Biomedical subjects
J C Thompson
Publications and source records attributed to J C Thompson.
The conversion of laevulose and fatty acid into glucose.
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The effect of aging on the growth of colon cancer.
Reports on the effect of patient age on the prognosis for colon cancer vary. We have tested the effect of aging using a model of murine colon adenocarcinoma in groups of mice of different ages. In experiment A, Balb/c mice of age groups 3-4 weeks, 10-12 weeks, 24-32 weeks and 40-48 weeks (13 mice/group) were injected with 5 X 10(4) MC-26 cells subcutaneously in the right flank. Tumors were measured twice weekly, and the rate of occurrence of tumor, mortality rate, and growth rate were calculated. In experiment B, the same plan as experiment A was used, except mice of age groups I (14 days), II (3-4 weeks), and III (20-22 months) were used with tumor doses of 1 X 10(4) cells and 5 X 10(5) cells (9-15 mice/group). In both experiments, the rate of growth of tumor, mortality rate, and sizes of tumors obtained were the same. In experiment A, the rate of occurrence of the tumors was the same in all groups, but in experiment B the occurrence of the tumor varied. A palpable tumor appeared earliest in the weanling mice (14 days), next in old mice (20-22 months), and last in the young adult group (3-4 weeks). Tumor doubling time was longest in the young adult mice (7 days), intermediate in the old mice (6.1 days), and shortest in the weanling mice (5.5 days). Established tumors grew at similar rates (as assessed by doubling time), independent of host age. Mortality rates were similar.(ABSTRACT TRUNCATED AT 250 WORDS)
Pentagastrin-stimulated DNA synthesis in mouse gut is influenced by the circadian system.
Gastrin is trophic for rodent gut mucosa. Proglumide, a competitive inhibitor of gastrin, can exert an antitrophic effect and can block pentagastrin-stimulated DNA synthesis. We have examined the influence of the circadian system on pentagastrin-stimulated DNA synthesis in the murine stomach (glandular and nonglandular stomach) and colon. We studied 224 male CD2F1 mice divided into four groups. Group A was ad lib fed (controls). Groups B, C, and D received 6-9 intraperitoneal injections of either NaCl, pentagastrin or pentagastrin + proglumide, at 8-h intervals prior to sacrifice. Mice from each group (A-D) were killed (by cervical dislocation) at 3-h intervals for 24 h. Incorporation of tritiated thymidine (DNA synthesis) was measured, and significant (p less than 0.001) circadian rhythms were found, which were not eliminated after treatment with either pentagastrin or pentagastrin + proglumide. DNA synthesis in the glandular stomach increased significantly after treatment with pentagastrin , but only during the span of time when DNA synthesis was increasing also in control mice; it had no effect at other times. Proglumide blocked the effect of pentagastrin only during the time of increasing DNA synthesis; it had no effect at other times. The identical regimen given at different times in the circadian cycle yielded significantly different results. In the intact animal, studies on the effects of various stimulators or inhibitors of DNA synthesis should be time-qualified.
Age-related changes in polyamine biosynthesis after fasting and refeeding.
The effect of aging on ornithine decarboxylase (ODC) activity and polyamine biosynthesis in the proximal small intestine was studied in two groups of male Fisher 344 rats (young [4-month old] and aged [26- to 27-month old]) using a fasting and refeeding model. In control (nonfasted) rats, levels of polyamines (putrescine, spermidine and spermine) and ODC activity were significantly higher in aged compared with young rats. In aged rats, fasting significantly reduced the levels of putrescine by 41%, spermidine by 23%, and spermine by 11%; however, fasting had no effect on polyamine levels in young rats. ODC activity was decreased 75% in young and 50% in aged rats after fasting compared with the respective age-matched controls. Conversely, 2 h after reinstituting a chow diet increased ODC activity by 17-fold in young rats but only 8-fold in aged rats. Putrescine levels were also increased in both age groups after refeeding; however, similar to ODC activity, these increases were much less in aged rats. In addition, spermidine and spermine levels remained significantly depressed in the aged groups even after 24 h of refeeding. These findings suggest that the normal rigid control of gut polyamine biosynthesis and proliferation noted in young rats is markedly altered with aging.
Experimental infection of sheep and cattle with Leptospira interrogans serovar balcanica.
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Peptide YY inhibits gastric acid secretion stimulated by the autonomic nervous system.
