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Biomedical subjects

J B Martin

Publications and source records attributed to J B Martin.

At least 217 records · Page 12Linked to original sources

Schalling-Sifneos personality scale: findings and recommendations.

Noting concerns for the measurement of alexithymia, the present study attempted (1) to provide descriptive data on the Schalling - Sifneos Personality Scale ( SSPS ); (2) to replicate previous factor-analytic findings on the SSPS , and (3) to suggest an alternative to the present method of scoring the SSPS . A sample of 430 undergraduates completed the SSPS . It was found (1) that the distribution of scores on the SSPS was approximately normal; (2) that the factor structure of the SSPS is robust over samples, and (3) that factor analyses identified factors representing characteristics consistent with those described by alexithymia. A subsequent factor analysis was performed to identify questionnaire items most relevant to the measurement of alexithymia. Nine questions were identified and were used in a revised scoring system. The distribution of revised scores is also approximately normal. It is suggested that this revised system is a more sensitive indication of the presence of alexithymia.

Adolescent↗

Opiate modulation of the anterior pituitary hormone response during suckling in the rat.

We have investigated the influence of endogenous opiates on hormone responses during suckling in the rat. In complementary experiments, opiate receptors were blocked by naloxone (NAL) or endogenous opiate release from the pituitary was inhibited by dexamethasone (DEX). Serial blood samples from unanesthetized suckled rats were then assayed for plasma PRL, beta-endorphin-like immunoreactivity (beta-END-LI), TSH, and GH levels. Identical studies were also done in saline-treated (control) suckled rats and in unsuckled rats exposed to control objects. Whereas suckling caused a rise in plasma PRL, beta-END-LI, and GH, introduction of plastic control objects did not elevate hormone levels. NAL blocked the GH rise and depressed TSH levels, but did not significantly inhibit the PRL or beta-END-LI response. DEX prevented the beta-END-LI rise and blocked the GH rise, but did not inhibit TSH. DEX enhanced PRL release during suckling. These results demonstrate that 1) the responses of beta-END-LI, PRL, and GH are not an artifact of the sampling procedure; 2) PRL release during suckling is independent of beta-END-LI release by the pituitary; and 3) suckling stimulates the release of ACTH, beta-END, and beta-lipotropin from the anterior pituitary. Our results are consistent with both a role of pituitary beta-END in the control of GH and a role of corticosterone in the control of PRL during suckling.

Animals↗

Evidence that thyrotropin-releasing hormone is not a major prolactin-releasing factor during suckling in the rat.

The purpose of this study was to investigate whether TRH could be an important PRL-releasing factor during suckling in the rat. Plasma PRL, TSH, beta-endorphin-like immunoreactivity, and GH responses in serial blood samples from unanesthetized suckled rats were determined. The resulting hormonal profile was compared with that obtained when TRH (500 ng/kg BW, iv) was injected at the onset of suckling. Suckling evoked a rise in plasma levels of PRL, beta-endorphin-like immunoreactivity, and GH, but not in TSH. In contrast, exogenous TRH caused a 9-fold increase in plasma TSH levels during suckling without further increasing the PRL response. Since plasma PRL responses are reportedly enhanced by previous suckling, we also determined plasma PRL and TSH levels when TRH (25 ng/rat, iv) was given 30 min after a brief suckling episode. TRH caused a 2.5-fold increase in plasma TSH, but did not significantly increase plasma PRL levels. Since suckling increases plasma PRL without increasing plasma TSH, and TRH increases TSH but not PRL levels, we conclude that TRH is not a major PRL-releasing factor during suckling.

Animals↗

The effects of growth hormone (GH)-releasing peptides on GH secretion in perifused pituitary cells of adult male rats.

