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Biomedical subjects

R Seth

Publications and source records attributed to R Seth.

At least 37 records · Page 2Linked to original sources
PubMed1997

Interleukin-8 and inducible nitric oxide synthase mRNA levels in inflammatory bowel disease at first presentation.

Interleukin-8 (IL-8) and nitric oxide (NO) may be important mediators in the pathogenesis of chronic idiopathic inflammatory bowel disease (CIIBD), but their roles in disease activity in ulcerative colitis (UC) and Crohn's disease (CD) are uncertain. The aim of this study was to measure mRNA for IL-8 and inducible NO synthase (iNOS) in small mucosal biopsies from untreated patients at first presentation and to relate these measurements to the histological levels of polymorph infiltration graded on a ten-point scale. For this purpose, a sensitive enzyme-linked oligonucleotide chemiluminescent assay (ELOCA) was developed to quantitate reverse transcription-polymerase chain reaction (RT-PCR) products amplified from RNA from paired biopsy samples. The levels of IL-8 and iNOS mRNAs were calculated as ratios of the RT-PCR products to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) RT-PCR product. In UC patients, median values of IL-8/GAPDH and iNOS/GAPDH were significantly elevated compared with controls and CD. However, in both UC and CD, the IL-8/GAPDH and iNOS/GAPDH ratios correlated significantly with polymorph infiltration. ELOCA enabled quantitation of multiple mRNAs in small mucosal biopsies from untreated patients with CIIBD and supported a role for IL-8 and iNOS in acute inflammation in both UC and CD.

Adult↗
PubMed1997

Male infertility caused by epididymal dysfunction in transgenic mice expressing a dominant negative mutation of retinoic acid receptor alpha 1.

Retinoids are thought to be required for the normal development and maturation of a number of tissues, including most epithelia. The action of retinoids appears to be mediated through the binding to retinoic acid receptors (RARs) in the nucleus. The activity of retinoic acid can be inhibited in cells carrying dominant negative mutations of RAR alpha. We created transgenic mice expressing a dominant negative mutant of RAR alpha driven by the murine mammary tumor virus promoter. Expression of the transgene was evident in the epididymis and vas deferens in transgenic males. These males were either infertile or had reduced fertility, and the epithelium lining the ducts of the epididymis and vas deferens had undergone squamous metaplasia. Sperm developed normally in the testis but degenerated in the epididymis and vas deferens because inspissated ductal fluid blocked the normal passage of the sperm.

Animals↗
PubMed1995

Stable-isotope studies of glutamate catabolism in Fusobacterium nucleatum.

Catabolism of glutamate was investigated in Fusobacterium nucleatum, an anaerobic micro-organism that is strongly implicated in periodontal disease. The distribution of labels in acetate and butyrate derived from [13C]glutamates was determined by NMR spectroscopy and MS. The label from L-[5-13C]glutamate was not incorporated, whereas C-1 of acetate and butyrate were efficiently labelled by L-[1-13C]glutamate; these results indicated that the hydroxyglutarate pathway predominated. In butyrate, enrichment at C-3 was smaller than C-1; that this was not due to participation of the methylaspartate pathway was demonstrated by the incorporation of label from L-[4-13C]glutamate into only C-2 of acetate and C-4 (major)/C-2 (minor) of butyrate. The presence of label at a second site in butyrate was attributed to the synthesis of butyrate from acetate and verified by the incorporation of label from [1,2-13C2]- and [2H3]-acetate.

Acetates↗
PubMed1994

Left ventricular remodelling and disparate changes in contractility and relaxation during the development of and recovery from experimental heart failure.