Peptide YY (PYY), a new peptide found primarily in mucosal endocrine cells of the terminal ileum and colon, inhibits pentagastrin-stimulated gastric acid secretion in several species, including man. Several studies indicate that PYY can affect autonomic neurotransmission, and we have recently shown that PYY can inhibit neurally stimulated release of insulin. The purpose of the present study was to examine the effect of PYY on gastric acid secretion stimulated by the autonomic nervous system. On separate days, 6 dogs that were prepared with chronic gastric cannulas were given 2-deoxy-D-glucose (2-DG; 90 mg/kg, i.v.) for 6 min, either alone, or in combination with PYY (100, 200, or 400 pmol.kg-1.h-1, i.v.) for 60 min. The effect of PYY, at 400 pmol.kg-1.h-1, on gastric acid secretion stimulated by either 2-DG or PG (1 micrograms.kg-1.h-1, i.v.) was studied after treatment with propranolol (0.5 mg/kg, i.v. bolus) or phentolamine 1 mg/kg, i.v. bolus). PYY reduced the 2-DG-stimulated secretion of gastric acid in a dose-dependent manner. PYY, given at 100 pmol.kg-1.h-1, reduced gastric acid output by 29 +/- 17%; PYY, at 200, by 41 +/- 7% (p < 0.05), and PYY, at 400, by 52 +/- 8% (p < 0.05). The inhibitory action of PYY on 2-DG-stimulated secretion of gastric acid persisted after treatment with phentolamine (69 +/- 14%; p < 0.05), but it was blocked by treatment with propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibitory action of peptide YY on pancreatic secretion is independent of secretin.
The purpose of this study was to characterize the effect of peptide YY (PYY) on acid-stimulated pancreatic bicarbonate secretion and to determine whether PYY affects the release of secretin in response to intraduodenal infusion of acid. Six dogs were prepared with gastric and pancreatic cannulas. In study 1, graded doses of hydrochloric acid (HCl) (3, 6, 12, and 24 mEq/h) were given intraduodenally alone or in combination with intravenous PYY (400 pmol/kg.h). In study II, and ED50 of intraduodenal HCl (6 mEq/h) was given alone or in combination with graded doses of PYY (12.5, 25, 50, 100, 200, and 400 pmol/kg.h, i.v.). Bicarbonate output was significantly inhibited during PYY infusion at 200 and 400 pmol/kg.h, but plasma secretin levels were unchanged. The calculated maximal response for bicarbonate secretion (5.1 +/- 1.3 mEq/15 min) was significantly reduced by PYY (2.1 +/- 0.7 mEq/15 min). We concluded that PYY can inhibit acid-stimulated pancreatic bicarbonate secretion without affecting the release of secretin. The mechanism of the inhibitory effect of PYY on acid-stimulated pancreatic bicarbonate secretion is compatible with a noncompetitive type of inhibition.
Effect of a cholecystokinin antagonist, proglumide, on cholecystokinin-8-induced gallbladder contraction in conscious dogs.
The objective of this study was to characterize the effect of proglumide, a cholecystokinin (CCK) antagonist, on gallbladder contraction stimulated by CCK in conscious dogs. The gallbladder contraction was monitored by a strain-gauge force transducer that was chronically sutured onto the serosal surface of the gallbladder. The results of this study show that proglumide, given as an intravenous bolus (2.5, 5, 10, 20, and 40 mg/kg) or as a continuous intravenous infusion (150 or 300 mg/kg/h, 10 min), can block the stimulatory action of CCK in a dose-related manner. Bolus administration of proglumide resulted in a transient inhibition, whereas continuous infusion of proglumide resulted in a prolonged antagonism of CCK-stimulated gallbladder contraction. Review of the data leads to the conclusion that the antagonistic action of intravenously administered proglumide on CCK-stimulated gallbladder contraction may be characterized as rapid and reversible.
Neurotensin secretion in response to intraduodenal and intraileal administration of fat in dogs.
Release of neurotensin from the small intestine in response to administration of fat directly into the duodenum and ileum was examined in conscious dogs. The present results show that: (1) intraduodenal administration of fat causes a diphasic release of neurotensin which is mediated, at least in part, by cholinergic mechanisms, and (2) both a fatty acid (sodium oleate) and a triglyceride, when infused directly into an isolated ileal loop, stimulate a significant release of neurotensin. Our findings indicate that release of neurotensin is triggered by mechanisms originating in the proximal small intestine and by a direct contact of nutrients with the ileal mucosa.
