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101.
Differential effects of atropine and a cholecystokinin receptor antagonist on pancreatic secretion 总被引:2,自引:0,他引:2
G Adler M Reinshagen I Koop B G?ke A Schafmayer L C Rovati R Arnold 《Gastroenterology》1989,96(4):1158-1164
The present study evaluates the effect of atropine and of the cholecystokinin receptor antagonist loxiglumide on feedback regulation of basal pancreatic secretion in 6 healthy volunteers. The intraduodenal instillation of the protease inhibitor camostate reduced enzymatic activities of trypsin and chymotrypsin by 80%. This was accompanied by a strong increase in amylase and lipase output. The intravenous infusion of atropine (5 micrograms/kg.h) completely abolished the stimulatory effect of camostate on enzyme output. The infusion of loxiglumide (10 mg/kg.h) caused no changes in camostate-induced stimulation of enzyme output. Plasma levels of cholecystokinin were not altered after intraduodenal instillation of camostate whether atropine, loxiglumide, or saline were infused. We suggest that the protease inhibitor camostate, by inhibition of the enzymatic activity of trypsin and chymotrypsin, interferes with feedback regulation of basal pancreatic secretion in humans, and this mechanism is predominantly mediated by the cholinergic system. 相似文献
102.
Leptin inhibition of insulin secretion from isolated human islets 总被引:10,自引:0,他引:10
H. C. Fehmann P. Berghöfer D. Brandhorst H. Brandhorst B. Hering R. G. Bretzel B. Göke 《Acta diabetologica》1997,34(4):249-252
Leptin is a hormone produced and secreted from the adipose tissue. Its physiological actions include the regulation of satiety,
food intake and energy balance. The production of leptin is increased by high insulin levels. Here, we demonstrate that leptin
acts as an inhibitor of glucose-induced (20 mM) insulin secretion from isolated human islets. No effect was observed in the
presence of lower glucose levels (2.8 and 10 mM glucose). The pancreatic β-cell might represent a target of a direct physiological action of leptin. We suggest the presence of an “adipo-insular axis”
in which leptin mediates negative feedback from the adipose tissue to the endocrine pancreas.
Received: 21 July 1997 / Accepted in revised form: 1 October 1997 相似文献
103.
John H. Krege Jeffrey B. Hodgin John F. Couse Eva Enmark Margaret Warner Joel F. Mahler Madhabananda Sar Kenneth S. Korach Jan-ke Gustafsson Oliver Smithies 《Proceedings of the National Academy of Sciences of the United States of America》1998,95(26):15677-15682
Estrogens influence the differentiation and maintenance of reproductive tissues and affect lipid metabolism and bone remodeling. Two estrogen receptors (ERs) have been identified to date, ERα and ERβ. We previously generated and studied knockout mice lacking estrogen receptor α and reported severe reproductive and behavioral phenotypes including complete infertility of both male and female mice and absence of breast tissue development. Here we describe the generation of mice lacking estrogen receptor β (ERβ −/−) by insertion of a neomycin resistance gene into exon 3 of the coding gene by using homologous recombination in embryonic stem cells. Mice lacking this receptor develop normally and are indistinguishable grossly and histologically as young adults from their littermates. RNA analysis and immunocytochemistry show that tissues from ERβ −/− mice lack normal ERβ RNA and protein. Breeding experiments with young, sexually mature females show that they are fertile and exhibit normal sexual behavior, but have fewer and smaller litters than wild-type mice. Superovulation experiments indicate that this reduction in fertility is the result of reduced ovarian efficiency. The mutant females have normal breast development and lactate normally. Young, sexually mature male mice show no overt abnormalities and reproduce normally. Older mutant males display signs of prostate and bladder hyperplasia. Our results indicate that ERβ is essential for normal ovulation efficiency but is not essential for female or male sexual differentiation, fertility, or lactation. Future experiments are required to determine the role of ERβ in bone and cardiovascular homeostasis. 相似文献
104.
