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Biomedical subjects

J B Martin

Publications and source records attributed to J B Martin.

At least 163 records · Page 9Linked to original sources
PubMed1986

Neuropeptide Y immunoreactivity is reduced in cerebral cortex in Alzheimer's disease.

Neuropeptide Y is a 36-amino acid peptide that is found in high concentrations in cerebral cortex and is contained in cortical neurons. We measured concentrations of this peptide in postmortem tissue from patients with Alzheimer's disease and controls using a sensitive and specific radioimmunoassay. High-performance liquid chromatography showed that more than 95% of immunoreactivity co-migrated with synthetic standards in both Alzheimer's disease and control frontal cortex. Significant reductions in neuropeptide Y-like immunoreactivity were found in eleven cortical regions, the hippocampus, and the locus ceruleus. The regions particularly affected included the temporal lobe, frontal lobe, and occipital cortex. As neuropeptide Y is co-localized with somatostatin in a considerable proportion of cortical neurons, the loss of immunoreactivity may in part reflect degeneration of these neurons. Further study of the selective vulnerability of these neurons in Alzheimer's disease cortex may provide clues to the nature of the underlying disease process.

Aged↗
PubMed1986

Widespread reduction of somatostatin-like immunoreactivity in the cerebral cortex in Alzheimer's disease.

Although several studies have documented reduced concentrations of somatostatin-like immunoreactivity (SLI) in the cerebral cortex in Alzheimer's disease, there is controversy concerning the extent and importance of these changes. We measured SLI in brains obtained post mortem from 12 patients with pathologically confirmed Alzheimer's disease and from 13 neurologically normal controls. All major cortical and subcortical regions were examined. Widespread reductions of SLI in Alzheimer's disease cerebral cortex were found, with the most profound changes seen in temporal lobe; but there also were major reductions in both the frontal and occipital cortex. There were no significant reductions in subcortical regions. Characterization of SLI by high-pressure liquid chromatography showed no significant difference in profiles between Alzheimer's disease and control frontal cortex. These results suggest that the reduction in somatostatin immunoreactivity in Alzheimer's disease may be caused by degeneration of intrinsic somatostatin cortical neurons.

Acetylcholinesterase↗
PubMed1986

Neuropeptides in neurological disease.

Neuropeptides are widely distributed in the central nervous system, where they serve as neuroregulators. Recent interest has focused on their role in degenerative neurological diseases. We describe the normal anatomy of neuropeptides in both the cerebral cortex and basal ganglia as a framework for interpreting neuropeptide alterations in Alzheimer's disease (AD), Huntington's disease, and Parkinson's disease. Concentrations of cortical somatostatin are reduced in AD and in dementia associated with Parkinson's disease. Concentrations of neuropeptide Y and corticotropin-releasing factor are also reduced in AD cerebral cortex. The reduced cortical concentrations of somatostatin and neuropeptide Y in AD cerebral cortex may reflect a loss of neurons or terminals in which these two peptides are co-localized. In Huntington's disease, basal ganglia neurons in which somatostatin and neuropeptide Y are co-localized are selectively preserved. Cerebrospinal fluid concentrations of neuropeptides in AD reflect alterations in cortical concentrations. Improved understanding of neuropeptides in degenerative neurological illnesses will help define which neuronal populations are specifically vulnerable to the pathological processes, and this could lead to improved therapy.

Alzheimer Disease↗
PubMed1986

A postmortem study of amino acid neurotransmitters in Alzheimer's disease.

Concentrations of putative neurotransmitter amino acids were measured in postmortem brains from 10 patients with Alzheimer's disease and 10 controls. Glutamate, aspartate, taurine, gamma-aminobutyric acid (GABA), and alanine levels were examined in 9 cortical regions, hippocampus, thalamus, and basal ganglia using high-performance liquid chromatography with electrochemical detection. There were no significant alterations in aspartate, taurine, or alanine levels in any of the regions examined. Widespread significant reductions in cortical GABA concentrations were observed in the Alzheimer's brains, with the largest decreases in the temporal lobe. Overall values for glutamate concentrations in temporal and frontal cortices showed a significant 12% reduction in Alzheimer's brains, but the only individual cortical region showing a significant reduction in glutamate was the inferior temporal gyrus. These results suggest that gamma-aminobutyric acidergic neurons in Alzheimer's cerebral cortex may be selectively vulnerable to the disease process.