The present study investigated the GH secretory activities of two distinctively different peptides: human pancreatic GH-releasing factor 44 (GRF-44) and a synthetic peptide His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GHRP). GH secretion was studied in perifused dispersed anterior pituitary cells from male rats 24 or 48 h postdispersion. GRF-44 was 60 times more potent than GHRP and elicited linear increases in GH secretion between 0.3 and 30 ng (0.06-6 pmol), whereas the GHRP dose range was 3-300 ng (3.44-344 pmol). Hourly pulses of GHRP (30 ng) and GRF-44 (12.5 ng) stimulated consistent GH responses. An apparent priming effect was observed with GRF-44 at a dose of 3 ng. Continuous infusion of either peptide resulted in desensitization, with GH secretion being monophasic during GHRP infusion and biphasic during GRF-44 infusion. These results demonstrate that GRF-44 and GHRP, two peptides that have striking differences in their structure and size, stimulate in vitro GH secretion with remarkable similarity. However, the differences in potency, slope of the dose response, and pattern of GH secretion during continuous GRF-44 or GHRP infusion suggest that each stimulates in vitro GH secretion by slightly different mechanisms. GHRP or similar synthetic peptides may be useful probes to study GH secretory mechanisms.

Animals↗

Cysteamine depletes prolactin (PRL) but does not alter the structure of PRL-containing granules in the anterior pituitary.

Cysteamine causes a profound depletion of PRL in the anterior pituitary and in the systemic circulation, as measured by RIA and bioassay. However, electron microscopic study of PRL-containing cells in rat anterior pituitary does not reveal changes in secretory granule or cytoplasmic structure during the interval of depressed PRL content and of subsequent recovery to normal levels. In contrast to the results obtained by RIA, PRL-like immunoreactivity as detected by immunocyto-chemistry is present and similar to that of control preparations after cysteamine administration. We suggest that cysteamine alters PRL structure in secretory granules, probably by interacting with the disulfide bonds of PRL, thereby altering bioactivity and immunoreactivity. The presence of cysteamine-altered PRL in secretory granules does not seem to trigger degradation of granules by the lysosomal system.

Animals↗

Somatostatin is increased in the nucleus accumbens in Huntington's disease.

Concentrations of somatostatin-like immunoreactivity (SLI) are elevated in the basal ganglia in Huntington's disease. The present study confirms these findings and, in addition, shows that concentrations of SLI are significantly elevated in the nucleus accumbens (4.04 +/- 0.66 versus 1.69 +/- 0.21 ng/mg protein in controls). This area is relatively spared pathologically and shows little atrophy in Huntington's disease. Since many patients with Huntington's disease are treated with haloperidol, we studied the effects of this drug in rats. There was a dose-dependent reduction of SLI in striatum, parietal cortex, and hippocampus. The elevated concentrations of SLI in the basal ganglia in Huntington's disease, therefore, do not appear to result from haloperidol therapy.

Adolescent↗

Huntington's disease: new approaches to an old problem. The Robert Wartenberg lecture.

Huntington's disease (HD) is an autosomal dominant disorder of midlife onset, characterized by progressive involuntary choreiform movements, psychologic change, and dementia. In 1980, funded by the NINCDS, we established a center for the study of HD. This report presents a summary of our contributions to the investigation of this tragic disorder and a review of current ideas about the disease.

Acetylcholine↗

Regional somatostatin distribution in the rat striatum.

Somatostatin-like immunoreactivity (SLI) was detected by a specific radioimmunoassay in extracts from rat striatum. There was a topographic distribution of somatostatin with the highest levels in the nucleus accumbens and ventromedial striatum and the lowest levels in the dorsolateral striatum. This suggests that somatostatin-containing afferents to the striatum may originate from limbic system nuclei which project in a similar distribution. Gel permeation chromatography showed 5 distinct peaks of immunoreactive somatostatin. The two largest peaks coeluted with somatostatin 14 (SS-14) and somatostatin 28 (SS-28) and accounted for 72 and 12% of the total immunoreactivity, respectively. Reversed phase high pressure liquid chromatography confirmed that the majority of immunoreactive material co-chromatographs with SS-14; a smaller amount co-chromatographed with SS-28.

Animals↗

A comparison of the effects of kainic acid on somatostatin, substance P and dopamine in the rabbit retina.

