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Biomedical subjects

J Park

Publications and source records attributed to J Park.

At least 415 records · Page 23Linked to original sources
PubMed1987

Potential mediation of somatostatin secretion from canine fundic D-cells by protein kinase c.

We examined the possible importance of protein kinase c-dependent mechanisms in mediating the stimulatory effects of gastrin and cholecystokinin (CCK) on the release of somatostatin-like immunoreactivity (SLI) from isolated canine fundic D-cells. Diacylglycerides, presumably the products of phosphoinositide breakdown that activate protein kinase c, and phospholipase C, which catalyzes the production of endogenous diacylglycerides from membrane phospholipids, both stimulated SLI secretion in a dose-dependent fashion. Both classes of agents potentiated the actions of adenosine 3',5'-cyclic monophosphate-dependent agonists but not those of gastrin and CCK. The stimulatory effects of gastrin and CCK correlated with their abilities to enhance the incorporation of 32P into membrane phosphatidyl inositol and phosphatidic acid and promote the release of [3H]inositol trisphosphate from prelabeled D-cells, two parameters of phosphoinositide turnover. These data suggest that protein kinase c may serve to transduce the signals activated by gastrin and CCK in D-cells.

Animals↗
PubMed1987

Glycine-extended progastrin processing intermediates: accumulation and cosecretion with gastrin.

Glycine-extended intermediates of peptide processing serve as substrates for carboxyl-terminal amidation, hence activation, of many brain-gut peptides. To explore the dynamics of accumulation and secretion of these important intermediates we utilized primary cultures of canine antral mucosal G-cells as a model system. Glycine-extended progastrin processing intermediates (G-Gly) accumulated rapidly in G-cells cultured in ascorbate-deficient media, exhibiting a fourfold increase over a 51-h culture period, while gastrin content fell to less than half of the initial level. In contrast, G-cells cultured in ascorbate-supplemented media accumulated G-Gly at a relatively low rate, while gastrin was preserved at a higher level. Under either condition, G-Gly and gastrin were progressively released into the culture media. The release of both immunoreactivities could be stimulated by bombesin and inhibited by somatostatin in similar fashion. By electron microscopy, the cultured G-cells exhibited no ultrastructural alterations. These data suggest that 1) the cellular homeostasis of G-Gly is regulated by the activity of an ascorbate-dependent amidation enzyme similar to one previously described in pituitary tissues, 2) carboxyl-terminal amidation is not an obligatory step for secretion of gastrin, and 3) the proportions of gastrin and G-Gly cosecreted from G-cells reflect their proportional accumulation within G-cell secretory granules. The physiological relevance of the released G-Gly has yet to be determined.

Animals↗
PubMed1987

Stimulation of gastrin release by bombesin and canine gastrin-releasing peptides. Studies with isolated canine G cells in primary culture.

Bombesin, a polypeptide derived from frog skin, has been shown to stimulate gastrin release from the gastric antrum in vivo and in vitro. To elucidate the mechanisms of this effect, we developed a method to culture isolated and enriched G cells from canine stomach. After digestion of antral mucosa with collagenase and EDTA, dispersed cells were fractionated by counterflow elutriation then cultured on a collagen support. Bombesin and three molecular forms of canine gastrin-releasing peptides all stimulated gastrin release from G cells in a dose-dependent manner. The effect of bombesin was suppressed by somatostatin and potentiated by dibutyryl cyclic AMP (10(-3) M) but not by carbachol (10(-6) M). Extracellular calcium depletion attenuated the stimulation of gastrin release by bombesin but not by forskolin. These findings suggest that the bombesin family peptides directly activate G cells through calcium-dependent mechanisms to cause gastrin release.

Animals↗
PubMed1986

Acute pancreatitis in elderly patients. Pathogenesis and outcome.

Forty patients over 70 years of age with acute pancreatitis were studied. The most common cause of pancreatitis was biliary tract disease (14 patients, 35 percent). Twelve patients (30 percent) were discharged with a diagnosis of idiopathic pancreatitis, but tests such as endoscopic retrograde cholangiopancreatography that might have established the cause of disease were frequently not employed. Eight of the 40 patients died, for a mortality rate of 20 percent. Significant morbidity occurred in an additional seven (17.5 percent). Multisystem failure was the cause of death in all eight patients, and only two patients with multisystem failure survived. The mortality rate was significantly higher in those patients with postoperative pancreatitis. Acute pancreatitis in the elderly carries a grave prognosis. All patients should undergo thorough evaluation, as biliary tract disease is the most common cause. Cholecystectomy should be performed in those with biliary disease to prevent recurrent attacks.

Acute Disease↗
PubMed1986

Comparative antigenic studies of species of Basidiobolus and other medically important fungi.