Aged↗
PubMed1986

Vasopressin in Alzheimer's disease: a study of postmortem brain concentrations.

Vasopressin (AVP) and its analogues are reported to improve learning- and memory-related performance in experimental animals, and perhaps also in humans. Memory impairment is a clinical hallmark of the dementing disorder, Alzheimer's disease. We have examined AVP concentrations in postmortem brain tissue from 12 patients with histologically confirmed Alzheimer's disease and 13 control subjects. AVP was measured by a highly specific and sensitive radioimmunoassay, validated by parallel inhibition curves and high-performance liquid chromatography. Alzheimer brains had either normal or slightly increased AVP levels in the neocortex, which does not have AVP cell bodies. Significant reductions in AVP content were found in the hippocampus, nucleus accumbens, and globus pallidus interna. Levels were normal in all other regions studied. Abnormalities of the brain vasopressin system may contribute to the memory deficit associated with Alzheimer's disease.

Adult↗
PubMed1986

Intracellular pH control in Dictyostelium discoideum: a 31P-NMR analysis.

Phosphorus metabolites and intracellular pH have been examined in the slime mold Dictyostelium discoideum by non-destructive 31P-NMR measurements. In a spectrum from a suspension of aerobic amoebae, the major peaks are inorganic phosphate, nucleotide di- and triphosphates. In the corresponding perchloric acid extract, resonances originating from purine and pyrimidine nucleotides are resolved. Adenine nucleotides are the most abundant components, but the other nucleotides are present in significant amounts. In a spectrum from intact spores in a dormant state, only inorganic phosphate and polyphosphates are detected and nucleotides are no longer present in large amounts. Of particular importance is the ability to observe separately in aerobic amoebae the resonance of inorganic phosphate localized in two different cell compartments: the cytosol and the mitochondria. The cytosolic pH and mitochondrial pH have been measured as 6.7 and 7.7, respectively, on the basis of intracellular inorganic phosphate chemical shifts. They are essentially unaffected over a large range of external pH and they are not modified transiently or permanently during the initiation of the developmental program of the organism. A weak acid, such as propionate, which modifies the progression of differentiation by favoring prestalk cells, perturbs intracellular pH gradients by selectively decreasing mitochondrial pH without any effect on cytosolic pH.

Carbonyl Cyanide m-Chlorophenyl Hydrazone↗
PubMed1986

Cysteamine decreases prolactin responsiveness to thyrotropin-releasing hormone in normal men.

Cysteamine depletes pituitary and plasma prolactin in rats. It acts through a nondopaminergic mechanism to alter both immunoactive and bioactive prolactin. The effect of cysteamine on prolactin secretion is reported in normal men. Six normal subjects received a control thyrotropin-releasing hormone (TRH) test at 0900 using 200 micrograms TRH intravenously; serum prolactin and TSH were measured at -10, 0, 10, 20, 30, 60, and 90 min after administration of TRH. Serum calcium and parathyroid hormones levels were measured at -10 min. Seven or more days later, they received cysteamine hydrochloride 15 mg/kg body weight orally every 6 hours for 5 doses. One hour after the last dose, the TRH test was repeated. Peak serum prolactin levels following TRH, prolactin levels at the 10-min time point, and total area from 0 to 30 min under the prolactin secretory curve were significantly decreased by cysteamine administration. TSH levels were unchanged. Serum calcium levels were significantly decreased by cysteamine administration, but parathyroid hormone levels were unchanged. It was concluded that cysteamine reduced TRH-stimulated prolactin secretion. Cysteamine also decreases serum calcium levels and suppresses the anticipated rise in serum parathyroid hormone levels. These effects on serum calcium and parathyroid hormone are similar to those previously shown for WR2721, another sulfhydryl compound. Cysteamine should be further considered as an alternative drug in the treatment of hyperprolactinemia and as a therapeutic agent for hypercalcemia.

Adult↗
PubMed1986

Somatostatin binding sites in human and monkey brain: localization and characterization.