Groups of adult, male Dutch belted rabbits received intravitreal injections of varying doses (30-240 nmol) of the excitatory neurotoxin kainic acid (KA) into one eye and saline vehicle into the other. One week later a segment of each retina was examined histologically and the remainder was assayed for somatostatin-like immunoreactivity (SLI), substance P-like immunoreactivity (SPLI), dopamine (DA) and protein. Histologically, KA at doses of 120 and 240 nmol produced destruction of the inner layers of the retina, with preservation of the photoreceptors. This damage is correlated with a dose-related depletion of retinal protein content. At KA doses of 120 and 240 nmol, both SPLI and DA content were reduced to 5-10% of control values. Although KA significantly reduced the retinal content of SLI even at a dose of 30 nmol, the greatest mean depletion of SLI observed at any dose was 50%. This failure of KA to reduce retinal SLI content by more than 50% at doses of KA which produce severe histologic damage to the neural retina and dramatic depletions of SPLI and DA content demonstrates that the SLI-containing structures of the rabbit retina are partially resistant to the neurotoxic action of KA. We hypothesize that SLI in the rabbit retina is contained in two pharmacologic types of cells in about equal abundance; one type is sensitive to and one type resistant to KA. In contrast, substance P- and dopamine-containing retinal neurons are uniformly sensitive to destruction by KA.

Animals↗

Effects of lesions on somatostatin-like immunoreactivity in the rat striatum.

Substantial amounts of somatostatin have been demonstrated in the basal ganglia and immunocytochemistry has demonstrated both somatostatin staining neurons and nerve terminals. In order to study possible sources of somatostatin input to the striatum a series of lesions were made. Lesions of the substantia nigra produced with either 6-hydroxydopamine or ibotenic acid and hemisections at the level of the globus pallidus (6.2 mm anterior) had no effect on striatal levels of somatostatin-like immunoreactivity (SLI). Similarly dorsal frontal or hemicortectomies had no effect on SLI in the striatum. Kainic acid injected directly into the striatum at 2 dose levels resulted in a 60% depletion of SLI on the ipsilateral side and a 25% reduction on the contralateral side. These results suggest that about half of the SLI in the striatum is localizable to intrinsic neurons; the source of the remaining SLI is presently unknown but does not appear to arise in the dorsal cortex, thalamus or brainstem.

Animals↗

Somatostatin is increased in the basal ganglia in Huntington disease.

Huntington disease (HD) is an autosomal dominant hereditary disorder characterized by premature cell death, predominantly in the neostriatum. Decreased concentrations of several neurotransmitters and neuropeptides have been reported in the basal ganglia in Huntington disease. We now report that concentrations of radioimmunoassayable somatostatin are increased in extracts of the caudate (mean +/- standard error of the mean, ng/gm net weight; 247 +/- 24 versus 85 +/- 11), putamen (275 +/- 48 versus 74 +/- 11), external globus pallidus (100 +/- 10 versus 27 +/- 6), and internal globus pallidus (108 +/- 21 versus 21 +/- 8) in the disease. The concentrations of immunoreactive substance P measured in the same extracts were markedly reduced in caudate (mean +/- standard error of the mean, pmol/gm wet weight; 25 +/- 3 versus 109 +/- 20), putamen (28 +/- 7 versus 88 +/- 28), external globus pallidus (39 +/- 9 versus 196 +/- 62), and internal globus pallidus (60 +/- 17 versus 263 +/- 39), as well as in both subdivisions of the substantia nigra. Gel permeation chromatography and high-performance liquid chromatography showed radioimmunoassayable somatostatin to include peptides with physicochemical properties of the tetradecapeptide somatostatin and larger substances, including somatostatin-28-like material. A single peak of immunoreactive substance P corresponding to synthetic substance P was found by high performance liquid chromatography. These results suggest that immunoassayable somatostatin-containing neuronal elements in the neostriatum and globus pallidus in Huntington disease are affected differentially by the disease process from neurons that contain immunoreactive substance P.

Adolescent↗

Relationship between the cytoplasm and the vacuole phosphate pool in Acer pseudoplatanus cells.