OBJECTIVES: Canine pacing induced heart failure is characterised by impaired left ventricular contractility and relaxation, and clinical recovery after cessation of pacing. It is unclear whether the impairment is responsive to adrenergic stimulation. The aim of this study was to assess left ventricular contractility and relaxation and their response to beta adrenergic stimulation during heart failure and after recovery. METHODS: Eight dogs were paced (250 beats.min-1) for 3 weeks to severe heart failure and recovered for 4 weeks after cessation of pacing. During these periods, haemodynamic and echocardiographic measurements were made with and without beta adrenergic stimulation. RESULTS: At heart failure, impaired left ventricular contractility was evidenced by reduced dP/dt [1412(SD 156) mm Hg.s-1 from 2437(382) mm Hg.s-1 at control, p < 0.01] and a downward displacement of the velocity of circumferential fibre shortening-end systolic wall stress relation. Impaired left ventricular relaxation was evidenced by raised end diastolic pressure [35(6) mm Hg from 7(4) mm Hg at control, p < 0.01] and prolonged relaxation time constant tau [28(4) ms from 17(6) ms, p < 0.01]. The ability of beta adrenergic stimulation to augment contractility was reduced: there was blunted dP/dt response to dobutamine. The ability of beta adrenergic stimulation to shorten relaxation was maintained: there was a similar degree of shortening of tau by dobutamine. At recovery, dP/dt returned to control and the shortening-stress relation moved upward, suggesting return of contractility. The response of dP/dt to dobutamine was restored. However, tau remained prolonged indicating persistent abnormal relaxation. CONCLUSION: In pacing induced heart failure, there is a dissociation between the normal ability of beta adrenergic stimulation to augment contractility and shorten relaxation, and a differential capacity for recovery of contractility and relaxation.

Animals↗
PubMed1994

Management of constipation and encopresis in infants and children.

Chronic functional constipation is common in childhood. Basic understanding of the defecation process is essential to formulate a rational diagnostic and therapeutic approach to pediatric patients with chronic constipation, with or without encopresis. Primary care physicians can perform a major preventive function by anticipatory guidance and early dietary intervention. Most patients referred to pediatric gastroenterologists can be effectively treated as outpatients with use of an approach consisting of colonic evacuation, stool softeners, dietary manipulations, bowel training, and behavioral management. Avoidance of painful (laxatives) and invasive (suppositories, enemas) modalities is an important part of successful management. Further evaluation, including manometric tests, are reserved for patients with a history or physical findings suggesting an underlying disorder predisposing the patient to difficulty with defecation. Biofeedback therapy is likely destined to play a role in the subgroup who respond poorly to traditional therapeutic methods.

Barium Sulfate↗
PubMed1993

Role of epidermal growth factor expression in early mouse embryo lung branching morphogenesis in culture: antisense oligodeoxynucleotide inhibitory strategy.

Epidermal growth factor (EGF) expression and branching morphogenesis were inhibited using a 5' 15-mer antisense oligodeoxynucleotide (ODN) directed against EGF precursor mRNA in embryonic mouse lung in culture under chemically defined, serumless conditions. Antisense EGF ODN resulted in > 90% inhibition of EGF immunoreactive peptide synthesis, 75% reduction in branching morphogenesis, 73% decrease in DNA content, 64% decrease in RNA content, 73% decrease in protein synthesis, and 65% decrease in [3H]thymidine incorporation into DNA compared to Embryonic Day 11 controls in culture for 4 days. Sense ODN results were similar to control. Supplementing antisense ODN with EGF partially reversed antisense effects. The results further support a role for EGF in pulmonary organogenesis.

Animals↗
PubMed1992

Epigenetic role of epidermal growth factor expression and signalling in embryonic mouse lung morphogenesis.

