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Biomedical subjects

H Nawata

Publications and source records attributed to H Nawata.

At least 307 records · Page 17Linked to original sources
PubMed1995

Direct contractile effect of endothelin-1 on isolated circular smooth muscle cells of guinea pig caecum.

Smooth muscle cells isolated from the circular muscle layers of the guinea pig caecum were used to determine whether endothelin-1 (ET-1) can cause contraction by exerting a direct action on smooth muscle cells. In addition, the inhibitory effects of 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8), an inhibitor of intracellular Ca2+ release, verapamil, a Ca2+ channel blocker, and removal of extracellular Ca2+ on the ET-1-induced muscle contraction were examined. ET-1 elicited a contractile response of isolated smooth muscle cells in a dose-dependent manner (ED50: 2 nM). TMB-8, verapamil, and removal of extracellular Ca2+ significantly inhibited the contraction produced by ET-1. These results strongly suggest that ET-1 has a direct contractile effect on circular smooth muscle cells of the guinea pig caecum, and that this contraction depends on both intracellular and extracellular Ca2+.

Animals↗
PubMed1995

Functional endothelin A receptor on gastric smooth muscle cells.

Smooth muscle cells isolated from the gastric muscle layers of the guinea pig were used to examine the functional endothelin receptor subtype responsible for gastric smooth muscle contraction by endothelin. Endothelin-1 induced the contraction of these cells in a dose-dependent manner, with an ED50 value of 0.2 nM. Endothelin-3-induced contraction was significantly less than that of endothelin-1. Sarafotoxin 6c (10(-11)-10(-7) M), endothelinB highly selective agonist, did not elicit the contraction of gastric smooth muscle cells. BQ-123, endothelinA selective antagonist, inhibited the contractile response produced by 10(-7) M endothelin-1 in a dose-dependent manner, with an IC50 value of 5 nM. These results strongly suggest that endothelin elicited the contraction of gastric smooth muscle cells via functional endothelinA receptor subtype.

Animals↗
PubMed1995

Up-regulation of high-affinity dehydroepiandrosterone binding activity by dehydroepiandrosterone in activated human T lymphocytes.

Although evidence indicates that dehydroepiandrosterone (DHEA) exerts direct physiological effects, its mechanism of action remains unknown. DHEA binding sites were examined using a whole-cell binding assay in a human T lymphoid cell line, PEER, revealing that a single class of high-affinity binding sites for DHEA (dissociation constant = 7.4 +/- 0.53 nmol/L, mean +/- SE, n = 4) was greatly increased when treated with DHEA, phorbol-12-myristate-13-acetate, and the Ca2+ ionophore A23187. Bound [3H]DHEA was displaced sensitively by DHEA and secondarily by dihydrotestosterone, but not effectively by other steroids, including DHEA sulfate. These results not only indicate the existence of a DHEA receptor, but also suggest that T cells become susceptible to regulation by DHEA during the process of signal-induced activation.

Binding Sites↗
PubMed1995

Insulin resistance associated with substitution of histidine for arginine 252 in the alpha-subunit of the human insulin receptor: trial of insulin-like growth factor I injection therapy to enhance insulin sensitivity.

Mutation of the insulin receptor gene can compromise the ability of the receptor to mediate insulin action. A homozygous point mutation that results in the substitution of histidine for arginine 252 in the insulin receptor alpha-subunit has now been identified by polymerase chain reaction and single stranded conformational polymorphism analysis in a 20-yr-old Japanese woman with type A syndrome and severe insulin resistance. The proband's consanguineous parents (diabetic mother and normal father) and her sister (impaired glucose tolerance), each of whom showed an exaggerated insulin response to an oral glucose load, were heterozygous for this mutation. Her brother showed a normal insulin response and lacked the mutation, as did 50 healthy Japanese control subjects. The chronic sc administration of insulin-like growth factor I (IGF-I) improved the patient's hyperglycemia and corrected certain metabolic abnormalities over a 9-month period, even though the binding of 125I-labeled IGF-I to her cultured fibroblasts was decreased by 40% relative to that to cells from healthy controls. Studies of the binding of 125I-labeled insulin to the proband's cultured fibroblasts, to COS-I cells transfected with complementary DNA encoding the mutant insulin receptor, and to partially purified mutant receptors revealed that the Arg252-->His mutation decreased both cell surface expression and the affinity for insulin for the receptor. These observations suggest that the homozygous Arg252-->His mutation is responsible for the type A insulin resistance of the proband, whereas in the heterozygous state, the mutation results in mild insulin resistance indistinguishable from that observed in noninsulin-dependent diabetes mellitus.