The aim of the study was to evaluate routine management of patients with community-acquired pneumonia (CAP) with regard to severity patterns, diagnostic approaches and results, as well as initial empiric antimicrobial treatment and its impact on outcome. Two hundred and thirty-two consecutive patients with CAP admitted to a primary care hospital were studied prospectively. Patients were classified according to Fine's severity score. Severe pneumonia was defined as admission at the ICU. Diagnostic approaches and initial antimicrobial treatment were judged according to the guidelines of the European Respiratory Society (ERS). Fifty-five patients (24%) had mild, 156 (67%) moderate, and 21 (9%) severe CAP. At least one microbial examination was performed in 124 patients (54%). There was no association between microbial investigation and severity of CAP. Inadequate initial antimicrobial treatment was significantly more frequent in severe (18/21, 86%), than in mild (5/55, 9%) and moderate CAP (39/156, 25%, P < 0.0001). Conversely, antimicrobial overtreatment occurred significantly more often in mild (30/55, 55%) and moderate (77/156, 49%) than in severe CAP (0/21, 0%, P < 0.0001). Inadequate initial antimicrobial treatment was more frequent in non-responders [18/62 (29%) vs. 31/170, (18%), RR 1.6 95% CI 0.9-2.6, P = 0.07] and was associated with a longer duration of hospitalization (17 +/- 11 vs. 14 +/- 8 days, P = 0.03). Mortality was not affected by inadequate initial antimicrobial treatment [5/62 (8%) vs. 10/170 (6%), RR 1.4 95% CI 0.5-3.9, P=0.55]. Principal conceptual weaknesses which might be subject to intervention were (1) the hospitalization of patients with mild pneumonia at low risk of mortality; (2) the lack of association between microbial investigation and severity of CAP; (3) antimicrobial overtreatment of patients with non-severe CAP; and (4) inadequate antimicrobial treatment with increased number of primary treatment failures and duration of hospitalization. 相似文献
105.
利用大鼠肾移植模型,以血、尿及移植肾组织免疫活性细胞、白细胞介素为研究指标,探讨GTW抗大鼠急性排异作用机理。结果量示,GTW可抑制移植肾组织排异反应。可减少肾移植大鼠外周血MRC OX-8阳性细胞(Tc/s,NK细胞)数量,抑制W3/2S(Th,单核细胞)、MRCOX-8(Ts/c,NK细胞)、MRCOX-19(T细胞)和IL-2R阳性细胞在移植肾组织内的浸润,减少尿IL-6的产生.斑点杂交未证实GTW可抑制移植肾组织IL-1α,βmRNA的表达. 相似文献
106.
Hertervig E Nilsson A Nilbert M Duan RD 《International journal of colorectal disease》2003,18(4):309-313
BACKGROUND AND AIMS. The sphingomyelin pathway is an important intracellular mechanism in regulating cell growth. The first step in this pathway is catalysed by sphingomyelinases. Alkaline sphingomyelinase is specifically located in the intestinal tract. Markedly reduced alkaline sphingomyelinase activities have been found in sporadic colorectal tumours and in familial adenomatous polyposis adenomas. Since the adenomatous polyposis coli (APC) gene is mutated in about 80% of sporadic colorectal tumors, and familial adenomatous polyposis is the consequence of a germline mutation of the same gene, we examined whether low alkaline sphingomyelinase activity is linked to APC gene mutations. PATIENTS AND METHODS. Both germline and sporadic adenomatous polyposis coli gene mutations were studied. Alkaline, neutral, and acid sphingomyelinase activities were measured in the intestinal mucosa and content of multiple intestinal neoplasia mice, a murine model of familial adenomatous polyposis and compared to control mice. Alkaline sphingomyelinase activity was also measured in 11 human rectal tumors with APC gene mutation and compared with 9 control tumors without mutation. RESULTS. Alkaline, neutral, and acid sphingomyelinase activities were present in the small intestine and colon in both mice types with no differences in hydrolytic capacity or distribution pattern. In sporadic rectal tumors similar alkaline sphingomyelinase activities were identified in tumors with somatic APC gene mutations as in samples without mutations. In the tumors without detectable APC mutations beta-catenin was analyzed, but no mutation was detected. CONCLUSION. Alkaline sphingomyelinase is not directly linked to adenomatous polyposis coli gene mutations. 相似文献
107.
