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Biomedical subjects

J Park

Publications and source records attributed to J Park.

At least 397 records · Page 22Linked to original sources
PubMed1990

Fetal genitourinary tract anomalies: evaluation, operative correction, and follow-up.

The prenatal diagnosis of a genitourinary anomaly was made in 53 fetuses. Sonographic findings, antenatal course, and postnatal treatment and outcomes were examined. No interventional therapy was undertaken in utero, and the natural history could be examined in the 44 of 53 (83%) who did not electively terminate their pregnancies. Twenty-three of the total 53 (43%) had unilateral disease and 30 (57%) had bilateral involvement. Thirty-five of 53 (66%) survived, with 22 undergoing operative therapy postnatally. In all but one of the 35 survivors, the anomaly was isolated to the genitourinary tract, and the majority of surviving fetuses had unilateral disease. Oligohydramnios was present in only three of 35 survivors, and none had severe oligohydramnios. Nine of 53 women underwent termination of pregnancy and nine others experienced a neonatal death. All 18 of their fetuses had bilateral disease, with oligohydramnios present in 14 (78%). All five fetuses with chromosomal abnormalities were found in this group of 18. The majority of fetuses with a genitourinary anomaly will do well postnatally. Pulmonary hypoplasia, extrarenal anomalies, and chromosomal defects are frequent findings in the minority with poor outcomes. A multidisciplinary approach to management of the pregnancy with a fetal genitourinary tract anomaly is essential to optimize outcome.

Abortion, Eugenic↗
PubMed1989

A role for protein kinase C in the membrane fusion necessary for platelet granule secretion.

The addition of 1-oleoyl-2-acetylglycerol (OAG), or phorbol-12-myristate-13-acetate (PMA) to platelets induced the phosphorylation of a 47,000 dalton protein (47 Kd), fusion of granule membranes with membranes of the surface connected canalicular system, the formation of large vesicles and the secretion of serotonin. 1-(5-isoquinolinesulfonyl)-2-methyl-piperazine (H7), and sphingosine, inhibitors of protein kinase C, significantly inhibited the ultrastructural changes and the phosphorylation of 47 Kd. N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA1004), structurally similar to H7, but a weaker inhibitor of protein kinase C, did not attenuate these responses to OAG or to PMA. H7, but not HA1004, also markedly inhibited secretion induced by the synergistic combination of OAG and the calcium ionophore A23187. Amiloride and 5-(N,N dimethyl)-amiloride, inhibitors of the Na+/H+ transporter, did not inhibit the ultrastructural response and the protein phosphorylation induced by OAG, or the secretion induced by the combination of A23187 and OAG. The results link the activation of protein kinase C by diglycerides to the labilization and fusion of granule membranes important for secretion.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1989

Metabolism and pharmacokinetic studies of propionylpromazine in horses.

The propionylpromazine concentrations in plasma after intramuscular administration to horses were determined using gas chromatography with nitrogen-phosphorus detection. After hydrolysis by beta-glucuronidase/arylsulphatase, the parent drug and three metabolites were detected in urine. The metabolites were identified as 2-(1-hydroxypropyl)promazine, 2-(1-propenyl)promazine and 7-hydroxypropionylpromazine by gas chromatography-mass spectrometry. No N-demethylated or sulphoxidated metabolites of propionylpromazine were observed in the horse urine.

Animals↗
PubMed1989

Studies on protein methyltransferase in human cerebrospinal fluid.

Protein methyltransferases, rich in most mammalian brains, were studied in human cerebrospinal fluid (CSF). Among several well-characterized groups of methyltransferases, protein methylase I (S-adenosylmethionine:protein-arginine N-methyltransferase, EC 2.1.1.23) was found in significant amounts in human CSF samples. Both myelin basic protein (MBP) -specific and histone-specific protein methylase I activities were observed, the latter being generally higher in most CSF. S-Adenosyl-L-homocysteine, a potent product inhibitor for the methyltransferase, inhibited approximately 90% of MBP-specific protein methylase I activity at a concentration of 1 mM. The optimum pH of the MBP-specific protein methylase I was found to be around 7.2. Identity of exogenously added MBP as the methylated substrate for CSF enzyme was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. An amino acid analysis of the [methyl-3H]protein hydrolysate showed two major radioactive peaks cochromatographing with monomethyl- and dimethyl (symmetric)-arginine. Human CSF contained relatively high endogenous protein methylase I activity (activity measured without added substrate protein): The endogenous substrate can be immunoprecipitated by antibody raised against calf brain MBP. Finally, CSF from several neurological patients were analyzed for protein methylase I, and the results are presented.

Humans↗
PubMed1989

Carbonic anhydrase II gene expression in isolated canine gastric parietal cells.

