[Effects of somatostatin and glucagon on secretion of bile lipids in man].
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Bile↗
Biomedical subjects
K Takebe
Publications and source records attributed to K Takebe.
10.5-kb homozygote of tumor necrosis factor-beta gene is associated with a better prognosis in gastric cancer patients.
BACKGROUND: In NcoI restriction fragment length polymorphism analysis of tumor necrosis factor-beta (TNF-beta) gene, the frequency of 10.5-kb homozygote is low in patients with lung cancer and is associated with a better prognosis. These results should be examined in other malignancies. METHODS: Using polymerase chain reaction, the authors performed NcoI restriction fragment length polymorphism analysis in 152 patients with gastric cancer, in 69 patients with benign gastric lesion, and in 141 healthy volunteers. RESULTS: In 3-year survival, the 10.5-kb homozygote showed a better prognosis (87.1%) than other alleles (5.5-kb homozygote, 52.5%; heterozygote, 79.1%), and there was a statistically significant difference between the 10.5-kb homozygote and the 5.5-kb homozygote. In 3-year survival for Stages III and IV, the 10.5-kb homozygote also showed a better prognosis (64.9%) than other alleles (5.5-kb homozygote, 16.7%; heterozygote, 41.4%). There were statistically significant differences (10.5-kb homozygote vs. 5.5-kb homozygote, P < 0.01; heterozygote vs. 5.5-kb homozygote, P < 0.05). There was a statistical difference between all patients and Stages III and IV (P < 0.05). CONCLUSIONS: The 10.5-kb homozygote of TNF-beta gene is associated with a prolonged survival in patients with gastric cancer, as has been shown in the patients with lung cancer.
Aged↗
Role of prostaglandins E1, E2 and F2 alpha in the brain in interleukin 1 beta-induced adrenocorticotropin secretion in the rat.
It is well known that interleukin (IL)-1 is a potent activator of the hypothalamo-pituitary-adrenal axis in the rat. Many studies have reported that prostaglandins (PGs), especially PGE2, in the brain may mediate the IL-1 stimulation of corticotropin-releasing hormone release, which then leads to adrenocorticotropin (ACTH) secretion. However, a general consensus has yet to emerge regarding whether PGE2 is the only or the most important PG in the brain mediating IL-1-induced ACTH secretion in the rat. To address this question, we examined the effect of intracerebroventricular (icv) administration of antisera against PGE1, PGE2 or PGF2 alpha, or normal rabbit serum on the ACTH response induced by an icv injection of IL-1 beta in the rat. Each antibody or normal rabbit serum (as the control) was given icv 15 min before an icv administration of human recombinant IL-1 beta (50 ng). IL-1 beta produced a significant rise in plasma ACTH levels, and this response was significantly suppressed by either of the three PG antibodies. Interestingly, the inhibitory effect of anti-PGE2 antibody seemed to be somewhat weaker than those of the other two antibodies. We conclude that not only PGE2 but also PGE1 and PGF2 alpha in the brain may mediate the IL-1 beta stimulation of ACTH secretion in the rat.
Adrenocorticotropic Hormone↗
Steatorrhea in Japanese patients with chronic pancreatitis.