The Pi concentration of Acer pseudoplatanus cells in the two major intracellular compartments, the cytoplasm and the vacuole, has been studied using 31P NMR. For sycamore cells containing approximately 2 mM of total Pi, the cytoplasmic Pi and the vacuolar Pi concentrations were approximately 6 and 1.5 mM, respectively. When the cells were transferred to a phosphate-deficient medium, the vacuolar Pi decreased rapidly while the cytoplasmic Pi decreased slowly during the first 48 h, indicating that Pi in the cytoplasm was maintained at the expense of the vacuolar Pi. When the Pi-starved cells (i.e., those containing less than 0.5 mumol of total Pi/g wet wt) were transferred to a medium containing 300 microM Pi, Pi entered the cells rapidly and accumulated in the cytoplasm. Once the cytoplasmic Pi pool was filled, Pi was taken up in the vacuole until the vacuole Pi pool was filled. On the contrary when the non-Pi-starved cells were transferred to a phosphate-rich medium (i.e., containing 45 mM Pi), Pi entered the cells slowly by diffusion and accumulated in the vacuole but not in the cytoplasm. These results demonstrate that the Pi content of the cytoplasm is maintained at the expense of the vacuolar Pi pool when sycamore cells are transferred to either a phosphate-deficient or a phosphate-rich medium.

Cell Compartmentation↗

Somatostatin radioreceptor assay: development and application to the measurement of somatostatinlike activity in the rat central nervous system.

Functional receptors for the neuropeptide somatostatin have previously been characterized in a clonal line (GH4C1) of rat pituitary tumour cells. We have utilized GH4C1 cell receptors to develop a radioreceptor assay for the measurement of somatostatinlike activity in biological samples. The concentration of somatostatinlike activity was determined in various regions of the rat central nervous system by both radioreceptor assay and two radioimmunoassays. For all tissue samples tested, less somatostatinlike activity was measured by radioreceptor assay than by radioimmunoassay. Furthermore, the ratio of the measured activity in the two assays varied from 0.31 to 0.76. It is likely that these differences are at least partially due to the different affinities of GH4C1 cell receptors and the two antibodies for somatostatin-14 and somatostatin-28 which are both present in the rat central nervous system.

Animals↗

Changes in cerebrospinal fluid and plasma vasopressin in the febrile sheep.

Plasma and cerebrospinal fluid (CSF) concentrations of vasopressin (AVP) were measured in conscious sheep during fever induced by iv endotoxin. Body temperature and blood pressure were also measured. AVP concentrations increased in both CSF and plasma although increases were not parallel. AVP concentrations in CSF were significantly correlated to increases in body temperature whereas plasma AVP concentrations were not. Neither CSF nor plasma AVP concentrations were correlated with changes in blood pressure. These data indicate that there may be independent regulation of AVP release into plasma and CSF compartments and supports the idea that AVP may have several physiological functions to perform during fever.

Animals↗

The effects of cysteamine on thyrotropin and immunoreactive beta-endorphin secretion in the rat.

We examined the effects of the thiol agent cysteamine (CSH), which is known to deplete the hypothalamus of immunoreactive somatostatin, on physiological TSH and beta- endorphin secretion in the adult male rat. CSH at doses of 90 and 300 mg/kg CSH produced a rapid decline in plasma TSH, whereas a dose of 30 mg/kg did not alter plasma TSH levels. After the higher doses of CSH, TSH levels in the blood remained lower than control values on day 2, but returned to normal by 1 week. This decrease in TSH within the plasma was not associated with a reduction in hypothalamic TRH concentrations. The TSH response to 500 ng/kg TRH was normal in CSH-treated animals. Blockade of norepinephrine synthesis with diethyldithiocarbamate (500 mg/kg) or fusaric acid (100 mg/kg) inhibited TSH secretion in a manner similar to that of CSH. beta-Endorphin-like immunoreactivity (bet-End-LI) was elevated in the plasma immediately after CSH (300 mg/kg) administration. This was associated with a 58% reduction in anterior pituitary beta-End-LI and no change in hypothalmic beta-End-LI. Plasma beta-End-LI returned to normal on day 2. The increase in plasma beta-End-LI induced by immobilization stress was not compromised by CSH treatment. The observed effects of CSH on both TSH and beta-End-LI are consistent with a reduction in central norepinephrine neurotransmission through the known actin of CSH to inhibit dopamine-beta-hydroxylase. Acute stress may play a role as well in the observed changes in TSH and beta-End-LI secretion.

Animals↗