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Biomedical subjects

B McDonald

Publications and source records attributed to B McDonald.

At least 91 records · Page 5Linked to original sources
PubMed1991

Presence of a soluble form of acetylcholinesterase in human ocular fluids.

Samples of ocular fluid obtained from normal persons at necropsy and during eye surgery have been assayed for the presence of acetylcholinesterase. Measurable levels could be detected in all samples examined, but levels of acetylcholinesterase in vitreous humour were consistently higher than those in aqueous humour, indicating a possible retinal origin. Polyacrylamide gel electrophoresis revealed that the enzyme of ocular fluid had the same mobility as that of acetylcholinesterase from cerebrospinal fluid. It is probable that acetylcholinesterase is secreted from neuronal structures in the retina into the ocular fluid in an analogous manner to the secretion of acetylcholinesterase from brain neurones into cerebrospinal fluid.

Acetylcholinesterase↗
PubMed1990

A point mutation uncouples human interleukin-1 beta biological activity and receptor binding.

Interleukin-1 proteins elicit a number of biological activities, but the molecular events following formation of a cell surface receptor-ligand complex have not been well defined. Conversion of Arg127 to Gly127 in the mature human interleukin-1 beta protein reduces bioactivity by 100-fold while the receptor binding affinity decreases by only 25%. The results suggest that the mutant IL-1 beta protein is defective in activating signal transduction events and indicate that binding of interleukin-1 beta protein to receptor is necessary but insufficient for biological activity. The finding that the features of the IL-1 beta protein responsible for receptor binding and biological activity are at least in part distinct may be clinically relevant to the design of interleukin-1 antagonists.

Amino Acid Sequence↗
PubMed1990

Recombinant interleukin-1 beta interacts with high-affinity receptors to activate neutrophil leukotriene B4 synthesis.

The capacity of interleukin-1 (IL-1) to function as a neutrophil (PMN) activator has been the subject of controversy. While IL-1 purified from mononuclear cell supernatants induced PMN activation, these observations have not been confirmed with recombinant IL-1. To document a cellular basis for a putative PMN-IL-1 interaction, we investigated the presence of IL-1 receptors on the PMN. Using an [35S]methionine-labeled preparation, specific binding of IL-1 to PMNs was demonstrated. Through Scatchard analysis PMNs were calculated to have a mean of 469 +/- 337 receptors per PMN with an affinity (Kd) of 0.32 +/- 0.09 nM. As IL-1 frequently activates arachidonic acid metabolism in other cell types, we investigated eicosanoid production as a putative consequence of the IL-1-PMN interaction. HPLC analysis of extracted supernatants of IL-1-treated PMNs demonstrated the release of leukotriene B4 (LTB4), its oxidative products, and 5-hydroxyeicosatetraenoic acid (5-HETE). Production of LTB4 was quantified using a commercial RIA. LTB4 secretion increased from 17.2 +/- 1.1 to 96.7 +/- 16.4 ng, also with 10.0 ng of IL-1. In time-course studies, it was shown that maximal eicosanoid secretion required a 30-min incubation with IL-1. These observations confirm the proinflammatory activity of IL-1 on neutrophils and resolve the controversy concerning a direct effect of IL-1 on neutrophils. In conclusion, recombinant IL-1 beta interacts with neutrophils through the presence on the PMN of a high-affinity receptor and results in the secretion of arachidonate metabolites.

Humans↗
PubMed1990

Increased tau messenger RNA in Alzheimer's disease hippocampus.

The microtubule-associated protein tau is present in the pathologic hallmarks of Alzheimer's disease and its production and deposition have been implicated in the pathogenesis of the disease. We detected tau mRNA using in situ hybridization histochemistry in the hippocampus, visual cortex, and cerebellum, and compared its level in Alzheimer's disease with controls. The amount of tau mRNA also was determined as a ratio of total polyadenylated mRNA in each area. A significant and gene-specific increase in tau mRNA hybridization was found in hippocampal fields CA4 and CA3, with a similar trend in the dentate gyrus. In contrast, no change was found in the visual cortex or cerebellum in Alzheimer's disease. Increased hippocampal expression of tau mRNA also was present in cases of non-Alzheimer's dementia. Enhanced tau mRNA may be a marker of attempted plasticity involving the cytoskeleton in neuronal populations affected by various neurodegenerative disorders.