Fecal fat excretion, fecal mass, fecal fat concentration, and the coefficient of fat absorption were evaluated in 31 normal Japanese subjects with a mean fat consumption of 61.8 g and compared with the values in 43 Japanese patients with chronic pancreatitis (CP) with a fat consumption of 40.2 g. Fecal fatty acids were analyzed by the gas chromatographic method. Fecal fat excretion by normal individuals was 1.7 +/- 1.0 (Mean +/- SD) g/day (range, 0.4-4.9 g/day). Steatorrhea was therefore defined as fecal fat excretion that exceeded 5.0 g/day. The patients with CP were divided into three groups: non-steatorrhea (fecal fat < 5.0 g/day), chemical steatorrhea (fecal fat > or = 5 g/day and no appearance of fatty stool), and manifest steatorrhea (evaluated from the appearance of fatty stool). In addition, we investigated the correlation between fecal fat excretion and pancreatic exocrine function, obtained by the pancreozymin-secretin (or secretin) test in 24 controls and 30 CP patients. Fecal fat excretion by CP patients was 9.1 +/- 8.8 g/day, which was significantly higher (P < 0.01) than that of controls. There were 28 (65%) CP patients with steatorrhea. Of these, 15 (35%) showed chemical steatorrhea and 13 (30%) manifest steatorrhea. In CP patients, the fecal mass (250.5 +/- 133.6 g vs control, 125.6 +/- 52.5 g), fecal fat concentration (3.40 +/- 2.16 g% vs control, 1.48 +/- 0.89 g%), and coefficient of fat absorption (77.3 +/- 20.2% vs control, 97.2 +/- 1.7%) all showed significant differences from the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
No negative feedback regulation between plasma CCK levels and luminal tryptic activities in patients with pancreatic insufficiency.
The study was conducted on five healthy subjects and six patients with calcifying pancreatitis (CP) and steatorrhea. Following overnight fasting, one tube each was placed in the stomach and the upper of the small intestine, respectively. Through the gastric tube, a test meal that included 30 g of fat (total calories, 625 kcal, 500 mL) was infused over a span of 30 min. Every 30 min (up to 150 min), fluid samples in the upper small intestine were collected and chilled, and the amylase, trypsin, and lipase levels were determined. In addition, in the case of the CP patients, a high-potency pancreatin preparation was infused into the stomach together with the test meal. In order to determine the plasma CCK level, blood sample were collected before test meal infusion and at 10, 20, 30, 45, 60, 90, 120, and 150 min subsequent to infusion. The plasma CCK was extracted using a Sep-Pak C-18 cartridge and analyzed with radioimmunoassay using an OAL-656 antibody. The result was converted to the CCK-8 level and expressed in pg/mL. The enzyme activities in the upper small intestine of the CP patients after test meal administration amounted to 22.8 (amylase), 10.8 (trypsin), and 16.9% (lipase) compared with the corresponding figures for the normal subjects. Following administration of a high-potency pancreatin in patients with CP, enzyme activities in the upper small intestine increased to 132.2 (amylase), 38.7 (trypsin), and 45.3% (lipase) compared with levels in the normal subjects. However, the healthy subjects and the CP patients, both with and without treatment with supplementary exogenous enzymes, all exhibited similar profiles in the plasma CCK response to stimuli. Based on these findings, we concluded that a negative feedback mechanism does not exist between the tryptic activity of the upper small intestine and the CCK secretory response in patients with chronic pancreatitis.
Adult↗
Central neuropeptide Y enhances bile secretion through vagal and muscarinic but not nitric oxide pathways in rats.
Neuropeptide Y (NPY) acts in the central nervous system to regulate gastrointestinal functions in rats and dogs. The effects of intracisternal injection of NPY on bile secretion and biliary components were investigated in urethane-anesthetized rats with bile duct cannula. Intracisternal NPY (0.02-0.12 nmol) dose-dependently increased bile secretion by 9.2-19.5%. The secretory response occurred within the first 20-40 min and lasted for the 120-min observation period. Intravenous injection of NPY (0.12 nmol) did not modify bile secretion under identical conditions. Biliary bile acid, phospholipid, and cholesterol secretion were not modified by intracisternal injection of NPY (0.12 nmol), whereas bicarbonate was increased by 19.0 +/- 1.7% from 40 to 120 min after NPY injection. Cervical cord transection at the C6 level, acute bilateral adrenalectomy (-120 min), or injection of NG-nitro-L-arginine methyl ester (10 mg/kg, IV, -15 min), an inhibitor of nitric oxide biosynthesis, did not alter intracisternal NPY (0.12 nmol)-induced stimulation of bile secretion. Atropine (2.0 mg/kg, IP, -30 min) and bilateral cervical vagotomy (-120 min) completely abolished the stimulatory effect of intracisternal NPY (0.12 nmol) on bile secretion. These findings indicate that NPY acts in the brain to stimulate bicarbonate-dependent bile secretion through vagal and muscarinic pathways and suggest that peptides in the central nervous system may be involved in the vagal regulation of bile secretion.
