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Biomedical subjects

K A Roth

Publications and source records attributed to K A Roth.

At least 109 records · Page 6Linked to original sources
PubMed1988

Methionine-enkephalin and thyrotropin-stimulating hormone are intimately related in the human anterior pituitary.

The tissue distribution and function of opioid peptides in humans is incompletely defined. We report here that, unlike that in other species, the human anterior pituitary gland contains high concentrations of methionine-enkephalin (met-enkephalin). The met-enkephalin immunoreactive material was isolated and identified as authentic met-enkephalin by fast atom bombardment-mass spectrometry and Edman degradation sequencing. The met-enkephalin was localized in a large subpopulation of TSH immunoreactive cells (thyrotrophs). No other proenkephalin-derived opioid peptides were found in the pituitary, and there was no overlap between proopiomelanocortin and met-enkephalin immunoreactive cells. These results suggest that the human anterior pituitary gland contains a novel met-enkephalin precursor and a possible role for met-enkephalin in regulating human thyroid function.

Adolescent↗
PubMed1987

Characterization of opioid peptides in human thyroid medullary carcinoma.

A thyroid medullary carcinoma from a man with the multiple endocrine neoplasia syndrome Type IIB was examined for the presence of opioid peptides. The tumor contained peptides derived from all three opioid precursors: pro-opiomelanocortin (POMC), pro-dynorphin, and pro-enkephalin. The tissue concentrations of the various opioid peptides varied considerably. beta-Endorphin, a POMC-derived peptide, was present in concentrations between 9 to 12 pmoles/g tissue; 8 pmoles/g tissue of alpha-neo-endorphin, a pro-dynorphin-derived product, were seen, whereas the pro-enkephalin-associated peptides were present in much lower concentrations (0.6-2.1 pmoles/g tissue). Immunohistochemical studies showed scattered opioid-positive cells in the tumor tissue and in two other thyroid medullary carcinomas. These data demonstrate that malignant neuroendocrine tumors may contain peptides derived from all three families of the endogenous opioids.

Adult↗
PubMed1987

Isolation and characterization of beta-endorphin-(1-9) from human and rat pituitaries.

Using a radioimmunoassay specific for the carboxyl terminus of beta-endorphin-(1-9) large amounts of beta-endorphin-(1-9)-immunoreactive material was detected in the human pituitary. The major peak of immunoreactivity was purified and characterized by fast atom bombardment-mass spectrometry and Edman degradation sequencing as authentic beta-endorphin-(1-9). In the rat pituitary the highest concentration of beta-endorphin-(1-9) immunoreactivity was in the posterior neurointermediate lobe. This material was identified as N-acetyl beta-endorphin-(1-9) by multiple radioimmunoassays, gel chromatography, and reversed-phase high-performance liquid chromatography. Control experiments determined that beta-endorphin-(1-9) was not formed postmortem or during the extraction procedure. These studies suggest that single lysine residues, similar to single arginine residues, are potential sites of posttranslational processing.

Adult↗
PubMed1986

Small cell carcinoma cell lines contain opioid peptides and receptors.

Two human small cell carcinoma cell lines were assayed for total opioid and beta-endorphin-like immunoreactivity. Small cell carcinoma cell line NCI-H146 contained approximately 1.1 pmol/mg protein of total opioid immunoreactivity. This material was similar in size and immunoreactive determinants to C-terminally modified beta-endorphin. Small cell carcinoma cell line NCI-H187 contained approximately 0.2 pmol/mg protein total opioid immunoreactivity, which was of low molecular weight. NCI-H187 also contained approximately 1.2 pmol/mg protein of material similar in size and immunoreactive determinants to beta-lipotropin. The two small cell carcinoma cell lines were also examined for opioid receptors with the use of [3H]-etorphine as ligand. Both cell lines contained between 50 and 100 fmol/mg protein of specific, saturable, high-affinity opioid receptor binding sites. Together, these findings suggest a possible autocrine role for opioids in small cell carcinoma of the lung.

