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Biomedical subjects

B Singh

Publications and source records attributed to B Singh.

At least 19 recordsLinked to original sources
PubMed1992

Novel cAMP PDE III inhibitors: 1,6-naphthyridin-2(1H)-ones.

Two series of medorinone (3) analogs were prepared by modifications at C(2) and C(5). The C(2)-series was prepared from 2-chloro-5-methyl-1,6-naphthyridine (4) by replacement of the chloro group with various nucleophiles. The C(5)-series was prepared from 5-acyl-6-[2-(dimethylamino)-ethenyl]-2(1H)-pyridinone (11), 5-bromo-1,6-naphthyridin-2(1H)-one (17), and 1,3-diketones 19 and 27. 1,6-Naphthyridin-2(1H)-ones are novel inhibitors of cAMP PDE III. Modification of the carbonyl group of 3 or N-methylation at N(1) resulted in a dramatic loss of enzyme activity. Absence of the C(5)-methyl group of medorinone (3) or its shift to C(3) or C(7) also resulted in reduced activity. Substitution at C(3) also diminished activity. However, substitution at C(5) by a wide variety of substituents led to improvement of enzyme activity and several C(5)-substituted analogs were more potent than milrinone.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

Cloning of HSP70 (dnaK) gene from Clostridium perfringens using a general polymerase chain reaction based approach.

A general method to clone the HSP70 gene from any species employing polymerase chain reaction and degenerate oligonucleotide primers for conserved regions of this protein family is described. Using this method, a clone containing the entire coding sequence for the HSP70 gene from Clostridium perfringens, has been isolated and sequenced. The HSP70s from C. perfringens as well as other Gram-positive groups of bacteria contain a large deletion of 25 amino acids, near the N-terminal end, which is not seen in HSP70 from other sources.

Amino Acid Sequence↗
PubMed1992

Cloning of HSP60 (GroEL) operon from Clostridium perfringens using a polymerase chain reaction based approach.

Using degenerate oligonucleotide primers for conserved regions of HSP60, a 0.6 kilobase fragment of Clostridium perfringens DNA was amplified by the polymerase chain reaction. The amplified fragment was used as a probe to isolate a genomic clone containing the C. perfringens HSP60 operon. The clone contained two open reading frames homologous to the GroES and GroEL (or HSP60) family of bacterial and eukaryotic proteins as well as other upstream and downstream sequences. The approach described here, employing this set of degenerate oligonucleotide primers, could be used to clone HSP60 gene/cDNA from any species.

Amino Acid Sequence↗
PubMed1992

Presence of pulmonary intravascular macrophages in the equine lung: some structuro-functional properties.

The pulmonary intravascular macrophages (PIMs) have been described in several species of animals. This study demonstrates for the first time that the equine lung has PIMs as resident phagocytes in its microvasculature. Their salient features such as globular surface coat, structures of the endocytic pathway, and related cell organelles closely resemble those of the calf, goat, and sheep. The exquisite organization of the coat globules in the form of a linear chain was structurally similar to the lipolytic lipase and the heparin-sensitive globular coat from PIMs of calf, goat, and sheep. Monastral blue (MB) when employed as a tracer to assess the phagocytic properties of equine PIMs induced similar modification of the globules of the coat into lipid droplets, reminiscent of neutral lipids. Lipids droplets (modified coat globules) were delivered into acid phosphatase-positive endosomes and lysosomes. Concurrently, the unaltered globules of the coat, probably internalized via fluid-phase constitutive pinocytoses, followed a different endocytic pathway. Large-scale platelet uptake by the PIMs was observed with thrombocytopenia in MB-treated ponies. The possible significance of hypothetical LDL-coat and the endocytic organelles as equivalents of synthetic apparatus of vasoactive lipids in the PIMs of horse needs to be assessed in future studies.

Acid Phosphatase↗
PubMed1992

The development of monoclonal antibodies to the human mitochondrial 60-kd heat-shock protein, and their use in studying the expression of the protein in rheumatoid arthritis.