Acetylcholine↗
Analysis of survival of allogeneic fetal liver fragments in rats.
The survival of allogeneic fetal liver fragments in the omentum was analyzed in rats. The lymphocyte subsets of the spleen and peripheral blood were also examined. When the fetal liver fragments were transplanted into the omentum, they survived for 2 wk, whereas adult liver fragments survived only 1 wk. In fetal liver fragments transplantation, the CD8 positive lymphocyte percentage in peripheral blood decreased significantly 3 wk after transplantation in comparison with that in adult liver fragment transplantation. The skin graft of the donor party showed a longer median survival time in rats receiving fetal liver fragment transplants than that in recipients of adult liver fragments. Although further study is needed, allogeneic fetal liver fragments survived longer in the omentum than reported elsewhere, and the decrease of CD8 positive peripheral blood lymphocytes may have been the reason for this.
Animals↗
Intragastric fermentation in patients with gastroparesis diabeticorum.
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Adult↗
A study on the role of circulating prostaglandin E2 in the adrenocorticotropin response to intravenous administration of interleukin-1beta in the rat.
It is almost generally agreed that prostaglandins (PGs), especially PGE2, may play a significant role in mediating corticotropin-releasing hormone (CRH) and adrenocorticotropin (ACTH) secretion by interleukin (IL)-1. The origin and site of action of PGE2 involved in this response appear to be within the brain, but the possibility has yet to be excluded that circulating PGE2, which increases after a systemic administration of IL-1, enters the brain to stimulate CRH and ACTH release. In this study, we attempted to answer the question utilizing in vivo experimental paradigms in conscious male rats. Intravenous bolus injection of recombinant human IL-1beta (3 mu g/kg) caused a prompt and robust rise in plasma ACTH (peak, 748 +/- 183 (-x +/- SE) pg/ml at 20 min), but this was not associated with a significant change in plasma PGE2 up to 120 min postadministration. Intravenous bolus injection of PGE2 at doses of 0.1 mg and 1.0 mg/kg BW resulted in dose-dependent significant elevations of the plasma ACTH with peak levels being 155 +/- 27 pg/ml (at 10 min) and 343 +/- 35 pg/ml (at 20 min), respectively. Peak PGE2 levels in the plasma which occurred 10 min after injecting either dose of PGE2 were 13,245 +/- 5,093 and 57,150 +/- 350 pg/ml, respectively. Thus the ACTH response which followed the plasma PGE2 levels of 13,000-57,000 pg/ml was even lower than the ACTH response to IL-1beta which did not cause a significant rise in the plasma PGE2. We conclude from these results that circulating PGE2 is not involved in the ACTH response to intravenous administration of IL-1beta. It is thus very likely that the source and site of action of PGE2 mediating the hormonal response are in the brain. However, this study does not exclude a possible role for other circulating PGs in the IL-1beta stimulation of ACTH secretion in the rat.
Adrenocorticotropic Hormone↗
Serum fatty acid composition in normal Japanese and its relationship with dietary fish and vegetable oil contents and blood lipid levels.
