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Biomedical subjects

M Carroll

Publications and source records attributed to M Carroll.

At least 145 records · Page 8Linked to original sources

Total and intrarenal flow distribution in healthy subjects: technique, acute effects of ibopamine and of indoramin.

A technique is described for measuring an index of cardiac output, total and individual renal plasma flow, cortical and juxtamedullary nephron flow non-invasively in man with a single injection of 123I-o-iodohippurate. Ibopamine, a dopamine analogue, was administered orally, 200 and 600 mg, in a double-blind, placebo-controlled cross-over study in 6 healthy subjects. No change in pulse, blood pressure, cardiac output, urea, creatinine or electrolytes was seen. Ibopamine reduced effective renal plasma flow and cortical nephron flow and increased urine flow significantly. This may be due to differential vasoconstrictor and vasodilator effects on the two populations of nephrons. Indoramin, and alpha-1 postsynaptic adrenoceptor blocker, was administered orally, 50 mg, in a double-blind, placebo-controlled cross-over study in 14 healthy young males. No change in pulse, cardiac output, urea, creatinine or electrolytes was seen. Indoramin significantly reduced upright but not supine blood pressure and significantly increased effective renal plasma flow. Cortical nephron flow and juxtamedullary nephron flow tended to rise. Plasma renin activity was significantly elevated although there was no change in urinary sodium output. The effect of drugs on intrarenal blood flow distribution may be relevant to the management of essential hypertension.

Adult↗

Gaucher disease (type 1): physical and kinetic properties of liposomal and soluble 'acid' beta-glucosidase.

'Acid' beta-glucosidase of human spleen, from either normal controls or patients with type 1 (adult) Gaucher disease, was incorporated into phosphatidylcholine liposomes. The non-incorporated (soluble) Gaucher-enzyme had a higher apparent molecular weight than had the corresponding control. Liposomal 'acid' beta-glucosidase prepared from Gaucher-spleen was more thermostable than was the corresponding normal enzyme; it was also stimulated by acidic lipids to a much lesser extent. The results suggest that the genetic mutation in type 1 (adult) Gaucher disease has multiple effects on the glycoprotein form of 'acid' beta-glucosidase.

Cell Membrane↗

Effect of vitamin D3 on imaging of experimental myocardial infarcts with technetium-99m pyrophosphate: further studies of the role of calcium.

We previously found that a pulse dose of vitamin D3 increased [99mTc]PPi uptake by rat myocardial necrosis. Vitamin D3 raised serum and lesion [Ca] but not, we now report, lesion [Fe]. We now also report that D3 increased [99Tc]PPi uptake by myocardial infarcts (L) in dogs from 0.345 +/- 0.007% administered (kg) dose/g in controls to 0.703 +/- 0.089 in treated (p less than 0.025). Vitamin D3 decreased uptake by dog bone (B) as measured in rib and sternum, increasing L/B from 1.10 +/- 0.23 to 2.30 +/- 0.52 (p = 0.06) X (L) was positively, (p less than 0.005) and uptake by sternum was negatively (p less than 0.05) correlated with serum [Ca] and [P], respectively. Scintigrams graded by a "blinded" observer, showed 4+, 4+, and 3+ infarcts, respectively, in three D3-treated dogs, and 2+, 2+, and 1+, respectively, in three untreated. One untreated and one treated dog were negative; the latter showed the least response to D3 in serum [Ca] and [99mTc] in tissue samples. Vitamin D3 can increase L/B in dogs, enhancing scintigraphic images.

Animals↗

Uptake of technetium-99m methylene diphosphonate by fractured and osteoporotic bone after a pulse dose of vitamin D3.

The effect of a pulse dose of Vitamin D3 on uptake of [99mTc]MDP by fractured and osteoporotic bone, respectively, was compared with D3's effect on uptake by normal bone in rats. At 4, 7, and 14 days, respectively, after femoral fracture, basal uptake was significantly (p less than 0.005) increased at the fracture site by 336.8, 276.1, and 183.5%, respectively, over the contralateral control site. D3-treated rats had lower uptakes than untreated controls at all three fracture sites and at 12 of 15 normal bone sites but analysis of variance showed the uptake differences were not significant. Cortisone-induced osteoporosis caused a significant (p less than 0.05) decrease in basal uptake. The decrease occurred in all nine bone areas studied. D3 caused a significant (p less than 0.05) increase (mean 16.2%) in uptake by these osteoporotic bones, but a significant (0.1 greater than p greater than 0.05) decrease (mean 13.0%) in uptake by the same bones in normal controls. Thus, D3 had an effect on uptake by the bone lesion, osteoporosis, that differed from D3's effect on uptake by fracture or normal bone.