OBJECTIVE: To assess the claim that the human 60-kd heat-shock protein (HSP) is highly expressed in the joints of patients with rheumatoid arthritis (RA), but is not readily detected in normal tissues. METHODS: Monoclonal antibodies were raised against the human 60-kd mitochondrial heat-shock protein (P1 protein; hsp60), and their specificity was established. They were then applied to synovial tissue. RESULTS: HSP was expressed similarly in normal, osteoarthritic, and RA synovium. Low levels of hsp60 were detected in synovial fluid by immunoprecipitation. CONCLUSION: Minor differences in the distribution of hsp60 in synovium from RA joints were attributable to increased cellularity and to the disorganization of the tissue architecture.

Animals↗
PubMed1992

Inhibition of superantigen recognition by peptides of the variable region of the T cell receptor beta chain.

T cells bearing certain variable (V) regions of the T cell receptor (TcR), including V beta 3, V beta 6, V beta 8.1 and V beta 9, are stimulated by one or more forms of the endogenous superantigen, mouse lymphocyte stimulatory (Mls) locus, encoded by the mouse mammary tumor virus, in the context of a non-polymorphic region of the class II molecules of the major histocompatibility complex (MHC). To identify putative sites of interaction of TcR-V beta region and Mls-1a, we examined the effect of peptides derived from the protein sequence of V beta 6 on recognition of Mls-1a by T cell hybridomas and show that three peptides corresponding to amino acid positions 1 to 20, 48 to 75, and 58 to 75 of the V beta 6 peptide sequence interfere with the activation of several V beta 6+ hybridomas by Mls-1a-bearing spleen cells, but not with that of a V beta 8+ hybridoma. The Mls-reactive hybridomas are specific for a synthetic peptide poly-18, poly EYK(EYA)5 and its peptide (EYA)5, in the context of I-Ad. This peptide does not require processing and the peptides 1-20, 48-75, and 58-75 do not inhibit recognition of (EYA)5 by the same V beta 6+ T cell hybridomas. The two sequences 1-20 and 58-75 are proposed to lie outside the putative binding domain of processed antigen, indicating that recognition by TcR of Mls-1a is different from the classical MHC-restricted recognition of processed antigen. These results suggest that the recognition of superantigen/class II MHC by T cells can be inhibited by peptides related to the site of interaction of the TcR, suggesting that such peptides could have possible regulatory effects on the induction and regulation of immune responses.

Amino Acid Sequence↗
PubMed1992

A phase I pharmacokinetic study of recombinant human tumor necrosis factor administered by a 5-day continuous infusion.

Nineteen patients with advanced cancer were entered into a phase I clinical trial of Tumor Necrosis Factor (TNF) which was designed to determine the pharmacokinetic profile, safety, and maximal tolerated dose (MTD) of the recombinant human cytokine in vivo. TNF was administered by continuous infusion for 24 hours followed by pharmacokinetics and a 120-hour infusion repeated every 3 weeks. The initial dose was 40 micrograms/m2 and was ultimately escalated to 200 micrograms/m2. A total of forty 5-day cycles were administered to 18 of these patients; and all were evaluable for toxicity. Toxicities in this trial included fever, chills, rigors, hypotension, headaches, seizures, lethargy, weight loss, and malaise. At all dose levels, but more significantly at the highest doses, hematological toxicities were observed and grade 3 neurotoxicity (headache and confusion), and hypotension were noted. Two patients expired during the study, and this was felt to be related to septic episodes. Because of these severe toxicities, 160 micrograms/m2 was defined as the MTD. At 160 micrograms/m2 peak serum levels occurred within 5-20 minutes of initiation and were not detectable 1 hour later. No anti-tumor responses were observed. No measurable plasma levels of TNF were observed with the administration of doses of 80 micrograms/m2. This dose level could be further studied in phase II studies alone and in combination with other agents, utilizing a continuous infusion schedule.

Adenocarcinoma↗
PubMed1992

Unusually diverse T cell response to a repeating tripeptide epitope.

