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Biomedical subjects

D Robinson

Publications and source records attributed to D Robinson.

At least 451 records · Page 25Linked to original sources

Measurement in human blood of fibrinogen/fibrin fragments containing the B beta 15-42 sequence.

This paper describes a radioimmunoassay for the B beta 15-42 peptide derived from human fibrinogen or fibrin. Iodinated B beta 15-42 is bound by specific antiserum and binding can be completely inhibited by excess of the non-iodinated B beta 15-42, B beta 1-42 or B beta 1-118. These peptides cannot be distinguished in this assay. Furthermore, fibrinogen can also completely inhibit binding of iodinated B beta 15-42 peptide. Due to the cross-reaction with fibrinogen, clinical blood samples require a processing step prior to their use in this radioimmunoassay. Ethanol precipitation allows for fibrinogen removal and a near quantitative recovery of both added B beta 15-42 peptide as well as of the endogenous blood peptide(s) containing the B beta 15-42 sequence. The mean level of B beta 15-42 immunoreactive material in normal individuals was found to be 0.41 pmol/ml while that in one group of patients was 20-40 times this value.

Adult↗

Molecular defect in combined beta-galactosidase and neuraminidase deficiency in man.

In normal human fibroblasts, an enzymically active 85,000-dalton precursor form of beta-galactosidase is processed, via a number of intermediates, into a mature 64,000-dalton form. In addition there is an enzymically inactive 32,000-dalton component and its 54,000-dalton precursor. In fibroblasts from patients with a combined deficiency of beta-galactosidase and neuraminidase these last two components are absent and hardly any mature beta-galactosidase can be demonstrated. Nevertheless, in the mutant fibroblasts, precursor beta-galactosidase is synthesized and processed normally. The excessive intralysosomal degradation that is responsible for the deficiency of mature beta-galactosidase can be partially corrected by addition of the protease inhibitor leupeptin, which results in the accumulation of 85,000-dalton precursor beta-galactosidase and of a partially processed 66,000-dalton form. When mutant cells were grown in the presence of a "corrective factor" purified from the medium of NH4Cl-stimulated cell cultures, both beta-galactosidase and neuraminidase activities were restored to low control levels. The immunoprecipitation pattern was completely normal after addition of the corrective factor, and mature 64,000-dalton beta-galactosidase accumulated in the mutant fibroblasts. We propose that the combined beta-galactosidase/neuraminidase deficiency is caused by a defective 32,000-dalton glycoprotein which is normally required to protect beta-galactosidase and neuraminidase against excessive intralysosomal degradation and to give these enzymes their full hydrolytic activity.

Cells, Cultured↗

Effects of restricted feeding in the growing and laying periods on the performance of White Leghorn by Australorp crossbred and White Leghorn strain cross chickens.

1. The effects of restricted feeding in the rearing and laying periods on the performance of three White Leghorn cockerel by Australorp pullet crossbred strains and one White Leghorn strain cross were studied in two experiments. 2. After feeding ad libitum in the rearing period, mean body weights of the three crossbred strains at 20 weeks of age were 1.75, 1.66 and 1.55 kg and that of the White Leghorn strain cross was 1.40 kg. The differing restrictions during rearing reduced mean body weight at 20 weeks by 14 to 33% and increased the time to sexual maturity by 8 to 23 d. 3. All restriction regimes during rearing increased mean egg weight and tended to reduce mortality in the laying period. Optimum hen-day egg number over 64 weeks of lay was obtained following mild restriction (14% body weight reduction) of the two heavier strains or ad libitum feeding of the lighter strains. Over 48 or 64 weeks of lay, egg number per hen housed (at 18 to 20 weeks of age) was optimised after moderately restricting (14 to 21% body weight reduction) the crossbred strains or feeding the White Leghorn strain cross ad libitum. 4. Over 64 weeks of lay, mortality was reduced from 19.3% to 10.5% in the lightest crossbred strains, in which a high proportion of deaths were associated with Marek's disease and lymphoid leucosis, by restriction during rearing. 5. Restricting food intake by 7 or 8% throughout the laying period reduced hen-housed egg number and mean egg weight of all four strains. The reduction in hen-day egg number associated with food restriction during lay was less for the heavier strains that had also been restricted during rearing. 6. Metabolisable energy intakes required to support maximum production over 64 weeks of lay were 1.23 to 1.36 MJ/d.

