Biomedical subjects

J B Martin

Publications and source records attributed to J B Martin.

At least 181 records · Page 10Linked to original sources

PubMed1985

Excitotoxin lesions do not mimic the alteration of somatostatin in Huntington's disease.

Huntington's disease is accompanied by severe neuronal death in the striatum, but despite this cell loss, there is a marked increase in the striatal concentration of somatostatin-like immunoreactivity (SLI). We attempted to examine the mechanism of this increase by using kainic or ibotenic acid to effect a unilateral lesion in the rat neostriatum. Graded doses of toxin cause a proportional decrease in the concentration of somatostatin-like immunoreactivity to a maximum of 50% of control, which is stable over an interval of 3 months. The increased somatostatin-like immunoreactivity in Huntington's disease is not mimicked by the excitotoxin lesions in rats. In addition we find that unilateral kainic acid lesions in the striatum reduce SLI in the contralateral striatum as well, although histologic evidence and assay of choline acetyltransferase activity indicate that damage is confined to the injected side. Immunocytochemistry demonstrates a loss of somatostatin-containing neurons on the lesioned side but no discernible loss in the contralateral striatum. The bilateral decrease in SLI following unilateral lesions suggests damage to a somatostatin projection to the contralateral striatum or a compensatory interaction between the two striatal nuclei.

Animals↗

PubMed1985

Topographical dopamine and serotonin distribution and turnover in rat striatum.

Topographic distribution of dopamine (DA), serotonin (5-HT), dihydroxyphenylacetic acid (DOPAC), hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) was determined in rat striatum using high-pressure liquid chromatography (HPLC) with electrochemical detection. The ratios of DOPAC:DA and 5-HIAA:5-HT were calculated as indices of turnover of DA and 5-HT. There was a rostro-caudal gradient for both DA and 5-HT, with DA highest in rostral striatum and 5-HT highest in caudal striatum (P less than 0.01). DA concentrations in the coronal plane showed a homogeneous distribution except at the level of the globus pallidus. DOPAC also showed a rostro-caudal gradient and concentrations were significantly increased in the nucleus accumbens (P less than 0.01). DOPAC:DA ratios were significantly increased in both the nucleus accumbens and the ventromedial striatum as compared to the remaining striatal punches. 5-HT was more heterogeneously distributed in the coronal plane with concentrations highest in the ventromedial and the ventrolateral quadrants, where they were 2-3-fold higher than in dorsal striatum (P less than 0.01). Concentrations of 5-HIAA were highest in the nucleus accumbens and ventromedial striatum but HIAA-5-HT ratios were highest in the dorsolateral striatum (P less than 0.01). DA turnover is therefore highest in limbic innervated (n. accumbens and ventromedial) striatum while 5-HT turnover is highest in sensorimotor innervated (dorsolateral) striatum. These findings provide further evidence for functional compartmentalization within the striatum.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1985

Selective sparing of a class of striatal neurons in Huntington's disease.

A distinct subpopulation of striatal aspiny neurons, containing the enzyme nicotinamide adenine dinucleotide phosphate diaphorase, is preserved in the caudate nucleus in Huntington's disease. Biochemical assays confirmed a significant increase in the activity of this enzyme in both the caudate nucleus and putamen in postmortem brain tissue from patients with this disease. The resistance of these neurons suggests that the gene defect in Huntington's disease may be modifiable by the local biochemical environment. This finding may provide insight into the nature of the genetically programmed cell death that is a characteristic of the disease.

Adult↗

PubMed1985

Somatostatin receptors: distribution in rat central nervous system and human frontal cortex.

Somatostatins are a brain peptide family centered on a 14-amino acid cyclic peptide (SS-14) and a 28-amino acid N-terminally extended form (SS-28). Using radioiodinated analogs of SS-14 and SS-28, we have identified specific binding sites in rat and human brain sections that display pharmacological properties anticipated for somatostatin receptors and discrete patterns of anatomical localization. High binding densities are found in many forebrain regions, with special densities in infragranular cerebral cortical laminae in rat and human brain. In the rat, other densities lie in olfactory zones, lateral and triangular septal nuclei, the CA-1 hippocampal region, and claustrum with moderate densities in the striatum. Discrete hypothalamic areas, especially the median preoptic, paraventricular, and periventricular nuclei, display elevated binding levels, while the thalamus shows only scattered areas of modest binding. Midbrain receptor concentrations are found in portions of the periaqueductal gray, interpeduncular nucleus, and the substantia nigra. Notable pontine and medullary densities lie in the locus coeruleus, fourth ventricular floor, parabrachial, solitary, prepositus hypoglossal, dorsal column, and caudal trigeminal zones. Although the cerebellar cortex shows unimpressive densities, each of the deep cerebellar nuclei is heavily labeled. Modest spinal cord receptor densities are concentrated in the substantia gelatinosa and central cord regions. These localizations show many parallels with the distributions of SS-immunoreactive neurons, fibers, and terminals determined previously by immunohistochemistry. They provide plausible loci for several reported physiological or pharmacological activities of the SS-peptides, and may improve understanding of the role of the SS alterations described in several human neurodegenerative disorders.