Carcinoma, Small Cell↗
PubMed1986

Affinity Purifications of Aldose Reductase and Xylitol Dehydrogenase from the Xylose-Fermenting Yeast Pachysolen tannophilus.

Although xylose is a major product of hydrolysis of lignocellulosic materials, few yeasts are able to convert it to ethanol. In Pachysolen tannophilus, one of the few xylose-fermenting yeasts found, aldose reductase and xylitol dehydrogenase were found to be key enzymes in the metabolic pathway for xylose fermentation. This paper presents a method for the rapid and simultaneous purification of both aldose reductase and xylitol dehydrogenase from P. tannophilus. Preliminary studies indicate that this method may be easily adapted to purify similar enzymes from other xylose-fermenting yeasts.

Journal Article↗
PubMed1986

Acromegaly and pheochromocytoma: a multiple endocrine syndrome caused by a plurihormonal adrenal medullary tumor.

A 42-yr-old man with congestive heart failure and diabetes mellitus was found to have acromegaly and a pheochromocytoma. Serum GH-releasing hormone (GHRH) levels were elevated (2.34 ng/dl; normal, less than 0.02 ng/dl), suggesting that the acromegaly was caused by ectopic secretion of GHRH. Postmortem examination revealed that the right adrenal gland contained a pheochromocytoma in which GHRH was demonstrated by immunohistochemical studies. Gel permeation chromatography combined with the use of two GHRH antisera showed that GHRH-(1-44)-NH2 was a predominant form of the hormone. When the RNA from the tumor was extracted and analyzed by Northern gel blotting, two mRNA species were identified, with transcripts corresponding to 1600 and 780 base pairs. The pituitary gland was enlarged, but no distinct adenoma was found. Diffuse and nodular hyperplasia of somatotrophs in some areas resembling adenoma was identified on histological examination. These findings indicate that GH excess accompanied by somatotroph hyperplasia and acromegaly were secondary to a pheochromocytoma which secreted not only catecholamines but also GHRH.

Acromegaly↗
PubMed1985

Isolation and characterization of substance P, substance P 5-11, and substance K from two metastatic ileal carcinoids.

Using an antiserum directed at the COOH-terminus of tachykinins, we have examined postmortem tissue from two cases of metastatic ileal carcinoid for the presence of tachykinin-like immunoreactivity. The vast majority of the immunoreactive tachykinin-like material eluted from a Sephadex G-50 column as two peaks at positions corresponding to molecular weights of 1300 and 850. The 1300 dalton peak was resolved by reverse-phase-HPLC into two components which by Edman sequencing, amino acid analysis, and fast atom bombardment (FAB)-mass spectrometry criteria, were identified as substance P and substance K. The 850 dalton peak was also resolved on RP-HPLC into two peaks which were resistant to Edman degradation but from amino acid analysis and FAB-mass spectrometry criteria were identified as pyro-Glu-substance P 5-11 and oxidized pyro-Glu-substance P 5-11. In control experiments substance P 5-11 was converted to pyro-Glu-substance P 5-11 during the extraction procedure. Both tumors also contained a minor immunoreactive peak which eluted from a Sephadex G-50 sizing column at a position corresponding to a molecular weight of 4000 which probably represents neuropeptide K. These results suggest that beta-preprotachykinin is preferentially expressed in carcinoid tumors and that substance K may also play a role in the carcinoid syndrome.

Amino Acid Sequence↗
PubMed1985

Epinephrine accumulation in rat brain after chronic administration of pargyline and LY 51641--comparison with other brain amines.

Concentrations of biogenic amines and metabolites were measured in regions of rat brain following administration of monoamine oxidase (MAO) inhibitors for 21 days. Epinephrine concentrations were increased from 350 to 500% following chronic administration of LY 51641, a selective inhibitor of MAO type A. Norepinephrine, dopamine and serotonin showed much less relative accumulation. The marked relative accumulation of epinephrine may be related to the efficacy of inhibitors of MAO type A in the treatment of depression.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Gastrin-releasing peptide immunoreactivity in intestinal carcinoids.