Aged↗
PubMed1990

The infant walker: an unappreciated household hazard.

The potential for infant walkers to cause injury to infants was demonstrated by the results of a survey of the practicing pediatricians in the state of Connecticut. There was a significant number of severe injuries reported. In addition, seven cases of infants hospitalized at Bridgeport Hospital because of injuries sustained while using an infant walker are included. The survey indicated adequate knowledge of the apparent danger by the practicing physicians, including discussion during anticipatory guidance. Despite this knowledge and guidance, significant morbidity continues to occur.

Accidents, Home↗
PubMed1989

Effects of estrogen in vivo and in vitro on spontaneous interleukin-1 release by monocytes from postmenopausal women.

Estrogen (E) inhibits bone resorption, but the mechanism of this effect is unknown. Interleukin-1 (IL-1) stimulates bone resorption in vitro and may be produced in bone by mononuclear phagocytes. Recently, the spontaneous release of IL-1 from peripheral monocytes was found to reflect bone formation in a subset of patients with idiopathic osteoporosis. We suspected that the action of E on bone is mediated indirectly by its effect on monocyte IL-1 activity. Eleven normal postmenopausal women taking no medications were given conjugated E (0.625 mg daily) for 3-9 weeks. Supernatants from cultured peripheral monocytes were analyzed for IL-1 production by stimulation of a cloned murine helper T-cell line. IL-1 release was expressed as a percentage of maximum release corrected for monocyte number. IL-1 release before E treatment was 11.0 +/- 0.2% (+/- SE), it was 7.8 +/- 1.6% after E treatment (P = NS). IL-1 release fell in each of the three women with the highest initial values (46% to 5%, 25% to 17%, and 18% to 12%). IL-1 release did not correlate with serum osteocalcin or fasting urinary calcium either before or after E treatment. Addition of 10(-7)-10(-10) mol/L 17 beta-estradiol to cultured monocytes obtained before E treatment caused an increase in IL-1 release that did not follow a dose-response relationship. Treatment of postmenopausal women with E did not affect spontaneous IL-1 release by peripheral monocytes in vitro. The addition of E in vitro did not produce consistent changes in IL-1 release by these cells. This does not exclude the possibility that E may affect monocyte IL-1 release in subsets of women with high spontaneous monocyte IL-1 release with or without osteoporosis.

Adult↗
PubMed1988

Biological activity and receptor binding of human prointerleukin-1 beta and subpeptides.

We report here that the human interleukin-1 beta precursor (proIL-1 beta) protein as well as several interleukin-1 beta (IL-1 beta) subpeptides bind cellular receptors specifically and exhibit biological activity by stimulating proliferation of helper T-cells. IL-1 beta polypeptides have been synthesized by in vitro translation of mRNAs transcribed from plasmid vectors containing the bacteriophage SP6 promoter joined to the complete IL-1 beta cDNA or to deletion constructs. The quantity of IL-1 beta in vitro translation products was increased significantly by replacing the cognate IL-1 beta untranslated leader sequence with a 37-nucleotide plant viral untranslated leader. Translation of chimeric mRNAs followed by direct bioactivity assay demonstrated that mature IL-1 beta-(117-269), proIL-1 beta-(1-269), and peptide IL-1-(71-269) were all biologically active. Specific binding to cellular receptors was observed with these three IL-1 beta molecules; moreover, several peptides with minimal biological activity also bound receptor specifically. The biological activity and receptor binding properties of the IL-1 beta proteins reported here contrast with those described by Mosley et al. (Mosley, B., Urdal, D. L., Prickett, K. S., Larsen, A., Cosman, D., Conlon, P. J., Gillis, S., and Dower, S. K. (1987) J. Biol. Chem. 262, 2941-2944; Mosley, B., Dower, S. K., Gillis, S., and Cosman, D. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 4572-4576), who reported that proIL-1 beta-(1-269) had no biological activity and does not bind receptor. Our results indicate that proIL-1 beta is active at a relatively high concentration, and analysis of the proIL-1 beta-(1-269) and IL-1-(71-269) bioactivity data suggests a possible relationship with membrane-bound IL-1.

