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Biomedical subjects

P Jenkins

Publications and source records attributed to P Jenkins.

At least 91 records · Page 5Linked to original sources

Congenital microvillous atrophy: specific diagnostic features.

Proximal small intestinal and colonoscopic mucosal biopsies from two children with the intractable diarrhea of infancy syndrome were examined by electron microscopy. Microvillous involutions were found in the small and large bowel of both patients. We suggest that this is a specific diagnostic finding for congenital microvillous atrophy, a distinct disorder within the intractable diarrhoea syndrome which has an extremely poor prognosis.

Atrophy↗

Nutritional control of branched chain alpha-ketoacid dehydrogenase in rat hepatocytes.

Branched chain alpha-ketoacid dehydrogenase (EC 1.2.4.4) complex, the rate-limiting enzyme of branched chain amino acid catabolism in most tissues, is subject to regulation by covalent modification, with phosphorylation inactivating and dephosphorylation activating the complex. The enzyme complex from liver of chow-fed rats is mainly in the active form but that from liver of rats fed a low-protein diet is mainly in the inactive form. Isolated hepatocytes were used to identify factors that affect interconversion of branched chain alpha-ketoacid dehydrogenase. The enzyme present in hepatocytes of rats fed a low-protein diet appears much more responsive to regulation by covalent modification than the branched chain alpha-ketoacid dehydrogenase present in hepatocytes of normal chow-fed rats. alpha-Chloroisocaproate, a specific inhibitor of the kinase responsible for phosphorylation and inactivation of the complex, greatly stimulates oxidation of alpha-keto[1-14C]isovalerate by hepatocytes prepared from rats fed a low-protein diet but not from normal chow-fed rats. Oxidizable substrates are also much more effective inhibitors of branched chain alpha-ketoacid oxidation with hepatocytes from rats fed a low-protein diet than from normal chow-fed rats. Activity measurements with cell-free extracts suggest that changes in flux through the dehydrogenase with intact hepatocytes prepared from rats fed a low-protein diet are explained in large part by changes in the proportion of the enzyme in the active, dephosphorylated form. Regulation of liver branched chain alpha-ketoacid dehydrogenase by covalent modification functions to conserve branched chain amino acids for protein synthesis during periods of restricted dietary protein intake.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

Plasma proinsulin and C-peptide concentrations in children with hyperinsulinaemic hypoglycaemia.

Plasma concentrations of proinsulin and C-peptide were measured in five children presenting with severe hypoglycaemia associated with elevated plasma levels of immunoreactive insulin (IRI) in order to determine whether the profile of circulating B-cell products related to the underlying pathophysiology of the pancreas. Results were compared with data from 13 normal infants. Four children, three neonates and a nine year old girl, were subjected to partial or total pancreatectomy. The neonates had nesidioblastosis, nesidioblastosis with a microadenoma, and a functional abnormality without histological derangement respectively; the older child had a localised adenoma. The remaining child, a neonate, had transient hypoglycaemia and elevated IRI levels associated with hyperlactataemia and hyperalaninaemia. All the children had markedly elevated plasma proinsulin concentrations; the highest levels were seen in the child with an isolated adenoma and in the neonate with nesidioblastosis and a microadenoma. Both of these children also had substantially elevated plasma C-peptide concentrations. The remaining three neonates had plasma C-peptide levels, which although in the normal range for normoglycaemia were inappropriately elevated during hypoglycaemia. It is concluded that elevated proinsulin and C-peptide concentrations are seen in children with hypoglycaemia associated with increased plasma IRI levels and that the profile of the concentrations does not provide a reliable marker for the nature of the underlying pancreatic abnormality.

Alanine↗

Enzymic fluorometric assay of plasma ammonia with a centrifugal analyzer.

This method for rapid plasma ammonia determination, supplied in the form of a commercially available kit, is based on a combination of enzymic reaction and fluorometry. Concentrations up to 350 mumol/L can be measured. The detection limit is 15 mumol/L. Intra-assay coefficients of variation for 30 and 100 mumol/L concentrations were 5.0% and 3.0%, respectively. The corresponding interassay CVs were 8.0% and 3.8%. Assay of 16 samples takes about 15 min. Only 25 microL of sample is required, which makes this assay suitable for pediatric use and small-animal research.

Ammonia↗

Immune recognition of Echinococcus granulosus. 1. Parasite-activated, primary transformation by normal murine lymph node cells.

Culture of murine lymph node cells together with living protoscolices of Echinococcus granulosus is described. The presence of the parasite induced potent blastic transformation in lymphocytes of unimmunized mice as indicated by tritiated thymidine incorporation. The response was markedly reduced by killing the parasite immediately prior to culture. No blastogenic activity was detectable in supernatants from living parasites cultured alone. Protoscolices from artificially infected syngeneic mice were effective stimuli, as were protoscolices from naturally infected horse and sheep. Stimulation was not detectably reduced by maintenance of the parasite in vitro for 72 h at 37 degrees C or for 46 days at 4 degrees C prior to culture. It is concluded that unprimed lymphocytes are stimulated to transform by surface contact with a stimulator synthesized, but not secreted, by the parasite. The biological significance of the reaction and its possible contribution to immunosuppression are discussed.

Animals↗

Reinforcement contingencies and signal detection.