An immunodiffusion technique was used to evaluate the antigenic relationship of various pathogenic and saprobic Basidiobolus spp., Conidiobolus spp., isolates of the order Mucorales, and several other medically important nonzygomycetous fungi. The antiserum to Basidiobolus haptosporus shared two lines of identity, designated inner (N) and outer (Y), when tested against exoantigens of known strains of B. haptosporus and Basidiobolus ranarum as well as exoantigens of a human Nigerian isolate and several wild isolates tentatively identified in B. ranarum. Both bands were heat stable at 56 degrees C for 30 min. Exoantigens of strains of Basidiobolus meristosporus, Basidiobolus microsporus, Conidiobolus incongruus, Conidiobolus coronatus, and other wild isolates of Basidiobolus spp. tested formed only the N immunoprecipitin band. Exoantigens of 10 isolates from other taxa did not produce any cross-reactive precipitin line. B. meristosporus antiserum that was tested against exoantigens of Basidiobolus spp. and of Conidiobolus spp. developed only an N band without a Y band. These data suggest that B. haptosporus and B. ranarum are antigenically similar to each other and distinct from B. meristosporus. Basidiobolus spp. and Conidiobolus spp. share a common N immunoprecipitin band, which implies a taxonomic relationship between these two genera. The absence of lines of identity between Basidiobolus spp. and other fungi tested suggests that, antigenically, Basidiobolus is a distinct genus.

Antibodies, Fungal↗
PubMed1986

Phorbol esters stimulate somatostatin release from cultured cells.

Recent studies suggest that 12-O-tetradecanoylphorbol 13-acetate (TPA), one of a family of phorbol esters that are known tumor promoters, can activate intracellular Ca2+, phospholipid-dependent protein kinase (protein kinase C) directly. To examine the possible involvement of protein kinase C-mediated mechanisms in regulating gastric somatostatin release, we studied the effects of TPA on isolated enriched canine gastric somatostatin cells in short-term culture. TPA markedly stimulated somatostatin release such that nearly 10% of total cellular content of somatostatin was released into media within 2 h of incubation. Among the phorbol compounds tested, TPA was the most potent, with half-maximum effective dose (ED50) obtained at a dose of 5 X 10(-9) M. Phorbol 12,13-dibutyrate (PDBu) also stimulated somatostatin release but with only 5% of the potency of TPA, whereas phorbol compounds with no biological activity in other systems failed to stimulate somatostatin release. In the absence of extracellular Ca2+, the effects of TPA were significantly attenuated. In contrast, stimulation of somatostatin release by forskolin (10(-4) M) was not affected by Ca2+ deprivation but was potentiated by TPA. No such potentiation was observed when TPA was combined with the Ca2+ ionophore A23187. Carbamylcholine (10(-5) M), which inhibits the stimulatory actions of beta-adrenergic agonists or dibutyryl cyclic adenosine monophosphate on somatostatin cells, also inhibited TPA-induced somatostatin release. These data suggest the presence of dual stimulatory mechanisms for gut somatostatin release, both of which are susceptible to inhibition by muscarinic agonists.

Animals↗
PubMed1985

Hemodynamic actions of bepridil during treatment of stable angina pectoris.

Bepridil, a new calcium-entry blocker, was evaluated in 13 patients with chronic stable angina in a single-blind trial that was placebo controlled within patients. Its antianginal effects were recorded and left ventricular (LV) function was assessed at rest and during exercise by gated blood pool scintigraphy. Mean anginal frequency was significantly reduced from 7.3 to 3.4 episodes/week (p less than 0.01). Total work performed increased from 336 to 625 kpm (p less than 0.01). Supine resting LV end-diastolic volume index, end-systolic volume index, stroke volume index, cardiac index and ejection fraction (EF) were not altered by bepridil. During supine exercise, the EF decreased from 60 to 55 during placebo therapy. Despite an increase in total work, the mean EF increased from 60 to 62 (p less than 0.05 versus exercise on placebo) during exercise with bepridil therapy. Maximal exercise stroke volume index and cardiac index were significantly greater during bepridil therapy. Exercise resulted in new or increased LV wall motion abnormalities in 7 of 13 patients during placebo therapy. During bepridil therapy, only 4 new or increased wall motion abnormalities were noted despite the increase in total work performed. Therefore, bepridil is an effective antianginal agent, allowing an increase in exercise workload while preserving LV performance.

Adult↗
PubMed1985

Cholecystokinin potently releases somatostatin from canine fundic mucosal cells in short-term culture.

