Search PubMed⌕ Search

Biomedical subjects

L Y Korman

Publications and source records attributed to L Y Korman.

At least 37 records · Page 2Linked to original sources
PubMed1989

VIP receptors and content after bowel transplantation.

Advances in immunosuppressive therapy have renewed interest in small bowel transplantation. Little is known, however, about the functional capacity of transplanted intestine. To clarify the potential for normal function, we investigated whether elements of the enteric nervous system are preserved after denervation in our rat model of intestinal transplantation. We investigated whether VIP, a major peptide neurotransmitter of the enteric nervous system, and its receptors are preserved in the bowel after transplantation. In our model of transplantation, avascular fetal jejunum from term Fisher rats is transplanted to the subcutaneous tissues of host syngeneic rats. This "neogut" becomes vascularized and develops characteristics of native small bowel. VIP content was measured by RIA and the in situ distribution of VIP receptors was determined by the technique of receptor autoradiography. Neogut was studied 1 and 3 weeks after transplantation and compared with age-matched rat pup jejunum. Autoradiographs showed high silver grain density, representing VIP binding sites, in the mucosal layers of all tissues studied. VIP content in the transplanted bowel was comparable to that of native gut and showed a rise with developmental age similar to that of native gut. VIP levels (pmole/mg protein, x +/- SEM) were neogut 1 week, 0.26 +/- 0.14; jejunum 1 week, 0.25 +/- 0.07; neogut 3 weeks, 0.60 +/- 0.21; and jejunum 3 weeks, 0.69 +/- 0.16. These results show that VIP receptors and content are preserved in this model of transplantation. This suggests that the enteric nervous system and receptors for peptide neurotransmitters remain intact after transplantation and may retain the potential for regulatory function.

Animals↗
PubMed1989

Hyperplastic colonic polyps as a marker for adenomatous colonic polyps.

Hyperplastic colonic polyps are generally regarded as being of little or no clinical consequence. Recently, however, hyperplastic polyps have been found to share numerous functional similarities with colorectal carcinoma. To determine whether the presence of an isolated left-sided colonic hyperplastic (metaplastic) polyp could serve as a marker for more proximal synchronous adenomatous colonic polyps, we retrospectively analyzed all consecutive colonoscopic polypectomies performed over an 18-month period at two medical centers. It is the policy at both institutions to remove or biopsy all polyps, regardless of size. Indications for colonoscopy included known or previous colonic polyps or carcinoma, hemoccult positive stool, lower gastrointestinal bleeding, iron deficiency anemia, abnormal barium enema, inflammatory bowel disease, abdominal pain, and family history of colon cancer. The location of adenomatous polyps and hyperplastic polyps was recorded and compared. One hundred sixty-three of 845 consecutive patients (19.3%) had at least one colonic polyp. The prevalence of adenomatous polyps alone was 10.3%, hyperplastic polyps 9%, and both types 1.9%. The prevalence rate for an adenomatous polyp in patients without a hyperplastic polyp was 15%. In contrast, among patients with a hyperplastic polyp, 49% had a synchronous adenomatous polyp. Only 3.4% of patients had an adenomatous polyp proximal to the splenic flexure when no polyps were present in the left colon. Conversely, among the 29 patients in whom an isolated hyperplastic polyp was found in the left colon, there was a 32.5% prevalence of adenomatous polyps in the proximal colon (p less than 0.01). The results of this study suggest that left-sided hyperplastic colonic polyps (generally within the reach of a screening sigmoidoscopy) serve as a marker for neoplastic polyps.

Adolescent↗
PubMed1988

Primary culture of the enteric nervous system from neonatal hamster intestine. Selection of vasoactive intestinal polypeptide-containing neurons.

