Search PubMed⌕ Search

Biomedical subjects

J C Thompson

Publications and source records attributed to J C Thompson.

At least 55 records · Page 3Linked to original sources
PubMed1996

Influence of nicotine on gastrin and peptide YY in the rat.

The objective of this study was to examine the effects of nicotine and high-fat diets on gastrin and peptide YY (PYY) homeostasis in the rat. Antral levels of gastrin mRNA and peptide and ileal and colonic levels of PYY mRNA and peptide were examined. Serum levels of gastrin in response to food were also measured. Control rats were ad-lib fed or pair-fed according to the daily food intake of nicotine-treated rats. The results of this study indicate that nicotine treatment and fat diets can influence gastrin and PYY gene expression in the gastrointestinal tract.

Animals↗
PubMed1996

Short-term caloric restriction augments age-related decreases in gastrin content and release.

Aging is associated with significant structural and functional changes in the gastrointestinal tract. Gastrin, a hormone produced by G cells in the antrum of the stomach, stimulates proliferation of gastric mucosa; its synthesis appears to decrease with age. Life-long restriction of caloric intake is the only experimental manipulation that has been shown to retard aging processes in rats. The purpose of this study was to examine the effect of short-term caloric restriction (CR) on the production and release of the hormone gastrin with aging. Aging causes a fall in both fasting plasma levels of gastrin and antral content of gastrin in Fischer 344 rats; short-term CR appears to augment this age-related decrease. Steady state levels of antral gastrin mRNA were decreased with aging, and short-term CR resulted in an augmented decrease in aged, but not in young rats. Our findings indicate that gastrin release, synthesis and gene expression decrease with age. Restriction of the caloric intake for a short period (i.e. 8 weeks) augments this age-related decrease in antral gastrin and fasting plasma levels. Short-term CR appears to decrease the production of gastrin at the level of gene expression.

Aging↗
PubMed1996

Mechanisms of bombesin on growth of gastrinoma (PT) in vivo.

The growth of the human gastrinoma model (PT) in athymic nude mice is stimulated by bombesin (BBS), an amphibian peptide homologous to both human gastrin-releasing peptide (GRP) and neuromedin B (NMB). The mechanism is not known, and a potent and specific GRP-R antagonist BIM26226, which has low affinity for NMB-R, was used in vivo in athymic nude mice bearing gastrinoma subcutaneously. Both the BBS and BIM26226 stimulated the growth of PT, and the growth stimulation was even greater when given together. RT-PCR study of gastrinoma revealed the presence of both GRP-R and NMB-R mRNA, but much more abundant NMB-R mRNA. We conclude that BBS-stimulated growth of gastrinoma involves both GRP-R and NMB-R, and our findings suggest that GRP-R mediates negative and NMB-R produces positive growth effects on gastrinoma.

Animals↗
PubMed1996

Hyperphosphorylation of retinoblastoma protein and stimulation of growth by okadaic acid in human pancreatic cancer.

Phosphorylation/dephosphorylation of intracellular proteins are important steps in the regulation of cell growth. Okadaic acid, an inhibitor of the serine/threonine protein phosphatases 1 and 2A, is a potent tumor promoter. This effect may be through the inhibition of dephosphorylation (termed "hyperphosphorylation") and subsequent inactivation of tumor-suppressor proteins. We examined whether okadaic acid regulates growth of human pancreatic cancer cells (MIA PaCa-2 and Panc-1) or alters the phosphorylation of the retinoblastoma tumor-suppressor protein. Growth studies, nuclear labeling analyses, and Western blotting for retinoblastoma protein were performed. Okadaic acid stimulated cell growth and induced hyperphosphorylation of the retinoblastoma protein. The growth-stimulatory effect of okadaic acid on these human pancreatic cancer cells may be mediated by inactivation of the growth suppressive effect of the retinoblastoma protein by hyperphosphorylation. These studies suggest that the growth of these human pancreatic cancer cells is still regulated by tumor-suppressor proteins.

Blotting, Western↗
PubMed1996

Field of dreamers and dreamed-up fields: functional and fake perimetry.