A major unsolved problem in developmental biology is to determine when and how time- and position-restricted instructions are signaled and received during secondary embryonic inductions such as branching morphogenesis. The mouse embryonic lung rudiment was used to test the hypothesis that endogenous peptide growth factors, specifically epidermal growth factor (EGF), serve as instructive epigenetic signals for morphogenesis. The presence of EGF precursor mRNA transcripts was detected using the reverse-transcriptase-coupled polymerase chain reaction both in E11-E17-day mouse embryo lung tissues in vivo and in E11-day lung cultured for up to 7 days in vitro under chemically defined, serum-free conditions. Immunolocalization identified a position-restricted distribution of EGF in and around the primitive airways both during in vivo lung morphogenesis and in culture. EGF receptors (EGFR) coimmunolocalized with EGF in the primitive airways. Addition of exogenous EGF to lungs in culture resulted in significant concentration-dependent stimulation of branching morphogenesis, DNA, RNA, and protein content, and in [3H]thymidine incorporation into DNA. Conversely, the addition of tyrphostin (specific EGF receptor kinase antagonist) to lungs in culture resulted in concentration-dependent inhibition of branching morphogenesis, DNA, RNA, and protein content, and in [3H]thymidine incorporation into DNA without apparent cytotoxicity. The inhibition of the EGF signal by tyrphostin was confirmed by immunoprecipitation of tyrosine phosphoproteins. We conclude that early mouse embryo lungs express EGF transcripts and corresponding EGF peptides in a specific position-restricted distribution which coimmunolocalizes with EGFR in the primitive airways, while stimulatory and inhibitory studies indicate a functional role for the transduced EGF signal in the epigenetic regulation of lung branching morphogenesis. We speculate that the peptide growth factor EGF serves a function in secondary embryonic morphogenetic inductions, which may be modulated by interaction with other growth factors.

Animals↗
PubMed1992

Production and utilisation of antibodies directed against oestrone sulphate using specific hapten synthesis.

Oestrone-3-sulphate (E13S) is an important metabolite of oestrone. Studies in cattle had previously shown that it is synthesised in the gravid uterus by the foetus, but not by the corpus luteum. Progesterone measurement in milk by radioimmunoassay (RIA) is routinely carried out in some laboratories as a pregnancy test for cattle. The major drawback of progesterone measurement in milk, by RIA, as a pregnancy test was the failure to detect the lack of conceptus in those cows where early embryonic death had occurred but the corpus luteum still persisted thereby giving false positive results. We have developed a direct RIA for E13S by raising antibodies to an immunogen prepared from a specific hapten synthesised by an unambiguous chemical synthesis. The sensitivity of the RIA in milk was found to be 0.368 nmol/l. The levels of E13S in non-pregnant cows are undetectable but during a viable pregnancy, the levels are elevated to greater than 0.40 nmol/l by day 100. There was no cross-reactions in the assay with any free oestrogens. The measurement of this metabolite of oestrone promises to provide an accurate marker for the detection of a viable conceptus in cattle.

Animals↗
PubMed1992

Combination treatment with noradrenalin and serotonin reuptake inhibitors in resistant depression.

Eight cases of resistant recurrent depression were treated with a combination of nortriptyline and a new serotonin reuptake inhibitor, with or without concurrent lithium therapy. Significant improvement was seen in all patients where other drug regimes and ECT had been ineffective. No adverse reactions occurred in any of our patients, seven of whom were elderly. The combination treatment was more effective than individual therapies alone.

1-Naphthylamine↗
PubMed1991

Circulating ICAM-1 isoforms: diagnostic prospects for inflammatory and immune disorders.

Intercellular adhesion molecule-1 (ICAM-1, CD54) is an important early marker of immune activation and response. Evidence on its role has come from immunohistological staining of tissues, since no free circulating ICAM-1 has been detected. By means of monoclonal antibodies against ICAM-1 and a sensitive chemiluminescence technique, free circulating ICAM-1 was detected in serum from sixteen healthy young volunteers. The concentrations varied among the subjects. Non-denaturing gel separation methods showed that ICAM-1 circulates in at least three isoforms, the proportions of which also varied. These findings have important implications for the investigation, diagnosis, and therapeutic monitoring of various inflammatory, neoplastic, and immune disorders.

Adult↗
PubMed1991

ICAM-2 peptides mediate lymphocyte adhesion by binding to CD11a/CD18 and CD49d/CD29 integrins.