Animals↗

Leukocyte activation in allergen-induced late-phase asthmatic reactions.

Some patients with allergen-induced asthma have both an early and late reaction to allergen (dual asthmatic reactions). To investigate the role of leukocyte activation in dual asthmatic reactions, we measured neutrophil chemotactic activity, percentages of neutrophil and monocyte complement rosettes, and one-second forced expiratory volume (FEV1) in 11 patients with allergen-induced dual asthmatic reactions after a challenge with allergen. To control for the effects of bronchoconstriction, the same studies were done after a challenge with methacholine. In all subjects there was a biphasic increase in neutrophil chemotactic activity and the percentages of neutrophil and monocyte complement rosettes, accompanied by a reduction in the FEV1. After methacholine, there were no significant changes in neutrophil chemotactic activity or percentages of complement rosettes, despite bronchoconstriction. Six patients with single-phase allergen-induced asthma had similar responses, but they were monophasic. We conclude that allergen-induced early and late asthmatic reactions are accompanied by activation of leukocytes and that these alterations probably reflect the release of mediators from mast cells rather than an effect of bronchoconstriction.

Adult↗

Memory impairment in multiple sclerosis.

The memory performance of 22 Multiple Sclerosis (MS) subjects and their matched controls was compared on three tasks: a perceptual memory test, a picture recognition test and a verbal recognition test. Results showed that perceptual memory does not suffer as a consequence of MS. Moreover, MS subjects are as sensitive as controls to deep semantic encoding of individual items in a picture recognition task. However, for a verbal recognition task, where a semantic encoding strategy was optional, MS subjects were less likely to report use of a strategy. Those MS subjects who did use a strategy, did more poorly on memory for verbal information than controls. The results suggest a specific inter-item semantic encoding problem in MS.

Adult↗

Assessment of the anti-tumor potential of glutathione.

This study assesses the effect of reduced glutathione (GSH) on regenerating liver, 3'-methyl-4-dimethylaminoazobenzene (3'-MDAB) hepatocarcinogenesis, and normal and transformed hepatocytes in vitro. GSH administered intragastrically caused only a 30% reduction in thymidine incorporation into liver DNA at 24 h after partial hepatectomy; there was no apparent effect on RNA and protein synthesis. Furthermore, in 3'-MDAB induced hepatocarcinogenesis, all GSH-treated animals developed hepatocyte nodules, and serum alpha-fetoprotein (AFP) levels were not reduced. In vitro, GSH was shown to be cytotoxic to both normal and transformed hepatocytes at serum concentrations under 10%. GSH inhibited [3H]thymidine incorporation slightly in 2 transformed hepatocyte lines, but not in normal hepatocytes.

Animals↗

Enzyme-linked immunosorbent assay for the ganglioside GM2-activator protein. Screening of normal human tissues and body fluids, of tissues of GM2 gangliosidosis, and for its subcellular localization.

An enzyme-linked immunosorbent assay was developed for the quantitation of the human activator protein for ganglioside GM2 degradation by beta-N-acetyl-D-hexosaminidase A. With this assay, various tissues and body fluids of normal subjects and of patients with variant forms of GM2 gangliosidosis were screened for their GM2-activator content. The highest content of this protein was found in kidney. Tissues from patients with variant AB of infantile GM2 gangliosidosis contained only low levels (up to 5% of that of normal controls) of cross-reacting material. On subcellular fractionation of normal human skin fibroblasts, the activator was found to co-distribute with the lysosomal marker enzyme beta-hexosaminidase.

Body Fluids↗

Complement receptor enhancement as evidence of neutrophil activation after exercise-induced asthma.

To determine whether neutrophils are activated after exercise-induced asthma, increases in neutrophil complement receptor numbers (complement receptor enhancement) were measured by the rosette technique. In twelve asthmatic patients there was a time-dependent rise in complement receptor numbers for up to 60 min after treadmill exercise. This enhancement of complement receptors was preceded by a rise in plasma neutrophil chemotactic activity and a reduction in the peak expiratory flow rate. These changes could be inhibited by prior administration of disodium cromoglycate. The changes were not observed in seven asthmatic patients in whom asthma was not induced by an identical exercise task. Complement receptor enhancement was also observed in vitro when partially purified neutrophil chemotactic activity from a patient with exercise-induced asthma was incubated with normal neutrophils. These findings suggest that inflammatory cells are activated after exercise-induced asthma, possibly as a result of the release of neutrophil chemotactic activity and other mast-cell-associated mediators.