PURPOSE: Hysterical and malingering patients can manifest visual field defects on perimetry (visual field testing), including defects suggestive of true visual pathway pathology. It has been shown that control subjects can easily imitate some pathologic defects with automated, computed perimetry. The authors sought to determine whether subjects could imitate the same pathologic defect with manual and automated perimetry. METHOD: Six subjects posed as patients with neurologic problems. They had manual perimetry with both an experienced and inexperienced technician followed by automated perimetry. They were later interviewed about the methods of the technicians and the difficulty of the exercise. RESULTS: Four of six subjects easily imitated the assigned defects with both technicians on manual perimetry and with automated perimetry. These included quadrantic, altitudinal, hemianopic, and enlarged blind-spot defects. Two subjects who were assigned cecocentral and paracentral scotomas instead produced enlarged blind spots by manual perimetry and defects suggestive of chiasmal pathology by automated perimetry. Paradoxically, some subjects found that experienced technicians were easier to fool than inexperienced technicians because of the systematic way in which experienced technicians defined defects. CONCLUSIONS: With minimal coaching, some subjects can imitate visual fields with enlarged blind spots, quadrantic, hemianopic, and altitudinal defects with ease and reproducibility by both automated and manual perimetry. Cecocentral and paracentral scotomas are harder to imitate but may be mistaken as representing chiasmal pathology. Paradoxically, experienced technicians may not be better at detecting hysterical or malingering individuals.

Adult↗
PubMed1996

Fetal and neoplastic expression of the neurotensin gene in the human colon.

OBJECTIVE: The authors identified various colon cancers that express the gene for the gut peptide neurotensin (NT/N). In addition, the authors sought to delineate the temporal pattern of NT/N gene expression in the human fetal colon. SUMMARY BACKGROUND DATA: Expression of NT/N is localized to the mucosa of the adult small bowel but also has been identified in the fetal colon, which resembles the small bowel until the end of the second trimester. Ectopic NT/N expression has been shown in certain types of colon cancer, suggesting a reversion to a fetal phenotype. METHODS: Sensitive ribonuclease protection assays were used to determine NT/N expression in colon cancers and adjacent normal mucosa as well as colon cancers established as tumor xenografts and fetal colon samples. RESULTS: NT/N gene expression was shown in 4 of 12 (25%) human colon cancer xenografts and in 11 of 40 (28%) freshly resected colon adenocarcinomas; NT/N gene expression was not expressed in any of the samples of normal colonic mucosa adjacent to the tumors. The NT/N gene was expressed maximally in the fetal colon between 16 and 18 weeks' gestation; NT/N expression was decreased between 19 and 22 weeks and was not apparent in either the 24-week fetal colon or the adult samples. CONCLUSIONS: The NT/N gene expression is expressed transiently in the fetal colon during a development stage that is characterized by morphologic similarity to the small bowel. In addition, NT/N is reexpressed in approximately one fourth of the human colon cancers, indicating that neoplastic transformation leads to reversion to a fetal phenotype in certain types of colon cancer. The NT/N gene will provide a useful model to further define the complex differentiation pathways in the normal gut as well as the process of fetal "dedifferentiation" in certain types of colon cancer.

Adenocarcinoma↗
PubMed1996

Caloric restriction increases the expression of heat shock protein in the gut.

OBJECTIVE: The authors determined whether caloric restriction (CR) either acutely or chronically, alters heat shock protein 70 (hsp70) gene expression in the gut. SUMMARY BACKGROUND DATA: Caloric restriction prolongs the life span and delays age-related disease (e.g., cancer) in mammals; the mechanisms responsible for these effects are not known. Heat shock proteins are a group of stress-responsive genes of which the most prominent member is hsp70. METHODS: In the first experiment, adult (4-month-old) rats (n = 3/group) were killed after a 48-hour fast or 6 and 24 hours after refeeding. In addition, three rats (controls) were killed without fasting or refeeding. The stomach was removed and RNA was extracted for hsp70 gene expression. In the second experiment, aged (22- to 26-month-old) rats were fed ad libitum (AL) or a CR diet (60% caloric intake of AL diet). Rats were killed, the stomach and duodenum were removed, and RNA was extracted for determination of hsp70 gene expression. RESULTS: In the first experiment, hsp70 mRNA levels were increased approximately threefold in the stomach of rats fasted for 48 hours; levels decreased to control values by 6 and 24 hours after refeeding. In the second experiment, hsp70 mRNA levels were increased significantly in both the stomach and duodenum of aged CR rats compared with AL controls. CONCLUSIONS: The authors have demonstrated that hsp70 mRNA levels are increased in the proximal gut of young and old rats, either acutely (with fasting) or with CR. Increased expression of the cytoprotective hsp70 gene in the gut may provide a possible cellular mechanism for the beneficial effects noted with CR.