Previous studies indicated that gastrin-17 (G-17) and the octapeptide of colecystokinin (CCK-8) were equally potent in their interaction with receptors for 125I-[Leu15]G-17 on isolated canine parietal cells. These findings were inconsistent with the poor efficacy of CCK-8 compared with G-17 as stimuli of acid secretion in dogs. The present study examines the effects of G-17 and CCK-8 on the release of somatostatinlike immunoreactivity (SLI) from a fraction of small canine fundic mucosal cells separated by elutriation and placed in short-term culture. CCK-8 was considerably more potent and more effective than G-17 as a stimulant of SLI release from these cultured cells. CCK-8 was slightly more potent than G-17 in inhibiting 125I-[Leu15]G-17 binding to receptors in the same elutriator fraction. Our present findings support the hypothesis that the poor efficacy of CCK compared with G-17 as a stimulant of acid secretion may reflect pronounced activation of somatostatin-mediated acid-inhibitory mechanisms by CCK-8. The present data indicate that differences in affinity between CCK-8 and G-17 at the 125I[Leu15]G-17 receptor probably do not account for the greater efficacy of CCK-8; the receptor or cell activation mechanisms underlying this greater efficacy of CCK-8 on SLI release remain to be elucidated.

Animals↗
PubMed1985

Drug and chemical related deaths: incidence in the State of Maryland--1975 to 1980.

The incidence of drug and chemical related deaths was studied over a six-year period in the State of Maryland. Deaths were classified into the following categories: alcohol, carbon monoxide (CO), single drugs, multiple drugs, and narcotism. The last three categories were further subdivided as to the specific drugs or chemicals involved. Over the six-year period the number of alcohol and CO deaths remained steady, the number of barbiturate and propoxyphene deaths declined, while the number of tricyclic antidepressant drug deaths increased.

Adolescent↗
PubMed1984

Evaluation of bepridil, a new antianginal agent: clinical and hemodynamic alterations during the treatment of stable angina pectoris.

The antianginal effects of bepridil, a new calcium entry blocker, were evaluated in 20 patients with chronic stable angina in a single-blind trial that was placebo-controlled within patients. Of the 20 patients, 13 also underwent rest and exercise gated blood pool scintigraphy to assess the effects of the agent on left ventricular (LV) performance. Mean anginal frequency was significantly reduced, from 7.3 to 3.1 episodes/week (p less than 0.01). Total work performed increased from 410 to 581 kpm (p less than 0.005), and exercise time increased from 5.3 to 6.6 minutes (p less than 0.005). Supine resting LV end-diastolic volume index, end-systolic volume index, stroke volume index, cardiac index and ejection fraction (EF) were not altered by bepridil. During supine exercise, EF decreased from 60 to 55% during placebo therapy. Despite an increase in total work, the mean EF increased from 60 to 62% (p less than 0.05 vs exercise placebo) during exercise with bepridil therapy. Maximal exercise stroke volume index and cardiac index were significantly greater during bepridil therapy. Exercise resulted in new or increased LV wall motion abnormalities in 7 of 13 patients during placebo therapy. During bepridil therapy, only 4 new or increased wall motion abnormalities were noted despite the increase in total work performed. Thus, bepridil is an effective antianginal agent. The drug allows an increase in exercise work load and preserves LV performance.

Adult↗
PubMed1984

Role of intron-contained sequences in formation of moloney murine leukemia virus env mRNA.

Formation of the Moloney murine leukemia virus envelope mRNA involves the removal of a 5,185-base pair-long intron. Deletion analysis of two Moloney murine leukemia virus-derived expression vectors revealed the existence of two short regions within the viral intron which are required for the efficient formation of the spliced RNA species. One region was present upstream from the 3' splice junction, extended at least 85 nucleotides beyond the splice site, and was not more than 165 nucleotides long. As yeast polymerase II introns, the Moloney murine leukemia virus intron contains the sequence 5'-TACTAAC-3' 15 nucleotides upstream from the 3' splice site. A second region located in the middle of the intron, within a 560-nucleotide-long sequence, was also essential for formation of the spliced RNA species. The efficient splicing of the env mRNA in the absence of expression of viral genes raises the possibility that similar mechanisms are used to remove introns of (some) cellular genes.

Base Sequence↗
PubMed1984

Release of somatostatinlike immunoreactivity from canine fundic mucosal cells in primary culture.

We have developed a model to allow study of the release of somatostatinlike immunoreactivity (SLI) from gastric mucosal cells. Collagenase-dispersed canine fundic mucosal cells were separated by counterflow elutriation. SLI-containing cells were identified in the fractions with small cells (9-11 microns), and these fractions were plated onto collagen. After 2 days in culture, SLI content of the cells was maintained; SLI-positive cells, detected by peroxidase-antiperoxidase immunohistochemistry, comprised 70 +/- 6% (mean +/- SE, n = 6) of these cultured cells. Release of SLI from these cultures into the medium was determined by radioimmunoassay. Epinephrine, dibutyryl cAMP, and gastrin each stimulated SLI release in a time-dependent manner, with a steady rate of secretion maintained for 120 min of incubation. Both epinephrine and dibutyryl cAMP markedly potentiated the release of SLI stimulated by gastrin but were not themselves mutually potentiating. Upon Sephadex G-50 column chromatography of incubation medium and extracts of cultured cells, SLI eluted primarily in a single peak that cochromatographed with synthetic somatostatin tetradecapeptide. Our data suggest that gastrin and adrenergic stimuli act directly on canine fundic somatostatin cells and that potentiating interactions between secretagogues may be important modulating elements in somatostatin cell secretory function.

