PubMed Health⌕ Search

Biomedical subjects

J McDevitt

Publications and source records attributed to J McDevitt.

12 recordsLinked to original sources
PubMed1995

Tyrosine phosphorylation in the human duodenum.

Many growth factor receptors including the epidermal growth factor receptor function through tyrosine kinase activity. The aim of this study was to examine the constitutive level of tyrosine phosphorylation in the normal duodenum and in the hyperproliferative coeliac duodenum. A flow cytometric assay was devised using monoclonal antibody to phosphorylated (but not native) tyrosine residues to determine the levels of tyrosine phosphorylation in both CD3 positive intraepithelial lymphocytes and CD3 negative epithelial cells obtained by EDTA treatment of endoscopically obtained duodenal biopsy specimens. In addition, immunohistochemistry was performed on 18 formalin fixed coeliac duodenal biopsy specimens and eight control specimens. Tyrosine phosphorylation could be detected by flow cytometry on duodenal enterocytes and this expression was up regulated by pretreatment with epidermal growth factor. Tyrosine phosphorylation decreased with progression from the villus to the crypt, however, and was virtually undetectable on crypt enterocytes. Immunohistochemistry of the coeliac duodenum showed virtually absent tyrosine phosphorylation in the crypt. Increased tyrosine phosphorylation was detected in the infiltrating T cells. In conclusion, tyrosine phosphorylation in the duodenum is confined to the non-proliferative villous epithelium and is virtually undetectable in the proliferative crypt compartment. These findings suggest that tyrosine kinase activity is not a significant factor in the regulation of crypt cell proliferation in the human duodenum either in normal subjects or in coeliac disease patients.

CD3 Complex↗
PubMed1994

Gastric T lymphocyte responses to Helicobacter pylori in patients with H pylori colonisation.

Helicobacter pylori has been identified as a dominant factor in the pathogenesis of duodenal ulcer. The aim of this study was to examine peripheral blood and gastric lymphocyte proliferation and cytokine production in patients with H pylori colonisation. Sixty five dyspeptic patients attending for endoscopy were studied; 35 of these were H pylori positive and 30 H pylori negative as assessed by culture, histology, and rapid urease test. H pylori antigen was capable of stimulating peripheral blood lymphocyte proliferative responses even in H pylori negative patients. Peripheral blood lymphocyte proliferative responses to H pylori (but not to purified protein derivative or phythaemagglutinin) were significantly lower in H pylori positive than H pylori negative patients. Similarly, antigen specific proliferative responses and interferon gamma production by gastric lamina propria lymphocytes were also depressed in H pylori positive patients compared with H pylori negative patients. CD8 and CD22 positive lamina propria lymphocytes were increased in H pylori positive patients. These data show that antigen specific responses to H pylori are significantly lower in H pylori positive patients and could indicate activation of antigen specific suppression.

Adolescent↗
PubMed1993

Changes in immunological parameters during interleukin 2 and interferon 2 alpha treatment of recurrent renal cell carcinoma and malignant melanoma.

Immunological parameters were studied in patients with either advanced renal cell cancer (n = 7) or advanced malignant melanoma (n = 6) during treatment with a low-dose continuous intravenous treatment with human recombinant interleukin-2 (hr IL-2) and recombinant interferon alpha-2a. Before treatment, natural killer (NK) cell activity was found to be significantly lower in these patients than in 10 normal controls. However, the numbers of NK cells in circulation were equivalent; following incubation of the patients' peripheral blood mononuclear cells (PBMC) with IL-2 for three days normal lymphokine activated killer (LAK) cell activities were induced. Thus, in-vitro incubation with IL-2 appeared to overcome a defect in NK activity. We next examined the effect of IL-2/IFN alpha therapy on in-vitro LAK induction. Treatment significantly increased in-vitro LAK activity in eight of nine patients tested, although in-vivo LAK cell activity was not altered during treatment. The numbers of NK cells (CD16+ CD56+) in peripheral blood showed a significant increase in seven of ten patients as a result of treatment. The three patients who showed the best clinical response also showed the highest increase in expression of these phenotypic markers. T cells were found to be activated in 8/10 patients as indicated by increased co-expression of CD3 with CD25 after completion of 4-day continuous intravenous infusion of IL2. Four days before the start of treatment, cancer patient PBMC stimulated with concanavalin A (con A) produced significantly greater amounts of TNF compared to normal controls. In-vitro inducible TNF was found to decrease following treatment. Since IL-2 production and lymphocyte proliferation in response to Con A were normal in the patient group and were not altered by treatment, the reduction in TNF levels seemed not to be a general inhibitory effect. Further study of these and other changes in the immune system during IL-2/IFN alpha treatment may help to understand how these immunoregulators cause tumour destruction and to predict their usefulness in individual patients.

Adult↗
PubMed1992

A phase 2 trial of recombinant interleukin-2 and 5-fluorouracil in patients with metastatic colorectal carcinoma.

The toxicity and efficacy of sequential 5-fluorouracil (5-FU) and recombinant interleukin-2 (IL-2) were evaluated in 12 patients with metastatic colorectal carcinoma. This combination of 5-FU and IL-2 produced a 10% partial response rate with 40% of patients remaining in stable disease while on therapy. No clear improvement in survival was demonstrable. In contrast to the disappointing response rates the overall level of toxicity was very low with no treatment related deaths. It is concluded that modifications in treatment schedules are required before further similar studies are commenced.

