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Biomedical subjects

J R Metz

Publications and source records attributed to J R Metz.

12 recordsLinked to original sources
PubMed2005

Alpha-MSH, the melanocortin-1 receptor and background adaptation in the Mozambique tilapia, Oreochromis mossambicus.

The regulation of skin darkness in vertebrates is mediated by alpha-melanophore-stimulating-hormone (alphaMSH). For this action, alphaMSH binds to the melanocortin (MC)-1 receptor, a 7-transmembrane receptor located in melanophore cell membranes. The Mozambique tilapia, Oreochromis mossambicus, can change the hue of its body in response to a change in background, a process that may involve alphaMSH and the MC1R. Scale melanophores were isolated from tilapia that were acclimatised for 25 days to a black, control grey or white background and then tested for their sensitivity to des-, mono-, and di-acetylated alphaMSH. On all backgrounds, mono-acetylated alphaMSH was the dominant isoform present in pituitary homogenates. Mono-acetylated alphaMSH also had the highest potency to disperse melanosomes. Black background adapted fish showed the highest dispersing response to alphaMSH, independent of the isoform applied. We elucidated the nucleotide and amino acid sequence of the tilapia MC1R. We show that its expression in skin does not change when tilapia are acclimatised for 25 days to a black, grey or white background, while a clear change in hue is visible. This finding, combined with the absence of differential MC1R gene expression following background acclimation indicates that the increased sensitivity to alphaMSH is most likely a result of changes in the intracellular signalling system in melanophores of black background adapted fish, rather than up-regulation of the MC1R.

Acetylation↗
PubMed2004

Plasma alpha-MSH and acetylated beta-endorphin levels following stress vary according to CRH sensitivity of the pituitary melanotropes in common carp, Cyprinus carpio.

Pituitary melanotropes release alpha-melanocyte-stimulating hormone (alpha-MSH) and acetylated beta-endorphin (NAc beta-end) during stress responses. However, effects of stressors on plasma concentrations of these hormones are highly inconsistent among fish species. Here, we show that also within a species, the common carp (Cyprinus carpio), fish sometimes respond with elevated alpha-MSH and NAc beta-end plasma levels, and at other times not. The origin of this variable response was investigated by (1) studying the effects of corticotropin-releasing hormone (CRH) on alpha-MSH and NAc beta-end release in vitro, (2) establishing where in the second messenger pathway coupled to CRH receptors melanotrope responsiveness is determined, and (3) testing modulatory actions of other hypothalamic factors (here opioid beta-endorphin). Melanotropes were in a high or low responsive state to CRH in vitro, which was especially evident when tissue was tested from fish kept at higher ambient water temperatures, and this correlates with the variability in alpha-MSH and NAc beta-end responses in vivo. Relative rates of alpha-MSH and NAc beta-end release following stimulation with CRH in vitro match plasma level changes in vivo, and this indicates that the CRH pathway does act in vivo. cAMP did not stimulate melanotropes in the low responsive state to release hormones in vitro. Thus, the mechanism that determines the cell status, occurs downstream of cAMP accumulation. Opioid beta-endorphin differentially modulated the actions of CRH, as NAc beta-end, but not alpha-MSH, release was inhibited. This response was not observed in the stress paradigms studied. We conclude that the variation in alpha-MSH and NAc beta-end stress responses in vivo correlates with many CRH responses in vitro; whether a cell is in a high or low responsive state to CRH is determined downstream of accumulation of the second messenger. We propose that melanotropes have to be in the high responsive state to be activated by CRH during stress in carp and other teleosts.

Acetylation↗
PubMed2004

Structural characterisation of a cyprinid (Cyprinus carpio L.) CRH, CRH-BP and CRH-R1, and the role of these proteins in the acute stress response.

We elucidated the structure of the principle factors regulating the initiation of the acute stress response in common carp: corticotrophin-releasing hormone (CRH), CRH-receptor 1 (CRH-R1) and CRH-binding protein (CRH-BP). Phylogenetic analyses reveal that these proteins are evolutionarily well conserved in vertebrates. CRH and CRH-BP expression are not co-localised in the same hypothalamic perikarya. On the contrary, CRH-BP expression is limited to the perimeter of the nucleus preopticus (NPO), but is abundant in other regions, including an area directly rostral from, and in close proximity to, the NPO. Despite the lack of co-expression, the nerve fibres projecting onto both the rostral pars distalis (rPD) as well as the large fibre bundles projecting onto the pars intermedia (PI) contain CRH as well as CRH-BP, suggesting that both ACTH release from the rPD as well as the release of PI melanotrope content is regulated via CRH and CRH-BP. Finally, we show via real-time quantitative PCR that expression of hypothalamic CRH and CRH-BP following a 24 h restraint significantly increases, whereas PD CRH-R1 expression decreases; this reflects desensitisation of the PD for hypothalamic CRH output. We conclude that these factors are actively involved in the regulation of acute stress responses in the teleost fish.

Amino Acid Sequence↗
PubMed2001

Identification of beta-endorphins in the pituitary gland and blood plasma of the common carp (Cyprinus carpio).

