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Biomedical subjects

J B Martin

Publications and source records attributed to J B Martin.

At least 127 records · Page 7Linked to original sources
PubMed1988

Clinical and neuropathologic assessment of severity in Huntington's disease.

Clinical records were evaluated for 163 Huntington's disease patients in whom postmortem brain specimens had been graded for degree of neuropathologic involvement in the striatum. Juvenile/adolescent onset (4 to 19 years of age) was associated with very severe neuropathologic involvement produced by an apparent rapid degenerative process. Cases of early (20 to 34 years) and midlife (35 to 49 years) onset had respectively less severe striatal involvement, suggesting a slower degenerative progression. High correlations among the grade of neuropathologic involvement, cell counts of neurons, and a rating of physical disability suggest that each represents a common underlying degenerative process of the disease. The relationship between the age at onset and the extent of neuropathologic involvement suggests that a single mechanism may determine both onset and rate of degenerative disease progression.

Aging↗
PubMed1988

Systemic approaches to modifying quinolinic acid striatal lesions in rats.

Quinolinic acid (QA) is an endogenous excitotoxin present in mammalian brain that reproduces many of the histologic and neurochemical features of Huntington's disease (HD). In the present study we have examined the ability of a variety of systemically administered compounds to modify striatal QA neurotoxicity. Lesions were assessed by measurements of the intrinsic striatal neurotransmitters substance P, somatostatin, neuropeptide Y, and GABA. Histologic examination was performed with Nissl stains. The antioxidants ascorbic acid, beta-carotene, and alpha-tocopherol administered s.c. for 3 d prior to striatal QA lesions had no significant effect. Other drugs were administered i.p. 1/2 hr prior to QA striatal lesions. The following were ineffective in blocking QA excitotoxicity: allopurinol, 50 and 100 mg/kg; ketamine, 75 mg/kg; nimodipine, 2.4, and 10 mg/kg; baclofen, 10 mg/kg; 2-amino-5-phosphonovalerate, 50 mg/kg; and 2-amino-7-phosphonoheptanoate, 50 mg/kg. Oral taurine administration for 4 weeks resulted in significantly increased levels of brain taurine but had no significant effect in blocking QA neurotoxicity. Systemic administration of the noncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801 resulted in a dose-responsive protection against QA toxicity, with complete block at a dose of 4 mg/kg. If the pathogenesis of HD involves QA or another excitotoxin acting at the NMDA receptor, it is possible that MK-801 could retard the degenerative process.

2-Amino-5-phosphonovalerate↗
PubMed1987

Molecular genetics: applications to the clinical neurosciences.

Application of molecular biology, by means of linkage analysis and DNA probes that demonstrate restriction fragment length polymorphisms (RFLPs), has resulted in the chromosomal localization of the genes responsible for a number of neurological disorders. Characterization of the structure and function of individual genes for these diseases is in an early stage, but information available indicates that the molecular mechanisms underlying phenotypic expression of neurological diseases encompass a wide range of genetic errors ranging from the most minor (a single-base pair mutation) to large chromosomal deletions. Linkage analysis can now be used for genetic counseling in several of these disorders.

Chromosome Mapping↗
PubMed1987

Identification of inositol hexaphosphate in 31P-NMR spectra of Dictyostelium discoideum amoebae. Relevance to intracellular pH determination.

A sugar phosphomonoester, myo-inositol hexakisphosphate (phytic acid), has been identified as a major phosphorylated metabolite in Dictyostelium discoideum amoeba. Its intracellular concentration was estimated to be 0.7 mM. The identification was made in perchloric acid extracts on the basis of 31P-NMR chemical shift values and their variations with pH, by addition of authentic compound and by hydrolysis with wheat phytase. Perchloric acid extracts were prepared so as to avoid losses of insoluble salts of polyphosphorylated compounds with divalent cations. The glycolytic intermediate, 3-phosphoglycerate accumulated intracellularly in amoebae incubated in the presence of fluoride. The pH sensitive NMR signal of 3-phosphoglycerate was used to monitor cytosolic pH and a value of pH 7.4 was found in aerobic Dictyostelium amoebae.

6-Phytase↗
PubMed1987

Phosphoethanolamine and ethanolamine are decreased in Alzheimer's disease and Huntington's disease.