Pigeons were trained to discriminate temporal stimuli in a discrete-trial signal-detection procedure. Pecks to one side key were reinforced intermittently after exposure to one duration, and pecks to the other side key were reinforced intermittently after exposure to a different duration. In Experiment I, the allocation of reinforcers was varied systematically for correct responses and for errors, using a procedure that controlled the obtained numbers of reinforcers. When reinforcers were allocated symmetrically, the level of discrimination decreased as the proportion of reinforcers for errors increased. When reinforcers were allocated asymmetrically, the decrease in discrimination was less systematic. Bias toward one or the other side key roughly matched the ratio of reinforcers obtained by pecks at those keys, independent of the level of discrimination. In Experiment II, the overall rate of reinforcement for correct responses was varied both within and between experimental conditions. The level of discrimination was positively related to the overall rate of reinforcement. The discrimination data of both experiments were interpreted in relation to the contingencies of reinforcement and nonreinforcement, characterized by the average difference in reinforcement probability for correct responses and errors.

Animals↗

A study of immunoregulation of BALB/c mice by Echinococcus granulosus equinus during prolonged infection.

Two models of intraperitoneal infection with E. granulosus equinus by protoscolices and by cyst passage in BALB/c mice were used to provide mesenteric lymph node cells for adoptive cell transfer into syngeneic recipient normal responder mice. The cell transfer inocula were shown to have depleted Thy-1 cells, but to be highly suppressive to the normal sheep erythrocyte response of the recipients. The nature of the depletion and non-specific suppression, and the infectious nature of the latter, are discussed in relation to other examples of mitogenic stimulation resulting in non-specific T cell suppressor activity. The functions of Ly-2,3+ cells, not only as suppressor, but as alloreactive cytotoxic cells, are discussed as a possible, autoimmune explanation for the longevity of the parasite within the mouse model, in contradistinction to the predictable early rejection of analogous xenografts.

Animals↗

Evidence for hepatitis B and other virus infection in HBsAg-negative chronic active hepatitis.

Antibody to the hepatitis B core antigen (anti-HBc) was detected in sera from 6 (19%) of 32 patients with HBsAg-negative chronic active hepatitis. In three cases with the highest anti-HBc titers, core antigen was detected in liver cell nuclei and in one case HBsAg was also present in hepatocytes, suggesting continuing hepatitis B virus infection. During follow-up, anti-HBc titers fell slowly in those with no viral antigens in liver tissue, and in two cases with virus in the liver at presentation, viral antigens were no longer demonstrable four and eight years later. In one case, clearance of virus was preceded by the appearance of HBsAg in liver and serum, suggesting reactivation of viral replication. In three of the anti-HBc-negative cases a nuclear antigen unrelated to the hepatitis B virus was detected by immunofluorescence, and it is possible that liver disease in these patients may be related to persistent non-A, non-B virus infection.

Adult↗

Mucociliary clearance in patients with chronic autonomic failure.

Mucociliary clearance was measured in four patients with chronic autonomic failure and normal ventilatory function using a method of scanning the clearance of inhaled polystyrene particles tagged with 99mTc. Previous surgical and experimental evidence has suggested that autonomic denervation might be expected to impair clearance. However, the four patients in this study showed no significant difference in clearance rate compared to groups of sex-matched control subjects. A fifth patient was found to have impaired mucociliary clearance. However she had the symptoms and ventilatory function of smoking-related chronic obstructive bronchitis, a condition which has previously been shown to impair mucociliary clearance.

Adult↗

Legionnaires' disease: a clinical description of thirteen cases.

We describe 13 patients with legionnaires' disease in Nottingham, all presenting with lobar pneumonia. Six patients required artificial ventilation and 2 died. No common source of infection has yet been identified, but the disease appears to be prevalent and possibly endemic in this city.

Adult↗

In vivo studies on suppressor lymphocyte activity following administration of Escherichia coli O138 lipopolysaccharide.

Evaluation of Escherichia coli vaccines used in veterinary practice usually relates to antibody formation and neglects the essential characteristics of cell function leading to this end. This paper attempts to investigate the cellular responses to E coli O138 lipopolysaccharide (LPS) administered subcutaneously in a dose range of 1 microgram to 200 microgram. Rosette-forming cell responses in the draining lymph node varied from antigenic at 10 microgram to tolerogenic at 200 microgram. The tolerogenic dose also caused a marked mitogenic response as can be seen by a fourfold increase in total lymph node cells. Fractionation of normal or LPS-responding, or LPS-tolerised lymph node cells into B cell-rich and T cell-rich fractions was carried out and these were adoptively transferred simultaneously with an antigenic dose of sheep erythrocytes (SRBC) into syngeneic recipient mice. Suppressor activity of the anti-SRBC response was found after transfer of 1 X 10(6) normal B cell fractions, 1 X 10(6) tolerised B cell fractions and 1 X 10(6) tolerised T cell fractions. LPS-antigenically stimulated lymph node cell fractions had no suppressor effect but when given with Freund's complete adjuvant ensuing T cell-rich fractions produced immunosuppression in recipient mice. The significance of these findings is discussed in relation to polyclonal B cell activation, helper and suppressor T cells, and possible feedback mechanisms between interacting subpopulations of lymph node cells.

Animals↗