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Biomedical subjects

M D Browning

Publications and source records attributed to M D Browning.

69 records · Page 4Linked to original sources
PubMed1987

Synapsin I, a phosphoprotein associated with synaptic vesicles: possible role in regulation of neurotransmitter release.

The data presented here provide evidence that the study of neuronal phosphoproteins can lead to the identification of previously unknown proteins and that these proteins may play important roles in neuronal communication. Specifically, in the case of synapsin I, direct evidence has been obtained that this phosphoprotein is involved in regulating neurotransmitter release. A tentative explanation of the results obtained in the micro-injection studies is as follows: synapsin I, in the dephosphostate, is bound to the cytoplasmic surface of synaptic vesicles and inhibits the ability of the vesicle to interact with the plasma membrane; increases in intracellular calcium activate calmodulin kinase II which in turn phosphorylates synapsin I and the phosphorylated synapsin I dissociates from the synaptic vesicle thus removing a constraint on the release of neurotransmitter. Clearly, more studies need to be done to rigorously test this hypothesis. Nevertheless these studies of synapsin I suggest that the study of previously unknown phosphoproteins will lead to the elucidation of previously unknown regulatory processes in neurons.

Animals↗
PubMed1987

Similarities between protein IIIa and protein IIIb, two prominent synaptic vesicle-associated phosphoproteins.

Protein IIIa (Mr 74,000) and protein IIIb (Mr 55,000) are 2 major phosphoproteins found in mammalian brain. It was previously shown in intact nerve cells that the phosphorylation state of these 2 proteins could be increased by electrical stimulation, by depolarizing agents in the presence of calcium, and by 8-bromo-cAMP. We now report that protein IIIa and protein IIIb possess significant structural homology, as indicated by immunochemical studies using polyclonal and monoclonal antibodies and by peptide-mapping studies. A quantitative radioimmunoassay using immunolabeling in SDS-polyacrylamide gels has been used to study the tissue distribution and regional and subcellular distribution in the brain of the 2 proteins. The 2 proteins were found only in nervous tissue and the adrenal medulla. Subcellular fractionation studies suggested that both proteins are associated with synaptic vesicles.

Animals↗
PubMed1985

Protein phosphorylation and neuronal function.

Studies in the past several years have provided direct evidence that protein phosphorylation is involved in the regulation of neuronal function. Electrophysiological experiments have demonstrated that three distinct classes of protein kinases, i.e., cyclic AMP-dependent protein kinase, protein kinase C, and CaM kinase II, modulate physiological processes in neurons. Cyclic AMP-dependent protein kinase and kinase C have been shown to modify potassium and calcium channels, and CaM kinase II has been shown to enhance neurotransmitter release. A large number of substrates for these protein kinases have been found in neurons. In some cases (e.g., tyrosine hydroxylase, acetylcholine receptor, sodium channel) these proteins have a known function, whereas most of these proteins (e.g., synapsin I) had no known function when they were first identified as phosphoproteins. In the case of synapsin I, evidence now suggests that it regulates neurotransmitter release. These studies of synapsin I suggest that the characterization of previously unknown neuronal phosphoproteins will lead to the elucidation of previously unknown regulatory processes in neurons.

Animals↗
PubMed1985

Ultrasonography and computed tomography in severe urinary tract infection.

A prospective study evaluated the utility of renal computed tomography (CT) and ultrasonography in 35 patients hospitalized for treatment of urinary tract infection. Renal computed tomograms were abnormal in 18 of 28 patients with acute pyelonephritis and three of four patients with urosepsis, showing findings consistent with pyelonephritis in 17 patients and intrarenal abscess or focal bacterial nephritis in four patients. Renal sonograms were abnormal in only eight patients, showing findings compatible with pyelonephritis in four and intrarenal abscess or focal bacterial nephritis in the other four. Flank tenderness was absent in only four patients with CT findings of pyelonephritis, of whom three were diabetic. We therefore found that (1) renal CT is a sensitive test for acute upper urinary tract infection, (2) ultrasonography detects focal bacterial nephritis and abscesses but is insensitive to uncomplicated upper urinary tract infection, and (3) painless pyelonephritis may be more common in patients with diabetes mellitus.

