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Biomedical subjects

K Takebe

Publications and source records attributed to K Takebe.

At least 55 records · Page 3Linked to original sources

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↗

Maternal hypothyroidism during early pregnancy and intellectual development of the progeny.

OBJECTIVE: To investigate whether maternal hypothyroidism before the onset of fetal thyroid function influences mental development of the offspring. DESIGN: We examined IQs in children in whom the mothers had been hypothyroid during early pregnancy (group 1). The IQs were compared with those of siblings who were not exposed to maternal hypothyroidism during gestation (group 2). PATIENTS: Group 1 consisted of eight children. Mothers were examined for thyroid status during the fifth to 10th gestational weeks and were found to have distinctly low thyroxine levels and high thyrotropin levels; the levels became normal after thyroxine supplementation by 13 to 28 weeks of gestation. Seven of the eight children had nine siblings who had not been exposed to maternal hypothyroidism during gestation (group 2). Ages at examination were 4 to 10 years in group 1 and 4 to 15 years in group 2. RESULTS: All children in group 1 showed normal IQs. There was no significant difference in the mean IQ between the children in group 1 who had siblings (112 +/- 11) and their siblings in group 2 (106 +/- 8). Even the subject whose mother had had the lowest thyroxine level (free thyroxine, 2.3 pmol/L) had an IQ similar to that of his sibling. CONCLUSION: These data provide evidence against the presence of adverse effects of maternal hypothyroidism during early pregnancy on the subsequent mental development of the offspring.

Adolescent↗

The study of tumor necrosis factor beta gene polymorphism in lung cancer patients.

BACKGROUND: In recent years numerous reports have discussed the relationship between the human leukocyte antigen and lung cancer. However, the genetic background of lung cancer has not yet been precisely clarified. METHODS: To investigate the genetic background of lung cancer, the human leukocyte antigens in 159 normal healthy control subjects and 102 lung cancer patients were studied, and restriction fragment length polymorphism analysis of the tumor necrosis factor (TNF) beta gene in 165 normal healthy control subjects and 135 lung cancer patients was performed. RESULTS: Lung cancer patients showed a high frequency of human leukocyte antigen B61; however, no statistical difference was found. In the lung cancer patients, the TNF beta 10.5/10.5-kb allele was found at a low frequency, 38.5%, compared to 53.3% in normal controls (chi 2 = 7.51, P = 0.011, corrected P = 0.033, relative risk = 0.77). In the relationship between the histologic types and the TNF beta gene, the TNF beta 10.5/10.5-kb allele showed low frequencies: 38.5% in adenocarcinoma, 38.2% in squamous cell carcinoma, and 27.8% in small cell carcinoma, although no statistical difference was shown. In relation to the postoperative survival period, the TNF beta 10.5/10.5-kb allele was associated with prolonged survival. CONCLUSIONS: The TNF beta 10.5/10.5-kb allele may be associated with resistance to lung cancer and with a better prognosis.

Adenocarcinoma↗

Dietary analysis of Japanese patients with chronic pancreatitis in stable conditions.

In order to examine the malnutritional condition of outpatients with pancreatitis, a dietary investigation was conducted in Japanese patients with chronic pancreatitis (n = 38) and healthy subjects (n = 35) of the same age for 3-7 consecutive days, and the characteristics of their food intake were examined. The patients with pancreatitis took in less calories, fat, carbohydrate, and protein than the healthy subjects, by 900 kcal, 20 g, 150 g, and 20 g, respectively. On the other hand, the fat energy ratio in the patients was 20%, similar to that in the healthy subjects. Also, when the fat intake was classified according to origin, i.e., animal, marine, or plant, the proportions for animal (g) and plant (g) were low, while marine fat accounted for a significantly higher percentage than in the healthy subjects. The intake of cholesterol and Ca in the patients was significantly smaller than that in the healthy subjects, but no significant difference was observed in the intake per body weight of proteins and Ca. It seems, possible that the low calorie, low protein, low fat, and low carbohydrate intake may be factors in the malnutritional condition of the patients with chronic pancreatitis. Analysis of covariance and principal component analysis showed that the body weight of the patients was closely correlated with decreases of caloric intake and intake of carbohydrate. The above results revealed that low body weight in patients with chronic pancreatitis was closely related to the decrease of calorie and carbohydrate intake, in addition to maldigestion and malabsorption of nutrients.