Aging↗
PubMed1996

Stimulation of pancreatic growth. Distal small bowel resection mediated by increased levels of cholecystokinin.

SUMMARY BACKGROUND DATA: Distal, but not proximal, resection of the small bowel induces growth of rat pancreas, but the mechanism of this phenomenon is poorly clarified. The release of cholecystokinin (CCK), a trophic hormone for the pancreas, is regulated by a negative-feedback control of bile salts. The ileum is a major site for reabsorption of bile salts. Thus, unsuppressed release of CCK due to deleted reabsorption of bile salts after distal small bowel resection may be a cause of pancreatic growth. In this study, the authors have examined whether pancreatic growth after distal small bowel resection was mediated by endogenous CCK and have determined whether the mechanism of this pancreatic growth required biosynthesis of polyamine. METHODS: Male Fischer 344 rats underwent 70% distal small bowel resection or transection of the ileum. Beginning 48 hours after surgery, CR1409 (a CCK-receptor antagonist) or saline was injected subcutaneously every 8 hours. All animals were pair-fed and killed 14 days after surgery. The pancreas from each rat was excised, weighed, and assayed for DNA, RNA, protein, and polyamine content. RESULTS: Distal small bowel resection increased pancreatic weight, DNA, RNA, and protein, as well as polyamine levels; all of these increases were significantly suppressed by CR1409. Postprandial release of CCK into the circulation was significantly increased after distal small bowel resection. CONCLUSIONS: Pancreatic growth after distal small bowel resection was associated with the stimulation of polyamine biosynthesis; growth appeared to be mediated by endogenous CCK.

Animals↗
PubMed1996

All-trans-retinoic acid inhibits growth of human pancreatic cancer cell lines.

Retinoids are a class of molecules structurally related to vitamin A that have potent antiproliferative and differentiating effects on a variety of normal and neoplastic tissues. All-trans-retinoic acid (ATRA) has become a first-line chemotherapeutic agent in the treatment of certain leukemias; however, the effect of ATRA on pancreatic tumors is unknown. The purpose of this study was to determine the effect of ATRA on the growth characteristics of both exocrine and endocrine human pancreatic cancer cell lines. The in vitro growth of four cell lines was examined after treatment with a wide dose range of ATRA. The growth of all tumor cell lines was inhibited by ATRA in a dose-dependent fashion beginning at 0.1 microgram M. The in vivo growth of functioning human pancreatic carcinoid (BON) xenografts in Balb/c athymic mice was determined by treatment with several doses of ATRA over 1 month. The growth of BON tumors was inhibited in a dose-dependent fashion. These results suggest that ATRA exerts direct antiproliferative effects on both exocrine and endocrine human pancreatic cancers and may be useful in the chemotherapy of these tumors.

Animals↗
PubMed1996

Growth hormone upregulates gastrin and peptide YY gene expression.

The purpose of these studies was to examine the effects of excess growth hormone (GH) on gastrin and peptide YY (PYY) gene expression. Transgenic mice with the bovine GH gene linked to a mouse metallothionein I promoter were used as a model of chronic GH excess. Antral gastrin mRNA and peptide levels were elevated significantly (P < 0.05) in GH transgenic mice compared with wild type littermates. Ileal PYY mRNA and ileal and colonic PYY levels were significantly elevated in GH transgenic mice compared with wild type littermates. The elevations in gastrin and PYY gene expression in GH transgenic mice were independent of food intake. Serum concentrations of gastrin and PYY were also elevated in GH transgenic mice. Immunohistochemical analysis showed that the density of PYY-containing cells in the colon of GH transgenic mice and wild type littermates did not differ. In addition, the mRNA and protein levels of chromogranin A, a marker of endocrine cells, were not increased in the colon of GH transgenic mice. Together, these data indicate that GH, insulin-like growth factor I, or both can upregulate gastrointestinal gastrin and PYY gene expression directly.