Abscess↗
PubMed1984

Clinical characteristics and response to therapy in Egyptian children infected with Schistosoma haematobium.

Forty-one Egyptian students with infections due to Schistosoma haematobium, who were selected by results of a urine screening examination, were evaluated for morbidity and response to chemotherapy. Symptoms associated with infection were hematuria, dysuria, and swimmer's itch. A positive correlation existed between the intensity of infection and frequency of exposure to water. Laboratory abnormalities included eosinophilia (41), anemia (9), hematuria (38), pyuria (33), and proteinuria (8). Three of 26 subjects had abnormalities intravenous pyelograms: hydroureter, bladder polyp , and bladder calcification. The bladder polyp was noted also by sonography. Cure rates were 66.7% in 18 subjects treated with two 10-mg/kg doses of trichlorfon and were 89.5% in 19 subjects given three doses. Those not cured had an average reduction in ova excretion of 96%. Follow-up at 12 months of 33 subjects showed that nine had S. haematobium ova in urine, although 75% admitted to exposure to canal or irrigation water in the interim.

Adolescent↗
PubMed1982

Purification and characterization of protein IIIb, a mammalian brain phosphoprotein.

The phosphorylation of a 55,000-dalton protein (Protein IIIb) present in mammalian brain was previously shown to be increased by depolarizing agents in the presence of calcium, by cyclic nucleotides, and by appropriate neurotransmitters. We now report that Protein IIIb has been purified 660-fold to near homogeneity and partially characterized. The hydrodynamic properties of the purified protein indicate that it exists as an elongated monomer. cAMP-dependent protein kinase catalyzes the incorporation of 0.82 mol of phosphate into serine/mol of protein. The protein is heterogeneous in isoelectric focusing, exhibiting multiple forms with isoelectric points ranging in pH from 6.6 to 7.3.

Amino Acids↗
PubMed1981

Validity of self-reported work experience among U.S. Navy divers.

The validity of self-reported diving experience was assessed among 49 U.S. Navy divers. They were asked to provide frequency estimates for the following four diving categories: total dives, dives to more than 31 m, night dives, and dives at surface temperatures of less than 10 degrees C. These estimates were then correlated with official Navy diving records. The resulting correlations ranged from nonsignificant to moderate across the four diving categories. The sample was then divided into three groups according to the extent to which they overestimated diving experience-Low, Medium, and High. The Low group made more total dives and more dives greater than 31 m than either the Medium or High groups. The High and Medium groups did not differ from each other. The groups were similar in overall health status (as indicated but sick call visits) but varied in previous diving accidents. The High and Medium groups incurred substantially more diving accidents per number of total dives made than the Low group. These results indicate that self-reported diving experience information should not be used for purposes in which accuracy is required. Determining discrepancies between estimated and actual experience may also be useful in diver selection and assignment.

Adult↗
PubMed1980

Comparisons of performance effectiveness among divers.

Using a criterion of performance effectiveness derived from actual dives made under operational conditions, comparisons were made between U.S. Navy divers identified as high and low in performance effectiveness. Comparison measures included intelligence, anxiety, disciplinary problems, and incidence of decompression sickness (DCS). As expected, the most effective divers made more frequent and more hazardous dives than the least effective divers. In addition they had fewer diving accidents and a lower incidence of DCS. While the most effective divers had lower intelligence scores than the least effective group, both groups were substantially above the Navy average. These findings indicate that intelligence appears to be a critical variable in the career retention of divers, as well as the frequency and types of dives to which divers are exposed. The higher incidence of diving accidents and complications, especially DCS, found among the least effective divers may also have been involved in the lower frequency of diving observed among the members of this group.

Accident Proneness↗
PubMedDate not supplied

Microwave radiation, in the absence of hyperthermia, has no detectable effect on synapsin I levels or phosphorylation.