The immune system utilizes a diverse T cell repertoire for the recognition of foreign antigens in the context of self MHC gene products. We have examined the potential diversity of the T cell response directed to a immunodominant repeating tripeptide epitope (EYA)5. This peptide represents one of the two T cell epitopes on the synthetic alpha-helical polypeptide antigen Poly 18, Poly EYK(EYA)5 in H-2d mice and does not require antigen processing prior to presentation to Poly 18-specific T cell hybridomas. The T cell response directed to the repeating tripeptide epitope (EYA)5 is extremely heterogenous even though the epitope has a relatively simple amino acid sequence. We have analyzed the fine specificity of 21 randomly chosen Poly 18-reactive, (EYA)5-specific and H-2d-restricted T cell hybridomas derived from H-2d, H-2bxd, and H-2b----H-2bxd Poly 18-responding mice to determine the number of unique antigen reactivity patterns represented by this T cell population. We used alanine- and/or lysine-substituted (EYA)5 peptides and a panel of haplotype-varied splenocytes and observed a great deal of microheterogeneity in response. We find that 13 of the 21 hybridomas have a distinct fine antigen specificity and T cell receptors. The binding of (EYA)5 to the antigen-binding groove of I-Ad appears to generate a highly diversified T cell response. Therefore, (EYA)5-I-Ad complex allows the activation of unrelated T cell clonotypes with the same overall antigen specificity and MHC restriction, but with distinct microheterogeneity in response and receptor usage.

Alanine↗
PubMed1992

Evidence for immunodominance between closely related epitopes in the selection of T cell repertoire: hierarchy of T cell epitopes in a repeating sequence.

In a protein antigen the number of epitopes that are presented by the MHC molecules to the T cells is generally limited. This phenomenon of immunodominance determines the T cell response to a given antigen. To understand the molecular basis of epitope selection we have analysed the hierarchy of T cell epitopes in a repeating synthetic polypeptide antigen Poly 18, Poly EYK(EYA)5 in the mice of H-2d haplotype. Because of its repeating nature, all the potential epitopes of Poly EYK(EYA)5 generated as a result of antigen processing will have extensive sequence overlap, therefore, providing an excellent system to investigate the molecular basis of T cell peptide epitope selection in vivo. We have synthesized a series of 12 and 15 amino acid peptides to mimic these epitopes. In H-2d mice Poly EYK(EYA)5 elicits T cell clones that optimally react with 15 amino acid peptides EYK(EYA)4 and/or (EYA)5. Similar results were obtained when related 12 amino acid peptides EYK(EYA)3 and/or (EYA)4 are used. (EYA)5 reactive T cell clones appear to be very heterogenous and much larger in number than EYK(EYA)4 reactive clones. (EYA)5 reactive clones could be elicited by at least three short Poly-18 derived epitopes (EYA)4, EYK(EYA)3 and (EYA)3EYK while EYK(EYA)4 reactive clones elicited only by the EYK(EYA)3 epitope. However, we observed the dominance of (EYA)5 reactive clones even when EYK(EYA)3 was used as an immunogen and this could be related to the degeneracy of their antigen specificity. Our earlier antigen competition studies suggest that (EYA)5 does not compete with EYK(EYA)4 epitope in binding to I-Ad. Therefore, there is no intramolecular competition between these epitopes to activate T cells. The epitope (EYA)3EYK appears to be subdominant since it can elicit Poly EYK(EYA)5 specific T cells upon immunization but does not appear to be part of Poly EYK(EYA)5 repertoire. Peptides such as (EYA)2EYKEYA or EYAEYK(EYA)2 with lysine substitution in the middle of the sequence were non immunogeneic. Similar results were obtained when the larger 15 amino acid peptides were used as antigen. Another level of epitope immunodominance is seen when substituted peptides of the two immunodominant epitopes are used. Some of these epitopes have potential to be part of the Poly 18 repertoire but they are greatly under represented when intact Poly 18 is used as antigen. The unusual hierarchy observed for immunodominance in these overlapping epitopes of EYK(EYA)5 sequence suggest a bias in the selection of T cell repertoire based upon the crossreactivity between potential epitopes generated as a result of antigen processing.

Amino Acid Sequence↗
PubMed1992

Doppler echocardiographic determination of aortic and pulmonary valve orifice areas in normal adult subjects.