Animals↗
PubMed1996

Glycine-extended gastrin potentiates gastrin-stimulated gastric acid secretion in rats.

The purpose of this study was to examine whether an intermediate form of amidated gastrin, glycine-extended gastrin (Gly-G), can stimulate gastric acid secretion in conscious rats prepared with gastric fistulas. Intravenous administration of Gly-G (20 nmol.kg-1.h-1) alone for 2 h did not stimulate gastric acid secretion; however, administration of Gly-G (20 nmol.kg-1.h-1) in combination with a bolus administration of gastrin (9.5 nmol/kg) potentiated acid secretion significantly. Gastric acid secretion in response to gastrin alone and gastrin plus Gly-G (2 nmol.kg-1.h-1) was 109.1 +/- 21.6 and 170.1 +/- 27.7 mueq.kg-1.h-1, respectively (P < 0.05). Gastric acid secretion in response to gastrin alone and gastrin plus Gly-G (20 nmol.kg-1.h-1) was 84.8 +/- 17.5 and 164.1 +/- 29.3 mueq.kg-1.h-1, respectively (P < 0.05). Intravenous administration of Gly-G (20 nmol.kg-1.h-1) failed to increase histamine (1 mg/kg)-stimulated acid output. These results demonstrate that Gly-G can selectively potentiate the stimulatory effect of gastrin on acid secretion in rats and that the unprocessed form of gastrin, Gly-G, can exert a biological effect in the stomach.

Animals↗
PubMed1996

Regulation of peptide YY homeostasis by gastric acid and gastrin.

Peptide YY (PYY) is a gut hormone localized primarily in the distal bowel. Because circulating PYY inhibits gastric acid secretion, we investigated the effects of gastric acid secretion and gastrin on gene expression and secretion of PYY. In conscious dogs, PYY release in response to oral food was inhibited (P < 0.05) by pharmacologic inhibition of gastric acid secretion (omeprazole, famotidine). In rats, omeprazole treatment resulted in a significant elevation in serum gastrin concentrations and a simultaneous decrease in PYY messenger RNA (mRNA) and peptide levels in the colon; administration of a gastrin receptor antagonist (L365, 260) prevented the inhibitory actions of omeprazole on colonic PYY mRNA levels. In athymic-nude mice, implantation of a human gastrinoma resulted in an elevation of serum gastrin concentrations and a concomitant depression of colonic PYY mRNA levels. We conclude that endogenous gastric acid secretion up-regulates PYY release and PYY mRNA expression. Circulating gastrin acts to down-regulate PYY release and PYY mRNA expression. This study provides evidence that foregut functions (i.e., gastric acid secretion and gastrin release) exert control over an antiacid signal (e.g. PYY release) emanating from the hindgut.

Animals↗
PubMed1996

Human monoclonal antibody against colon cancer.

The purpose of the study was to produce human monoclonal antibodies (hMcAb) against human colon cancer for use in radioimmunoimaging. Human-mouse heterohybridomas were developed by fusing SHM-D33 mouse-human hybrid heteromyeloma cells with human lymphocytes from colon cancer tumor-draining lymph nodes. The hybridomas capable of secreting human monoclonal antibodies were screened by using human colon cancer cell lines and pathological biopsies with ELISA and immunohistochemical methods. hMcAb clone H11 was selected for a large-scale antibody production, which was purified from mouse ascites. Biodistribution study demonstrated that specific uptake of 125I-hMcAb H11 by human colon cancer xenografts was significantly higher than by normal tissues. Radioimmunoimaging of human colon cancer xenografts exhibited distinct tumor visualization during the period of 72-96 hr after intraperitoneal injection of 125I-hMcAb H11. The development of human monoclonal antibodies such as hMcAb H11 may be useful for radioimmunodetection and therapy of colon cancer.

Animals↗
PubMed1996

Pulse oximetry correction for smoking exposure.