A radioiodinated analogue of somatostatin 28, 125I [Leu8,D-Trp22,Tyr25] SS-28, was used to localize and characterize somatostatin binding sites in both human and monkey brain. High-affinity binding sites (approximately 1 nM) were found in cerebral cortex. The highest binding was in cerebral cortex with intermediate binding found in hippocampus, striatum, and amygdala and low binding in hypothalamus and brainstem. There was a rough correlation between somatostatin receptor binding and concentrations of somatostatin-like immunoreactivity (SLI) in human brain. Somatostatin receptors were stable for up to 24 h in an animal model simulating human autopsy conditions and there was no correlation between postmortem interval and receptor binding in human brain. Pharmacologic characterization in human cortex showed that there was a correlation between the inhibition of receptor binding by somatostatin analogues and their known abilities to inhibit growth hormone secretion. These findings demonstrate that a highly specific membrane-associated receptor for somatostatin is present in both monkey and human brain. Examination of somatostatin receptor binding in Alzheimer's disease and Huntington's disease may improve understanding of the role of somatostatin in both these illnesses.

Animals↗
PubMed1986

Influence of alexithymic characteristics on physiological and subjective stress responses in normal individuals.

Individual differences in response to stress have been linked to the development of stress-related disorders through the presence of a dissociation between physiological and subjective stress responses. It has been suggested that the presence of alexithymic characteristics may constitute a new source of individual response differences and thereby contribute to the development of a stress-related disorder. However, it is also possible that the presence of alexithymic characteristics is simply a new name for a preexisting construct. The present study examined subjective and physiological stress response patterns in normal individuals with high or low presence of alexithymic characteristics, and the relationship between alexithymia and potentially equivalent constructs. The results revealed that the presence of alexithymic characteristics is independent of repression, trait anxiety, and social desirability. As well, high alexithymics appear to manifest high levels of sympathetic activity, and a dissociation between subjective and physiological stress responses. These results are discussed in terms of the potential contribution of alexithymic characteristics to the development of stress-related disorders.

Adult↗
PubMed1986

Prediction of alexithymic characteristics from physiological, personality, and subjective measures.

Noting concerns for a comprehensive conceptualization of alexithymic characteristics, the present study examines the potential utility of considering these characteristics as manifestations of deficits in cognitive schemata. Research guided by this conceptualization has identified physiological, subjective, and personality features of alexithymic characteristics. It is reasoned that if this conceptualization has merit, it should be possible to predict the presence of alexithymic characteristics from these features. Results of the present study indicate that a combination of physiological, subjective, and personality variables significantly predicts the presence of alexithymic characteristics as measured by the Schalling-Sifneos Personality Scale. These results are discussed in terms of their implications for a more comprehensive description of alexithymia and the value of the cognitive schema conceptualization.

Adolescent↗
PubMed1986

Growth hormone secretion in genetic large (LL) and small (SS) rats.

We investigated whether genetic selection for growth influences pituitary GH secretion in two strains of rats, LL (large) and SS (small). Animals were bled every 15 min for 6 h via an indwelling atrial Silastic catheter, and GH levels were determined by RIA. LL and SS males displayed a low frequency, high amplitude episodic pattern of GH secretion, with surges of GH occurring at 3- to 4-h intervals, separated by trough periods of approximately 60-120 min. In contrast, LL females showed a high frequency, low amplitude pattern of GH secretion, with GH pulses occurring every 1-2 h. The number of GH pulses in SS females was lower than that in LL females. SS males and SS females displayed lower peak amplitudes and lower baseline levels and, therefore, lower mean plasma GH levels compared to LL animals. The anterior pituitary GH content was not significantly different in LL and SS animals of either sex. Thus, the reduction of GH levels in SS animals is most likely the result of reduced release of GH-releasing factor from the hypothalamus or an attenuated pituitary sensitivity to GH-releasing factor.

Animals↗
PubMed1986

Influence of sex steroid hormones on rat growth hormone-releasing factor and somatostatin in dispersed pituitary cells.

