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Biomedical subjects

J B Martin

Publications and source records attributed to J B Martin.

At least 199 records · Page 11Linked to original sources

Somatostatin release from the median eminence of unanesthetized rats: lack of correlation with pharmacologically suppressed growth hormone secretion.

We describe a push-pull perfusion technique to investigate the role of somatostatin in the pharmacological suppression of growth hormone (GH) secretion. Immunoreactive somatostatin (IRS) released from the median eminence (ME) was studied in chronically cannulated, unanesthetized male rats. In control rats which received vehicle injection, plasma GH levels showed a normal ultradian rhythm and relatively stable levels of IRS (around 30 pg/15 min) appeared in the perfusate during the 6-h perfusion. Intracerebroventricular (i.c.v) administration of human growth hormone (40 micrograms), neurotensin (2 micrograms), glucagon (25 micrograms) or intravenous (i.v.) injection of oxymetazoline (50 micrograms/kg b.w.), an alpha-adrenergic agonist, or endotoxin (150 micrograms/kg b.w.) suppressed subsequent GH surges. In these rats, however, IRS levels in the ME perfusate failed to change significantly compared to control rats. These results suggest that changes in somatostatin release may play a minor role in the suppression of plasma GH levels caused by these substances, and that major regulatory effects may be achieved via the suppression of growth hormone-releasing factor release.

Animals↗

The stress-alexithymia hypothesis: theorectical and empirical considerations.

An association has been noted between the presence of alexithymic characteristics and psychosomatic/stress-related illness. A hypothesis is presented here outlining the mechanisms through which stress and alexithymic characteristics contribute to the development of stress-related illness. This hypothesis, the stress-alexithymia hypothesis, is considered here in the context of stress research from both theoretical and empirical perspectives. From these considerations, it appears that the stress-alexithymia hypothesis does have a theoretical basis. Additionally, there is indirect empirical evidence supporting the proposed influence of alexithymic characteristics on the physiological stress response. It is suggested that future research should directly examine the influence of alexithymic characteristics on stress responding and use alexithymic characteristics heuristically to explore the role of affect in the illness process.

Affect↗

Dose-response characteristics of various peptides with growth hormone-releasing activity in the unanesthetized male rat.

The characterization of GH-releasing peptides in vivo has been complicated by the effects of endogenous hypothalamic regulation of GH secretion. We describe a model to minimize endogenous hypothalamic interference by pretreating adult male rats with iv diethyldithiocarbamate and antisomatostatin serum. This pretreatment regimen established stable, detectable basal levels of plasma GH and eliminated spontaneous GH pulses for 12 h. Repeated pulsatile administration of 400 ng/kg iv rat hypothalamic GH-releasing factor (rGRF) produced consistent GH responses. Linear, nearly identical, dose responses (from 300-5000 ng/kg) were observed with rGRF and human pancreatic GH-releasing factor (GRF44) with ED50 values of 1059.3 and 1116.9 ng/kg, respectively. We also investigated a synthetic hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP), which was previously reported to have potent GH-releasing activity. In contrast to either rGRF or GRF44, repeated administration of the same dose of GHRP did not produce consistent GH responses. The first bolus of GHRP produced a larger GH pulse than the second (P less than 0.01), followed by increasing GH responses from injections 2 to 7. GHRP was about 2 log orders less potent than either rGRF or GRF44 on a molar basis. The disparity between the native peptides and GHRP suggests that the synthetic peptide may act to release GH through a different mechanism(s). In summary, these data indicate that the diethyldithiocarbamate/anti-somatostatin serum-treated animal may be a useful model for investigating the pituitary actions of GH-releasing peptides.

Animals↗

Effects of rat growth hormone (rGH)-releasing factor and somatostatin on the release and synthesis of rGH in dispersed pituitary cells.