Measurements of both phosphoethanolamine (PEA) and ethanolamine (EA) were made in postmortem brain samples from patients with Alzheimer's disease (AD) and Huntington's disease (HD) using high-performance liquid chromatography with electrochemical detection. In AD levels of PEA were significantly reduced by 64% in temporal cortex, 48% in frontal cortex and 40% in hippocampus. In HD concentrations of PEA were significantly reduced by 76% in the caudate, 53% in putamen and 48% in the nucleus accumbens. EA concentrations showed similar but smaller reductions in both diseases. Both PEA and EA are involved in phospholipid metabolism and can be released with depolarizing stimuli in some circumstances. Since two diverse neuropathologic processes can result in depleted levels of both amines in their respective regions of pathologic predilection, it is likely that the depletions accompany neuronal death.

Aged↗
PubMed1987

Subset of neurons characterized by the presence of NADPH-diaphorase in human substantia innominata.

The substantia innominata encompasses an area of the basal forebrain that is ventral to the lenticular nucleus and anterior commissure, medial to the claustrum and external capsule, and lateral to the hypothalamus. The nucleus basalis of Meynert consists primarily of large acetylcholinesterase (AchE)-positive neurons embedded within the substantia innominata. Damage to these neurons may be important in the pathogenesis of cortical dysfunction in Alzheimer's disease. In order to characterize other neuronal elements in the substantia innominata and their relationship to the nucleus basalis, we chose to study a biochemically distinct neuronal subset containing the enzyme nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d). The substantia innominata was blocked from six normal brains obtained postmortem and fixed in neutral-buffered formalin at 4 degrees C for 48 hours. Free-floating 50-micron sections from several levels were stained for NADPH-d or AchE activities. Selected sections were double stained for NADPH-d and AchE. NADPH-d activity was present in a network of pleomorphic neurons that extended through all levels of the substantia innominata and into the striatum and amygdala. NADPH-d neurons were particularly numerous at the level of the anterior commisure and were closely associated with the cholinergic neurons of the nucleus basalis. They were not seen in the ventral pallidum, or the vertical limb of the diagonal band of Broca or in the islands of Calleja. The cell bodies of NADPH-d neurons were quite varied in shape, ranging from ovoid to fusiform, and about half the cells were bipolar. Where neuronal density was high, their dendrites formed an interlacing pattern. NADPH-d-positive fibres were seen coursing through the external capsule, hypothalamus, and amygdala. This novel set of neurons in the substantia innominata may be part of a more extensive network that interacts with the magnocellular basal forebrain system at the level of the nucleus basalis. Whether other neurotransmitters are present within these neurons and whether NADPH-d neurons are involved in Alzheimer's disease remain to be elucidated.

Aged↗
PubMed1987

Sparing of acetylcholinesterase-containing striatal neurons in Huntington's disease.

The present study demonstrates that large aspiny neurons, containing the enzyme acetylcholinesterase (AChE), are relatively preserved in the caudate nucleus and putamen in Huntington's disease (HD). Although histochemical evidence indicates that AChE and choline acetyltransferase (ChAT) co-localize within the same striatal neurons, measurements of ChAT activity showed significant reductions in enzyme activity, as others have reported. Reduced ChAT activity in the presence of presence of persistent AChE-positive neurons may be a consequence of loss of synaptic terminals resulting from the death of spiny neurons. The selectivity of neuronal sparing in HD may be related to the patterns of synaptic contact or a paucity of excitatory amino acid receptors on striatal aspiny neurons.

Acetylcholinesterase↗
PubMed1987

The effect of amphetamine on the in vivo release of dopamine, somatostatin and neuropeptide Y from rat caudate nucleus.

Somatostatin, neuropeptide Y and dopamine release from the conscious rat caudate nucleus were investigated using the push-pull perfusion method. Significant reductions in somatostatin and neuropeptide Y release coincided with increased dopamine release, suggesting that dopamine has an inhibitory effect on the release of both peptides. Changes in the levels of both peptides were positively correlated, consistent with their co-release from neuropeptide Y- and somatostatin-containing striatal neurons.

Amphetamine↗
PubMed1987

23Na NMR study of intracellular sodium ions in Dictyostelium discoideum amoeba.