Asthma↗

Physical and kinetic properties of beta-glucosidase in Gaucher disease.

Membrane-bound 'acid' beta-glucosidase of human spleen was solubilized with either sodium cholate or 'Cutscum'. The solubilized enzyme in type 1 (adult) Gaucher disease was less heat-stable than the normal enzyme, and when precipitated by ammonium sulphate it had a higher apparent molecular weight than the corresponding normal enzyme. The normal beta-glucosidase was activated by taurocholate, whereas the Gaucher enzyme was inhibited. The decrease in 'acid' beta-glucosidase activity in Gaucher disease was associated with a profound deficiency of that form of the enzyme which bound to Concanavalin A. The results are consistent with faulty processing of newly synthesized 'acid' beta-glucosidase in type 1 Gaucher disease.

Chemical Phenomena↗

Effects of naloxone on self-injurious behavior: a case study.

A clinical trial of naloxone to treat head banging behavior in a severely mentally retarded 8-year-old boy is reported. A double blind procedure was employed to concurrently contrast effects of two dosages of naloxone with saline solution placebo. No quantitatively measurable change in response rate occurred compared either with baseline or placebo. However a qualitative reduction in intensity of response was noted clinically. Implications for the use of beta-endorphine therapy for self-injurious behavior was discussed.

Child↗

Defective chemotactic factor-induced monocyte complement receptor enhancement in lung cancer.

We have studied monocyte complement (C3b) rosettes, and chemotactic factor (CF)-induced enhancement of rosettes, in 37 patients with bronchial carcinoma (BC), and compared these findings to those obtained from nine age and sex matched patients with non-malignant respiratory disease (NMRD), and 38 normal healthy controls (HC). No differences in monocyte C3b rosettes were found when BC was compared with NMRD or HC. In contrast, there was a highly significant inhibition of CF-induced complement receptor enhancement (CRE) in monocytes from patients with extensive or metastatic BC compared to NMRD or HC. These differences increased with time of incubation and concentrations of CF, and occurred when either f-met-leu-phe, leukotriene B4 (LTB4) or casein were used as the enhancing agent. The defect in monocyte CRE was related to the stage of the disease (with the rank order, metastatic greater than confined to chest greater than localized tumour) but not to the pathohistological type. A similar impairment in CRE was observed when neutrophils from BC were compared to HC. These experiments suggest that, in patients with advanced bronchial carcinoma, monocyte and neutrophil C3b receptors have impaired responsiveness to chemotactic factors.

Adult↗

Genetic heterogeneity of membrane-bound beta-glucosidase in Gaucher's disease.

Membrane-bound beta-glucosidase of leukocytes exists in two forms, one with optimal activity at about pH 4.5, whereas the other is most active at pH 5.5-6.0. In one case of type 1 (adult) Gaucher's disease, the pH 4.5 activity was totally deficient, but the pH 5.5 activity was present in normal amounts; obligate heterozygotes had half the normal activity at pH 4.5. In two different cases, the membrane-bound beta-glucosidase was completely absent when assayed at either pH 4.5 or pH 5.5. Two further cases had residual activity at both ph values; however, the residual enzymes had different thermostability properties than the corresponding enzymes of control leukocytes. The results are consistent with the existence of at least three genetic variants of type 1 (adult) Gaucher's disease.

Cell Membrane↗

Multiple forms of membrane-bound beta-glucosidase in Gaucher's disease.

Two forms of membrane-bound beta-glucosidase in the spleen of normal individuals were distinguished by their thermostability properties. The heat-labile form A predominates; it catalyzes the hydrolysis of the natural substrate, glucosylceramide, and is activated by the detergent, sodium taurocholate. The minor heat-stable form B is inactive against glucosylceramide and is inhibited by taurocholate. The activity of form A increases from childhood to adult life, as does the activity of the soluble beta-glucosidase and of glucosylceramide beta-glucosidase. In the spleen of nine patients with different types of Gaucher's disease the residual membrane-bound beta-glucosidase was predominantly heat-stable and inhibited by taurocholate. There was no clear correlation between the properties of the residual enzyme in the different types of the disorder and their respective clinical severity. The results are discussed in relation to the biochemical pathogenesis and the enzymatic diagnosis of Gaucher's disease.

Adult↗