The participation of carbonic anhydrase (CA II) in the gastric acid secretory process has been the subject of considerable controversy. We utilized a cDNA probe for CA II to measure CA II gene expression in canine gastric parietal cells that had been stimulated with the three principal acid secretagogues, carbachol, gastrin, and histamine. Hybridization to dot blots of total parietal cell RNA showed a significant increase in specific CA II mRNA content within minutes of secretagogue addition: carbachol stimulation led to an increase of 52 +/- 8.9%, reaching a maximum within 20 min; gastrin stimulation led to an increase within 60 min of 104 +/- 10.6%; stimulation with histamine was followed within 20 min by an increase of 30 +/- 7.2%. We also measured transcription rates for the CA II gene in cells stimulated by each agent and found an increase within 15 min. Our results show that CA II gene expression is regulated by agents that stimulate the parietal cell to secrete acid and that the accumulation of CA II mRNA subsequent to the initial interaction of stimulant appears to result from new transcription of the CA II gene. These data suggest the participation of CA II in the acid secretory response of the parietal cell to secretagogues.

Animals↗
PubMed1989

Somatostatin receptors on canine fundic D-cells: evidence for autocrine regulation of gastric somatostatin.

Somatostatin is known to have inhibitory effects on the release and action of a wide variety of gut peptides. Previous studies in vivo have suggested a potential inhibitory role for somatostatin even on its own secretion. To determine whether this autoregulatory effect is the result of a direct action of the peptide on the cell that is responsible for its secretion, we examined the effect of a non-immunoreactive but biologically active analogue of somatostatin ([Leu8-D-Trp22-Tyr25]S28) on release of somatostatin-like immunoreactivity (SLI) from isolated canine fundic D-cells. We identified somatostatin binding sites with dissociation constants of 1.2 X 10(-9) and 3.8 X 10(-8) M that coenriched with D-cells. Somatostatin 14, somatostatin 28, and [Leu8-D-Trp22-Tyr25]S28 were equivalent in displacing 125I-[Leu8-D-Trp22-Tyr25]S28 from the binding sites. [Leu8-D-Trp22-Tyr25]S28 inhibited SLI release from D-cells stimulated with (DBcAMP), and pentagastrin. Pertussis toxin pretreatment prevented the inhibitory effects of [Leu8-D-Trp22-Tyr25]S28 on both SLI secretion and cAMP accumulation by on both SLI secretion and cAMP accumulation by D-cells stimulated with epinephrine and forskolin. In contrast, [Leu8-D-Trp22-Tyr25]S28 inhibition of SLI release induced by DBcAMP and pentagastrin was not altered by pertussis toxin. Our data suggest that somatostatin autoregulates its own secretion via specific receptors on D-cells. This inhibitory effect is mediated by mechanisms that are both dependent on and independent of pertussis toxin-sensitive inhibitory guanine nucleotide binding proteins.

Amino Acid Sequence↗
PubMed1988

Carbamoylcholine and gastrin induce inositol lipid turnover in canine gastric parietal cells.

The potential role of inositol phospholipid turnover in mediating acid secretion was examined in a preparation enriched for isolated canine gastric parietal cells. The stimulatory effects of carbamoylcholine (carbachol) and gastrin on parietal cell uptake of [14C]aminopyrine were linked to dose- and time-dependent selective reduction in cellular phosphatidylinositol content, although the specific fatty acid composition of the phosphoinositides was not altered. Analysis of [3H]inositol phosphates accumulated in cells prelabeled with [3H]inositol revealed an increase in labeled inositol trisphosphate by 5 min of incubation with either carbachol or gastrin. Furthermore, after preincubation of parietal cells in medium containing [32P]orthophosphate, the two secretagogues elicited a time-dependent decrease in 32P labeling of phosphatidylinositol 4,5-bisphosphate and concomitant increase in labeling of phosphatidic acid. These data demonstrate that the acid secretagogue actions of carbachol and gastrin are correlated with turnover of cellular inositol phospholipids in a preparation consisting predominantly of parietal cells.

Aminopyrine↗
PubMed1988

Biosynthesis of somatostatin in canine fundic D cells.