The effects of rat hypothalamic GH-releasing factor (GRF) and somatostatin (SRIF) on the release and biosynthesis of rat GH were studied by RIA and quantitative immunoprecipitation using monolayer cultures of rat anterior pituitary cells. In kinetic studies, GRF stimulation of GH release appeared at the first sampling time (20-min incubation) and the effect began to diminish after 2-h incubation with GRF. On the other hand, total (cell plus medium) content of GH significantly increased only after 24-h incubation. To examine the GH-synthesizing effect of GRF more directly, newly synthesized GH labeled by [35S]methionine during incubation with GRF was quantified by immunoprecipitation. The amount of immunoprecipitable GH increased significantly and specifically (compared with the total amount of labeled proteins) also only after 24-h incubation. When GH pools were labeled with [35S]methionine under different schedules, the basal release of newly synthesized GH, which was labeled for 1 h immediately before chase incubation was lower during the first 15 min than stored GH which had been labeled earlier. Basal newly synthesized GH secretion exceeded stored GH secretion after 30 min. GRF stimulated the release of GH from both pools but the stimulation of stored GH was greater. In this system, SRIF suppressed both the basal and stimulated release of GH but did not modify GH biosynthesis under either condition. Newly synthesized GH showed significant degradation during 24-h incubation; neither GRF nor SRIF affected the rate of GH degradation during the same incubation period. These results indicate that 1) GRF stimulates both release and synthesis of GH; 2) these two effects have different kinetics and different sensitivities to SRIF; and 3) GRF stimulates the release of GH from heterogeneous pools disproportionally.

Animals↗

The mechanism of action of cysteamine in depleting prolactin immunoreactivity.

The thiol reagent cysteamine (CSH) depletes anterior pituitary cells of immunoreactive PRL both in vivo and in vitro. We examined the hypothesis that CSH affects either the solubility or immunoreactivity of PRL through a mechanism involving thiol-disulfide exchange. Adult female rats were treated with either CSH (300 mg/kg, sc) or an equimolar dose of ethanolamine as a control. Anterior pituitary glands were extracted in 0.1 M sodium borate buffer, pH 9.0. Treatment of pituitary extracts with beta-mercaptoethanol (BME) destroys the immunoreactivity of PRL. However, extraction in the presence of reduced glutathione or CSH of pituitaries of rats treated with CSH restores immunoreactive PRL to control levels. Extracts were also subjected to polyacrylamide gel electrophoresis (PAGE). On gels of pituitary extracts of CSH-treated rats, the band that comigrates with purified PRL is diminished compared to that in ethanolamine-treated controls. This is found regardless of whether the borate extracts are treated with BME. However, extraction of the pituitaries in sodium dodecyl sulfate-containing buffer followed by chemical reduction with BME restores the PRL band. Therefore, CSH acts on PRL through a thiol-related mechanism to yield a product that is poorly soluble in aqueous buffer at pH 9 and is poorly immunoreactive. Dispersed anterior pituitary cells in tissue culture were incubated with L-[35S]methionine to radiolabel newly synthesized peptides. These cultures were incubated in the presence of either CSH or ethanolamine. PAGE followed by autoradiography confirmed the above results obtained in vivo. Also, extracts of CSH-treated cultures were subjected to gel permeation chromatography. As determined by PAGE, at least some of the radiolabeled PRL can be recovered from void volume fractions by reduction with BME, indicating that CSH induces the formation, through disulfide exchange, of a high mol wt form of PRL, possibly PRL oligomers.

Animals↗

Cysteamine-induced depletion of somatostatin and prolactin.

Cysteamine (2-aminoethanethiol [CSH], given in vivo or in vitro, rapidly but reversibly depletes immunoreactive somatostatin (irSS) in the central nervous system and gut as well as biological and immunological prolactin (PRL) activity in both the anterior pituitary and blood of the rat. This depletion of irSS and PRL is dose dependent and cannot be accounted for by release of either compound. Basal and potassium-stimulated SS release is reduced from hypothalamic tissue in vitro in CSH-treated animals. PRL secretion induced both pharmacologically and physiologically is abolished after CSH administration. Furthermore, CSH reduces cellular PRL content in a number of hyperprolactinemic states. The mechanism by which CSH reduces PRL levels is not clear, but it does not appear to act through the dopamine receptor nor does it alter the morphological structure of the lactotrope in normal animals. Most likely, CSH acts by interacting with the disulfide bonds of PRL, thus rendering the molecule both immunologically and biologically inactive.