Human neuroendocrine tumors are known to demonstrate immunoreactivity to the amphibian peptide bombesin. The recent observation that gastrin-releasing peptide (GRP), a 27 amino acid peptide first isolated from porcine intestine, may be the mammalian analog of bombesin led us to look for this peptide in intestinal carcinoid tumors. Formalin-fixed tissues from 20 of these tumors were examined by the immunoperoxidase technic, using specific antisera to the GRP molecule (1-27) and the GRP fragment (1-16). Intense diffuse cytoplasmic immunoreactivity was observed in carcinoids from the small intestine (7/10), appendix (4/5), and colon (1/5). In each positive case, the pattern of staining for GRP (1-16) and GRP (1-27) was identical. These findings indicate that bombesin-like immunoreactivity in human intestinal carcinoid tumors is attributable to GRP-like molecules and that GRP is a useful marker for neuroendocrine differentiation.

Adult↗
PubMed1984

Gastrin-releasing peptide, a mammalian analog of bombesin, is present in human neuroendocrine lung tumors.

Several reports have indicated that the amphibian peptide bombesin is present in oat-cell carcinoma of the human lung. The recent observation that gastrin-releasing peptide (GRP), a 27-amino acid peptide isolated from porcine intestine, may be the mammalian analog of bombesin led the authors to look for this peptide in human pulmonary tumors. Examination of 36 human lung tumors (8 carcinoids, 8 oat-cell carcinomas, and 20 non-oat-cell carcinomas) by immunohistochemistry and radioimmunoassay demonstrated the presence of high, although variable, levels of GRP in neuroendocrine tumors, and not in other histologic types. These findings indicate that bombesin immunoreactivity in human lung tumors should be attributed to GRP or GRP-like molecules and that GRP may be a useful marker of neuroendocrine differentiation.

Animals↗
PubMed1983

Identification of gastrin releasing peptide-related substances in guinea pig and rat brain.

Rat and guinea pig brain extracts were examined for the occurrence of gastrin-releasing peptide (GRP)-like substances by sequence specific radioimmunoassays interfaced with gel filtration and reversed phase high performance liquid chromatography (RP-HPLC). Tryptic digestion of the immunoreactive peptides followed by RP-HPLC was used to further characterize GRP-related peptides in brain. Using these analytical techniques it was found that guinea pig brain extracts contained a peptide with characteristics identical to authentic GRP (27 amino acid residues long). A carboxyterminal fragment with the characteristics of GRP(18-27) as well as a respective aminoterminal fragment with the characteristics of GRP(1-16) were also present in guinea pig brain extracts. The GRP(18-27) seems to correspond to the bombes in related material that has been described previously in mammalian brain extracts. Rat brain extracts also contained a peptide with the characteristics of GRP(18-27). The corresponding aminoterminal fragment, however, behaved differently on RP-HPLC from authentic GRP(1-16) and it was not recognized by antibodies directed to the aminoterminal tridecapeptide fragment of authentic GRP. Similarly the GRP-like peptide from rat brain did not comigrate on RP-HPLC with authentic GRP and was unreactive to antibodies directed toward the aminoterminus of GRP.

Animals↗
PubMed1983

Immunoreactive dynorphin-(1-8) and corticotropin- releasing factor in subpopulation of hypothalamic neurons.

Immunoreactive corticotropin-releasing factor (CRF) and dynorphin-(I-8) were visualized in rat hypothalamus by immunohistofluorescence with specific antibodies. In brains from colchicine-treated, adrenalectomized rats, neuronal perikarya with immunoreactive CRF were observed in the paraventricular nucleus of the hypothalamus. The CRF occurred together with the dynorphin-(1-8). However, the CRF immunoreactivity occurred only in a subpopulation of the dynorphin-(1-8) immunoreactive cells. These findings suggest that there may be a functional interrelationship of CRF with dynorphin-related opioid peptides and provide further evidence that neurons may contain more than one bioactive substance.