Adult↗

Lack of involvement of the cholinergic mechanism in vasoactive intestinal peptide- and peptide-histidine methionine-induced growth hormone (GH) responses in acromegaly: comparison with the GH responses to thyrotropin-releasing hormone and GH-releasing hormone.

We examined whether the cholinergic mechanism is involved in the paradoxical GH responses to vasoactive intestinal peptide (VIP) and peptide histidine methionine (PHM) in acromegaly. 28 patients with active acromegaly underwent i.v. bolus injections of thyrotropin-releasing hormone (TRH, 500 micrograms), GH-releasing hormone (GHRH, 100 micrograms), VIP (100 micrograms), and PHM (100 micrograms) with or without a prior atropine treatment (1 mg, i.m., 30 min before). Blood samples were collected before and at intervals up to 120 min after the injection, and plasma GH levels were measured. In response to TRH, GHRH, VIP and PHM, 23 (82%), 24 (86%), 13 (46%) and 7 (25%) patients, respectively, responded with a significant GH increase (> 50% and 6 micrograms/l above the basal level). The effect of atropine pretreatment was examined in only these responders to the respective peptides. When the GH responses were estimated by the area under the response curve, the atropine pretreatment was able to significantly suppress the GH response to GHRH, but not to TRH, VIP, or PHM. Although the lack of cholinergic involvement in the TRH-induced GH release in acromegaly is confirmatory to previous reports, the same results with the VIP- and PHM-induced GH release are novel. The present study may suggest that in acromegaly the physiological GH response is mediated by the cholinergic mechanism, but the paradoxical ones are not.

Acetylcholine↗

Quantification of serum-soluble HLA class I antigens in patients with gastric cancer.

The amount of sHLA-I in serum was examined in 74 patients with gastric cancer and 15 normal healthy controls. For mAbs, W6/32 specific for HLA-A, -B, -C, and biotin IOT2 specific for HLA class I associated with beta 2 microglobulin, were used to determine the values of sHLA-I using an ELISA. The patients in stage-IV gastric cancer showed lower values of sHLA-I (445.4 +/- 247.1 ng/ml) than those in stage I (725.9 +/- 575.8 ng/ml), stage II (752.8 +/- 255.0 ng/ml), and normal controls (868.9 +/- 715.0 ng/ml) (P < 0.05). In analysis of the patients with HLA-A24, the allele that has been reported to secrete more sHLA-I than other alleles, the results were nearly the same. These results suggest that the secretion of sHLA-I is low in patients with very advanced cancer. However, there was no correlation between the sHLA-I level and the metastasis or prognosis in longitudinal studies in 11 patients.

Adult↗

Correlation between bile acid malabsorption and pancreatic exocrine dysfunction in patients with chronic pancreatitis.

Fecal bile acid and fecal fat were determined in 18 normal subjects and 22 patients with chronic pancreatitis, and the relation of fecal bile acid excretion to exocrine pancreatic dysfunction was studied. In chronic pancreatitis fecal bile acid was approximately three times that of control subjects, and large amounts of primary bile acid were detected. A significant correlation between fecal bile acid excretion and bicarbonate secreted from the pancreas was found. This evidence of bile acid malabsorption was not observed until bicarbonate output was < 0.05 mEq/h/kg. A slight correlation between fecal bile acid and absorption rates of fat was demonstrated. These results suggest that bile acid malabsorption observed in chronic pancreatitis is related to an impairment of pancreatic bicarbonate secretion.

Adult↗

Lipid composition of platelets in patients with non-insulin-dependent diabetes mellitus: studies before and after treatment of diabetes.