The observation that virtually all of the somatostatin-like immunoreactivity in the stomach consists of somatostatin-14 (S14), to the exclusion of somatostatin-28 (S28), suggests a unique pattern of prosomatostatin posttranslational processing. In order to examine the mechanisms by which S14 is produced from its precursor in the stomach, we investigated the biosynthesis of somatostatin in isolated canine fundic D cells. D cells pulse-labeled with [35S]cysteine revealed a cycloheximide inhibitable time-dependent incorporation of radioactivity into S14. A small fraction of radioactivity was incorporated into S28 but not into larger precursors. However, when the cells were incubated with monensin (1 microM), incorporation of radioactivity into a presumed somatostatin precursor was noted. Upon transfer of [35S]cysteine prelabeled cells to radioactivity-free medium, no conversion of S28 to S14 could be detected and the decrease of labeled S14 in cells correlated with a complimentary increase in the culture medium. Exogenous somatostatin inhibited somatostatin biosynthesis in a fashion that could be blocked by pertussis toxin pretreatment. Stimulation of prelabeled D cells with tetradecanoyl phorbol 13-acetate (10(-7) M) or forskolin (10(-4) M) for 2 h resulted in release of 41 and 33% of the newly synthesized radioactive S14, respectively, while only 9 and 6% of the total cell content of radioimmunoassayable somatostatin was secreted. These data suggest that: (a) somatostatin is synthesized in fundic D cells primarily as S14, (b) S14 is produced by rapid processing of a larger precursor but there is little, if any, conversion of S28 to S14, (c) somatostatin biosynthesis is autoregulated, and (d) newly synthesized S14 is preferentially released from D cells in response to stimulation.

Animals↗
PubMed1988

Chromogranin A biosynthetic cell populations in bovine endocrine and neuronal tissues: detection by in situ hybridization histochemistry.

Chromogranin A is a highly acidic protein that is found in the secretory granules of many endocrine and neuronal cells. To localize bovine cell populations involved in chromogranin A biosynthesis, the distribution of the mRNA encoding this protein was determined with in situ hybridization histochemistry. In the adrenal gland, the mRNA was found in the chromaffin cells of the medulla but was absent from the cortex. The distribution of the mRNA in the medulla was uneven; cells located at the periphery were more heavily labeled than those in the center of the gland. Because the adrenal medulla is composed of several cell types, the chromogranin A-containing cells were further characterized for the presence of neuropeptide and adrenergic markers. Adjacent sections were examined for the mRNAs encoding enkephalin and phenylethanolamine N-methyltransferase (PNMT), the enzyme that catalyzes the formation of epinephrine from norepinephrine. Both mRNAs were present in a narrow band of cells at the periphery of the medulla. However, in contrast to the distribution of chromogranin A mRNA, the enkephalin and PNMT mRNAs were detected in only a small number of cells in the inner medullary region. The difference in the distribution of the enkephalin and PNMT mRNAs from that of chromogranin A suggests that the expression of these genes is differentially regulated. In addition to the adrenal gland, chromogranin A mRNA is expressed by many other tissues. In the parathyroid gland, which is rich in the mRNA but exhibits little chromogranin A-like immunoreactivity, the message was present in most cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1988

Immunostimulating agents against influenza virus infection in senescent rats.

This study investigated the nonspecific immunomodulatory effects of Bacillus Calmette-Guerin (BCG), muramyl dipeptide (MDP) and ascorbic acid (vitamin C) on virus infection of the respiratory tract in Fischer-344 rats. Groups of young adult (12-16 months old) and aged (24-30 months old) rats were given BCG or MDP intranasally or vitamin C orally 6 weeks and again 3 days before an intranasal challenge with influenza virus A/Bangkok/H3N2 (10(6) 50% EID). Titers of hemagglutinin in lung homogenates and the presence of leukocytes in the respiratory tracts served as indices of infection. Lung macrophage functions of animals were determined by measuring random migration and phagocytic yeast cell killing in vitro. Clearance of Staphylococcus aureus from the respiratory tracts of the animals was also measured 4 hours after challenge. - Following BCG treatment, significantly fewer animals developed virus infection. MDP and vitamin C treatments also reduced the numbers of infected rats but did not differ significantly from the untreated control groups. BCG and MDP treatments significantly reduced the numbers of lung leukocytes in virus infected animals. Mean virus titers in the lung homogenates were significantly lower in all treatment groups by the third day of infection. Following all treatments, duration of virus infection was significantly shorter in the aged compared to the young adult groups. Lung macrophage functions increased in all treatment groups. The improvement of aged groups over their controls was greater than that of the young adults compared to their controls. BCG had the greatest protective effects in both the young adult and aged animals; MDP and vitamin C, in that order, were less effective.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1987

Mechanisms for direct inhibition of canine gastric parietal cells by somatostatin.