Pulse oximetry oxygen saturation (SpO2) does not distinguish carboxyhemoglobin (COHb) from oxyhemoglobin (O2Hb), giving a false impression of the apparent degree of oxyhemoglobin saturation in smokers who have elevated levels of COHb. We questioned whether accounting for smoking exposure history could improve description of pulse oximetry by correcting for COHb levels. We evaluated smoking history and %SpO2 as predictors of %O2Hb and %COHb by CO-oximetry of arterial blood in 18 actively smoking and 18 age-matched nonsmoking patients in a clinical pilot study. The difference between %SpO2 and %O2Hb was significantly greater (p < 0.001) in the smokers (5.6 +/- 3.1) than the nonsmokers (2.1 +/- 2.1). This difference correlated with %COHb (rp = 0.789; p < 0.001) and the smoking exposure score (SES, rp = 0.621; p < 0.001), a six-point index we developed based on whether patients were active smokers, refrained from smoking prior to testing, or were exposed to passive smoking in the home or workplace. The following formula summarizes the correction: %O2Hb = 0.882[%SpO2] - 0.968[SES] + 9.245 (rp = 0.841; SES = 2.478; p < 0.001). This pilot study suggests that smoking exposure history correlates with COHb levels and that correction for smoking exposure improves the accuracy of pulse oximetry.

Carboxyhemoglobin↗
PubMed1995

Frequent loss of heterozygosity in human primary squamous cell and colon carcinomas at 7q31.1: evidence for a broad range tumor suppressor gene.

Consistent deletions and loss of heterozygosity (LOH) in polymorphic markers in a determinate chromosomal fragment are known to be indicative of a closely mapping tumor suppressor gene. Deletion of the long arm of chromosome 7 is a frequent trait in many kinds of human primary tumors. We studied LOH of 14 markers on chromosome 7q in order to determine the location of a putative tumor suppressor gene in human primary squamous cell carcinoma of the head and neck and in human primary colon carcinomas. Samples were obtained from 18 primary squamous cell carcinomas of the head and neck and 18 primary colon carcinomas surgically removed from patients at the Fox Chase Cancer Center. Loss of heterozygosity was studied performing PCR amplifications of a set of 14 CA microsatellite repeats encompassing 7q21-qter. Of 18 squamous cell carcinomas of the head and neck cases studied, 12 had LOH at one or more loci on 7q. Fifty-three percent of 15 informative cases had LOH of the CA microsatellite dinucleotide repeat marker D7S522 at 7q31.1-7q31.2. Eleven of 18 colon carcinoma cases had LOH of one or more markers assayed, and the maximum LOH (80% of 10 informative cases) was at D7S522. Distributions of percentage of LOH in both tumor types were normally distributed around microsatellite D7S522. The high incidence of LOH in both tumor types studied suggests that a tumor suppressor gene relevant to the development of epithelial cancers is present on the 7q31.1-31.2, confirming our previous functional evidence for a tumor suppressor gene on chromosome 7.

Carcinoma, Squamous Cell↗
PubMed1995

Growth of mouse hepatocytes is stimulated by gastrin.

Hepatocyte growth is regulated by various growth factors, including epidermal growth factor (EGF) and insulin. Recently, several additional peptide hormones have been shown to stimulate growth of hepatocyte only in the presence of EGF or insulin and are thus termed secondary mitogens. Gastrin regulates growth of normal and neoplastic gastrointestinal tissues, but the effect on growth of hepatocyte is unknown. We examined the effect of gastrin on growth of a normal mouse hepatocyte (NMH) line established in our laboratory. Effect of gastrin-17 (G-17) (10(-8) to 10(-6) M) on growth of NHM cells was examined in either the presence or absence of EGF in the culture medium. Growth of NMH cells was evaluated by incorporation of either bromodeoxyuridine (BrdU) or 3H-thymidine and by counting cells. Presence of a cell-surface receptor for G-17 was determined by Scatchard analysis using 125I-G-17. In the presence of EGF, gastrin stimulated growth of NMH cells; in the absence of EGF, gastrin did not affect growth. The stimulatory effect of gastrin on NMH cells was blocked by JMV 320, a CCK-B type receptor antagonist. NMH cells possess a single, high affinity binding site for gastrin (Kd = 1.2 nM); EGF increased the gastrin binding capacity compared to non-treated cells (3.5 +/- 0.4 vs. 2.2 +/- 0.6 fmol/10(6) cells). G-17 stimulated growth of NMH cells through a single high affinity receptor for G-17 which pharmcologically appears to be the CCK-B type only in the presence of EGF and thus can be considered a secondary mitogen.

Animals↗