A survey was conducted on 110 normal Japanese adults (55 men and 55 women) to determine their caloric intake, dietary fat content and its origin (animal, plant, or marine). In addition, their blood lipid levels and fatty acid compositions were examined. Men in their 30s-50s consumed 2,600-2,800 calories and 60 g of fats, while women in the same age range consumed 2,000-2,200 calories and 52-58 g of fats. In both sexes, caloric, fat, and cholesterol intakes were lower for those in their 60s but protein and crude fiber consumption remained generally unchanged. When the dietary fats were classified according to origin, men and women in their 30s were found to consume less oil of marine origin. This appeared to be the result of a western style diet for Japanese adults in their 30s. Compared with men, women exhibited lower blood lipid levels. As age increased, the total cholesterol level of the blood rose in women. Thus the blood lipid level was generally equal in the two groups in their 60s. There was a positive correlation between the blood eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels and dietary consumption of fish oil. The marine/plant lipid ratio was positively correlated with the blood EPA/arachidonic acid ratio. Therefore, it was believed that the origin of the dietary fats consumed is a factor in determining the blood fatty acid profile. The linoleic acid (18:2), arachidonic acid (20:4), and 18:2 + 20:4 contents were negatively correlated to the total cholesterol level in the blood but positively correlated to the HDL-cholesterol level. Polyunsaturated fatty acids (18:2 + 20:4 + 20:5 + 22:6) were negatively correlated with the blood triglyceride level. From the findings presented above, we concluded that dietary fats not derived from animal sources should be classified into fish and vegetable oils to evaluate their dietary significance. We also noted that Japanese in their 30s consume less fish oil, indicating the western trend in their dietary lipid consumption.
Adult↗
A case of cyclical Cushing's disease associated with corticosteroid-binding globulin deficiency: a rare pitfall in the diagnosis of Cushing's disease.
We experienced an extremely unusual combination of Cushing's disease and corticosteroid-binding globulin (CBG) deficiency that has been reported in only one similar case to date. A 53-year-old woman presented at a medical clinic with clinical Cushing's disease. However, her plasma levels of adrenocorticotropin (ACTH) and cortisol were in the normal range. Six months later, during a second visit, a high urinary excretion of 17-hydroxycorticosteroids was found, but plasma ACTH and cortisol levels were normal again. Further investigation revealed a decreased CBG concentration. Free plasma cortisol levels were clearly elevated. Furthermore, the Cushing's disease of our patient was complicated by periodic secretion of ACTH and cortisol, with high or normal outputs of corticosteroids occurring alternately every 1-3 days, which explained the occasionally normal plasma ACTH and cortisol levels. A combination of a decreased serum CBG concentration and periodic secretion of ACTH can be an important pitfall in the diagnosis of Cushing's disease.
17-Hydroxycorticosteroids↗
[Relationship between insulin secretion and insulin resistance in nondiabetic subjects with myotonic dystrophy--a case control study].
Hyperinsulinemia in myotonic dystrophy (MyD) is generally considered as a result of insulin resistance. However, as a consequence of abnormality in systemic membrane fluidity in this disease, abnormal insulin clearance or intrinsic pancreatic beta-cell dysfunction could also contribute to the hyperinsulinemia. To clarify the cause of hyperinsulinemia in MyD, we examined the insulin resistance, insulin clearance and the capacity of insulin secretion in 6 patients with MyD. They received a euglycemic hyperinsulinemic (insulin 40 mU/m2/min) clamp study for the quantification of insulin resistance by the glucose infusion rate (GIR). We evaluated their capacity of insulin secretion by the ratio of increment of serum insulin level to that of plasma glucose level 30 minutes after a 75 g oral glucose load (insulinogenic index; I.I.) and the ratio of area under the curve of serum insulin levels to that of plasma glucose levels during a 75 g oral glucose load (AUCIRI/AUCPG). The I.I. (1.1 +/- 0.6 vs 0.4 +/- 0.3, p < 0.05) and the AUCIRI/AUCPG (0.5 +/- 0.2 vs 0.2 +/- 0.1, p < 0.01) in MyD were significantly greater than those of GIR, body mass index and sex matched 6 non-diabetic controls respectively. Insulin clearance, estimated by the level of insulin and C-peptide before and during a euglycemic clamp study did not differ between the two groups. These results indicate that the postload hyperinsulinemia observed in MyD is not solely resulted from insulin resistance. Other factors, such as intrinsic beta-cell disorder may be involved.