The intracellular sodium concentration in the amoebae from the slime mold Dictyostelium discoideum has been studied using 23Na NMR. The 23Na resonances from intracellular and extracellular compartments could be observed separately in the presence of the anionic shift reagent Dy(PPPi)7-2 which does not enter into the amoebae and thus selectively affects Na+ in the extracellular space. 31P NMR was used to control the absence of cellular toxicity of the shift reagent. The intracellular Na+ content was calculated by comparison of the intensities of the two distinct peaks arising from the intra- and extracellular spaces. It remained low (0.6 to 3 mM) in the presence of external Na+ (20 to 70 mM), and a large Na+ gradient (20- to 40-fold) was maintained. A rapid reloading of cells previously depleted of Na+ was readily measured by 23Na NMR. Nystatin, an antibiotic known to perturb the ion permeability of membranes, increased the intracellular Na+ concentration. The time dependence of the 23Na and 31P NMR spectra showed a rapid degradation of Dy(PPPi)7-2 which may be catalyzed by an acid phosphatase.

Cations, Monovalent↗
PubMed1987

Biochemical changes during sucrose deprivation in higher plant cells. Phosphorus-31 nuclear magnetic resonance studies.

An experimental arrangement was described that enables nuclear magnetic resonance spectra of compressed plant cells to be recorded while circulating a medium through the sample. The system provided a convenient arrangement for monitoring by 31P NMR the behavior of plant cells over a long period of time under different conditions such as sucrose starvation. Perfusion of compressed sycamore cells with sucrose-free culture medium triggered a progressive decrease in the glucose 6-P and uridine-5'-diphosphate-alpha-D-glucose resonances over 30 h. When almost all the intracellular carbohydrate pool had disappeared the nucleotide triphosphate resonances decline progressively. These changes were accompanied by a Pi accumulation in the vacuole and a phosphorylcholine (P-choline) accumulation in the cytoplasm. The very long lag phase observed for ATP and P-choline evolution was comparable with that observed for the progressive intracellular digestion of cytoplasmic constituents (Journet, E., Bligny, R. and Douce, R. (1986) J. Biol. Chem. 261, 3193-3199). Addition of sucrose in the circulating system after a long period of sucrose starvation led to a disappearance of the cytoplasmic Pi resonance and a marked increase in that of glucose 6-P. Under these conditions the vacuolar Pi pool did not fluctuate to buffer the Pi in the cytoplasm. The results suggest that Pi which has been sequestered in the vacuole during the course of sucrose starvation is not restored to the cytoplasm for rapid metabolic processes. Furthermore, the presence of P-choline in plant cells in large excess should be considered as a good marker of membrane utilization after a long period of sucrose starvation and is very likely related to stress.

Adenosine Triphosphate↗
PubMed1987

A comparison of somatostatin and neuropeptide Y distribution in monkey brain.

The concentrations of both somatostatin-like immunoreactivity (SLI) and neuropeptide Y-like immunoreactivity (NPYLI) were measured in all major cortical and subcortical regions of monkey brain. High concentrations of both SLI and NPYLI were found in cerebral cortex where they were significantly correlated, supporting a colocalization of the two peptides in cortical neurons. There were no significant differences between the right and left hemispheres. Subdissections of the basal ganglia showed that concentrations of both SLI and NPYLI were 3-fold higher in the nucleus accumbens than in the remainder of the striatum, where concentrations of the peptides were evenly distributed. SLI and NPYLI levels were significantly correlated in the striatum, supporting a colocalization of the two neuropeptides in striatal neurons. Concentrations were low in the globus pallidus. Limbic system nuclei including the amygdala, bed nucleus of the stria terminalis and substantia innominata had relatively high concentrations of both SLI and NPYLI. In several subcortical regions concentrations of the neuropeptides were dissociated, suggesting separate neuronal populations. The distribution of both neuropeptides in monkey brain closely resembles that in human brain. The high levels in cerebral cortex and basal ganglia suggest that somatostatin and neuropeptide Y may play a role both in cognition and in normal motor function.

Amygdala↗
PubMed1987

Somatostatin and neuropeptide Y are unaltered in the amygdala in schizophrenia.