Chromosome Deletion↗
PubMed1988

Normal splenic function in children with the nephrotic syndrome.

Children with the idiopathic nephrotic syndrome (NS) are known to be susceptible to bacterial infections. A recent report suggested that splenic hypofunction may be responsible for this immunological defect. We assessed splenic function by counting the circulating pocked red blood cells (PkRBCs) using interference phase contrast microscopy. PkRBCs are removed by the spleen, so that normal eusplenic individuals have less than 2% PkRBCs while asplenics have 15%-30%. Intermediate values are seen in hyposplenism. Thirty-three measurements of PkRBCs were made in 19 children with NS (mean age 7.5 +/- 0.8 years). PkRBCs were normal in all children tested (range 0-0.8%), including two patients with bacterial peritonitis associated with relapse. Thus we were unable to find evidence of hyposplenism in children with NS.

Adolescent↗
PubMed1987

Pentachlorotoluene and pentabromotoluene: results of a subacute and a subchronic toxicity study in the rat.

Pentachlorotoluene (PCT) and pentabromotoluene (PBT) are environmental contaminants detected in the Great Lakes ecosystem. In view of the paucity of toxicity data and the potential for human exposure, a subacute (28 day) and a subchronic (91 day) study were conducted in the rat. In the subacute study, groups of 10 male and 10 female rats were fed the diet containing PCT or PBT at 0, 0.5, 5.0, 50 or 500 ppm for 28-days. In the subchronic study, the group size was increased to 15, the dose levels were 0, 0.05, 0.5, 5.0, 50 and 500 ppm in the diet and the exposure period was 91 days. Growth rate and food consumption were not affected by exposure to either chemical in the subacute and subchronic study. Clinical observations revealed no abnormalities. Decreased hemoglobin was observed in female rats fed 5.0 ppm PCT and higher levels in the subacute (28 day) study. In the same study the hematocrit value and erythrocyte numbers of females fed 5.0 or 500 ppm PCT diets were significantly lower than the control. In both subacute and subchronic studies mild dose-dependent histopathological changes were observed in the thyroid, liver and kidney of rats fed PCT and PBT diets. In general male rats were more susceptible than females to the treatment of PCT and PBT. Based on these data, it was concluded that the no observable adverse effect level for PCT was 50 ppm in the diet (3.5 mg/kg b.w./day) and that of PBT was 5.0 ppm (0.35 mg/kg b.w./day).

Animals↗
PubMed1986

Progression of orthostatic proteinuria to focal and segmental glomerulosclerosis.

Focal glomerulosclerosis, with the nephrotic syndrome and progressive renal insufficiency, developed in a 15-year-old boy who presented initially 1 year earlier with orthostatic proteinuria. Although generally considered to be a benign disorder, this case suggests that on rare occasions, serious glomerular diseases may develop in patients with orthostatic proteinuria or that significant glomerular disease may occasionally present with postural proteinuria.

Adolescent↗
PubMed1985

Continuous ambulatory venous pressure for diagnosis of venous insufficiency. Preliminary report.