Animals↗

Health behaviors and beliefs of four allied health professions regarding health promotion and disease prevention.

Certified nurse midwives, certified physician assistants, registered dental hygienists, and registered dietitians were surveyed to determine to what extent important health promotion and disease prevention behaviors are a part of their lifestyle. Also assessed were beliefs about health promotion and disease prevention practices. The study found that the respondents perceive themselves as important providers of health promotion and preventive services. Although most of the respondents are good health role models, many should consider changes in their own behaviors. Additionally, continued learning by many of these professionals appears warranted, particularly in recognizing the significance of certain health behaviors as they relate to preventing disease and promoting health.

Allied Health Personnel↗

A computer-aided system for planning acute care bed need in Michigan.

As part of an effort within Michigan to promote cost containment and equitably distribute hospital resources, the Acute Care Bed Need Methodology (ACBNM), a model for determining bed need based on normative use rates, was created. We describe herein the ACBNM, the associated interactive computer system, and the data base requirements, and make suggestions for improving the methodology. We also discuss the functions the ACBNM has served in Michigan and the role it could serve in future health planning efforts.

Age Factors↗

Surgically-related applications of computerized operating room data.

ORMIS data are currently used in a wide range of surgically-related applications--surgical activity reporting, graduate education and residency reporting, clinical research, surgically-related administration and surgical suite administration. Use of the system within Henry Ford Hospital has been increasing as it becomes better known and as its potential usefulness becomes better understood. Willingness to use ORMIS data depends, in large part, upon the perceived accuracy of the stored data and the ease with which these data can be retrieved and reported in a useful form. A high degree of confidence in ORMIS data has been achieved through considerable surgical staff involvement in the ongoing operation of the system. Surgeons participate in the coding of operative procedures, and the provision of surgeon-specific logs has established a feedback loop whereby surgeons can easily verify the accuracy of ORMIS data. Furthermore, special care has been taken to maintain the integrity of ORMIS data by developing extensive error detection and correction facilities. The multifaceted, successful applications reported herein show the increasing importance and usefulness of computerized data in contemporary surgical services.

Computers↗

Impact of administrative technology on acute care bed need.

This article reports an evaluation of the impact of three administrative technologies--Admission Scheduling (AS) Systems, Outpatient Surgery (OPS) Programs, and Preadmission Testing (PAT) Programs--on the number of acute care beds required by a hospital. The evaluation mechanism reported here is called the ADTECH Computerized Planning Model. ADTECH uses parameters of each technology, identified from previous literature and discussions with health care professionals, to predict the changes in bed requirements resulting from implementation of these programs. Data from eight hospitals of various characteristics and sizes were run to test the ADTECH model. The results from these test runs indicate that the proper implementation of AS, OPS, and PAT can significantly influence a hospital's required bed complement.

Ambulatory Surgical Procedures↗

Whither neurology?

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Internship and Residency↗

Depletion of striatal somatostatin by local cysteamine injection.

Local injection of cysteamine into rat striatum resulted in a dose-dependent reduction in somatostatin-like immunoreactivity (SLI). The effect was seen at 1 h, and persisted for up to 72 h, but was reversible at 1 week. The maximal depletion of SLI was approximately 50%. Histologic damage was largely confined to the needle tract. Of interest was a depletion of SLI in the contralateral striatum beginning at 3 h and maximal at 72 h. Cysteamine induced depletion of striatal SLI was not accompanied by alterations in dopamine or serotonin metabolism. Cysteamine is a useful pharmacologic tool for local somatostatin depletion.

Animals↗

Effects of neuroleptic drugs on brain somatostatin-like-immunoreactivity.

We previously found a dose-dependent reduction in striatal somatostatin-like immunoreactivity (SLI) following chronic haloperidol therapy. In the present experiments the effect was shown to be specific for the striatum and nucleus accumbens. With pimozide reductions in SLI were seen in the striatum, nucleus accumbens, amygdala, hypothalamus, bed nucleus of the stria terminalis and central grey matter. Other neuroleptics including chlorpromazine and fluphenazine also resulted in reduced concentrations of SLI in the striatum, nucleus accumbens and amygdala. A time course experiment showed that effects were demonstrable by 3 days and maximal at two weeks. The present findings provide further evidence of an interaction between somatostatin and dopaminergic neurons in the striatum.