Carp beta-endorphin is posttranslationally modified by N-terminal acetylation and C-terminal cleavage. These processes determine the biological activity of the beta-endorphins. Forms of beta-endorphin were identified in the pars intermedia and the pars distalis of the pituitary gland of the common carp (Cyprinus carpio), as well as the forms released in vitro and into the blood. After separation and quantitation by high performance liquid chromatography (HPLC) coupled with radioimmunoassay, the beta-endorphin immunoreactive products were identified by electrospray ionisation mass spectrometry and peptide sequencing. The release of beta-endorphins by the pituitary gland was studied after stimulation with corticotrophin-releasing factor (CRF) in vitro. In the pars intermedia, eight N-acetylated truncated forms were identified. Full length N-acetyl beta-endorphin(1-33) coeluted with N-acetyl beta-endorphin(1-29) and these forms together amounted to over 50% of total immunoreactivity. These products were partially processed to N-acetyl betaendorphin(1-15) (30.8% of total immunoreactivity) and N-acetyl beta-endorphin(1-10) (3.1%) via two different cleavage pathways. The acetylated carp homologues of mammalian alpha- and gamma-endorphin were also found. N-acetyl beta-endorphin(1-15) and (1-29) and/or (1-33) were the major products to be released in vitro, and were the only acetylated beta-endorphins found in blood plasma, although never together. CRF stimulated the release of opioid beta-endorphin from the pars distalis. This non-acetylated beta-endorphin represents the full length peptide and is the most abundant form in plasma.

Animals↗
PubMed2000

alpha-MSH acetylation in the pituitary gland of the sea bream (Sparus aurata L.) in response to different backgrounds, confinement and air exposure.

MSH is a pituitary hormone derived by post-translational processing from POMC and involved in stress and background adaptation. N-terminal acetylation of MSH to monoacetyl alpha-MSH or diacetyl alpha-MSH increases the bioactivity of the peptide. The aim of this study was to characterize alpha-MSH acetylation in the sea bream (Sparus aurata L.) pituitary gland in response to the stressors air exposure and confinement, as well as in fish adapted for 15 days to a white, gray or black background. Pituitary homogenates were purified by reversed-phase HPLC (RP-HPLC). The alpha-MSH content of fractions was measured by RIA. Immunoreactive RP-HPLC fractions were further analyzed by electrospray mass spectrometry and the peptide sequence determined as SYSMEHFRWGKPV-NH2. In the pituitary gland of sea bream, des-, mono- and diacetyl alpha-MSH were identified. Then plasma alpha-MSH levels were measured in sea bream adapted to different backgrounds. Surprisingly, we found the highest plasma alpha-MSH levels in white-adapted as compared with black-adapted sea bream with intermediate values for gray-adapted fish. This observation is in contrast with results that have been obtained in eel, trout or terrestrial vertebrates. Next, des-, mono- and diacetyl alpha-MSH forms were measured in homogenates of the pituitary gland and in plasma of sea bream exposed to air, to confinement, or to different backgrounds. Monoacetyl alpha-MSH was the predominant form in all control and experimental groups. The lowest content of monoacetyl alpha-MSH relative to des- and diacetyl alpha-MSH was found in white-adapted fish. Levels of des- and diacetyl alpha-MSH forms were similar under all conditions. We observed that monoacetyl alpha-MSH is the most abundant isoform in the pituitary gland after background adaptation, confinement and air exposure, in sea bream. These data indicate that the physiologically most potent isoform of alpha-MSH may vary from species to species.

Acetylation↗
PubMed1991

Hypertrophic gastropathy symptoms responsive to prednisone. A case report and a review of the literature.

We describe a 33-year-old man with giant hypertrophic gastropathy (Menetrier's disease), which, on operative biopsy of the stomach, showed a significant inflammatory component. The patient was treated with prednisone and quickly responded. Although a review of the literature revealed only two cases similarly treated, with equivocal results, spontaneous remission, does occur. Symptoms associated with this disease may respond to corticosteroids, which may offer effective therapy while awaiting involution of the gastropathy. Thus total gastrectomy may be avoided.

Adult↗
PubMed1978

The retrorectal space.

Ninety-nine adults with an enlarged retrorectal space on barium enema examination have been evaluated. Measurements were based on previously described methods using the lateral view of the barium filled rectum. In 38.4% of the cases there was no lesion (normal variations). The rest were classified as inflammatory conditions, tumours, and miscellaneous lesions. It is concluded that an increased width of the presacral space per se does not necessarily connote a lesion. Pathological widening of the space is usually associated with changes of the contour of the rectum, abnormalities of the sacrum, or other alterations of the presacral soft tissues.

Barium Sulfate↗
PubMed1976

A pediatric screening examination for psychosocial problems.

In an effort to avert the cumulative effects of unresolved emotional problems on children's social and school adjustment, a psychosocial phase was added to a pediatric multiphasic examination. Based upon a cumulative stress concept, the screening procedures included child behavior and family stress questionnaires for parents, and abbreviated standard psychological tests for children, administered by specially trained aides. Computerized results were reported to the child's pediatrician. Follow-up by mental health counselors attached to the pediatric clinic was provided for patients identified as being at high risk of serious psychosocial problems. Evidence of validity of the screen, factors affecting the scores, and effectiveness of clinical follow-up of high-risk patients are discussed. Valid semicomputerized screening of school-age children for serious psychosocial problems can be carried out routinely and at relatively low cost by paraprofessional personnel in a pediatric setting. Impediments to effective use of the screening results on the part of both health care provider and patient are discussed.

Adolescent↗