We have found that the venous pressure slope during minimal exercise is a sensitive measurement of venous disease. This parameter differed greatly in our two study populations. Due to increased venous pressure, venous insufficiency syndrome patients have a greater volume of pooled blood, which results in smaller pressure changes with each muscle contraction. In patients with incompetent valves, blood flows in a retrograde fashion in the vein, which leads to a higher steady state minimal pressure and notably to a decreased venous pressure slope. Venous pressure slope is a particularly sensitive measurement and a good prognosticator of venous insufficiency syndrome before symptoms become disabling to the patient. Our data indicate a strong correlation between venous pressure slope and venographic results. In fact, patients with abnormal venographic results invariably have demonstrated venous pressure slopes in the abnormal range.

Ambulatory Care↗
PubMed1985

Cardiac output and muscle blood flow in exercising dogs.

Average blood flow (q) was determined by trapping of 15 micron radioactive microspheres in the vastus lateralis, the gastrocnemius-flexor digitorum superficialis and the triceps brachii of five 18 kg untrained mongrel dogs at rest and during graded treadmill running. Oxygen uptake (VO2) and cardiac output (Qco) were simultaneously determined. q leveled off in all investigated muscles at 60-100 ml X 100 g-1 X min-1 when VO2 was ca. 70% of peak VO2. Qco increased linearly with VO2 up to peak VO2. The regional blood flow (qR) distribution pattern within the muscle was found to be extremely scattered around q, both at rest and at heavy exercise. qR ranged from approximately 5 to approximately 55 ml X 100 g-1 X min-1 at rest and from approximately 10 to approximately 200 ml X 100 g-1 X min-1 at maximal exercise. No significant topographic pattern was observed in the qR distribution of the gastrocnemius muscle which was essentially similar to that previously found for the isolated-perfused muscle preparation. The results indicate that maximal limb muscle blood flow and/or its uneven distribution may be the primary limiting factor to peak VO2 in untrained running dogs.

Animals↗
PubMed1985

Pneumococcal carriage amongst Australian aborigines in Alice Springs, Northern Territory.

In Alice Springs and its vicinity, a single nasal swab was collected from 282 Australian aborigines in May 1981 to determine nasal carriage rates of pneumococci. Each swab was inoculated on blood agar and on gentamicin blood agar. The carriage rates were 89% in children, 39% in adolescents and 34% in adults. In all, 27 serotypes of pneumococci were met with and 15 (4%) of subjects yielded two or more serotypes. In children, types 23, 19, 6, 22 and 6 were predominant (in that order), whereas type 3 was commonest in older subjects. Approximately 25% children and 5% adults yielded drug-insensitive pneumococci. Resistance to benzylpenicillin, tetracycline and co-trimoxazole was met with, resistant pneumococci showed five resistance patterns and belonged to nine serotypes, predominantly types 19 and 23. All isolates were sensitive to chloramphenicol, erythromycin, lincomycin and rifampicin. The carriage rate of drug-insensitive pneumococci was 100-fold higher amongst children sampled than in non-aboriginal children in Australia.

Adolescent↗
PubMed1985

Biochemical markers and skeletal metabolism in carcinoma of the prostate. Use of decision matrix theory and ROC analysis.

The discriminative ability of several skeletal and tumour markers was assessed in 102 patients with prostatic disease. These comprised serum acid and alkaline phosphatase, serum albumin and osteocalcin, urinary excretion of calcium, hydroxyproline and 6-oxo prostaglandin F1 alpha. None of the tests was of value in distinguishing patients with benign prostatic disease from those with tumour not involving the skeleton. Values of serum osteocalcin, urinary excretion of calcium and urinary 6-oxo prostaglandin F1 alpha failed to discriminate significantly between patients with or without metastases. The remaining four markers were compared by decision matrix analysis and receiver operating characteristic (ROC) curves. Serum alkaline phosphatase provided the most sensitive marker of skeletal metastases (80.5%), followed by serum acid phosphatase (80%), hydroxyproline (68%) and albumin (30%). ROC analysis suggested that alkaline phosphatase conformed most closely to the "ideal marker" with highest specificity and sensitivity.

6-Ketoprostaglandin F1 alpha↗