Adolescent↗
PubMed1995

Impaired feedback inhibition of insulin secretion by hyperinsulinemia in patients with insulinoma.

By means of the euglycemic three step hyperinsulinemic clamp technique, suppression of endogenous C-peptide secretion by exogenous insulin infusion was evaluated in patients with insulinoma (n = 8) and healthy controls (n = 20). Euglycemic hyperinsulinemic clamp studies were performed with an artificial pancreas (STG-22 NIKKISO, Tokyo, Japan). Insulin (Actrapid human insulin) was infused at the rate of 1.12, 3, and 10 mU/kg/min. Plasma glucose levels were clamped at 80 mg/dl, and high insulin levels were maintained in all subjects (833 +/- 78 microU/ml at the rate of 10 mU/kg/min insulin infusion). During the clamp studies, plasma C-peptide levels in normal subjects declined from 2.0 +/- 0.2 to 0.9 +/- 0.2 ng/ml, indicating suppression of endogenous insulin secretion by exogenous insulin infusion. In patients with insulinoma, plasma C-peptide levels were 3.1 +/- 1.6 ng/ml in the basal state, and were not suppressed even during exogenous hyperinsulinemia. We concluded that the feedback inhibition of insulin secretion by exogenous insulin infusion is attenuated in patients with insulinoma, and that the hyperinsulinemic clamp technique may be a useful method for the diagnosis of insulinoma.

Adult↗
PubMed1995

Glycation accelerates the oxidation of low density lipoprotein by copper ions.

We investigated the in vitro effect of glycation on LDL oxidation. Native LDL (nLDL) was glycated in 0, 5, 10, or 20 mM glucose. This glycated LDL (gLDL) was oxidized by 1 microM copper ion. Compared to nLDL and gLDL, oxidized gLDL (ogLDL) has a greater negative charge. The thiobarbituric acid reactive substance (TBARS) value of ogLDL increased with the glucose concentration tested during glycation in a dose-dependent manner. OgLDL glycated in 20 mM glucose had a significantly higher TBARS level than did oxidized LDL incubated without glucose. In conclusion, LDL glycated in vitro is prone to oxidation. Thus, glycated LDL, which increases in the diabetic state, may contribute to the pathogenesis of atherosclerosis in diabetic patients.

Copper↗
PubMed1995

Secretion of insulin and glucagon by the perfused pancreas of genetically obese (fa/fa) Zucker rats and its alteration with aging.

To evaluate the sequential changes in secretion of insulin and glucagon by the pancreas of Zucker fa/fa rats, we examined the secretion of these peptides by the perfused pancreas of the rats and by that of their lean littermates aged 9, 18, and 54 wks. Obese rats weighted significantly more than lean rats at all ages and had increased plasma insulin except for those at 54 wks of age. Isolated pancreas of obese rats at 9 wks showed greater insulin secretion response to glucose and arginine than that of lean rats at the same age. Insulin secretion response to arginine from pancreas of obese rats at 18 wks was also greater than that from pancreas of lean rats at 18 wks. Increased glucose concentration in the perfusion medium caused less suppression in obese rats than in lean rats. 10 mM arginine stimulation resulted in a higher secretion response in lean rats than in obese rats at 18 and 54 wks. Impairment of glucagon secretion was observed even at 54 wks of age, when the obese rats no longer had significantly increased plasma insulin. This suggested that abnormal glucagon secretion was due not only to hyperinsulinemia, but also to a possible defect in the secretory mechanism.

Aging↗
PubMed1995

Premature termination mutation (772Glu-->stop) in the hormone-binding domain of the androgen receptor in a patient with the receptor-negative form of complete androgen insensitivity syndrome.

We have characterized the androgen receptor in a Japanese infant with complete androgen insensitivity syndrome (or androgen resistance), and have investigated the molecular basis. Androgen binding was undetectable in cultured genital skin fibroblasts from this patient by whole-cell androgen receptor binding assay. Sequence analysis of the entire coding region of the androgen receptor gene from this patient revealed a single nucleotide substitution (G-->T) at nucleotide position 2676 in exon E (or 5), resulting in conversion of glutamine codon (GAG) to amber stop codon (TAG) at amino acid position 772 within the hormone-binding domain of the androgen receptor. This premature termination mutation (or nonsense mutation), introducing a truncated androgen receptor that lacks most of its androgen binding capacity, is though to cause the receptor-negative form of complete androgen insensitivity syndrome in this patient.

Base Sequence↗
PubMed1995

In vivo and in vitro evidence for the production of inhibin-like immunoreactivity in human adrenocortical adenomas and normal adrenal glands: relatively high secretion from adenomas manifesting Cushing's syndrome.