The study was designed to investigate whether impaired composition of platelet lipids in untreated diabetic patients improved after diabetic treatment. Fourteen untreated patients with non-insulin-dependent diabetes mellitus (NIDDM) and 15 healthy control subjects were studied. In the diabetic patients, the ratio of free cholesterol to phospholipid (FC/PL) in platelets of 0.33 +/- 0.02 (mean +/- SEM) at pre-treatment, which was statistically (p < 0.05) higher than that of 0.26 +/- 0.02 in control subjects, was significantly decreased to the value of 0.29 +/- 0.02 (p < 0.01) after insulin therapy. Platelet FC level of 9.77 +/- 0.77 micrograms 10(-8) cells pre-treatment was significantly (p < 0.01) reduced to the value of 7.72 +/- 0.38 micrograms 10(-8) cells post-treatment. Platelet PL level showed no significant changes after the treatment. There was a significantly (p < 0.01) positive correlation between the decrease in FC/PL of platelets and that in haemoglobin A1c (HbA1c) after treatment for diabetes (rs = -0.729). These results indicate that the impaired lipid composition in platelets can be improved after an adequate glycaemic control in patients with NIDDM.

Blood Platelets↗

Effects of intravenous administration of interleukin-1-beta on the release of prostaglandin E2, corticotropin-releasing factor, and arginine vasopressin in several hypothalamic areas of freely moving rats: estimation by push-pull perfusion.

Utilizing the push-pull perfusion technique, we examined the effect of an intravenous bolus injection of recombinant human interleukin (IL)-1 beta on the release of prostaglandin E2 (PGE2), CRF, and AVP in several hypothalamic areas of freely moving rats, simultaneously monitoring plasma ACTH levels. Perfused hypothalamic areas were the median eminence (ME), the paraventricular nucleus (PVN), and the medial preoptic area (MPOA). During the period 12:00-15:00 h, perfusates and blood samples were collected every 10 min (between 13:00 and 13:40 h) or 20 min (between 12:00 and 13:00 h, and between 13:40 and 15:00 h). IL-1 beta (1.0 micrograms/rat) or vehicle only (in control groups) was injected at 13:00 h. In both the ME and the PVN but not in the MPOA, the outputs of CRF and AVP were significantly stimulated by IL-1 beta, prior to the rise in plasma ACTH. A significant stimulation of PGE2 by IL-1 beta was observed only in the PVN, and its temporal profile was very similar to those of CRF and AVP in the PVN. These results suggest that PGE2 may be a trigger in the PVN for the activation of CRF and AVP neurons, and thereby ACTH secretion, which follows IL-1 beta injection.

Adrenocorticotropic Hormone↗

Treatment of malignancy-associated hypercalcemia with YM175, a new bisphosphonate: elevated threshold for parathyroid hormone secretion in hypercalcemic patients.

The effect of a new third generation bisphosphonate, YM175 (cycloheptylamino-methylene bisphosphonate), on serum calcium (Ca) and intact PTH levels was examined in 79 malignancy-associated hypercalcemia patients with serum Ca levels higher than 2.75 mmol/L. A single infusion of 2.5, 5, and 10 mg YM175 reduced serum Ca levels in a dose-dependent manner. YM175 was about 6 times more potent than 3-amino-hydroxypropylidene-1,1-bisphosphonate. Among 23 patients treated with 10 mg YM175, serum Ca decreased by more than 0.5 mmol/L in 20 patients and was normalized in 11 patients. Serum intact PTH was subnormal in all of these patients before treatment and remained subnormal in 12 patients (suppressed PTH group), but was elevated to normal or high levels after treatment in the remaining 11 patients (responsive PTH group). Serum Ca was significantly higher throughout the study period in the suppressed PTH group, and mean serum Ca at the nadir did not decrease below 2.90 mmol/L in this group. However, the rate or magnitude of reduction in serum Ca was not different in the two groups. Polynomial regression analysis revealed that the threshold of serum Ca for PTH secretion was elevated to 2.75 mmol/L in the responsive PTH group, whereas it was about the upper limit of normal when both groups were combined (2.59 mmol/L). Furthermore, in the responsive PTH group, the threshold for PTH secretion during the decreasing serum Ca phase (days 4 and 6) was higher than that during the increasing serum Ca phase (days 10 and 14). The changes in the threshold for PTH secretion were also observed in patients treated with lower doses of YM175. These results demonstrate that YM175 is one of the most potent currently available bisphosphonates, and that the threshold for PTH secretion is elevated in at least some malignancy-associated hypercalcemia patients. In addition, there appears to be a difference in the threshold for PTH secretion between the decreasing and increasing serum Ca phases similar to the previously reported hysteresis phenomenon.