Animals↗
PubMed1984

Autonomic regulation of somatostatin release: studies with primary cultures of canine fundic mucosal cells.

Using a newly developed system for culturing canine fundic mucosal cells, we examined regulation of the secretion of somatostatinlike immunoreactivity (SLI) by cholinergic and adrenergic transmitters. Enzyme-dispersed canine fundic mucosa cells were enriched in SLI content by counterflow elutriation and cultured on collagen for 42 h. Epinephrine alone, and in combination with gastrin, stimulated SLI secretion in a dose-dependent fashion. Propranolol did not alter the response to dibutyryl cAMP or gastrin but produced a parallel, rightward shift of the epinephrine dose-response curve with the dissociation constant (Ki) determined to be 14 nM by nonlinear curve fitting. Phentolamine, an alpha-adrenergic antagonist, enhanced SLI secretion in response to epinephrine, an effect reversed by the alpha 1-agonist methoxamine but not by the alpha 2-agonist clonidine. However, neither methoxamine nor clonidine alone inhibited the response to the beta-selective adrenergic agonist isoproterenol; thus, the existence of an adrenergic alpha 1-inhibitory receptor remained uncertain. Carbachol noncompetitively inhibited SLI secretion stimulated by gastrin, epinephrine, and dibutyryl cAMP. Atropine produced a parallel rightward shift of the carbachol dose-response curve (Ki = 0.4 nM). Pirenzepine also inhibited the effects of carbachol (Ki = 35 nM). Our studies suggest that SLI-containing cells in the canine fundic mucosa possess stimulatory beta-adrenergic receptors and inhibitory muscarinic receptors.

Adrenergic alpha-Agonists↗
PubMed1984

Gastrin receptors on nonparietal cells isolated from canine fundic mucosa.

The cellular localization of gastrin receptors was studied using dispersed canine fundic mucosal cells. In previous studies 125I-[Leu15]gastrin-17 (125I-[Leu15]G-17) binding was found to parietal cells, but gastrin binding was also found in the small-cell elutriator fractions (SCEF). In the present study a density gradient was used to further separate the SCEF and the distribution of 125I-[Leu15]G-17 binding correlated with cellular content of somatostatinlike immunoreactivity (SLI). In contrast, 125I-[Leu15]G-17 binding was inversely correlated with the histamine content of the fractions. 125I-[Leu15]G-17 binding to the SCEF was rapid and reversible. Total binding was 0.29 +/- 0.02 fmol/10(6) cells (mean +/- SE, n = 15); excess unlabeled G-17 inhibited 85% of this binding. G-17, [Leu15]G-17, and 127I-[Leu15]G-17 were equipotent in inhibiting 125I-[Leu15]G-17 binding and stimulating SLI secretion from the SCEF placed in short-term culture, whereas 127I-G-17 had a low potency for both effects. Proglumide, known to inhibit cholecystokinin binding to pancreatic acinar cell receptors, also inhibited 125I-[Leu15]G-17 binding to the SCEF and inhibited G-17 stimulated SLI release. We conclude that in the canine fundic mucosa gastrin interacts with receptor sites on parietal cells and somatostatin cells but probably not on fundic mucosal histamine-containing cells. These receptor sites for gastrin may activate counterbalancing mechanisms regulating the secretion of acid.

Animals↗
PubMed1984

Radiation induced brain edema in primates, studied with sequential brain cat scanning and histopathology. Protective effect of sodium meclofenamate. A preliminary report.

Four Cynomologous monkeys (Mecaca fascicularis) received 2000 Rad whole brain irradiation. One remained untreated and exhibited loss of hair, facial edema, brain edema and hydrocephalus. There was loss of alertness and motor activity. One was scheduled to be treated with phenobarbital, but died in 24 hours after irradiation. One animal received 2 mg/kg dexamethasone I.M. daily. It died two weeks after irradiation apparently due to treatment related infection. One animal received 20 mg/kg sodium meclofenamate (Meclomen) orally daily. This animal showed no brain edema and only minimal hydrocephalus, delayed and incomplete hair loss and no facial edema. Further studies of this treatment appear to be justified.

Animals↗