To examine the potential mechanisms by which somatostatin inhibits gastric acid secretion we studied its effects on isolated canine gastric parietal cells. Using 125I-[Leu8-D-Trp22-Tyr25]somatostatin-28 as ligand, we identified somatostatin-binding sites in parietal cell-enriched fractions of fundic mucosa. Two binding sites with respective dissociation constants of 3.2 X 10(-9) and 2.1 X 10(-7) M were identified. Somatostatin-14 and -28 were equally potent both in displacing bound ligand and in inhibiting parietal cell activity as measured by [14C]aminopyrine uptake. Pertussis toxin reversed the ability of somatostatin to inhibit the uptake of [14C]aminopyrine and production of cAMP by parietal cells stimulated with histamine and forskolin but not with dibutyryl cAMP or pentagastrin. Furthermore, somatostatin had no effect on parietal cell membrane inositol phospholipid turnover or changes in protein kinase C (Ca2+/phospholipid-dependent enzyme) activity induced by carbachol or pentagastrin. These data indicate that somatostatin directly inhibits parietal cell activity via mechanisms both dependent on and independent of the pertussis toxin-sensitive inhibitory guanine nucleotide-binding protein.

Aminopyrine↗
PubMed1987

Peripheral acid inhibitory action of corticotropin releasing factor: mediation by nongastric mechanisms.

Corticotropin releasing factor (CRF) inhibits gastric acid secretion via both central neural and peripheral mechanisms. We examined whether local gastric factors may mediate the peripheral action of CRF. In pylorus-ligated anesthetized rats, CRF infusion (15 nmol/kg X h) produced roughly 60% inhibition of pentagastrin (16 micrograms/kg X h)-stimulated acid secretion. Similarly, in the gastric fistula dog, CRF (1 nmol/kg X h) inhibited pentagastrin-induced acid secretion by 74%. This action of CRF did not result from direct inhibition of gastric parietal cells, as concentrations of the peptide ranging from 10(-11) to 10(-6) M had no effect on the activity of isolated parietal cells in the unstimulated state or after stimulation with pentagastrin (10(-8) M), histamine (10(-5) M), or carbachol (10(-5) M), against a background of isobutylmethylxanthine (10(-4) M). To determine whether local hormones may mediate CRF-induced acid inhibition, we examined the peptide's effect on the release of somatostatin and gastrin from cultured canine gastric D and G cells and from isolated perfused rat stomachs. Corticotropin releasing factor in doses ranging from 10(-11) to 10(-6) M had no influence on release of either gastric peptide under basal conditions or after stimulation of gastrin with carbachol (10(-6) M) and somatostatin with isoproterenol (10(-8) M). These data suggest that the peripheral acid inhibitory action of CFR is mediated by nongastric mechanisms.

Animals↗
PubMed1987

Gastrin receptor characterization: affinity cross-linking of the gastrin receptor on canine gastric parietal cells.

We applied affinity cross-linking methods to label the gastrin receptor on isolated canine gastric parietal cells in order to elucidate the nature of its chemical structure. 125I-labeled Leu15-gastrin and 125I-labeled gastrin2(-17) bound to intact parietal cells and their membranes with equal affinity, and half-maximal inhibition of binding was obtained at an incubation concentration of 3.2 X 10(-10) M unlabeled gastrin. 125I-gastrin2(-17) was cross-linked to plasma membranes or intact parietal cells by incubation in disuccinimidyl suberate. The membrane pellets were solubilized with or without dithiothreitol and applied to electrophoresis on 7.5% sodium dodecyl sulfate polyacrylamide gels. Autoradiograms revealed a band of labeling at Mr 76,000 and labeling of this band was inhibited in a dose-dependent fashion by addition of unlabeled gastrin to the incubation mixture. Dithiothreitol in concentrations as high as 100 mM did not alter the electrophoretic mobility of the labeled band. After taking into account the molecular weight of 125I-gastrin2(-17), our results suggest that the gastrin receptor on parietal cells is a single protein of Mr 74,000 without disulfide-linked subunits.

Animals↗
PubMed1987

Biological activity of progastrin posttranslational processing intermediates.

We recently identified carboxyl-terminally extended progastrin posttranslational processing intermediates in G cells of the gastric antrum and demonstrated that they are cosecreted with gastrin. To determine the physiological significance of these intermediates, we examined the biological activity of two synthetic gastrin precursor analogues that correspond to hexagastrin with carboxyl-terminal extensions, Tyr-Gly-Trp-Met-Asp-Phe-Gly (GL-7) and Tyr-Gly-Trp-Met-Asp-Phe-Gly-Arg-Arg (GL-9) on gastric parietal and D cells isolated from canine fundic mucosa. Both analogues were as efficacious as gastrin heptadecapeptide in displacing 125I-[Leu15]gastrin from binding sites on the two cell types and in stimulating [14C]aminopyrine uptake by parietal cells and somatostatin release from D cells. However, both analogues were 10(4)- to 10(5)-fold less potent than gastrin heptadecapeptide in these activities. Our results indicate that progastrin processing intermediates do not have physiologically relevant actions under normal circumstances and support the notion that carboxyl-terminally amidated peptides such as gastrin require the amide moiety for biological activity.

Aminopyrine↗