = .03). Among all 629 subjects, oseltamivir reduced illness duration (76.3 hours and 74.3 hours for 75 mg and 150 mg, respectively, vs 97.0 hours for placebo; P = .004 for both comparisons) and illness severity (686 score-hours and 629 score-hours for 75 mg and 150 mg, respectively, vs 887 score-hours for placebo; P < .001 for both comparisons). Nausea and vomiting occurred more frequently in both oseltamivir groups (combined, 18.0% and 14.1%, respectively; P = .002) than in the placebo group (7.4% and 3.4%; P < .001). CONCLUSIONS: Our data suggest that oral oseltamivir treatment reduces the duration and severity of acute influenza in healthy adults and may decrease the incidence of secondary complications.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
In general nucleoside analogues were found to possess in vitro amoebicidal property against trophozoites of Entamoeba histolytica. The acid-labile nature of these compounds completely destroyed their ability to cure caecal amoebiasis of rats. However the therapeutic efficacy of one of these compounds yielded most promising results, with 10% cures when it was administered as enteric coated formulation.
PURPOSE: In an attempt to define the sonographic characteristics of gallbladder cancer, we retrospectively analyzed the sonographic findings in 203 cases of gallbladder cancer confirmed by cytology or histopathology. Patients and Methods Patients with proven gallbladder cancer presenting to a single surgical unit between 1991 and 1995 were identified through a records search. All patients underwent sonographic examination followed by fine-needle aspiration (FNA), biopsy, or laparotomy for establishing the diagnosis. RESULTS: A mass in the gallbladder and gallbladder wall thickening (> 12 mm) were cardinal sonographic findings of carcinoma. Liver infiltration was correctly identified in all patients who had it. Sonography was highly accurate for detecting mass lesions, gallstones, liver infiltration, metastasis, and ascites. However, visualization of lymph nodes, common bile duct infiltration, and peritoneal dissemination was poor. CONCLUSIONS: Sonography was found to be a good diagnostic tool for carcinoma of the gallbladder; however, its sensitivity was poor for staging nodal spread of the disease.
DNA-binding proteins present in fourth instar larvae of Anopheles stephensi were isolated by affinity chromatography on native and denatured DNA cellulose columns and analyzed by electrophoresis on polyacrylamide gels. A denatured DNA-specific protein with an approximate molecular weight of 30 kDa was the predominant DNA binding protein of larvae. This protein was purified to electrophoretic homogeneity by ammonium sulfate fractionation followed by phosphocellulose chromatography. The purified 30 kDa binding protein showed an endonucleolytic activity capable of converting pBR 322 supercoiled DNA to the circular form. Maximum endonucleolytic activity was observed in the presence of 5 mM Mg(2+) at pH 7.4. Enzyme activity was completely inhibited by EDTA.
Explore the source record for details and available documents.
BACKGROUND: Mild hypotension (drops of systolic blood pressure of > or = 20 mmHg) occurs in 14-38% of dobutamine stress echo (DSE) and carries a good prognosis for subsequent cardiac events. The incidence and significance of more profound hypotension (PH) (> or = 50 mmHg) is unknown. HYPOTHESIS: The aim of the study was to determine the incidence of PH during DSE and its prognosis for subsequent cardiac events. METHODS: We reviewed 617 DSE performed at our institution between 1992 and 1996 and identified two DSE subgroups. The first group (PH group) consisted of all patients with PH during DSE. A second group was selected with baseline characteristics similar to the PH group but without PH during DSE (non-PH group). Follow-up was by a physician chart review and direct telephone contact. Cardiac event rates were determined for hard [myocardial infarction (MI), or cardiac death] and soft (angina, congestive heart failure, coronary angioplasty, or coronary bypass surgery) events occurring after the DSE. RESULTS: Of the 617 DSE performed, 16 (3%) patients developed PH (PH group) during DSE, with 13 showing no inducible ischemia. The hard and soft cardiac event rate in this 13 PH group was 46% (mean follow-up of 28.7 +/- 18 months). Of the non-PH group, 32 patients had a negative DSE with a coronary event rate of 12.5%. Profound hypotension correlated with a significantly higher cardiac event rate (p < 0.02). CONCLUSIONS: The incidence of PH during DSE is low (3%) and appears to predict a worse prognosis for subsequent cardiac events.
Methemoglobin, a toxic ferric form of hemoglobin, is continuously formed in normal erythrocytes, but during abnormal situations in situ, the level is enhanced. 8-Amino-quinolines and related compounds are causative agents for methemoglobin formation. Employing oxyhemoglobin, methemoglobin toxicity was about six times higher with primaquine compared to CDRI Compound 80/53 at 10(-9) M concentration. Methemoglobin reductase activity was also completely inhibited by primaquine, whereas 24% inhibition was noted in the case of 80/53 at the same concentrations. Mastomys, a rodent animal model, was found to be equally good for comparative evaluation of methemoglobin toxicity. Further, with the use of primaquine transdermal tape on the Mastomys model, a rise in methemoglobin occurred with increase in time. In conclusion, the study presents simple, economical, less time-consuming methods for the evaluation of methemoglobin toxicity, in vitro and in vivo, without employing the conventional Beagle dog model.
Although hypersensitivity to foods is often linked to exacerbations of symptoms of respiratory allergy, no such information is available regarding the foods traditionally considered to play a probable etiological role in respiratory allergy in India, which are in fact quite different from the ones implicated in the West. The present study was undertaken to investigate whether the practice of withholding certain common foods by parents and practitioners of indigenous systems of medicine (i.e. Ayurvedic and Unani systems of medicine) in children suffering from respiratory allergy had any scientific basis or explanation as judged by modern techniques of investigation. Skin prick tests were performed on 64 children with symptoms pertaining to respiratory allergy (32 each in study and control group) using crude antigenic food extracts. Oral food challenges were administered to children to confirm or rule out allergenicity of food (s) incriminated on the basis of the clinical history and/or a positive skin test. Parental history of food restriction alone, in absence of positive skin prick test was of little value in predicting a positive response to the food challenges (1 challenge positive out of 77 based on food restriction: 1.29%). Only 27.02% and 18.75% of positive skin tests were found to be clinically significant in study and control groups respectively. Traditionally, food beliefs were upheld in only 12.5% children for immediate onset clinical reactions (with 5.31% of the foods restricted in their diet) and 9.37% children for delayed onset clinical reactions (with 3.19% of the foods restricted in their diet). The present study shows that even though food restriction is a common practice in patients with respiratory allergy in India, objective documentation of Type I reactions due to these foods cannot be obtained in a majority of such children.
Cystic hygromas occur most commonly in the neck. Rarely are they known to involve the axilla, groin, mediastinum, retroperitoneum, pelvis, mesentery, omentum and spleen. We successfully managed a case of cystic hygroma of gluteal region in a one and half year old child who presented with a cystic, non transilluminant swelling in this region since birth. The diagnosis of cystic hygroma was made by surgery and subsequently confirmed after histopathological examination. Because of rarity of cystic hygroma in gluteal region this case in being reported.