Animals↗

PubMed1985

31P-nuclear magnetic resonance analysis of the intracellular pH in the slime mold Dictyostelium discoideum.

Amoebae of the slime mold D. discoideum were studied by phosphorus nuclear magnetic resonance. Under aerobic conditions, major intracellular phosphate compounds included phosphomonoesters, inorganic phosphate (Pi), ADP and ATP. Nucleotides were essentially as magnesium complexes. Two intracellular Pi resonances were clearly resolved and the corresponding pHs determined by the chemical shifts characteristics were 7.7 and 6.7. These intracellular pHs were strictly constant over an extracellular pH range between 5.0 and 7.5. The two cellular compartments defined by the Pi resonances were assigned to mitochondria (pH 7.7) and cytosol (pH 6.7) on the basis of their response to anaerobiosis or to carbonylcyanide-m-chloro phenylhydrazone (CCCP), an uncoupler of oxidative phosphorylation, which equilibrate the two intracellular pHs.

Adenosine Triphosphate↗

PubMed1985

Topography of nicotinamide adenine dinucleotide phosphate-diaphorase staining neurons in rat striatum.

A new modification of the nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase reaction was used to study the distribution of a specific subset of neurons in rat striatum. These neurons are known to also contain somatostatin-like immunoreactivity (SLI). We have previously found a heterogeneous distribution of SLI in rat striatum. In the present study, we found NADPH-diaphorase neurons to be evenly distributed throughout the striatum and nucleus accumbens. There was no increase in the number of NADPH-diaphorase neurons in ventromedial striatum or nucleus accumbens where concentrations of SLI are highest. This suggests that there may be somatostatin afferents to ventromedial striatum and nucleus accumbens. In addition, the NADPH-diaphorase reaction was stable for up to 24 h in an animal model stimulating human autopsy conditions.

Amygdala↗

PubMed1985

Reduced numbers of somatostatin receptors in the cerebral cortex in Alzheimer's disease.

Somatostatin receptor concentrations were measured in patients with Alzheimer's disease and controls. In the frontal cortex (Brodmann areas 6, 9, and 10) and temporal cortex (Brodmann area 21), the concentrations of somatostatin in receptors in the patients were reduced to approximately 50 percent of control values. A 40 percent reduction was seen in the hippocampus, while no significant changes were found in the cingulate cortex, postcentral gyrus, temporal pole, and superior temporal gyrus. Scatchard analysis showed a reduction in receptor number rather than a change in affinity. Somatostatin-like immunoreactivity was significantly reduced in both the frontal and temporal cortex. Somatostatin-like immunoreactivity was linearly related to somatostatin-receptor binding in the cortices of Alzheimer's patients. These findings may reflect degeneration of postsynaptic neurons or cortical afferents in the patients' cerebral cortices. Alternatively, decreased somatostatin-like immunoreactivity in Alzheimer's disease might indicate increased release of somatostatin and down regulation of postsynaptic receptors.

Adult↗

PubMed1985

Immunoreactive somatostatin-28(1-12) is increased in Huntington's disease.

Somatostatin-28(1-12) concentrations were measured in Huntington's disease (HD) postmortem tissue using a specific radioimmunoassay. Concentrations of immunoreactive somatostatin-28(1-12) were significantly increased in the caudate and putamen but were unchanged in cortical areas A9 and A17. Since somatostatin-28(1-12) terminates with the amino acids Arg-Glu-OH, we examined whether this dodecapeptide compound might exert a neurotoxic effect. Injections of somatostatin-28(1-12) into rat striatum showed no evidence of histologic damage.

Adolescent↗

PubMed1985

Two types of somatostatin receptors differentiated by cyclic somatostatin analogs.

