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Biomedical subjects

U Shah

Publications and source records attributed to U Shah.

At least 37 records · Page 2Linked to original sources
PubMed1993

Geographic and temporal distribution and molecular characterization of two highly pathogenic clones of Streptococcus pyogenes expressing allelic variants of pyrogenic exotoxin A (Scarlet fever toxin).

The molecular population genetics and pathogenic potential of North American and European invasive strains of Streptococcus pyogenes were assessed. Isolates from recent invasive infections and from infections in the 1920s and 1930s were characterized for multilocus enzyme genotype and allelic variation in the gene (speA) that encodes streptococcal pyrogenic exotoxin (SPE) A (scarlet fever toxin). A subset of strains was studied for allelic variation in genes that encode SPE B and streptokinase. All contemporary strains assigned to electrophoretic types (ETs) 1 and 2 that synthesize SPE A have the speA2 and speA3 allelic variants, respectively, and their relative virulence in two mouse models is similar to that of strains of the same ET and M protein types recovered earlier. In contrast, ET 1 and 2 isolates from disease episodes in the 1920s and 1930s contain the speA1 allele. The data suggest there may be temporal and geographic variation in the occurrence of clone--virulence factor allele combinations, an observation that may in part explain fluctuations in disease frequency, severity, and character.

Alleles↗
PubMed1993

Penicillin-resistant Streptococcus pneumoniae strains recovered in Houston: identification and molecular characterization of multiple clones.

A sample of 48 penicillin-resistant Streptococcus pneumoniae (PRSP) strains recovered between January 1989 and May 1991, primarily from infected children in Houston, was characterized by multilocus enzyme electrophoresis and repetitive extragenic palindromic-polymerase chain reaction genomic profiling. A heterogeneous array of 22 clonal genotypes was identified, but 64% of the PRSP strains in the sample were assigned to five clones that are closely similar in overall chromosomal character and express serotype 6 capsule. A close genetic association between these five clones and penicillin-resistant 6B clones recovered in Alaska, Iceland, and Spain was identified by multilocus enzyme electrophoresis. Taken together, the results suggest either that the common resistant 6B clones in Alaska, Iceland, Spain, and Houston have a recent ancestor or that isolates of a certain pneumococcal phylogenetic lineage are more likely to develop penicillin resistance.

Base Sequence↗
PubMed1992

Serum levels of immunoreactive thymosin alpha 1 and thymosin beta 4 in large cohorts of healthy adults.

Enzyme linked immunosorbent assays were used to measure serum levels of immunoreactive thymosin alpha 1 and thymosin beta 4 in 681 healthy adults (range 18 yr-101 yr). Immunoreactive thymosin alpha 1 was found to occur at a geometric mean of 540 pg/ml with a range from 252 to 1158 pg/ml. There were no differences in the levels when analyzed according to race, sex or age. Immunoreactive thymosin beta 4 was measured at a geometric mean of 12.6 ng/ml with a range from 6.9 to 23.0 ng/ml. There were no differences in the levels when analyzed according to race or sex, however, there was a slight upward trend with increasing age. This data may be useful as a reference when monitoring clinical studies, determining the kinetics of drug metabolism and distinguishing patient groups with elevated levels of either of these peptides.

Adolescent↗
PubMed1991

Low interleukin-2 synthesis by type 1 diabetics is regulated at the pretranslational level.

Insulin-dependent diabetes mellitus (IDDM) is believed to be a consequence of an autoimmune attack on beta cells by T cells. We have previously reported that T cells from the majority of patients with IDDM produced decreased levels of interleukin-2 (IL-2) following activation with phytohemagglutinin. In this study we began to characterize the basis for this defect. First, we tested whether the decreased IL-2 synthesis was due to the secretion of a factor which inhibited the ability of indicator cells to respond to IL-2 or which inhibited IL-2 release by responder cells. Second, we examined steady-state levels of IL-2 mRNA in IDDMs and controls. To make this feasible, given the limited number of peripheral blood lymphocytes (PBL) available from our patients, we depended upon an approach which enabled the generation of large numbers of resting T cells, called G0/G1 cells, from small numbers of PBL. Preliminary experiments demonstrated that G0/G1 cells from IDDMs reproduced the IL-2 defect seen originally with PBL. Our results suggested that the secretion of inhibitory factors could not explain the IL-2 defect. A comparison of steady-state levels of IL-2 mRNA from activated T cells of IDDMs and age-matched controls, however, demonstrated lower levels of IL-2 mRNA in IDDMs compared to controls. Finally, we observed that the IL-2 mRNA in IDDM T cells was less stabile than that in the control cells, suggesting a possible mechanism for the defect.