Adult↗
PubMed1991

Effect of the intestinal flora on the urinary organic acid profile of rats ingesting a chemically simplified diet.

In order to estimate the influence of gut bacteria on animal metabolism, the excretion of organic acids, as monitored by gas-liquid chromatography, was compared in the urines of conventional and germ-free rats. Rats were maintained on a chemically simplified diet in order to minimize the effect of strictly exogenous compounds on the organic acid profile. Initial analysis of the excretion rates of 68 compounds, found reproducibly in the profile, indicated significant day-to-day and rat-to-rat variation, suggesting that haphazard comparison of experimental groups of animals might yield spurious differences with no biological significance. When repeated measures of the profile were analysed by a random effects analysis of variance model, no compound was found exclusively in the urine of either conventional or germ-free rats. Nevertheless, tricarballylate was significantly higher and both tartronate and vanillate significantly lower in conventional rat urine. The flora was implicated in these differences because caecal contents of conventional rats were found to convert such tricarboxylic acids as cis- and trans-aconitate to tricarballylate and to cause the dissimilation of both vanillate and tartronate, the latter compound being of dietary origin.

Analysis of Variance↗
PubMed1991

Thyroid dysfunction can predict response to immunotherapy with interleukin-2 and interferon-2 alpha.

Thyroid dysfunction is a well-recognised side-effect of treatment with interleukin-2 (IL2). We assessed the correlation between the development of abnormal thyroid function and tumour response in 13 patients receiving IL2 and interferon-2 alpha (IFN2 alpha) for advanced malignancy. Seven patients had normal thyroid function during treatment, and all of these patients have since died of progressive disease. Of six patients who did develop thyroid dysfunction during treatment, one patient has died of progressive disease. However, statistically we were unable to confirm a definite correlation between the development of thyroid dysfunction and survival in this small group of patients.

Adult↗
PubMed1990

Urinary organic acid profiles in fatty Zucker rats: indications for impaired oxidation of butyrate and hexanoate.

The urinary excretion of 45 organic acids, monitored by gas-liquid chromatography, was compared in fatty (fa/fa) and lean (Fa/?) Zucker rats maintained on a chemically simplified diet. At the age of 6, 16, and 22 weeks, fatty rats excreted more of the various organic acids than their lean counterparts. However, the greatest difference was in the excretion of ethylmalonate, even when excretion data were normalized to body weight. The next highest excretion difference was in adipate and an unknown compound, and the third highest in pyruvate. A second group of rats examined at 7 weeks also excreted an excess of these four acids, as well as glucuronate and indole-3-acetate. The excessive excretion of ethylmalonate and adipate, which is characteristic of human genetic defects in short- and medium-chain fatty acid oxidation, suggested that the oxidation of butyrate and hexanoate might be impaired in the fatty rat. Thus, as a test of their capacity to oxidize medium- and short-chain fatty acids, two groups of fatty and lean rats were transferred to diets enriched with either trioctanoylglyceride, a medium-chain triglyceride (MCT), or sodium butyrate, a short-chain fatty acid. Both lean and fatty rats on the MCT diet, but only the lean rats on the butyrate-enriched diet, increased their excretion of adipate. However, on both the MCT and butyrate diet, ethylmalonate excretion increased only in lean rats, almost reaching amounts found previously in fatty rats. These results suggest that the fatty rat has an impairment of the beta-oxidation of butyrate and hexanoate, a defect that might increase intracellular concentrations of butyryl-CoA, the optimal primer for the synthesis of long-chain fatty acids.

Acids↗
PubMed1984

Efficacy of ceftizoxime administered twice daily in hospitalized patients with respiratory tract infections.

The efficacy and safety of ceftizoxime administered twice daily were evaluated in 215 hospitalized patients with documented lower respiratory tract infections. The majority of patients received 1 to 2 gm of ceftizoxime intramuscularly or intravenously every 12 hours; the mean dosage was 2 gm/day, and the mean duration of therapy was 8.9 days. Clinical cure was achieved in 204 (95%) of the 215 patients with lower respiratory tract infection. One hundred and thirty-eight patients were both clinically and bacteriologically evaluable. The clinical response rates, by organism, were: Streptococcus pneumoniae, 100% (50/50); Haemophilus influenzae, 96% (25/26); gram-negative bacilli (Escherichia coli, Proteus mirabilis, Enterobacter sp, Serratia sp, Pseudomonas sp, Klebsiella sp, Citrobacter sp, and Morganella morganii), 86% (32/37); and Staphylococcus aureus, 92% (12/13). In the other 77 patients with clinical symptoms, no pathogen was isolated or insufficient follow-up data were collected to assess bacteriologic response. Adverse reactions, which were infrequent, were similar to those reported in other US trials of the drug. The findings indicate that ceftizoxime, 1 to 2 gm BID, is effective and safe in the treatment of lower respiratory tract infections in hospitalized patients. This low-dose regimen can significantly reduce the cost of cephalosporin therapy.

Adolescent↗