Cheol-Hee Choi Hyun Bark Jae Myung Chung Eui Kyun Park Sang-Hyun Kim 《Immunopharmacology and immunotoxicology》2013,35(3):545-555
The multidrug resistance-associated protein (MRP1) mediates cellular efflux of various xenobiotics and cellular resistance to heavy metals. Previously we reported that MRP1 mediates resistance to mercury exposure and possible mechanism mediating MRP1 expression after mercury exposure. This study was designed to investigate the role of reactive oxygen species (ROS) and glutathione on the resistance of AML-2/DX100 cells to mercuric chloride. The MRP1 overexpressing cells (AML-2/DX100) cells showed less scavenging activity to ROS induced by mercury while no difference in the basal glutathione levels between AML-2/WT and AML-2/DX100 cells. Mercury induced the activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) but not c-jun-N-terminal kinase in AML-2/DX100 cells. The specific inhibitor for p38 MAPK and ERK, and antioxidant decreased the production of MRP1 and therefore resistance of AML-2/DX100 cells against mercury exposure. These results suggest that induction of ROS and downstream p38 MAPK and ERK were involved in the resistance of cells to mercury by expression MRP1 in AML-2/DX100 cells. 相似文献
108.
Sofi Isaksson Pär-Ola Bendahl Annette Salomonsson Mats Jönsson Monica Haglund Alexander Gaber Karin Jirström Per Jönsson Åke Borg Leif Johansson Johan Staaf Maria Planck 《Virchows Archiv : an international journal of pathology》2013,463(6):755-764
We investigated the epidermal growth factor receptor (EGFR) status in early stage lung cancer in Southern Sweden, a population for which there are no previous reports on the EGFR mutation frequency. Three hundred fifty small cell lung cancers, adenocarcinomas (AC), squamous cell carcinomas (SqCC), and large cell carcinomas were analyzed using a combination of techniques for the analysis of protein expression, gene copy numbers, and mutations. Immunohistochemical (IHC) staining with antibodies for the EGFR mutations L858R and del E746-A750 revealed intratumoral heterogeneity and several discrepant cases when compared to mutation-specific polymerase chain reaction (PCR)-based analysis. The frequencies of these two mutations, when considering IHC staining with mutation-specific antibodies in a cohort of 298 cases and subsequent confirmation by PCR, were 10 % in AC and <2 % in SqCC. Furthermore, screening by sequencing of EGFR in a cohort of 52 lung AC and squamous carcinomas demonstrated a more diverse mutation spectrum, not covered by the mutation-specific antibodies. High expression of total EGFR protein was correlated to high gene copy numbers but did not reflect the mutational status of the tumors. We believe that the mutation spectra in a Southern Swedish population is too diverse to be covered by the mutation-specific antibodies, and we also raise some other issues regarding the use of the mutation-specific antibodies, for example concerning heterogeneous expression of the mutated protein, optimal antibody dilution, and discrepancies between staining results and PCR. 相似文献
109.
110.
Catharina Müller Oskar Rosmark Emma Åhrman Hans Brunnström Katharina Wassilew Annika Nybom Barbora Michaliková Hillevi Larsson Leif T. Eriksson Hans H. Schultz Michael Perch Johan Malmström Jenny Wigén Martin Iversen Gunilla Westergren-Thorsson 《The American journal of pathology》2021,191(8):1398-1411