Adult↗

Clinical characteristics in non-insulin-dependent diabetic patients with long duration in Japan--relation to risk factors for vascular complications.

In this study, we evaluated the control state of body weight, blood pressure, and blood glucose during the recent 10 years in 82 patients of non-insulin-dependent diabetes mellitus (NIDDM) who had long duration of diabetes for 20-25 years without ischemic heart disease (IHD) and diabetic nephropathy (Neph). The patients without either IHD or Neph showed significantly lower incidences of obese (11 vs. 40%, p < 0.05), hypertensive (0 vs. 20%, p < 0.05) and poor glycemic control state (7 vs. 27%, p < 0.05) for 10 years than the patients with IHD alone, and showed significantly lower incidences of hypertensive (0 vs. 20%, p < 0.05) and poor glycemic control state (7 vs. 33%, p < 0.01) than the patients with Neph alone. The control state of body weight was similar between the patients without either IHD or Neph and with Neph alone. In addition, the patients without either IHD or Neph showed significantly lower incidences of obese (11 vs. 56%, p < 0.01) and hypertensive control state (0 vs. 40%, p < 0.01) for 10 years than the patients with both IHD and Neph. The control state of blood glucose was similar between the two groups. These results suggest that for long survival of NIDDM patients without development or progression of IHD and Neph, non-obese and non-hypertensive state as well as good glycemic control should be maintained for long time.

Aged↗

Decreased gastric secretory functions in diabetic patients with autonomic neuropathy.

A total of 37 subjects consisted of 10 healthy subjects (Group III), 15 diabetic patients without autonomic neuropathy (Group II), and 12 diabetic patients with autonomic neuropathy including gastroparesis in 6 cases (Group I). All three groups were comparable in age. In order to clarify the gastric function in diabetic patients with autonomic neuropathy, secretion of serum gastrin, gastric secretory function, endoscopic Congo red test of fundic glands, and coefficiency of variance of electrocardiographic beat-to-beat intervals (C.V. R-R) were examined. In Group I, 5 patients had hypergastrinemia, but its elevation was inhibited when an acid solution was injected into the stomach. Gastric secretion and C.V. R-R were markedly lower in Group I, compared with Groups II and III. In Group I, the area of fundic glands (parietal cells) was reduced considerably. The C.V. R-R was significantly correlated with fasting serum gastrin concentration and with maximal acid output. From these results, in diabetic patients with autonomic neuropathy (vagal neuropathy), gastric acid secretion in response to tetragastrin stimulation was lowered with a reduction in area of fundic gland distribution. Hypergastrinemia may reflect a negative feedback mechanism responding to decreased acidity of gastric content in the antrum.

Adult↗

Lipoprotein(a) as an independent risk factor for diabetic retinopathy in male patients in non-insulin-dependent diabetes mellitus.

Relationship of the lipoprotein(a) [Lp(a)] concentration as a risk factor independent of other factors with the severity of diabetic retinopathy were evaluated by multiple regression analysis. The subjects were 158 patients with non-insulin-dependent diabetes mellitus (NIDDM). Multiple regression analysis was carried with the severity of diabetic retinopathy as the dependent variable and 13 independent variables, namely the Lp(a) concentration, sex, age, body mass index, duration of diabetes, ischemic heart disease, fasting plasma glucose, glycosylated hemoglobin A1c, total cholesterol, triglyceride, high-density lipoprotein cholesterol, anti-diabetic treatments, and diabetic nephropathy. The analysis was performed separately in all subjects, males only, and females only. The standard partial regression coefficient of Lp(a) was significant (0.293, p < 0.01), and the multiple correlation coefficient was 0.611 in the males. However, the standard partial correlation coefficient of Lp(a) was not significant in all patients and in females only. The rank of contribution of Lp(a) to retinopathy was the third in males, following triglyceride and nephropathy and followed by anti-diabetic treatments. These results suggest that Lp(a) might be an independent risk factor for diabetic retinopathy in male patients with NIDDM.

Aged↗

Increased plasma gluconeogenic and system A amino acids in patients with pancreatic diabetes due to chronic pancreatitis in comparison with primary diabetes.