The enteric nervous system is a major division of the autonomic nervous system and is responsible for the regulation of gastrointestinal function. The objective of the present study was to develop a simple and effective technique for isolating and culturing neurons of the enteric nervous system that would permit characterization of their development and regulatory peptide content. This was accomplished using a dispersed intestinal cell preparation cultured under conditions designed to support the growth and differentiation of neurons and neuroendocrine cells. Newborn hamster intestine was digested in 0.1% collagenase, mechanically dispersed, and cultured in RPMI 1640 supplemented with 2.5% serum and other additives. Phase and bright-field microscopy demonstrated neuronal cells and fibers after the second day in culture. This was confirmed by immunohistochemistry using antibodies directed against neurofilament and vasoactive intestinal polypeptide. Acetic acid extracts of the culture indicated that during the first 4 days of the culture the content of vasoactive intestinal polypeptide increased, whereas the content of substance P, mammalian bombesin, and neurotensin declined. High-performance liquid chromatography and fast protein liquid chromatography confirmed that the immunoreactive vasoactive intestinal polypeptide coeluted with synthetic and iodinated forms of the peptide. This study describes a technique for primary culture of intestinal tissue that supports the survival of enteric neurons and permits analysis of the development and synthetic and secretory characteristics of the enteric nervous system.

Animals↗
PubMed1988

Somatostatin inhibits the secretion of bombesin-like peptides from small cell lung cancer cells.

The effects of somatostatin (SRIF) on small cell lung cancer (SCLC) cell line NCI-H345 was investigated. SRIF had no effects on the basal cAMP levels or the secretion rate of bombesin-like peptides. VIP (1 microM) increased the cAMP levels approximately 10-fold and the secretion rate of bombesin-like peptides 3-fold. SRIF and its analogues inhibited the increase in the cAMP levels and the secretion rate of bombesin-like peptides caused by VIP. The order of peptide potency was (D-Trp8)SRIF > SRIF-28 = (Tyr11)SRIF > SRIF. These data suggest that functional SRIF receptors may be present on SCLC cells.

Bombesin↗
PubMed1988

The release of bombesin-like peptides from small cell lung cancer cells.

High levels of BN/GRP are present in classic SCLC and lung carcinoids, whereas BN immunoreactivity is absent in variant SCLC, adenocarcinoma, large cell carcinoma, squamous cell carcinoma, and mesothelioma cell lines. BN-like peptides are secreted from classic SCLC into the tissue culture medium. The secretion rate of BN-like peptides from cell line NCI-H345 was increased 3-fold by VIP (1 microM). Also, VIP increased the cAMP levels in cell line NCI-H345 by an order of magnitude. Therefore, SCLC cells have functional VIP receptors which regulate the secretion of BN-like peptides. Also, SRIF (100 nM) inhibits the VIP-stimulated increase in cAMP levels and secretion rate of BN-like peptides from SCLC cells. Because BN stimulates colony formation, VIP and/or SRIF may be able to alter the growth of SCLC cells. BN-like peptides are secreted from SCLC cells into the plasma. The levels of BN immunoreactivity in the plasma of SCLC patients with extensive disease is 2- to 40-fold greater than that of patients with limited disease. Secretin infusion into patients with extensive disease produces a transient increase (7-fold) in the plasma concentration of BN-like peptides. BN-like peptides are also present in the CSF of SCLC patients. When released from SCLC cells, BN-like peptides may interact with cell surface receptors. [Tyr4]BN binds with high affinity (Kd = 0.5 nM) to a single class of sites (1500/cell) on cell line NCI-H345. The carboxyl terminus of BN or GRP is essential for high-affinity binding activity. BN-like peptides elevate cytosolic Ca2+ levels as a result of increased phosphatidylinositol turnover. The putative BN receptor antagonist [D-Arg1, D-Pro2, D-Trp7,9, Leu11]substance P inhibits high-affinity [Tyr4]BN binding, the ability of BN to elevate cytosolic Ca2+ levels, and colony formation of SCLC cells. Therefore, BN receptor antagonists may serve as useful agents to inhibit the growth of SCLC.

Bombesin↗
PubMed1988

BN/GRP-like peptides and receptors in small cell lung cancer.

