Reflections of a pediatrician on his gastroenterological roots.
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Biomedical subjects
Publications and source records attributed to M Davidson.
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ELISA is the currently accepted method for screening rodent colonies for Mycoplasma pulmonis infection. While this assay has greatly improved mycoplasmal detection, it suffers from major defects. Cross-reactions with M. arthritidis are the major technical problem, and prevent definitive diagnosis. Current methods for obtaining a definitive diagnosis are accurate in about 80% of cases, and include ELISA testing for both organisms, immunoblot analysis, and blocking of the murine reaction with heterologous serum. Another technical difficulty is the inherent variability in the assay, which can be overcome by rigid quality control measures and careful attention to detail. The difficulties that arise from the natural history of mycoplasmal infection in barrier-maintained colonies, i.e., low incidence of infected animals and delayed antibody response in animals infected with low numbers of organisms, seriously limit the usefulness of the ELISA. While the assay can be extremely useful in screening breeding colonies and in eliminating mycoplasmas from such colonies, it cannot easily be used to screen potential sources of weanling animals for experimental use.
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The interaction between horse heart cytochrome c and Chromatium vinosum flavocytochrome c-552 was studied using the water-soluble reagent 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). Treatment of flavocytochrome c-552 with EDC was found to inhibit the sulfide: cytochrome c reductase activity of the enzyme. SDS gel electrophoresis studies revealed that EDC treatment led to modification of carboxyl groups in both the Mr 21 000 heme peptide and the Mr 46 000 flavin peptide, and also to the formation of a cross-linked heme peptide dimer with an Mr value of 42 000. Both the inhibition of sulfide: cytochrome c reductase activity and the formation of the heme peptide dimer were decreased when the EDC modification was carried out in the presence of cytochrome c. In addition, two new cross-linked species with Mr values of 34 000 and 59 000 were formed. These were identified as cross-linked cytochrome c-heme peptide and cytochrome c-flavin peptide species, respectively. Neither of these species were formed in the presence of a cytochrome c derivative in which all of the lysine amino groups had been dimethylated, demonstrating that EDC had cross-linked lysine amino groups on native cytochrome c to carboxyl groups on the heme and flavin peptides. A complex between cytochrome c and flavocytochrome c-552 was required for cross-linking to occur, since ionic strengths above 100 mM inhibited cross-linking.
The cyclic adenosine monophosphate (cAMP) responses to prostaglandin E1 (PGE1) in platelets and leukocytes from drug-free schizophrenic patients, depressive patients, and normal controls have been compared. Both schizophrenic and depressive patients had a significantly lower platelet cAMP response to PGE1 than controls. The platelet cAMP response to PGE1 did not discriminate among exacerbated, remitted, and poor-prognosis schizophrenic patients, or between exacerbated and remitted depressive patients. The cAMP response to PGE1 was negatively correlated with global symptom severity in actively ill schizophrenic patients, but was not correlated with symptom severity in exacerbated depressive patients. The leukocyte cAMP response to PGE1 did not differ among normal controls, schizophrenic patients, and depressive patients. These data indicate that a diminished platelet cAMP response to PGE1 may be a marker common to both schizophrenia and depression but that this effect does not extend to a cAMP-linked PGE1 receptor on another blood cell type.
Production of interferon (IFN)-gamma by peripheral blood leukocytes (PBL) was examined in cultures of unseparated fresh whole blood exposed to phytohemagglutinin (PHA), concanavalin A (Con A), or pokeweed mitogen (PWM). The yield of IFN-gamma was measured by a newly developed immunoradiometric assay. Nine of 14 patients with acute pulmonary tuberculosis (TB) showed a depressed IFN-gamma response to Con A and/or PWM. Only four of these TB patients also showed a depressed IFN-gamma response to PHA. Stimulation of the patients' PBL cultures with PHA in the presence of exogenous interleukin 2 (IL 2) produced normal IFN-gamma yields in all but the most severely depressed patients. PBL cultures of TB patients with defective IFN-gamma production in response to mitogenic lectins also produced less IFN-gamma after stimulation with tuberculin PPD. Although some patients showed a moderate degree of lymphopenia, their OKT4/T8 lymphocyte ratios were mostly normal or close to normal, with the notable exception of one TB patient who has been diagnosed to have the acquired immune deficiency syndrome (AIDS).