Cross-sectional and Doppler echocardiography were performed in 36 healthy adult subjects (aged 19 to 50 yr, mean 28 +/- 9; male 23, female 13) to establish normal values for aortic and pulmonary valve orifice areas. Standard continuity equation using echo-determined ventricular outflow tract diameters and Doppler-determined flow-velocity integrals from the outflow tracts and the corresponding great arteries, was employed to calculate the valve areas. Mean left ventricular outflow tract diameter was 1.92 +/- 0.17 cm (range 1.5-2.3 cm) and right ventricular outflow tract diameter was 1.80 +/- 0.18 cm (range 1.5-2.2 cm). Calculated aortic valve orifice area was 2.63 +/- 0.31 cm2 (1.76 +/- 0.2 cm2/m2) and correlated poorly with body surface area (r = 0.31, p > 0.05). Mean pulmonary valve orifice area was 3.01 +/- 0.36 cm2 (2.02 +/- 0.20 cm2/m2) and had a modest correlation with body surface area (r = 0.38, p < 0.05). No difference was observed between males and females for indexed aortic and pulmonary valve orifice areas. These data provide normal values for echocardiographically determined semilunar valve orifice areas and question the practice of indexing valve area for body surface in adult subjects.

Aortic Valve↗
PubMed1992

Congestive heart failure: survival trial of antiarrhythmic therapy (CHF STAT). The CHF STAT Investigators.

This study is a prospective, double-masked, randomized, clinical trial to determine the effect of anti-arrhythmic drug therapy on mortality in patients with congestive heart failure and ventricular arrhythmia. Patients will be assigned to receive either amiodarone or placebo. Eligible patients include those with ischemic and nonischemic congestive heart failure (New York Heart Association class III or VI) and with 10 or more ventricular premature beats per hour. All patients must have shortness of breath with minimal exertion or paroxysmal nocturnal dyspnea, a left ventricular internal dimension (LVIDd) by echocardiogram of 55 mm or greater (> or = 55 mm) or a CT ratio of greater than 0.5, and an ejection fraction of 40% of less. Patients will be entered into the study for 2.5 years and followed for an additional 2 years. Drug therapy will be continued for all patients throughout the entire study unless adverse reactions occur that necessitate individualized treatment. The expectation is that 674 patients are to be entered into the study from 25 participating centers. This sample size will allow for the detection of a 33% decrease in 2-year mortality (20% vs. 30%) in the treated patients as compared to those in the placebo group with a power of 0.90 and a two-sided alpha level of 0.05. Intermittent Holter monitoring, radionuclide ventriculograms, pulmonary function tests, echocardiograms, and blood tests, including arterial blood gases, will be required for each patient. The study analysis will address differences in total mortality, cardiac mortality, and sudden cardiac death between patients receiving anti-arrhythmic drug therapy and those receiving placebo. Other factors to be examined include the effects of antiarrhythmic therapy on suppression of arrhythmias, on ejection fraction, and relation of ischemic events to mortality.

Amiodarone↗
PubMed1992

Combined internal maxillary and anterior ethmoidal arterial occlusion: the treatment of choice in intractable epistaxis.

Whilst it is generally accepted that the standard management for anterior or benign epistaxis is either cautery or anterior nasal packing, that of posterior or intractable epistaxis remains controversial. Various modalities of treatment, ranging from posterior nasal packing to arterial ligation and embolization, have been advocated but none have been unanimously accepted as the treatment of choice. The purpose of this paper was to determine the efficacy of internal maxillary arterial ligation versus combined internal maxillary arterial ligation and anterior ethmoid arterial coagulation in intractable epistaxis. Over a six year period, from 1985 to 1990, 454 patients were admitted and treated for epistaxis. Forty-seven patients were diagnosed as having intractable epistaxis on the basis that the epistaxis failed to settle on anterior nasal packing. They were moved to the next step in management, which was combined anterior and posterior nasal packing. There were 30 failures, one was found to have choriocarcinoma of the maxilla, and was treated with cytotoxics, and the other 29 were moved to the next step, which was arterial ligation. Fifteen patients had internal maxillary arterial ligation, and 14 combined internal maxillary arterial ligation and anterior ethmoidal arterial coagulation. Large windows were created in both the anterior and posterior walls of the maxillary sinuses and all identifiable branches of the internal maxillary artery were dissected out carefully and two medium size ligating clips were placed over the main trunk, the sphenopalatine and the descending palatine branches. Single clips were placed on all other identifiable branches. Coagulation of the anterior ethmoidal artery was performed with a bipolar cautery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Tuberculosis of the parotid gland: clinically indistinguishable from a neoplasm.