BN/GRP-like peptides are produced in high concentrations in SCLC cell lines and in low concentrations in beta-lymphoblastoid cell lines. The BN/GRP-like peptides are secreted from SCLC cell line NCI-H345 by stimuli which elevate the intracellular cAMP levels. These stimuli include theophylline, PHI, secretin and VIP. Also, elevated plasma levels of BN/GRP-like peptides are found in patients with extensive SCLC. In these patients the levels of BN/GRP-like peptides can be increased further approximately 5-fold after secretin infusion. Because SCLC cells make and secrete BN/GRP-like peptides, they may function as regulatory peptides in this disease.

Carcinoma, Small Cell↗
PubMed1986

Secretin stimulates cyclic AMP formation in the rat brain.

The effects of secretin on cyclic AMP levels in the rat brain were determined. Incubation of rat brain frontal cortex slices with secretin or the structurally related peptides peptide histidine leucine (PHI) or vasoactive intestinal polypeptide (VIP) in the presence of 10 mM theophylline resulted in a dose-dependent increase in the cyclic AMP levels. The half-maximal increase in cyclic AMP occurred using a 1 microM dose of secretin or a 2 microM dose of PHI or VIP. Preincubation of slices with secretin-(5-27) produced a dose-dependent inhibition of the secretin but not VIP- or PHI-stimulated increase in the cyclic AMP content. Also, in receptor binding studies, secretin-(5-27) produced a dose-dependent inhibition (Ki = 400 nM) of 125I-secretin but not of 125I-VIP binding to rat brain membranes. Guanyl-5'-yl imidodiphosphate decreased the affinity of radiolabelled secretin binding as a result of an increased rate of dissociation of bound 125I-secretin. These data suggest that secretin receptors in the rat brain may be coupled to adenylate cyclase in a stimulatory manner and that secretin-(5-27) may function as a central secretin receptor antagonist.

Amino Acid Sequence↗
PubMed1986

Secretin/vasoactive intestinal peptide-stimulated secretion of bombesin/gastrin releasing peptide from human small cell carcinoma of the lung.

Bombesin/gastrin releasing peptide-like immunoreactivity (BLI) is found in the majority of small cell carcinoma of the lung (SCCL) cell lines examined. Because BLI is present in high concentration in SCCL we studied the mechanism of BLI secretion from several SCCL cell lines and in patients with SCCL. In cell line NCI-H345 the structurally related polypeptide hormones secretin, vasoactive intestinal peptide, and peptide histidine isoleucine as well as theophylline, a phosphodiesterase inhibitor, N6,O2'-dibutyryl cyclic adenosine 3':5'-monophosphate, a cyclic nucleotide analogue, increased BLI release by 16-120% and cyclic adenosine 3':5'-monophosphate by 36-350%. Similar results were obtained in SCCL cell line NCI-H209. i.v. injection of secretin (2 units/kg) significantly increased plasma BLI in 2 patients with extrapulmonary SCCL. These data suggest that SCCL cells possess receptors for secretin/vasoactive intestinal peptide and that receptor occupation stimulates in vitro and in vivo BLI secretion.

Alprostadil↗
PubMed1985

Neurotensin is produced by and secreted from classic small cell lung cancer cells.

The presence of neurotensin in various human tumor cell lines was investigated by radioimmunoassay. High concentrations (0.06-5.1 pmol/mg protein) were detected in 50% of the classic but not variant small cell lung cancer or other human tumor cell lines examined. Biochemical studies indicated that the main peak of immunoreactivity coeluted with synthetic neurotensin using gel filtration and high pressure liquid chromatography techniques. Also, the rate of neurotensin secretion increased approximately 2-fold when theophylline was added which elevated intracellular levels of cAMP 4-fold. Because neurotensin is present in and secreted from many classic small cell lung cancer cells, it may function as a regulatory peptide in this disease.