Adult↗
[A comparative study of tazobactam/piperacillin and piperacillin in bacterial pneumonia].
The efficacy, safety and usefulness of tazobactam/piperacillin (TAZ/PIPC), in bacterial pneumonia and lung abscess were determined with PIPC as the control in a multi-institutional comparative study a penicillin antibiotic for injection prepared by combining a newly developed beta-lactamase inhibitor, tazobactam (TAZ), with a broad spectrum penicillin antibiotic, piperacillin (PIPC), at a ratio of 1:4. TAZ/PIPC was intravenously injected at a dose of 2.5 g (titer) twice a day, and PIPC at a dose of 2.0 g (titer) twice a day as a rule for 14 days. The following results were obtained: 1. The efficacy rates for bacterial pneumonia and lung abscess were 94% (80/85) in TAZ/PIPC group and 89% (70/79) in PIPC group, showing no significant difference between the two groups. 2. In a comparison of degrees of improvement in clinical symptoms, signs and laboratory findings, there were no significant differences between the two groups except for results on thoracic rales after three days of administration. 3. As for bacteriological effects, the elimination rates of causative organisms were 98% (40/41) in the TAZ/PIPC group and 80% (28/35) in the PIPC group. Thus, the TAZ/PIPC group was significantly superior to the PIPC group. The TAZ/PIPC group showed significantly better eradication of bacteria as well. Bacteria considered to be pyogenic were detected in 80 patients (43 administered TAZ/PIPC and 37 administered PIPC), but beta-lactamase production was confirmed in only 11 patients of each group. There were no significant differences in bacteriological effects among these patients. Minimum inhibitory concentrations of TAZ/PIPC against beta-lactamase producing organisms were distinctly superior to those of PIPC. 4. Side effects occurred in 10% (10/96) of the TAZ/PIPC group and 7% (7/95) of the PIPC group. Abnormal clinical laboratory test values were observed in 22% (20/92) of the TAZ/PIPC group and 18% (17/93) of the PIPC group. Thus, there were no significant differences between the two administration groups. 5. The usefulness rate in the TAZ/PIPC group was 87% (75/86) and it was 85% (67/79) in the PIPC group, showing no significant difference between them. The results suggest that TAZ/PIPC administered at a dose of 2.5 g (titer) twice a day is more useful than PIPC administered at a dose of 2.0 g (titer) twice a day in the treatment of bacterial pneumonia.
Adult↗
[17-Hydroxycorticoids (17-OHCS) and its fractions].
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17-Hydroxycorticosteroids↗
The influence of fatty liver on insulin clearance and insulin resistance in non-diabetic Japanese subjects.
OBJECTIVE: To determine whether fatty liver impairs insulin clearance and contributes to insulin resistance in obese and lean healthy non-diabetic men and women. DESIGN: Cross-sectional, descriptive. SETTING: Medical outpatient clinic; university hospital. SUBJECTS: Twenty-seven (14 men) non-diabetic obese (Body fat % = 31.5 +/- 9.3; mean +/- s.d.) and 19 (13 men) non-diabetic non-obese (body fat % = 19.0 +/- 6.8; P < 0.01 vs obese) healthy subjects aged 31-64 without liver disease. MAJOR OUTCOME MEASURES: Liver density relative to the spleen on CT scan (LFS), glucose infusion rate (GIR) and metabolic insulin clearance rate (MIC) during euglycemic hyperinsulinemic clamp; anthropometric (waist-hip ratio: WHR) and CT-determined (visceral fat area: VFA) measures of fat distribution. RESULTS: Fatty liver was inversely related to MIC (r = -0.39; P < 0.01) with a positive correlation with fasting p-insulin (r = 0.39; P < 0.01). There were no statistically significant correlations between BMI, body fat % or WHR and MIC. GIR was inversely related to body fat % (r = -0.49; P < 0.01), VFA (r = -0.56; P < 0.01) and WHR (r = -0.36; P < 0.01) in all subjects, with an inverse relationship to fatty liver in men (r = -0.43; P < 0.05). CONCLUSION: Increased steatosis of the liver is associated with reduced insulin clearance, contributing to insulin resistance in non-diabetic Japanese men and women.