To clarify whether adrenal gland secretes inhibin in vivo in physiological or pathological conditions, we measured the levels of inhibin-like immunoreactivity (inhibin-LI) in adrenal veins (A-vein) and compared them with those in inferior vena cava (IVC) using blood samples obtained at catheterization of adrenal vein in the patients with adrenal adenoma manifesting Cushing's syndrome (Cs), aldosterone-producing adenoma, clinically non-functioning adenoma and normal adrenal gland. The tumor sides of A-veins in the patients with adenomas and also both sides of A-veins in subjects with normal adrenal glands showed significantly higher contents of inhibin-LI than their IVC. When the inhibin-LI secretion rate from adrenal gland was estimated by the difference between the levels of A-vein (tumor side) and IVC, Cs adenomas showed the highest secretion rate. Similarly, the tissue inhibin-LI content and the basal secretion rate of inhibit-LI from primary cultured cells were the highest in Cs adenomas. These findings indicated that normal adrenal glands and adrenocortical adenomas produced and secreted inhibin-LI into the general circulation in vivo and Cs adenomas have relatively high capacity for secreting inhibin-LI, and the present study provided the first in vivo evidence for adrenal inhibin-LI production in pathological conditions.

Adrenal Cortex Neoplasms↗
PubMed1995

Ectodermal dysplasia syndrome in siblings with true keloids, stenosis of the esophagus after operations for congenital achalasia and renovascular hypertension due to stenosis of renal artery.

Ectodermal dysplasia syndrome (EDS) is a rare hereditary disease, with symptoms brought about by dysplasia of ectodermal tissue (such as skin, teeth, nails, and hair). This report details the cases of two siblings (41 and 43 year old sisters) with autosomal recessive and hydrotic EDS complicated by esophageal achalasia, postoperative stenosis of esophagus, true keloids, renovascular hypertension, incomplete malrotation of the bowel, and demyelination of the brain.

Adult↗
PubMed1995

Cushing's disease preceding sarcoidosis.

We present a 32-year-old-woman with Cushing's disease and sarcoidosis. She had been diagnosed as having Cushing's disease in 1985. She had transsphenoidal surgery followed by pituitary radiation. Subsequently her plasma cortisol level gradually decreased to normal range. In 1991, she manifested bilateral hilar lymphadenopathy on chest X-ray, erythema nodosum, subcutaneous nodules and granulomatous uveitis. From the histological findings of the skin lesions, the patient was diagnosed as having sarcoidosis. Interestingly, an inverse relationship between the disease activity of sarcoidosis and the level of serum cortisol in Cushing's disease was observed in the clinical course of this patient. Co-existence of Cushing's disease and sarcoidosis is very rare. Since the therapeutic significance of steroids in sarcoidosis has been well established, this case provides insight to the relationship between sarcoidosis and steroids.

Adrenocorticotropic Hormone↗
PubMed1995

Effect of endothelin-1 on the development of hemorrhagic pancreatitis in rats.

BACKGROUND: It has been hypothesized that microcirculatory disturbance plays an important role in the development of severe pancreatitis. In this study we investigated the effects of exogenous endothelin-1 on the development of severe pancreatitis in rats. METHODS: Acute pancreatitis was induced by two intraperitoneal injections of cerulein (10 micrograms/kg body weight). Endothelin-1 was administered via an abdominal aortic catheter as a bolus of 250-750 pmol/kg BW every hour for 4 h. RESULTS: Remarkable morphologic changes in the pancreas, including hemorrhage, and increases in serum amylase level and active elastase content in pancreatic tissue were observed in rats treated with cerulein plus endothelin-1 in a dose-dependent manner 5 h after the first cerulein injection. Local pancreatic blood flow decreased significantly, and microcirculatory disturbances in the pancreas were demonstrated. CONCLUSIONS: These results suggest that endothelin-1 causes pancreatic microcirculatory disturbance and might be a contributing factor in the aggravation of acute pancreatitis.

Acute Disease↗
PubMed1995

Which progenitor is the target cell in the development of acute promyelocytic leukemia?

Acute promyelocytic leukemia (APL) is characterized by the t(15;17) which involves the PML gene and the retinoic acid receptor alpha (RAR alpha) gene, and the subsequent PML/RAR alpha fusion gene is a key event in the leukemogenesis of APL. We found that the PML/RAR alpha fusion gene was expressed in both granulocytic/macrophage and erythroid colonies in a few patients with APL. In some instances of acute myelogenous leukemia (AML), erythrocytes or platelets also expressed the glucose-6-phosphate dehydrogenase (G-6-PD) isoenzymes which were detected in the leukemic cells. Some APL cells show basophilic and monocytoid differentiation and these findings suggest that the leukemic precursor of APL is derived from a more primitive cell stage than the promyelocyte. The precursor cells appear to be derived from heterogeneous levels.