Recent reports have indicated that microwave radiation can produce effects on a variety of cell types in vitro. To determine whether microwave radiation might be neurotoxic, the effects of microwave radiation on synapsin I have been examined. Synapsin I is a neuron-specific phosphoprotein that is present in all neurons, where it is localized to the presynaptic terminal and is associated with synaptic vesicles. O'Callaghan and Miller have demonstrated that studies of such neuron-specific proteins can provide reliable indices of neurotoxicity. We have used a radioimmunoassay for synapsin I to determine whether microwave irradiation has any effect on the levels of synapsin I. Neither acute nor chronic exposure to microwave irradiation had any detectable effect on synapsin I levels. We have also examined the calcium-dependent phosphorylation of synapsin I in synaptosomes isolated from rats that had been subjected to microwave radiation. The phosphorylation of synapsin I in synaptosomes reflects numerous components of the presynaptic aspect of neuronal transmission. At intensities below that required to produce mild hyperthermia, no effects of microwave irradiation were seen on synapsin I phosphorylation.

Animals↗
PubMedDate not supplied

Deficits in the expression of the NR2B subunit in the hippocampus of aged Fisher 344 rats.

The NMDA receptor (NMDAR) has been implicated in the induction of LTP at hippocampal synapses, and has been proposed to play a significant role in the involvement of the hippocampus with learning and memory. Aged rats are known to have deficits in LTP, learning and memory. We tested the hypothesis that aged rats might have deficits in expression of NMDAR subunits. Aged rats have significantly lower levels of NR2B mRNA and protein compared to young animals. This complements a recent report which showed improved learning and memory in mice which overexpress NR2B. No changes were seen in either the mRNA or the protein levels of the NMDAR subunit NR2A, nor in the alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate receptor (AMPAR) subunit GluR2. Our data support the hypothesis that age related alterations in the expression of the NMDAR NR2B subunit might underlie deficits in LTP and learning and memory in aged animals.

Age Factors↗
PubMedDate not supplied

Amelioration of age-related deficits in the stimulation of synapsin phosphorylation.

In a previous report we demonstrated that aged (24-26 month) rats have deficits in long-term potentiation, a form of synaptic enhancement that is dependent on protein phosphorylation (Moore et al., Hippocampus, 3:57-66; 1993). In the present study we demonstrate that aged rats have a deficit in the phosphorylation of the synaptic vesicle associated protein synapsin I. Specifically, aged animals exhibit defective phorbol ester-induced stimulation of synapsin phosphorylation at its calcium/calmodulin dependent protein kinase II sites. We also examined the effects of caloric restriction and antioxidant therapy on this age-related deficit. We found that either life-long caloric restriction or treatment with 16 mg/kg N-tert-butyl-alpha-phenylnitrone (PBN) for 2 weeks can at least partially ameliorate the age-related deficit in the phorbol ester stimulation of synapsin phosphorylation.

Aging↗
PubMedDate not supplied

Protein III, a neuron-specific phosphoprotein: variant forms found in human brain.

Protein III is a neuron-specific phosphoprotein which consists of two polypeptides, IIIa (Mr 74 kD) and IIIb (Mr 55 kD). This phosphoprotein has previously been shown to be associated with synaptic vesicles. In the present investigation, we have examined Protein III in human brain tissue. In contrast to observations in rat brain, where only one form of Protein IIIb (Mr 55 kD) has been found, in human brain tissue three variants of Protein IIIb, designated Protein IIIb1 (Mr 55 kD), Protein IIIb2 (Mr 57 kD) and Protein IIIb3 (Mr 59 kD), were observed by both biochemical and immunochemical assays. Protein IIIa from human brain also exhibited three variants in electrophoretic mobility. Peptide maps of Proteins IIIa and IIIb revealed that the differences in electrophoretic mobility of the variants of these proteins were preserved in variants (Mr 18kD, Mr20kD, and Mr22kD) of a smaller peptide fragment. These variant forms of Protein III were studied in brains from individuals without any history of neurological or psychiatric illness, as well as from individuals who had suffered from one of several types of neuropathological conditions, such as chronic alcoholism, Alzheimer's disease, multi-infarct dementia, and Parkinson's disease. Some differences were observed in the distribution of variants among the various clinical categories.

Adult↗