Adipose Tissue↗
The effect of dietary 7-ketocholesterol, inhibitor of sterol synthesis, on hepatic microsomal cholesterol 7 alpha-hydroxylase activity in rat.
A group of oxygenated sterols has been identified as physiological regulators of hepatic cholesterol biosynthesis. However, the regulatory effects of these oxysterols on cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in bile acid biosynthesis, is not clearly elucidated. We administered 0.1% 7-ketocholesterol (15 mg/day), a strong inhibitor of sterol synthesis, to rats orally for 6 days. Then, the levels of accumulated oxysterols in liver microsomes and microsomal 7 alpha-hydroxylase activity were determined. The results were compared to those in the groups of rats treated with either control diet or diets containing 0.1 or 1% cholesterol, 0.1% butylated hydroxytoluene, 3% cholestyramine or 1% taurocholate. 7-Ketocholesterol feeding resulted in significant increase of both 7-ketocholesterol and 7 beta-hydroxycholesterol in microsomal fraction (449.4 +/- 36.8 and 438.2 +/- 46.8 ng/mg protein, respectively; mean +/- S.E.). Hepatic microsomal 7 alpha-hydroxylase activity in the rats fed 7-ketocholesterol was significantly elevated as compared with those of control rats; 44.70 +/- 5.97 vs. 16.57 +/- 2.46 pmol/min per mg protein. Addition of BHT to 7-ketocholesterol reduced the accumulation of 7 beta-hydroxycholesterol, and the stimulatory effect of 7-ketocholesterol on 7 alpha-hydroxylase activity was suppressed. Our results demonstrate that oxysterols do not inhibit but rather stimulate hepatic microsomal 7 alpha-hydroxylase.
Animals↗
Quantitative autoradiographic distribution of glutamate receptors in the cervical segment of the spinal cord of the wobbler mouse.
The reduction of glutamate content has been observed in the spinal cord of the wobbler mouse, a purported model of amyotrophic lateral sclerosis (ALS). To elucidate glutamate receptors in the wobbler spinal cord, we measured densities of N-methyl-D-aspartate (NMDA), kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) and metabotropic glutamate (mGlu) binding sites using in vitro autoradiography. In wobbler mice, NMDA, kainate, and AMPA binding sites were increased in the dorsal horn and kainate binding sites were also increased in the intermediate zone. However, mGlu binding was unchanged. These results disagree with those observed in ALS spinal cords, in which NMDA and kinate binding sites are decreased. The wobbler mouse may have the glutamate dysfunction, but in a different way from ALS.
Animals↗
Neuropeptide Y potentiates the luteinizing hormone (LH) response to LH-releasing hormone in men.
It has been demonstrated in several animal species that neuropeptide Y (NPY) exerts a modulatory effect on luteinizing hormone (LH) secretion. However, whether NPY plays a similar role also in humans has yet to be determined. Therefore, in this study we examined the effect of human NPY on the anterior pituitary hormone secretion in 6 normal men. Intravenous bolus injection of 100 micrograms of human NPY alone did not affect the secretion of any anterior pituitary hormone or cortisol. However, when NPY (100 micrograms) was administered simultaneously with LH-releasing hormone (LHRH, 100 micrograms), a significant potentiation was observed for LHRH-induced LH secretion. Similarly, follicle-stimulating hormone (FSH) response to LHRH was slightly potentiated by the coadministration of NPY, although this effect was not statistically significant. This is the first study to demonstrate that NPY can augment the LHRH-induced LH secretion in humans.
Adult↗