Two treatment regimes were used to produce preneoplastic foci (as determined by the presence of gamma-glutamyl transferase) in rat liver. Increased [14C]acetate incorporation into cholesterol and 3-hydroxy-3-methyl glutaryl CoA reductase activity were associated with high levels of gamma-glutamyl transpeptidase and foci formation. Dietary feedback inhibition of both [14C]acetate incorporation and 3-hydroxy-3-methyl glutaryl CoA reductase activity was reduced at a selected time when gamma-glutamyl transpeptidase activity was high. These changes could not be accounted for by a regenerative response in the liver.
Previous experiments suggest that pharmacological perturbations of the brain dopaminergic system may be reflected by concentrations of plasma homovanillic acid. This study examined the ability of apomorphine infusion to reduce plasma homovanillic acid concentrations in normal subjects. The data suggests that apomorphine does not reduce plasma homovanillic acid concentration.
The immunogenic effect of recombinant yeast and plasma-derived hepatitis B vaccines administered at 0, 1 and 6 months was evaluated in 334 seronegative health professionals. The seroconversion rates following 10 micrograms, 5 micrograms and 2.5 micrograms doses of recombinant vaccine were similar to those observed after 20 micrograms doses of plasma-derived vaccine. The geometric mean antibody titres (G.M.T.) induced by 10 micrograms and 5 micrograms doses of recombinant vaccine were similar to those observed after 20 micrograms doses of plasma-derived vaccine. The G.M.T. values were lowest after 2.5 micrograms doses of recombinant vaccine. However, the recipients of the 2.5 micrograms had a significant anti-HBs response after a fourth (booster) dose of recombinant vaccine was given at 12 months. A booster dose of recombinant hepatitis B vaccine was given to 31 health professionals who had been successfully immunised with plasma-derived vaccine 5-7 years previously. A significant anamnestic response was observed in 30 (97%) of these individuals in spite of the fact that 16 (52%) had low or undetectable levels of anti-HBs before the booster dose was given.
An 11 year old girl developed progressive upper gastrointestinal ulceration and recurrent episodes of intravenous catheter associated polymicrobial septicaemia. Evaluation failed to establish a cause. After exclusion of the parents and careful surveillance of the patient she improved, supporting the diagnosis of suspected child abuse (a form of Meadow's syndrome).
The ventricle-brain ratio (VBR) of 28 drug-free male schizophrenic inpatients was significantly higher than that of 21 matched normal control subjects and was not related to severity of positive or negative symptoms. Response to haloperidol in an open 6-week trial using a fixed-dose schedule was not predicted by severity of positive or negative symptoms or by VBR. The nine severely deteriorated patients with chronic "Kraepelinian" schizophrenia had left lateral ventricles 28% larger than their right, whereas the control subjects and other schizophrenic patients did not show ventricular asymmetry.
CSF homovanillic acid levels showed a significant negative correlation with ventricle-brain ratios (VBRs) in a group of drug-free chronic schizophrenic male veterans, while CSF 5-hydroxyindoleacetic acid levels showed a similar, nearly significant trend. The response of plasma human growth hormone to 0.75 mg of apomorphine also demonstrated a significant negative correlation with VBR in this group, but other measures of central neurotransmitter activity were unrelated to ventricular size.
We studied a girl with an infantile syndrome of limb weakness, seizures, cortical blindness, and corneal opacifications; she died at age 7 months of respiratory failure. There was no consanguinity or family history of neuromuscular diseases. Histochemical and biochemical studies of muscle showed mildly increased glycogen content and markedly decreased PFK activity (1.4% of the normal mean). Anaerobic glycolysis in vitro confirmed the metabolic block. Immunofluorescence and immunotitration by ELISA using monoclonal antibodies against subunit M of PFK showed a normal amount of cross-reacting material. The brain showed typical features of neuroaxonal dystrophy. This variant of PFK deficiency may be due to a distinct genetic defect.
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