Although a biochemical abnormality has been postulated in the etiology of schizophrenia, evidence supporting this hypothesis has been conflicting. Because of the presence of somatostatin-like immunoreactivity (SLI) in limbic system nuclei of the brain, we examined postmortem concentrations of SLI in patients dying with schizophrenia and in normal controls. Concentrations of SLI in Brodmann cortical area 38, hippocampus, caudate, putamen, nucleus accumbens, and both segments of the globus pallidus were not significantly different from controls. In addition, we examined both SLI and neuropeptide-Y-like immunoreactivity (NPYLI) in subnuclei of the amygdala and the substantia innominata. There were no significant alterations in either neuropeptide as compared with controls.

Amygdala↗
PubMed1987

23Na and 31P NMR studies of the effects of salt stress on the freshwater cyanobacterium Synechococcus 6311.

We have used 23Na and 31P nuclear magnetic resonance (NMR) spectroscopy to elucidate some of the bioenergetic changes that occur in the freshwater cyanobacterium Synechococcus 6311 after a transition from growth medium (Na concentration 0.01 M) to medium containing 0.5 M NaCl. 23Na NMR analysis showed Na rapidly penetrates the cells under dark aerobic conditions; cells grown for several days in high salt medium, however, reestablish a low internal sodium content, comparable to control cells. For 31P NMR analysis, a system was devised to aerate and illuminate cell suspensions during spectral acquisition. The NMR spectra showed that when cells are presented with 0.5 M NaCl (final concentration), nucleotide triphosphate peaks decrease, the inorganic phosphate peak increases, and the cytoplasmic pH transiently increases from 7.4 to 7.9. Pyrophosphate added to cell suspensions is hydrolyzed to inorganic phosphate apparently by an extracellular phosphatase, allowing external and internal pools of inorganic phosphate to be distinguished. Nucleotide triphosphate levels fall almost as much when cells are incubated in darkness as under anoxia, indicating that both respiration and photosynthesis contribute to the maintenance of intracellular ATP levels. Cells grown in high salt medium for several generations exhibited a pattern of 31P metabolites similar to control cells, except that they produced more (and more intense) peaks in the monoester phosphate region, presumably signals from sugar phosphates.

Anaerobiosis↗
PubMed1987

Amino acid neurotransmitters in postmortem human brain analyzed by high performance liquid chromatography with electrochemical detection.

In the present study we have developed a method of measuring putative neurotransmitter amino acids using high performance liquid chromatography (HPLC) with electrochemical detection. The assay had a sensitivity in the low pmol range and sample turnover time was 30 min. The postmortem stability of amino acids was examined in an animal model simulating human autopsy conditions. Aspartate concentrations increased 15% between 4 and 24 h postmortem while gamma-aminobutyric acid (GABA) concentrations rose 35% by 4 h but were stable thereafter. Glutamate and taurine were stable at all time points. The assay has been used to examine concentrations of neurotransmitter amino acids in 15 patients without neurological or psychiatric disease. Results agree well with previous work and knowledge of amino acid neurotransmitter pathways. The current technique provides a reliable method for the study of amino acid transmitter abnormalities in neurological illness.

Aged↗
PubMed1987

Neuropeptide Y gene expression in PC12 cells and its regulation by nerve growth factor: a model for developmental regulation.

Neuropeptide Y (NPY) is a 36 amino acid neuronal peptide which has previously been described within a subset of sympathetic neurons. The presence of the messenger RNA that encodes NPY (NPY mRNA) has been studied in the PC12 cell line, as this is commonly used as a model of neuronal differentiation. Low levels of the NPY mRNA were identified in resting naive cells. Levels were induced five-fold by the addition of nerve growth factor to the medium at a dose of 30 ng/ml. Lower doses of nerve growth factor had no effect on NPY mRNA. The effect was rapid in onset being apparent within 12 h and near maximal at 24 h. A smaller two-fold increase in NPY mRNA was observed in cells treated with epidermal growth factor (3 ng/ml) over the same time course but no effect was observed with fibroblast growth factor (3 ng/ml), bradykinin (10(-6) M) or dexamethasone (10(-6) M). These results indicate that NPY gene expression is regulated in PC12 cells at the level of NPY mRNA.

Animals↗