Adenocarcinoma↗
PubMed1985

Characteristics of the interaction of the glucagon receptor, cAMP, and insulin secretion in parent cells and clone 5F of a cultured rat insulinoma.

Rat insulinoma cells, which grow in culture and secrete insulin, were used to study the mechanism of stimulation of insulin release by glucagon. The parent cell line (RIN-m) and a clone that secretes high levels of insulin (5F) had been shown to possess specific receptors for glucagon. Glucagon (1 microM) stimulated a rapid increase in cyclic adenosine 3':5'-monophosphate (cAMP) that was followed by an increase in insulin secretion in both cell lines. The concentration of glucagon necessary for half-maximal stimulation of cAMP was 50 nM in parent and approximately 0.5 microM in 5F, whereas the concentration required to inhibit binding by 50% was 0.5 nM and 30 nM, respectively. In 5F, the dose-response relationships for cAMP and insulin secretion were superimposable. The glucagon effects on insulin secretion and cAMP did not require either glucose or amino acids in the incubation media. No refractoriness to glucagon stimulation of cAMP or insulin was noted. It may be concluded that there are significant differences between glucagon binding and glucagon responses in parent cells and clone 5F, there are glucagon receptors that are not coupled to adenylate cyclase, and cAMP mediates glucagon-stimulated insulin release.

Adenoma, Islet Cell↗
PubMed1984

Significance of a positive test for occult blood in stools of patients taking anti-inflammatory drugs.

Physicians often attribute positive Hemoccult card tests in patients taking anti-inflammatory drugs to the irritant effects of these drugs on the gastrointestinal (GI) tract mucosa. A study of 167 patients attending a rheumatic disease clinic showed that 145 (86.8%) were taking an anti-inflammatory drug, but only eight of these patients (4.8%) had positive tests for occult blood. An investigation revealed that three patients had neoplasms, two had inflammatory bowel disease, one had a bleeding internal hemorrhoid, one had a bleeding diverticulum, and one had peptic ulcer disease. Anti-inflammatory agents appear to have caused or contributed to the GI tract bleeding only in the patient with peptic ulcer disease. The study shows that the Hemoccult card test is usually not positive in patients receiving anti-inflammatory medications. Accordingly, physicians should not attribute a positive Hemoccult card test to these drugs until other appropriate studies have ruled out the existence of underlying GI tract lesions.

Adrenal Cortex Hormones↗
PubMed1983

Reliability of symptoms in assessing control of gastric acid secretion in patients with Zollinger-Ellison syndrome.

In the present study we explored whether the presence or absence of symptoms could provide a reliable way of assessing the adequacy of control of gastric secretion in patients with Zollinger-Ellison syndrome who were treated medically. Over a 5-yr period, 26 Zollinger-Ellison syndrome patients were entered into a prospective study which examined the presence or absence of symptoms that are associated with gastric hypersecretion, the presence of absence of upper gastrointestinal pathology, and the degree of control of gastric acid secretion. During their last admission, 15 of the 26 patients (58%) were symptomatic, but post-drug gastric acid secretion for the 2 h before the next dose of medication was not significantly different from that in asymptomatic patients. This lack of correlation between the presence or absence of symptoms and post-drug gastric acid secretion was evident for the group as a whole, as well as for 8 to 12 patients who underwent multiple admissions. Of 23 patients who underwent upper gastrointestinal endoscopy of x-ray, or both, on their last admission, 12 had pathology. Post-drug gastric acid secretion was less in patients without pathology than in those with pathology. Furthermore, in patients in whom post-drug gastric acid secretion was less than or equal to 10 mEq/h, the criterion of acceptable control used in this study, pathology did not occur. These findings demonstrate that the presence or absence of symptoms cannot be used to assess the adequacy of medical control of gastric acid secretion in patients with Zollinger-Ellison syndrome. In our opinion, maintenance of post-drug gastric acid secretion less than or equal to 10 mEq/h for the 2 h before the next dose of medication is an acceptable criterion for long-term control of gastric secretion in patients with Zollinger-Ellison syndrome.