Three fifteen-amino-acid polypeptides designated peptides 1, 2 and 3 were synthesised as likely candidates for mimicking the role of ICAM-2 as a ligand. The ability of each peptide to bind lymphoid cells was tested. Peptide 2 largely mediated cell attachment of unstimulated cells and this binding was only marginally increased by stimulating the cells with phorbol dibutyrate (P(Bu)2). Peptide 3 mediated minimal spontaneous cell attachment, but this binding was significantly enhanced following P(Bu)2 stimulation. Peptide 1 had no effect on cell attachment with or without stimulation. The cell attachment to peptide 2 was both temperature- and cation-dependent. Studies using specific monoclonal antibodies showed that with unstimulated cells, anti-VLA-4 alpha(CD49d) or beta chain (CD29) antibodies (KD4-13 and 4B4) and anti-CD18 (1B4) each partially inhibited the cell binding. Monoclonal antibodies against CD54 (ICAM-1; 84H10 or LB2), MHC class 1 (W6/32) and control mouse IgG had no effect. When anti-CD29 and anti-CD18 monoclonal antibodies were used concurrently, there was almost complete inhibition of the cell attachment. These observations indicated that cell adhesion via ICAM-2 is mediated: (i) predominantly by peptide 2 in unstimulated and P(Bu)2-stimulated cells, and also, to some extent, by peptide 3 in P(Bu)2-stimulated cells and (ii) by binding to both CD11/CD18 and CD49d/CD29 integrins.

Amino Acid Sequence↗
PubMed1991

Protein phosphorylation and dephosphorylation in type II pneumocytes.

Protein phosphorylation and dephosphorylation are a major mechanism for regulating cellular activity. Substantial evidence exists for ascribing a key role of protein phosphorylation and dephosphorylation in the regulation of surfactant secretion from type II pneumocytes, yet understanding of the specific molecular mechanisms is generally lacking. Herein, we report two-dimensional electrophoretic mapping of proteins phosphorylated in type II pneumocytes in primary culture, the response to protein kinase C simulation with phorbol ester, and the response to protein phosphatase inhibition with okadaic acid. Exposure of cells for 15 min to phorbol ester at a concentration (10(-4) M) which maximally stimulated both translocation of protein kinase C from cytosol to membranes and surfactant secretion increased phosphorylation (50-80% compared with control) of three specific proteins (50 kDa, pI 5.8 and 5.7; 25 kDa, pI 5.7). Exposure of cells for 2.5 h to okadaic acid (10(-6) M), a concentration that inhibited 90% of protein phosphatase activity, resulted in greatly increased phosphorylation (200-1,500% compared with control) of five specific proteins (50 kDa, pI 5.7 and 5.6; 45 kDa, pI 5.5; 40 kDa, pI 5.5; 25 kDa, pI 5.5). Combined treatment with okadaic acid and phorbol ester resulted in further increases (145-3,080% compared with control) in phosphorylation of four specific proteins (50 kDa, pI 5.6; 45 kDa, pI 5.5; 40 kDa, pI 5.5; 25 kDa, pI 5.5). We conclude that these respective proteins comprise major substrates for protein kinase C-dependent phosphorylation and for protein phosphatases in type II pneumocytes in primary culture. Furthermore, we speculate that these proteins will prove to play key roles in the regulation of type II pneumocyte function.

Animals↗
PubMed1991

Psychiatric illnesses in patients with HIV infection and AIDS referred to the liaison psychiatrist.

All referrals made to the liaison psychiatric service for HIV and AIDS patients over one year were reviewed. ICD-9 and CDC diagnoses were applied to each case at presentation. Sixty HIV-positive patients were assessed, of whom 35 had affective disorder, which was significantly associated with CDC group IV disease (AIDS). Adjustment reaction was seen in nine patients, paranoid states in six, dementia in four, personality changes in four and paranoid schizophrenia in two. CT scans of the brain were performed on 23 of the patients: 17 of these showed abnormalities. The proportion of registered AIDS patients who were referred was five times the proportion of HIV patients.

AIDS Dementia Complex↗