Somatostatin receptors in rat brain, pituitary, and pancreas were labeled with two radioiodinated analogs of somatostatins 14 and 28. Two cyclic analogs of somatostatin, SMS201-995 and cyclo(Ala-Cys-Phe-D-Trp-Lys-Thr-Cys), showed biphasic displacement of binding to somatostatin receptors by these radioligands. In contrast, all other somatostatin analogs, including somatostatin-14, competed for the receptor sites with monophasic displacement of radioligand receptor binding. Thus two types of somatostatin receptors were identified. It was found that the pituitary and pancreas have predominantly one type of somatostatin receptor whereas the brain has both, and that different regions of the brain have various proportions of the two types. These findings suggest methods to characterize other types of somatostatin receptors subserving somatostatin's diverse physiological functions, including a potential role in cognitive function and extrapyramidal motor system control.

Animals↗

PubMed1985

Effects of lesions in the amygdala and periventricular hypothalamus on striatal somatostatin-like immunoreactivity.

Somatostatin has been found in substantial amounts in the basal ganglia by radioimmunoassay and has been demonstrated in both neurons and nerve terminals. Since the levels of somatostatin have been shown to vary in Huntington's and Alzheimer's disease it was of interest to see whether such changes could be produced experimentally. Lesions of the periventricular nucleus of the hypothalamus and knife cuts adjacent to this nucleus had no effect on striatal somatostatin-like immunoreactivity (SLI). Similarly lesions of medio-dorsal frontal cortex, and those isolating pyriform cortex or the olfactory bulb had no effect on striatal SLI. Removal of the amygdala resulted in significant increases in SLI in the ipsilateral striatum and nucleus accumbens, suggesting loss of an inhibitory interaction. Stria terminalis lesions failed to reproduce this effect suggesting that it is mediated via amygdalo-striatal projections traveling in the dorsal longitudinal bundle. Other findings support a somatostatin projection to the amygdala from the bed nucleus of the stria terminalis and one from the amygdala to the ventromedial hypothalamus.

Amygdala↗

PubMed1985

Effect of sucrose starvation on sycamore (Acer pseudoplatanus) cell carbohydrate and Pi status.

The mobilization of stored carbohydrates during sucrose starvation was studied with sycamore (Acer pseudoplatanus) cells. When sucrose was omitted from the nutrient medium, the intracellular sucrose pool decreased rapidly during the first hours of the experiment, whereas the starch content remained practically unchanged. After 10h of sucrose starvation, starch hydrolysis replaced sucrose breakdown. From this moment, the phosphate-ester pool and respiration rate decreased with time. Conversely, the intracellular Pi concentration increased. 31P n.m.r. of intact sycamore cells indicated that, under these conditions, most of the Pi accumulated in the vacuole. These results strongly suggest that starch breakdown, in contrast with sucrose hydrolysis, is not rapid enough to maintain a high cellular metabolism.

Carbohydrate Metabolism↗

PubMed1985

Effects of neuroleptic drugs on brain beta-endorphin immunoreactivity.

The effect of chronic haloperidol on brain beta-endorphin immunoreactivity was examined in rats. Chronic haloperidol resulted in significant reductions of beta-endorphin immunoreactivity within the striatum, but other brain regions were uneffected. When a variety of neuroleptic drugs were tested, fluphenazine, chlorpromazine and haloperidol resulted in comparable reductions in beta-endorphin immunoreactivity in the striatum. These findings suggest a functional interaction between beta-endorphin and dopamine systems in the striatum.

Animals↗

PubMed1985

Late-onset Wilson's disease with neurological involvement in the absence of Kayser-Fleischer rings.

We report a patient with Wilson's disease whose case is unusual in two respects. First, the patient was 58 years of age when the diagnosis was made based on urinary, serum, and hepatic copper studies, as well as liver histological investigation. Second, despite the patient's neurological impairment, Kayser-Fleischer rings had not developed. We conclude that in patients with chronic, degenerative neurological disease, particularly when associated with hepatic dysfunction, the diagnosis of Wilson's disease should be considered regardless of age at onset or the absence of Kayser-Fleischer rings on slit lamp examination.

Age Factors↗

PubMed1985

Human cerebrospinal fluid somatostatin in neurologic disease.