Adolescent↗
PubMed1991

The response pattern of human T cells to stimulation following expansion in IL-2.

The ability to stimulate and induce responses of T cells is influenced by their age and state of differentiation. We have examined the response upon restimulation of T cells expanded in IL-2. Our results demonstrate that large numbers of T cells, which after activation react by secreting IL-2, can be obtained from small numbers of PBL. In this study T cells were grown in IL-2 and, after 12-14 days, IL-2 was withdrawn in order to deprive them of growth factors. Our findings showed that after resting for 48 hours without IL-2, IL-2-dependent cells reverted to small lymphocytes, ceased to incorporate 3H-TdR, and had no mRNA for activation antigens such as Tac or IL-2. The cells could be reactivated to proliferate by stimulation with a calcium ionophore ionomycin and phorbol dibutyrate (PdB). Cells from insulin dependent diabetes mellitus patients with a defined immunoregulatory defect were then studied. Our results demonstrated that the IL-2 expanded cells evidenced the immunoregulatory defect for IL-2 synthesis that we had initially defined using virgin T cells from peripheral blood. These results demonstrate that studies of immune function can be undertaken in donors from whom limited numbers of peripheral blood lymphocytes are available using primed cells which have been allowed to dedifferentiate.

Antibodies, Monoclonal↗
PubMed1988

Etodolac, a novel antiinflammatory agent. The syntheses and biological evaluation of its metabolites.

The syntheses of five metabolites of the antiinflammatory drug etodolac (1,8-diethyl-1,3,4,9-tetrahydropyrano-[3,4-b]indole-1-acetic acid) are described, viz. 6-hydroxyetodolac, N-methyletodolac, 4-ureidoetodolac, 8-(1'-hydroxy)etodolac, and 4-oxoetodolac. These syntheses were used to confirm the identities of the metabolites. The metabolites themselves, as well as the previously reported metabolite 7-hydroxyetodolac, were tested in a rat adjuvant edema model and in vitro for their capacity to block prostaglandin production in chondrocyte cells. All either were inactive or possessed only marginal activity. The isolation of N-methyletodolac and 4-oxoetodolac from human and rat urine, respectively, is also described.

Animals↗
PubMed1988

Structure-activity relationships among analogues of pemedolac, cis-1-ethyl-1,3,4,9-tetrahydro-4-(phenylmethyl)pyrano[3,4-b]indo le-1-a cetic acid, a potent analgesic agent.

The syntheses of analogues of pemedolac (cis-1-ethyl-1,3,4,9-tetrahydro-4-(phenylmethyl)pyrano[3,4-b]indol e-1-acetic acid), a potent analgesic, are described. They were tested for analgesic and antiinflammatory effects in vivo and for inhibition of prostaglandin production in vitro. Analysis of structure-activity relationships shows that analgesic activity in this series is associated with 1S-cis stereochemistry, the presence of a pi-system (allyl or benzyl) at position 4, and a log P value greater than 4.0.

Animals↗
PubMed1985

Epidemiology training: a necessity for primary health care.

In spite of planned development and expansion of health services, especially in rural areas in India, mortality due to preventable conditions has remained unacceptably high. Important reasons for failure of the health system to detect the problems early are centrally planned programmes based on inadequate data and time-bound numerical targets for achievement. This promotes a tendency for passive implementation which destroys initiative and incentive for conceptualisation of problems and strategies. For health programmes to be far more successful, the entire health team needs to be given training in epidemiology appropriate to the level of each category, so that programme planning based on epidemiologically determined local needs can be done at district level by the District Health Organisation. Participation of health workers and the community will then be more active and relevant to the needs of the community.