Adult↗
PubMed1982

Mechanism of action of ATP on intestinal epithelial cells. Cyclic AMP-mediated stimulation of active ion transport.

ATP, ADP and AMP but not adenosine increased cyclic AMP in dispersed enterocytes prepared from guinea pig small intestine. This action of ATP was augmented by IBMX and was reproduced by App(NH)p or App(CH2)p. ATP also increased the formation of cyclic [14C]AMP in enterocytes that had been preincubated with [14C]adenine. Gpp(NH)p and NaF each caused persistent activation of adenylate cyclase in plasma membranes from enterocytes and ATP caused significant augmentation of this persistent activation. In addition to increasing cellular cyclic AMP and augmenting Gpp(NH)p and NaF-stimulated persistent activation of adenylate cyclase, ATP increased the Isc across mounted strips of small intestine and inhibited net absorption of fluid and electrolytes in segments of everted small intestine. These results indicate that intestinal epithelial cells possess a receptor that interacts with ATP and other adenine nucleotides and that receptor occupation by ATP causes activation of adenylate cyclase, increased cyclic AMP and changes in active ion transport across intestinal mucosa.

1-Methyl-3-isobutylxanthine↗
PubMed1982

Effects of inhibitors of cyclic nucleotide phosphodiesterase on the actions of vasoactive intestinal peptide and secretin on pancreatic acini.

Theophylline, 3-isobutyl-1-methylxanthine (IBMX), and Ro 20-1724 each augmented the increase in cAMP and the stimulation of amylase secretion caused by vasoactive intestinal peptide (VIP) or secretin. With IBMX the dose-response curve for the stimulation of amylase secretion caused by VIP or secretin spanned a range of lower concentrations than did that obtained with Ro 20-1724, which in turn spanned a range of lower concentrations than did that obtained with theophylline. The configuration of the dose-response curve for the action of VIP on cAMP differed with each phosphodiesterase inhibitor tested. With Ro 20-1724 the dose-response curve was monophasic, whereas with the two methylxanthines the dose-response curve was biphasic. With theophylline the magnitude of the second component of the dose-response curve was larger than the first; with IBMX the magnitude of the first component was larger than the second. The configuration of the dose-response curve for the action of secretin on cAMP also differed with each phosphodiesterase inhibitor tested. With theophylline the dose-response curve was monophasic, whereas with Ro 20-1724 and IBMX the dose-response curve was biphasic. With Ro-20-1724 the magnitude of the second component of the dose-response curve was larger than the first; with IBMX the magnitude of the first component was larger than the second. These results indicate that cAMP is compartmentalized in pancreatic acinar cells and that the different compartments of cAMP are affected differently by various inhibitors of cyclic nucleotide phosphodiesterase. These findings also suggest that the different compartments of cAMP are acted on by phosphodiesterases with different sensitivities to various inhibitors.

1-Methyl-3-isobutylxanthine↗
PubMed1980

Action of theophylline on secretagogue-stimulated amylase release from dispersed pancreatic acini.

In dispersed acini from guinea pig pancreas, theophylline did not alter basal amylase release, but had three functionally distinct modes of action on the stimulation of amylase release caused by various secretagogues. 1) At relatively low concentrations (0.1-1.0 mM), theophylline augmented the increase in enzyme secretion caused by vasoactive intestinal peptide, secretin, or 8-bromoadenosine 3',5'-monophosphate, but did not alter the increase in amylase release caused by other secretagogues. 2) At intermediate concentrations (1-10 mM), theophylline selectively altered the increase in enzyme secretion caused by carbamylcholine, but did not alter the effects of cholecystokinin or bombesin, secretagogues whose modes of action are similar to that of cabamylcholine. 3) At high concentrations (greater than 10 mM), theophylline inhibited the increase in enzyme secretion caused by all secretagogues tested.

Amylases↗