Cell Transformation, Neoplastic↗
PubMed1995

Detection of minimal residual disease by reverse transcriptase polymerase chain reaction for the PML/RAR alpha fusion mRNA: a study in patients with acute promyelocytic leukemia following peripheral stem cell transplantation.

Acute promyelocytic leukemia (APL) is a subtype of acute myelogenous leukemia (AML) that is characterized by the presence of a PML/RAR alpha fusion gene resulting from t(15;17). Peripheral stem cell transplantation (PSCT) has been used to treat patients with AML. To assess the presence of minimal residual disease (MRD) and the contamination of leukemic cells in peripheral stem cells (PSCs), we examined six patients with APL who were undergoing PSCT, using reverse transcriptase polymerase chain reaction analysis to detect the mRNA of the PML/RAR alpha fusion gene. The fusion gene was expressed in the bone marrow cells during the early phase of a complete remission and in some of the PSCs. Detection of the fusion gene can be useful in monitoring for leukemic cell contamination of PSCs and for predicting a relapse of APL.

Base Sequence↗
PubMed1995

The use of percutaneous ethanol injection therapy for recurrence of hepatocellular carcinoma.

Forty patients with hepatocellular carcinoma were treated with percutaneous ethanol injection therapy. All patients had fewer than three tumors of less than 30 mm in diameter. Additionally, all recurrences with fewer than 3 tumors of less than 30 mm in diameter was repeated for 33 recurrences and discontinued in 17 cases. Duration between treatments became significantly shorter with successive treatments. There was no significant difference in the duration between treatments in patients classified by tumor size (less than 20 mm vs. 20 mm or more), whereas there was a significantly lower recurrence rate in patients with solitary tumors as compared with those with multiple HCC. Laboratory data before successive PEI-treatments were also compared, and showed that hepatic functional reserve did not decrease with repeat percutaneous ethanol injection. The cumulative survival rate in all 40 patients after the first treatment was significantly higher than in the 17 patients for whom treatment was discontinued.

Carcinoma, Hepatocellular↗
PubMed1995

Diagnostic value of endoscopic ultrasonography in an unusual case of gastric cyst.

Using endoscopic ultrasonography, we diagnosed a gastric antral submucosal cyst with a papillous protrusion in a 71-yr-old woman, apparently the first such case to be detected by this method. Endoscopic ultrasonography demonstrated a well-marginated hypoechoic area with papillary tumor in the submucosal layer that did not extend to the muscularis propria. The lesion was diagnosed as a gastric submucosal cyst. CT and transabdominal ultrasound each failed to detect the intracystic papillary tumor. Follow-up endoscopic ultrasonography performed 6 months later revealed an increase in the diameter of the cyst and the papillary tumor. The patient then underwent a partial gastrectomy for a suspected malignancy. The resected specimen showed a cystic lesion with papillary tumor. Although no malignancy was present, examination of cross-sections of the resected specimen gave results consistent with the endoscopic ultrasonographic findings. Endoscopic ultrasonography is thus useful in assessing the nature of a submucosal gastric cyst in detail and in monitoring patients with this lesion.

Aged↗
PubMed1995

Etiology and prognosis of liver cirrhosis in elderly patients.

We compared the etiology and prognosis of liver cirrhosis in patients age 60 and older with that of patients under age 60 during the 1980s (1981-89, n = 207). Non-A, non-B hepatitis (NANB) was significantly more prevalent in the elderly (p < 0.05), and the mean age of NANB and alcoholic cirrhosis (Alc) were significantly older than those with hepatitis B virus (HBV) (p < 0.05). Evaluation using hepatitis C virus (HCV) antibody also revealed significantly higher mean age of HCV (p < 0.05). Male patient was predominant in the younger patients than in the elderly patients. (M/F = 2.94 and 1.33, respectively) The estimated 5-year survival rate was 73.1% in the younger patients and 60.2% in the elderly patients (p < 0.05). Multivariate analysis revealed that male sex, a lower serum albumin level, and the presence of the encephalopathy were significantly associated with poor prognosis in the elderly, while a lower serum cholinesterase level and a higher indocyanin green retention rate at 15 minutes (ICGR15) were significantly associated with poor prognosis in younger patients. However, causes of deaths were not significantly different between the younger patients and the elderly patients, the proportion of deaths unrelated to liver disease predominated in the elderly patients. Thus, the etiology and the prognostic factors of liver cirrhosis in elderly patients differ from those in younger patients.

Age Factors↗