Animals↗

Long oesophageal myotomy for diffuse spasm of the oesophagus.

The symptoms of chest pain and dysphagia together with the typical radiological features of non-peristaltic segmental oesophageal contractions allowed the diagnosis of diffuse oesophageal spasm to be made in ten patients at The Prince Charles Hospital over the last six years. Eight patients have undergone long oesophageal myotomy with sparing of the lower oesophageal sphincter. All patients had immediate postoperative relief of symptoms, with postoperative cine radiographic examination in all patients demonstrating an inert oesophagus with adequate drainage and no gastro-oesophageal reflux. Two patients subsequently developed progressive dysphagia, one requiring a modified Heller's procedure. Because of the good result in six patients, sparing of the lower oesophageal sphincter with long oesophageal myotomy is recommended.

Adult↗

Consumer information about prenatal and obstetric drugs.

This study investigated the amount of information that mothers have about the drugs to which they are exposed during pregnancy and childbirth as well as the correlates of this information, in particular perceived and actual control over life and health-related events. Subjects were 304 randomly chosen inpatients interviewed within 48 hours after childbirth. The results show that mothers know very little about the medications they took prenatally and even less about the medications they were administered during labor and delivery. Failing adequate information, a large number of mothers and babies were exposed to drugs with teratogenic or toxic potential. With but one exception, these drugs had not been approved by the F.D.A. for use in pregnancy, labor, and delivery. Scores on the Rotter Locus of Control Scale reliably predicted prenatal drug information.

Adolescent↗

Turnover of beta-galactosidase in fibroblasts from patients with genetically different types of beta-galactosidase deficiency.

The turnover of lysosomal beta-galactosidase was studied in fibroblast cultures from patients with Gm1-gangliosidosis and combined beta-galactosidase and neuraminidase deficiency, which had 5-10% residual beta-galactosidase activity. beta-Galactosidase was specifically inactivated with the suicide substrate beta-D-galactopyranosylmethyl-p-nitro-phenyltriazene (beta-Gal-MNT) and from the subsequent restoration of enzyme activity in cell cultures turnover times were calculated. By using [3H]beta-Gal-MNT, the hydrolytic activity per molecule of beta-galactosidase was determined. 3H-labelled beta-D-galactopyranosylmethylamine, the precursor of [3H]beta-gal-MNT, was obtained by Raney-nickel-catalysed exchange with 3H2O. The rate of synthesis of beta-galactosidase in normal and all mutant cells tested was found to be 0.4-0.5 pmol/day per mg of cellular protein. The GM1-gangliosidosis cells tested contain the normal amount of 0.5 pmol of beta-galactosidase/mg of protein with a normal turnover time of about 10 days, but only 10% of beta-galactosidase activity per enzyme molecule. Cells with combined beta-galactosidase and neuraminidase deficiency contain only 0.3 pmol of beta-galactosidase/mg of protein with a decreased turnover time of 1 day and normal hydrolytic properties (200 nmol of 4-methylumbelliferyl galactoside/h pmol of beta-galactosidase).

Binding Sites↗

Chronic depressions. Part 1. Clinical and familial characteristics in 137 probands.

Factors associated with chronicity in 137 probands with 2 or more years of low-grade intermittent depression were evaluated in a naturalistic setting. Four groups were tentatively identified and chronicity related to: (1) early onset (less than 25 years) intermittent subsyndromal or dysthymic depressions with positive family history for both unipolar and bipolar illness; (2) a spectrum of 'unstable' characterologic disorders with history for childhood object loss; (3) pre-existing non-affective psychiatric or incapacitating medical disorders, especially in combination; (4) incomplete remission from late-onset primary unipolar episode(s) with strong familial background for affective illness, multiple object losses, alcohol and sedative hypnotic dependence, superimposed incapacitating medical disorders, use of depressant antihypertensive agents, disabled spouses, and 'marital deadlock'. Beneficial effects of thymoleptic drugs and practical psychotherapy occurred in 45% of the total sample and were largely limited to groups 1 and 4. These findings argue against a common clinical stereotype that equates all chronic depressions with character disorder.