Animals↗

The effect of somatostatin on striatal catecholamines.

Somatostatin and several analogues were injected into rat striatum and their effects on dopamine, serotonin and their metabolites were examined at 1 h. Somatostatin induced a dose-dependent increase in dopamine turnover in the ipsilateral striatum accompanied by a reduction in turnover on the contralateral side. There was no effect on serotonin turnover. Long-acting somatostatin analogues (D-Trp-8-somatostatin, SMS-201-995) had similar effects. These results suggest that somatostatin is involved in local regulation of striatal dopaminergic transmission and that it plays a role in regulation of dopamine release in the contralateral striatum.

Animals↗

An integrated surgical suite management information system.

The operational aspects, application areas, and results achieved from an integrated surgical suite management information system are described. The system, which has been operating within Henry Ford Hospital in Detroit, Michigan, for 4 years, captures comprehensive data for each surgical episode, performs extensive edits on these data to assure data base integrity, and utilizes this data base in multiple applications. These applications include fixed-format reporting for medical staff and management; ad hoc retrieval capabilities to support research, education, and decision making; and linkage to other hospital systems to reduce both data redundancy and paper flow.

Hospital Departments↗

Implications of neuropeptides in neurological diseases.

Neuropeptides are sufficiently stable to allow valid radioimmunoassay of peptide concentrations in post-mortem human nervous tissue and in human cerebrospinal fluid. Studies have now documented abnormalities of peptide concentrations in degenerative diseases of the brain. Somatostatin concentration is reduced in the hippocampus and neocortex of patients dying with Alzheimer's type dementia. In Huntington's disease, there are reduced concentrations of substance P, met-enkephalin and cholecystokinin in the basal ganglia; in contrast the concentrations of somatostatin and TRH are increased. Immunocytochemical and experimental lesion studies are underway in an attempt to localize the peptide-containing cells affected by these disorders; and the potential role of alterations in neuropeptide function in the pathogenesis, clinical manifestations and therapy of these illnesses is of great interest. Although alterations of CSF peptide concentrations have been reported in a variety of human diseases, interpretation of these results requires knowledge of the origin and disposition of CSF peptides. Future research into the pathology of peptidergic systems will depend on the development of specific peptide antagonists to probe dynamic aspects of peptide function and on the application of the tools of molecular biology, such as specific mRNA assays, to human material.

Alzheimer Disease↗

Endogenous prostaglandins affect growth hormone and thyrotropin release at a hypothalamic, not a pituitary level.

The role of prostaglandins (PGs) in the physiological secretion of the adenohypophyseal hormones, growth hormone (GH) and thyrotropin (TSH), in the unanesthetized, freely behaving male rat was investigated using pharmacological agents. Confirming previous observations, PG synthesis-inhibiting drugs, salicylate and indomethacin (INDO), reduced GH and TSH secretion. Another PG synthesis-inhibiting drug, acetaminophen, also reduced GH and TSH secretion. Antisomatostatin serum administered to INDO-treated rats indicated that somatostatin has a relatively small role in the GH and TSH suppression caused by PG synthesis inhibitors. Stimulation of GH secretion by the alpha 2-adrenergic receptor agonist, clonidine, and by morphine was similar in control and INDO-treated rats whereas PGE2 evoked a significantly greater release of GH in INDO- than in DDC- (dopamine beta-hydroxylase inhibitor-)treated rats. Stimulation of TSH secretion was similar in response to thyrotropin-releasing hormone (TRH) in INDO-treated and control rats and was also similar in response to PGE2 in INDO- and DDC-treated rats. However, clonidine evoked a significantly greater rise in TSH secretion in control than in INDO-treated rats. These results confirm the observation that PGs are important in physiological GH and TSH secretion in the rat and suggest that PGs are involved in GH secretion by interaction proximally to the adrenergic synapse on growth hormone-releasing factor (GRF) neurons and are involved in TSH secretion by interaction postsynaptically to the adrenergic synapse on TRH neurons.

Animals↗