Animals↗
PubMed1983

Gastrin-releasing peptide-related peptides in a human malignant lung carcinoid tumor.

Recent immunohistochemical findings have indicated the presence of gastrin-releasing peptide in normal and pathological human lungs. Gastrin-releasing peptide is a 27-amino acid peptide isolated from porcine gut which bears considerable carboxyterminal homology with bombesin. We have characterized the gastrin-releasing peptide-like peptides present in a human malignant lung carcinoid tumor by gel chromatography and reverse-phase high-performance liquid chromatography. Our results show that this tumor did not contain bombesin; however, this tumor expressed a gastrin-releasing peptide-like compound, several amino-terminal fragments, and a carboxy-terminal fragment of gastrin-releasing peptide.

Amino Acid Sequence↗
PubMed1982

Epinephrine, norepinephrine, dopamine and serotonin: differential effects of acute and chronic stress on regional brain amines.

Following acute cold swim stress, hypothalamic epinephrine concentrations were markedly lowered and remained decreased for 24 h, while norepinephrine concentrations were decreased, but returned to baseline within 14 h. With oscillation stress repeated daily for 21 days, hypothalamic norepinephrine, hypothalamic epinephrine, and hippocampal norepinephrine turnover were decreased and absolute concentrations were increased. Repeated stress had little effect on serotonin, dopamine or their metabolites. These results suggest that hypothalamic epinephrine concentration and turnover are particularly responsive to acute and chronic stress. The decreased epinephrine and norepinephrine turnover under chronic stress may be responsible in part for the behavioral and endocrine changes observed in chronically stressed rats.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Immunohistochemical distribution of alpha-neo-endorphin/dynorphin neuronal systems in rat brain: evidence for colocalization.

alpha-Neo-endorphin and dynorphin immunoreactivities in rat brain were visualized by double antibody immunofluorescence of frozen sections. Antibodies were used that were specific for their respective antigens. The pattern of neuronal immunostaining produced by alpha-neo-endorphin and dynorphin antisera in adjacent serial sections was completely superimposible. No areas were found in which alpha-neo-endorphin or dynorphin immunoreactivities existed alone. The following brain regions contained alpha-neo-endorphin/dynorphin-immunoreactive fibers and terminals: the median forebrain bundle, the internal capsule, the substantia nigra, the hypothalamus, the nucleus accumbens, the hippocampus, and the medulla oblongata. A few fibers were seen in the cerebral cortex and in the corpus striatum. In many regions, this neuronal fiber system seems to overlap the neuronal system previously described to contain [Met]-/[Leu]enkephalin-immunoreactive material. In brains from colchicine-treated animals, numerous alpha-neo-endorphin/dynorphin-immunoreactive neuronal cell bodies were seen in the supraoptic, retrochiasmatic supraoptic, paraventricular, and magnocellular accessory nuclei of the hypothalamus. It is concluded that alpha-neo-endorphin-like and dynorphin-like immunoreactivities are part of the same neuronal system.

Animals↗
PubMed1982

Nicotinic-catecholaminergic interactions in rat brain: evidence for cholinergic nicotinic and muscarinic interactions with hypothalamic epinephrine.

The i.p. injection of nicotine produced several changes in regional catecholamine concentrations in rat brain. These changes were blocked by the centrally active nicotinic antagonist mecamylamine, but not by the quaternary nicotinic antagonist hexamethonium. An examination of the effects of various cholinergic agents on hypothalamic epinephrine concentrations revealed several interesting findings. Central muscarinic antagonism or peripheral muscarinic agonism decreased hypothalamic epinephrine concentrations. The anticholinesterase physostigmine decreased hypothalamic epinephrine concentrations and this effect was blocked by the centrally acting nicotinic antagonist mecamylamine, but not by hexamethonium, scopolamine or methscopolamine. These findings indicate an interaction of cholinergic receptors, both nicotinic and muscarinic, with hypothalamic epinephrine.

Animals↗