Adolescent↗

Mutagenicity of alkyl glycidyl ethers in three short-term assays.

The mutagenic potential of glycidol and 7 alkyl glycidyl ethers having straight alkyl chains of 2, 4, 6, 8, 10, 12, and 14 carbon atoms were examined in a battery of in vitro assays. The battery consisted of the Salmonella/mammalian microsome assay, the L5178Y mouse lymphoma assay, and unscheduled DNA synthesis using W138 cells. The mutagenic potential of the compounds ranged from strongly mutagenic to non-mutagenic; glycidol exhibited the greatest activity. All the ethers through C-4 showed a definite response whole the C-8 or higher ethers showed very weak or no responses. Dose-response curves were obtained by all 3 assays for those compounds that exhibited mutagenic activity. The sensitivity of each assay is discussed, as are the effects of the liver microsome systems used for metabolic activation.

1-Propanol↗

Measurement of fibrinopeptide A in the evaluation of heparin activity and fibrin formation during hemodialysis.

In order to monitor heparin activity during hemodialysis, were evaluated three commonly used methods; measurement of whole blood activated coagulation time (WBACT), whole blood thrombin time (WBTT) and heparin concentration in plasma, determined with a chromogenic substrate. Studies were performed on six regular dialysis patients during 4-hour dialysis sessions, employing three different heparin regimens; a single intravenous loading dose only, priming of the dialyzer with heparin followed by a heparin infusion and a pharmaco-kinetic model. Efficacy of heparinization was assessed by determination of fibrinopeptide A (FPA) which is a peptide split product of the fibrinogen molecule formed during thrombin-induced conversion to fibrin. There was a linear correlation (r = 0.95) between FPA-production in the dialyzer and the FPA content of the blood at the inlet to the dialyzer; the slope of the correlation line indicates that at least 65% of FPA formed in the dialyzer is disposed during passage through the patient. Considerably higher production of FPA was noted when the heparin concentration was below 0.5 IU/ml than at a higher level. This was a common finding at the end of a dialysis, regardless of regimen. No consumption of antithrombin (AT III) occurred during a dialysis with any of the heparin regimens. Good correlations were found between WBACT, WBTT and heparin concentration. Heparin activity during a dialysis may be monitored with any of these three methods with equal reliability. However, from a practical point of view, WBACT appears most attractive because of its simplicity. FPA generation, frequency of visible clots in the dialyzer and hemorrhagic manifestations were essentially the same for each of the heparin dose regimens. The simple administration of a single loading dose was as safe as the more complicated infusion technique.

Female↗

Adverse occurrences in intensive care units.

Analysis of 145 reports of adverse occurrences involving patients in a medical-surgical intensive care unite (ICU), during the yearts 1974 through 1978, disclosed 92 instances of human error and 53 cases of equipment malfunction. A peak occurrence of reported incidents was found between midnight and 1 AM. Harm occurred more frequently if the patient was unattended (72%) than attended (49%) during the incident. Mortality for patients with an incident report filed during their ICU admission (41%) was higher than for all ICU patients (21%). The importance of a well-structured incident-reporting program to minimize problems of human error and device malfunction is stressed.

Accidents↗

Comparison of the alpha-mannosidases in fibroblast cultures from patients with mannosidosis and mucolipidosis II and from controls.

The intracellular and extracellular acidic alpha-mannosidase in cultures of fibroblasts from mucolipidosis-II patients has normal kinetics. The extracellular activity in cultures of cells from mannosidosis patients is normal, but a mutant enzyme is associated with the cell surface and intracellular fraction. The results support the involvement of membrane cycling and recognition markers in lysosomal enzyme localization.

Cells, Cultured↗