Transmembrane signalling of cholinergic-stimulated contraction in isolated rat glomeruli.
Exposure of isolated rat glomeruli to carbachol (Carb) 1 mM induces glomerular (mesangial cell) contraction which is inhibited by pirenzepine. To identify the cellular signalling mechanism, we analyzed Carb-activated phosphoinositide hydrolysis in myo-[2-3H] inositol preloaded cells of isolated rat glomeruli. Carb evoked a rapid (5 s, 30.4 +/- 8.3% of basal) and sustained (60 s, 157.2 +/- 1.2% of basal) inositol trisphosphate (IP3) response. Acetylcholine 100 microM (Ach) in the presence of eserine also evoked IP3 formation. Mobilization of Ca2+ was monitored by preloading glomerular cells with 45Ca2+ (200 microCi/ml) and analyzing the cellular efflux using a constant perifusion system. Both Carb and Ach induced transient 45Ca2+ efflux, with peak values above baseline of 69.0 +/- 19.9 and 71.5 +/- 7.9%, respectively. Incubation with pirenzepine or prior release of Ca2+ from an IP3-sensitive intracellular pool by Thapsigargin (2 microM) prevented Carb-evoked Ca2+ release (100 and 60%, respectively). Therefore, glomerular cells possess functional cholinergic receptors which stimulate contraction via IP3-mediated intracellular Ca2+ release.
Behavioral changes in Huntington Disease.
OBJECTIVES: This study aimed to gain a better understanding of behavioral abnormalities in Huntington disease (HD) and to develop a method for reliably assessing these changes. BACKGROUND: Behavioral changes are a central feature of HD and often cause considerable distress and difficulty to patients and their relatives. However, they have received little attention from research despite their prevalence and clinical significance. METHODS: One hundred thirty-four patients with HD were assessed using the Problem Behaviors Assessment for Huntington Disease (PBA-HD), an instrument for rating the presence, severity and frequency of behavioral abnormalities in HD. RESULTS: The findings confirm that behavioral problems are common among patients with HD. The most common symptoms were loss of energy and initiative, poor perseverance and quality of work, impaired judgment, poor self-care and emotional blunting. Affective symptoms such as depression, anxiety and irritability occurred in around half the patients studied. Psychotic symptoms (hallucinations and delusions) were rarely reported. Factor analysis distinguished three clusters of behavioral symptoms, which were interpreted respectively as reflecting Apathy, Depression and Irritability. The 'Apathy' factor was highly correlated with duration of illness, whereas no such relationship was observed for the 'Depression' and 'Irritability' factors. CONCLUSIONS: The results suggest that certain behavioral changes are fundamental to the progression of HD, whereas others have a more complex relationship to the disease process. The findings have implications for the choice of behavioral measures used to evaluate efficacy of therapeutic interventions.
Program evaluation within a health promotion framework.
Program evaluation can assist in assessing the conceptualization, design, implementation and utility of health promotion action. Evaluation of health promotion, with multiple strategies combining individual, social and policy action, lends itself to an evaluation-as-politics paradigm. Consideration of the interests of all major stakeholders, use of a series of related studies, and a commitment to multiple methods and multiple perspectives characterize this paradigm. Simple, practical research that is adequate for answering relevant questions is required. The program evaluator is not a neutral, scientific observer--he/she is a participant in the political arena along with other stakeholder groups. A model of the areas of interest in evaluation of health promotion, some potential evaluation questions, and a health promotion impact evaluation model are presented to emphasize unique aspects involved in evaluation of health promotion action. The evaluator can take a proactive role and challenge problems in conception and implementation of health promotion action. He/she can advocate for health promotion.
Change in endocrine pancreatic function in short-term diet restriction.