Community Health Workers↗
PubMed1984

Pyrido[3',2':4,5]thieno[3,2-d]-N-triazines: a new series of orally active antiallergic agents.

A new series of orally active mediator release inhibitors, pyrido[3',2':4,5]thieno[3,2-d]-N-triazines, was synthesized and evaluated for antiallergic activity. Several products showed high activity as inhibitors or wheal information in the rat passive cutaneous anaphylaxis screen and as inhibitors of histamine release from passively sensitized rat mast cells. Many compounds were orally active in the PCA test. The most potent compound, 7-phenylpyrido-[3',2':4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)- one (10) with an I50 value of 0.05 microM, was 60 times more potent than disodium cromoglycate (DSCG) in the RMC assay.

Administration, Oral↗
PubMed1984

Perinatal mortality in rural India: a strategy for reduction through primary care. I Stillbirths.

In a prospective community based study of the distribution and determinants of stillbirths in a rural area of Maharashtra, India, that was carried out for two years, 3129 singleton and 22 twin births were recorded in a population of 47 000. Of the 3173 babies, 85 singletons and five of the twins were stillborn giving a stillbirth rate of 28.4/1000 births. The causes of stillbirths are analysed and the possibility of reducing the unacceptably high stillbirth rate by adequate training of grassroot level workers in screening pregnant women for detection of "at risk" mothers and their timely referral is discussed.

Community Health Workers↗
PubMed1984

Perinatal mortality in rural India: intervention through primary health care. II Neonatal mortality.

Early neonatal mortality is unacceptably high in most developing countries. A large majority of births in rural areas of these countries occur at home, attended by relatives or traditional birth attendants and without easy access to skilled professional care. Under these circumstances cause of death has to be based on lay descriptions of terminal events. Analysis of cause of death shows that 74% of the early neonatal deaths are amenable to intervention. Admittance to hospital of the "at risk" neonates is not practicable. Intervention through primary health care can be effective if based on scientific principles and offered through female community health workers. Objectives of domiciliary care given by these workers should be to educate and guide the mother to protect the delicate newborn from the effects of adverse environmental conditions, to ensure adequate nutrition, and to prevent infections. Interventions supporting beneficial traditional cultural practices as well as simple techniques for care of the newborn are discussed.

Adult↗
PubMed1981

The role of radioimmunodetection in the management of testicular cancer.

Five patients with testicular cancer received an intravenous injection of between 1 and 2.5 mCi of iodine 131-labeled antibody to human chorionic gonadotropin (HCG) or alpha-fetoprotein (AFP), followed by total-body photoscanning to visualize areas of abnormal radioactivity. Blood-pool and nontarget sites of radioactivity were reduced by subtracting the images derived by injection of technetium Tc 99m-labeled components from the iodine 131 scans. The HCG-immune scintiscans proved helpful in tumor localization and in the selection of appropriate therapy, while the AFP scan presented corroborative evidence of widespread tumor. Elevated serum levels of these two markers did not hinder successful tumor detection and localization by this method of radioimmunodetection. Cancer radioimmunodetection with antibodies to HCG and to AFP appears to be a useful procedure for the pretreatment and posttreatment evaluation of patients with testicular cancer and can reveal sites of tumor not detected by other methods.

Adult↗
PubMed1980

Comparison of sustained-release and standard methylphenidate in the treatment of minimal brain dysfunction.

In a randomized, double-blind study the effects of the standard form of methylphenidate (10 mg given twice daily) were compared to those of a sustained-release form of methylphenidate (20 mg given once daily) in outpatient children with minimal brain dysfunction. The study was 2 weeks in duration and involved 30 children. Psychometric tests completed by the children, as well as physician, teacher and parent questionnaires were used to measure drug effects. Comparisons between the 2 methylphenidate treatment groups showed no consistent significant changes which could be deemed clinically favorable for one group over the other nor were there significant improvements over pretreatment measurements for either group. Adverse reactions--headache, hyperactivity, restlessness were reported by 5 patients receiving the sustained-release and 2 receiving the standard methylphenidate.

Adolescent↗