Tuberculosis of the parotid gland may be clinically indistinguishable from a neoplasm. This poses a problem with regard to management, because the treatment of tuberculosis is medical, whilst that of the majority of tumours is surgical. If radical surgery with resection of a branch or branches of the facial nerve is embarked upon in a patient with tuberculosis, without prior histological diagnosis, unnecessary permanent disability will result. Two cases of tuberculosis of the parotid gland are reported, demonstrating the clinical similarity of tuberculosis to a parotid neoplasm and the absolute need for histological diagnosis before embarking on surgery that will require resection of the branches of the facial nerve. The conclusion is that although tuberculosis of the parotid gland is rare, it still exists and must be thought of as one of the differential diagnoses of a parotid tumour. This must be kept in mind, especially when the decision to sacrifice branches of the facial nerve is indicated, in order to get a tumour-free margin on an excisional biopsy. If the suspicion of tuberculosis is high, a therapeutic trial of antituberculous chemotherapy, for one week, can be diagnostic.

Adult↗
PubMed1992

An evaluation of Lawsonia alba extract as hepatoprotective agent.

The hepatoprotective activity of an ethanol-water (1:1) extract of Lawsonia alba has been studied against CCl4-induced liver toxicity. The effects of the extract on hexobarbitone-induced sleep, BSP clearance, and on certain biochemical parameters indicated its protective role. There was no effect on bile flow. The extract did not show any signs of toxicity and the minimum lethal dose was greater than 2.0 g/kg p.o. in mice.

Animals↗
PubMed1992

Structure and hepatoprotective activity of a biflavonoid from Canarium manii.

Canarium manii (Burseraceae) was chemically investigated and the presence of the biflavonoid agathisflavone is reported for the first time from this plant. Pharmacologically, this biflavonoid in doses 50.0 mg and 100.0 mg given orally exhibited dose-dependent hepatoprotective activity against experimentally-induced carbon tetrachloride-hepatotoxicity in rats and mice.

Animals↗
PubMed1992

Seroprevalence of HIV infection in rural South Africa.

OBJECTIVES: To establish the prevalence of HIV infection in rural South Africa and to investigate demographic factors that influence this prevalence. DESIGN: An anonymous HIV seroprevalence survey was performed in conjunction with a population-based malaria surveillance programme. SETTING: The rural area of northern Natal/KwaZulu, South Africa. PARTICIPANTS: A total of 5023 black African participants were recruited by malaria surveillance agents during house-to-house visits; each house in an endemic malaria area is visited approximately once every 6 weeks. Participants included 4044 healthy and 979 febrile individuals (i.e., suspected of having malaria). MAIN OUTCOME MEASURES: HIV-1 and HIV-2 serological status, degree of mobility, age and sex. RESULTS: Sixty of the 5023 blood specimens were confirmed to be HIV-1-antibody-positive by Western blot, an overall prevalence of 1.2% (95% confidence interval, 0.9-1.5). None of the specimens was positive for HIV-2 antibodies. After adjusting for age, presence of fever and migrancy, women had a 3.2-fold higher prevalence of HIV-1 infection than men. HIV-1 infection was approximately three times more common among subjects who had changed their place of residence recently (2.9 versus 1.0%, P < 0.01). CONCLUSIONS: The prevalence of HIV-1 infection is higher among women than men resident in rural Natal/KwaZulu, South Africa. This is at least in part the result of oscillatory migration, particularly of men who work in urban areas but have families and homes in rural areas. Migration is associated with a higher prevalence of HIV-1 infection, suggesting that improving social conditions so that families are not separated and become settled in their communities is one way to help reduce the spread of HIV-1.

Adolescent↗