Long-term diet restriction can retard the aging process. Lower sustained plasma glucose levels may be one of the key factors for prolongation of life. The purpose of this study was to determine the effects of short-term diet restriction on the endocrine pancreas in rats. One hundred 5-wk-old male Sprague-Dawley rats were fed ad libitum for 1 wk, and then 10 rats (5 fed, 5 fasted for 24 h) were killed. The remaining 90 rats were divided into two groups, either fed ad libitum or maintained on a restricted food intake (60% of control/day). At regular intervals after the start of food restriction, rats from each group were killed, and plasma and the pancreas were collected for measurements of glucose, insulin, and glucagon concentration and content. At the end of the study, isolated pancreatic perfusions were performed to examine dynamic insulin response to glucose. Throughout the study, plasma glucose and insulin levels were lower in fed rats from the diet-restricted group than in fed rats from the normally fed group. Furthermore, there were no differences in plasma glucose or insulin levels between fed and fasted rats in the diet-restricted group. Pancreatic perfusion showed that the second phase of insulin release was significantly lower in rats from the diet-restricted group than in rats from the normally fed group. Decreased content of spermine in the pancreas of the diet-restricted rats may correlate with a decreased second phase of insulin release. These findings may partly explain why lowered plasma insulin levels are observed in diet-restricted rats.
Autoimmune hemolytic anemia with both cold and warm autoantibodies.
Of 144 patients with a positive direct antiglobulin test and having autoimmune hemolytic anemia (AIHA), 12 (8.3%) satisfied diagnostic criteria for both warm antibody AIHA and cold agglutinin syndrome. All 12 patients had IgG and C3d sensitizing their erythrocytes, and samples of their serum contained IgM cold autohemagglutinins optimally reactive at 4 degrees C, but with a high thermal amplitude to 37 degrees C, and IgG warm autoantibodies. All red blood cell eluates contained IgG warm autoantibodies. The 12 patients had severe hemolytic anemia that responded dramatically to corticosteroid therapy, with the mean hemoglobin level increasing from 6.3 to 12.9 g/dL. Five patients (42%) had systemic lupus erythematosus, one patient (8%) had a non-Hodgkin's lymphoma, and six patients (50%) had idiopathic AIHA; four patients (33%) had concomitant thrombocytopenia (Evans' syndrome). Nine patients (75%) were female. Four patients had unexpected alloantibodies potentially capable of in vivo hemolysis of transfused blood. Because of the severe hemolysis, the serologic findings, and the dramatic initial clinical response to corticosteroid therapy, these patients represent a distinct catagory of AIHA and should be given corticosteroid therapy quickly.
Mentoring: a professional commitment.
Nursing professionals have an obligation to increase the number and quality of nurses of color in the profession. Nursing students of color are often at risk of dropping out of the nursing program. Leaders of the National Black Nurses Association recognize the value of mentoring to improve student retention. Mentors help others reach their life goals by offering their proteges support, nurturing, and professional contacts. Non-traditional students over the age of 25 and students of color especially need the benefits of a mentor to help overcome inherent prejudicial assumptions in the educational system. The Board of Regents of the University of the State of New York recommended support systems to improve retention of students of color. The Queens County Black Nurses Association developed a pilot mentor project in 1991, establishing ten mentor-protege relationships. In 1992, five more relationships were added. Of the initial group, two proteges graduated and completed the NCLEX-RN exam. One student left for failure to meet academic requirements. The remaining seven are making progress, but more programs are needed. Professional nurses who have achieved success are reaching out to assist others whose potential has yet to be tapped. The QCBNA's project goes on, guaranteeing a continuous body of well-trained nurses of color to meet the health care needs of a growing, underserved population.
Bombesin stimulates in vitro growth of human breast cancer independent of estrogen receptors status.
BACKGROUND: Approximately 180,000 women will be found to have breast cancer this year in the United States. Chemotherapy has limited success in advanced disease and the effect of tamoxifen appears to require a functional estrogen-receptor (ER). Our aim was to determine whether bombesin (BBS) regulates growth of human breast cancer cells. METHODS: Estrogen-dependent (MCF-7), estrogen-responsive (ZR-75-1) and estrogen-independent (MDA-MB-231) human breast cancer cells were studied. Receptors were identified by cross-linking methods and radioligand binding assays; intracellular calcium ([Ca2+]i) was measured after BBS treatment to confirm functional status of the receptor; and the effect of BBS on cell growth was measured directly. RESULTS: All three cell lines had a high affinity BBS receptor (Kd = 1-7 nM; molecular weight 75 kDa). BBS stimulated [Ca2+]i levels as well as cell growth in all three cell lines; the trophic effect was blocked by BBS receptor antagonists. CONCLUSIONS: We conclude that BBS is trophic for human breast cancers independent of ER status, and that antagonism of the BBS receptor may be a useful target for hormonal therapy in ER-negative breast cancer.