We examined the plasma amino acid profiles of 17 patients with pancreatic diabetes in comparison with those of 14 healthy subjects and 16 patients with primary diabetes of similarly poor glycemic control. We also measured fasting plasma glucagon and free insulin levels in patients with pancreatic diabetes and in those with primary diabetes. The fasting plasma amino acid level was highest in patients with pancreatic diabetes. Furthermore, the plasma glucagon level in patients with pancreatic diabetes was significantly low, and negative correlations were found between glucagon and glucagon-related System A and gluconeogenic amino acids. On the other hand, the levels of branched-chain amino acids (BCAA) and System L amino acids, which are subjected to change in the state of diabetes mellitus, increased in patients with pancreatic diabetes. From the above results, we determined that the amino acid profile in patients with pancreatic diabetes resembled that in patients with total pancreatectomy. It is our opinion that the increases of amino acid levels (gluconeogenic and System A amino acids) in patients with pancreatic diabetes is not dependent on maldigestion/malabsorption under treatment, but is mainly dependent on glucagon deficiency.

Amino Acids↗

Decreased counterregulatory hormone responses to insulin-induced hypoglycemia in patients with pancreatic diabetes having autonomic neuropathy.

Thirteen patients with pancreatic diabetes caused by calcifying pancreatitis were divided into 2 groups; 5 with diabetic autonomic neuropathy [AN(+) group] and 8 without [AN(-) group]. They were subjected to an insulin-induced hypoglycemic stress test to evaluate their blood pancreatic glucagon, adrenalin, and cortisol responses. When a blood glucose level below 45 mg/100 ml was defined to be hypoglycemia, all the patients in the AN(-) group exhibited peripheral adrenalin responses, with a significant increase (mean, 19.0 times the basal level) in the blood adrenalin level. Among the AN(+) group, on the other hand, central nervous symptoms became evident rather than the peripheral adrenalin response (the blood adrenalin level hardly exceeded the basal level). With the exception of a single patient, none exhibited responses in the blood pancreatic glucagon levels. Only one patient showed a minimal cortisol response but the remaining 12 reacted normally in the cortisol release. The findings are summarized as follows: in pancreatic diabetes, insulin-induced hypoglycemia causes little change in pancreatic glucagon secretion; when the condition is complicated with autonomic neuropathy, central nervous symptoms develop while the blood adrenalin level hardly increases. These findings indicated that patients with pancreatic diabetes complicated with diabetic autonomic neuropathy have a risk of lapsing into an acute hypoglycemic coma and difficulty in recovering from the hypoglycemic state.

Alcoholism↗

Diabetic retinopathy in Japanese patients with long-standing pancreatic diabetes due to calcifying pancreatitis.

This study analyzed the prevalence, aggravating factors (including duration of diabetes, glycemic control, body mass index, hypertension, serum total cholesterol, changes of ST on ECG and diabetic therapies) and characteristics of diabetic retinopathy in 75 patients with pancreatic diabetes resulting from calcifying pancreatitis. The patients were divided into three Groups: Group I (27 patients in whom diabetes was detected earlier than pancreatic stones), Group II (36 patients in whom diabetes and pancreatic stones were simultaneously detected) and Group III (12 patients in whom pancreatic stones were detected earlier than diabetes). The prevalence of retinopathy was dependent on the duration of diabetes as well as poor glycemic control. It was significantly (p < 0.01) higher among the patient with the duration of diabetes that was more than 5 years than that of the patients whose duration was less than 5 years. The prevalence of retinopathy in Group I (63%) was significantly (p < 0.05) higher than that in Group II (30.6%) and Group III (12.5%). Proliferative retinopathy was not found in any patients with a duration of diabetes less than 5 years, while it was found in 5 patients with a duration of more than 5 years (5 cases out of 31 patients). Diabetic retinopathy was correlated with the duration of diabetes and glycemic control, and was not linked to frequency of hypoglycemia and family history of diabetes. From the results above, we concluded that diabetic retinopathy in patients with pancreatic diabetes due to calcifying pancreatitis might be taken as evidence that such complications are primarily due to chronic hyperglycemia and the duration of diabetes mellitus rather than to genetic factors and other factors (body mass index, hypertension, serum total cholesterol and diabetic therapies).

Adult↗