The modulatory effects of glucocorticoid and sex steroid hormones on the effects of rat GH-releasing factor (GRF) and somatostatin (SRIF) on GH release and biosynthesis were studied in monolayer cultures of rat anterior pituitary cells with RIA and quantitative immunoprecipitation methods. Dexamethasone (10(-7) M), a potent synthetic glucocorticoid, increased both the sensitivity and maximum response of GH release stimulated by GRF. Progesterone (10(-7) M) also enhanced GH release stimulated by GRF. The stimulatory effects of dexamethasone and progesterone were dose dependent and required a latent period of at least 24 h to be evident. Testosterone, dihydrotestosterone, and 17 beta-estradiol showed no apparent influence on GRF-induced GH release under the same conditions. None of the hormones studied showed significant influences on basal or SRIF-suppressed GH release. Progesterone added to the maximally effective concentrations of dexamethasone had no additional effects on GRF-induced GH release. The effect of progesterone was attenuated by both 5 alpha-dihydronorethindrone, a progesterone antagonist and 17 alpha-methyltestosterone, a glucocorticoid antagonist. In terms of GH synthesis, stimulatory effects of GRF on GH synthesis were apparent only when pituitary cells were pretreated with dexamethasone. These results indicate that: pretreatment with glucocorticoid or progesterone enhances the effects of GRF on GH release and/or synthesis; these two steroids share at least one common step to enhance GRF effects; and steroid hormones have little influence on basal or SRIF-suppressed GH release.

Animals↗
PubMed1986

Growth hormone-secretory patterns in androgen-resistant (testicular feminized) rats.

To investigate the role of androgen receptors in the expression of the male GH-secretory pattern in adult rats, the GH-secretory patterns in androgen-resistant (testicular feminized) rats were compared with their normal male and female littermates. All animals were prepared with intraatrial Silastic catheters and bled every 15 min for 8 h (0800-1600 h). Normal male littermates displayed a characteristic low frequency, high amplitude pattern of GH secretion with bursts of GH occurring every 2.5-3 h and separated by prolonged trough periods where GH values remained low or undetectable (less than 5 ng/ml) for 45-90 min. Normal female littermates showed a characteristic high frequency, low amplitude pattern of GH secretion with pulses of GH occurring every hour. Compared to normal male littermates, females had lower individual GH peak amplitudes and shortened GH-trough periods which contain higher GH levels. GH-secretory profiles displayed by testicular-feminized animals qualitatively and quantitatively resembled those of the normal female littermates. These data suggest that androgen receptors are necessary for the expression of masculine GH-secretory patterns.

Age Factors↗
PubMed1986

CSF somatostatin-like immunoreactivity in dementia.

Concentrations of somatostatin-like immunoreactivity (SLI) in CSF were reduced in Alzheimer's disease (AD) and multi-infarct dementia (p less than 0.01), but not in normal-pressure hydrocephalus, Parkinson's disease, and Huntington's disease. This suggests that reduced SLI content in AD cerebral cortex is reflected in CSF. Chromatographic characterization of CSF SLI showed no differences between AD and controls. Concentrations of SLI in AD patients overlapped those in both normal subjects and patients with multi-infarct dementia, so that changes in CSF SLI have no diagnostic specificity.

Age Factors↗
PubMed1986

CSF vasopressin concentration is reduced in Alzheimer's disease.

The concentration of arginine vasopressin (AVP) was measured in cerebrospinal fluid (CSF) by radioimmunoassay. Serial dilution curves and reversed-phase high-pressure liquid chromatography (HPLC) showed that the material measured behaved identically to authentic vasopressin. Levels of CSF AVP were reduced by 37% in Alzheimer's disease, but were normal in Huntington's disease, normal-pressure hydrocephalus, and several other neurologic disorders. On direct comparison, the CSF AVP concentration was significantly lower in Alzheimer's disease than in normal-pressure hydrocephalus. Low CSF levels of AVP may therefore assist in the identification of demented patients who are not likely to benefit from ventricular shunting.

Aged↗
PubMed1986

Neuropeptides in Alzheimer's disease. Clinical implications.

Since the isolation and sequencing of the enkephalins in the mid-1970s, there has been an explosion of knowledge concerning putative peptide neurotransmitters in the brain. This article focuses on selected developments in neuropeptide research that may have bearing on our understanding of and clinical approach to the dementing degenerative disorder Alzheimer's disease (AD), a cardinal feature of which is impairment of memory.

Adrenocorticotropic Hormone↗