Concentrations of somatostatin-like immunoreactivity (SLI) were examined in human cerebrospinal fluid (CSF). To validate the assay it was shown that CSF which had been run over a somatostatin immunoaffinity column showed no interference with binding of synthetic standards. Reversed phase HPLC showed that the immunoreactive material coeluted with SS14 and SS28 as well as a higher molecular weight precursor. Concentrations of human CSF SLI were stable at both room temperature and 4 degrees C for up to 72 h while repeated freezing and thawing resulted in a significant loss of immunoreactive material after the 3rd repetition. In normal control patients less than 55 years of age, CSF SLI was 54.7 +/- 1.9 pg/ml, while in those older than 55 CSF SLI was 56.2 +/- 2.2 pg/ml. Febrile infants had significantly higher levels (75.4 +/- 7.3) pg/ml. CSF SLI was normal in patients with aseptic meningitis (54.4 +/- 3.4 pg/ml), suggesting that increased CSF protein and white cell counts do not affect concentrations. Concentrations of CSF SLI were significantly increased in intervertebral disc disease (65.1 +/- 5.6 pg/ml), intrinsic spinal cord pathology (101.0 +/- 23.9 pg/ml), central nervous system tumors (78.0 +/- 7.8 pg/ml) and acute cortical damage of varied etiology (277.8 +/- 81.6 pg/ml). Patients with pseudotumor cerebri had concentrations of 43.2 +/- 2.5 pg/ml. Concentrations of CSF SLI were significantly reduced (P less than 0.01) in multiple sclerosis (38.8 +/- 5.5 pg/ml) and old cortical pathology (23.2 +/- 3.9 pg/ml). Serial CSF analysis in patients with acute CNS lesions, suggest that CSF SLI may be a neurochemical marker of acute pathology, as the initially elevated levels fell to or below normal with resolution of the pathologic process.

Adolescent↗

PubMed1985

Causal links between plasma and CSF endorphin levels in stress: vector-ARMA analysis.

To explore causal links between vital sign responses and immunoreactive beta-endorphin ("i-BE") rises in blood and CSF during ovine endotoxin stress, we analyzed concurrent i-BE levels in these two compartments by a "vector-ARMA" (= autoregressive moving average) method. This technique--widely used for modeling in other applications--has not to our knowledge been employed to study dynamic relationships of neuropeptides. Log-transformed i-BE levels were first "filtered" by repeated observations ANOVA to confirm significance of rises in both compartments. Next, vector-ARMA methodology was applied to derive an optimal causal model of vital sign changes and i-BE entry into plasma vs. CSF pools. The model indicated that reflux of i-BE from blood into CSF contributed to increases in CSF levels of this hormone. This novel application to neuroendocrinology of this approach illustrates its utility in evaluating changes in one or more neuropeptide levels in multiple compartments to indicate potentially causal relationships.

Animals↗

PubMed1985

Laparoscopic salpingectomy for ectopic pregnancy.

In selective cases operative laparoscopic salpingectomy is an alternative to laparotomy in the surgical treatment of ectopic pregnancy. The obvious advantages of this procedure are decreased morbidity and surgical pain, lower cost, shorter hospitalization and convalescence, and less disability, as well as a cosmetic surgical scar. Because the procedure is so cost-effective, and since the tools are familiar to most gynecologists, we hope it will gain wider utilization. Laparoscopic salpingectomy is not a difficult procedure when the basic principles of surgery are followed. Depending on the fertility desires of the patient and the condition of the opposite tube, this procedure may be preferable to laparotomy. If a complication such as bleeding does occur and fails to respond to cauterization, laparotomy can be done as usual for an ectopic pregnancy.

Adult↗

PubMed1985

Late onset of Huntington's disease.

Twenty-five patients with late-onset Huntington's disease were studied; motor impairment appeared at age 50 years or later. The average age at onset of chorea was 57.5 years, with an average age at diagnosis of 63.1 years. Approximately 25% of persons affected by Huntington's disease exhibit late onset. A preponderance of maternal transmission was noted in late-onset Huntington's disease. The clinical features resembled those of mid-life onset Huntington's disease but progressed more slowly. Neuropathological evaluation of two cases reveal less severe neuronal atrophy than for mid-life onset disease.

Age Factors↗

PubMed1985

Endotoxin increases vasopressin release independently of known physiological stimuli.

Plasma vasopressin (AVP) increases after endotoxin administration in freely behaving unanesthetized rats. The present experiments sought to determine the factors that mediate this vasopressin response. Endotoxin (150 micrograms/kg iv) elicited a significant increase in plasma AVP concentration. This response was accompanied by unchanged plasma osmolality, hypotension, increased hematocrit (reflecting decreased plasma volume), hypothermia, and hyperglycemia. Pretreatment with the prostaglandin synthesis inhibitor, indomethacin (5 mg/kg sc), had no effect on the vasopressin response to endotoxin but abolished or significantly attenuated the changes in blood pressure, hematocrit, temperature, and plasma glucose while leaving plasma osmolality unaltered. These investigations indicate that endotoxin stimulates vasopressin secretion into plasma independently of changes in plasma osmolality, systemic blood pressure, plasma volume, body temperature, or plasma glucose. The results also suggest that vasopressin responses to endotoxin are not mediated by prostaglandins, whereas prostaglandins do play a role in endotoxin's effects on blood pressure, plasma volume, temperature, and plasma glucose.

Animals↗