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Biomedical subjects

H Nawata

Publications and source records attributed to H Nawata.

At least 271 records · Page 15Linked to original sources
PubMed1996

Prostacyclin-stimulating factor, novel protein, and diabetic angiopathy.

We recently purified and cloned a new protein that stimulates the synthesis of prostacyclin (PGI2) by the vascular endothelial cells (ECs). We have termed this protein "PGI2-stimulating factor" (PSF). The present study evaluated the expression of PSF mRNA in tissues of Wistar rats, including the kidneys of rats with streptozotocin-induced diabetes, and in cultured cells. Furthermore, we evaluated the presence of PSF in human sera and the immunohistochemical localization of PSF in tissues of patients obtained at autopsy. The latter included a coronary atherosclerotic lesion of a patient who died of acute myocardial infarction. PSF was observed by Northern blot analysis to be expressed in all rat tissues examined (brain, lung, liver, kidney, skeletal muscle, and fat tissue) and was expressed in cultured vascular ECs, smooth muscle cells (SMCs), and fibroblast cells (FCs). A decreased expression of PSF was observed in the kidneys of diabetic rats versus those of normal rats. The presence of PSF in human serum was confirmed by Western blot analysis. In humans, PSF was mainly localized in vascular ECs and SMCs of arterial media and in SMCs of bronchi. Reduced staining for PSF was found in an atherosclerotic versus a normal coronary artery of humans. PSF may be involved in the production of PGI2 in the vessel wall and may participate in the maintenance of vascular homeostasis. PSF abnormalities may be involved in the development of such vascular lesions as atherosclerosis and diabetic angiopathy.

Amino Acid Sequence↗
PubMed1996

Vitamin E normalizes diacylglycerol-protein kinase C activation induced by hyperglycemia in rat vascular tissues.

Hyperglycemia, a major cause of vascular complications in diabetes, has been shown to activate the diacylglycerol (DAG)-protein kinase C (PKC) pathway in vascular tissues. We have found that D-alpha-tocopherol (vitamin E) treatment reversed the adverse effects of hyperglycemia both in vitro and in vivo. In aortic smooth muscle cells (ASMCs), the PKC specific activity from the membranous fraction and total DAG were increased by 31 +/- 4% (P < 0.05) and 50 +/- 7% (P < 0.05), respectively, when the glucose levels were changed from 5.5 to 22 mmol/l. D-alpha-tocopherol prevented the glucose-stimulated increases in DAG level and PKC activity as well as the amount of PKC beta II isoform in ASMCs cultured with elevated glucose levels. Comparing streptozotocin-induced diabetic rats after 2 weeks of disease to controls, specific membranous PKC activities and total DAG levels were increased in aorta (162%, P < 0.05; 60%, P < 0.05). Intraperitoneal injection of D-alpha-tocopherol (40 mg/kg) every other day resulted in a significant decrease of the elevated membranous PKC specific activity and total DAG levels in parallel with a significant increase of D-alpha-tocopherol content in the aorta. These findings suggested that D-alpha-tocopherol can prevent the activation of PKC in the vascular cells and aorta induced by hyperglycemia by normalizing the elevated levels of DAG.

Animals↗
PubMed1996

Risk factor analyses for macrovascular complication in nonobese NIDDM patients. Multiclinical Study for Diabetic Macroangiopathy (MSDM).

To examine the characteristic features of risk factors for macroangiopathy (MA) in nonobese Japanese NIDDM patients, 899 NIDDM patients with and without MA were registered from 40 facilities. Of these, 386 subjects were identified as having any form of MA (total MA); these included 211 with ischemic heart disease (IHD), 163 with cerebrovascular disease (CVD), and 77 with peripheral vascular disease (PVD). Univariate analyses revealed the following common risk factors for total MA, IHD, CVD, and PVD: age, hypertension, systolic blood pressure (sBP) or diastolic blood pressure (dBP), duration of diabetes, diabetic microangiopathy (retinopathy, nephropathy, and neuropathy), low HDL cholesterol level, and higher LDL cholesterol/HDL cholesterol ratio. Additional significant risk factors for specific conditions were also identified, respectively, as male sex for total MA, IHD, and PVD, smoking for IHD and PVD, and high fasting plasma glucose level for total MA and CVD. With stepwise multivariate logistic regression analysis, older age, duration of diabetes, smoking, and low LDL cholesterol/HDL cholesterol ratio were identified as significant and independent risk factors for total MA, IHD, CVD, and PVD. Other risk factors identified were high dBP for IHD, CVD, and PVD, high sBP for total MA, and low BMI for PVD. These results clearly demonstrated that duration of diabetes, smoking, hypertension, and dyslipidemia are major risk factors for MA in NIDDM patients. Since the mean BMI was similar for both groups (approximately 23 kg/m2) and there were no significant differences in immunoreactive insulin levels before and after 75-g oral glucose challenge testing, obesity and hyperinsulinism at the time of the analyses were not considered to play an important role for the pathogenesis of MA in Japanese NIDDM patients. By using the chi 2 test, cutoff points were determined for six of the most commonly measured risk factors. The cutoff point was the level beyond which a significantly higher prevalence of MA occurred. The cutoff points (rounded slightly upward in some cases) for fasting plasma glucose, sBP, dBP, serum total cholesterol level, serum triglyceride level, and BMI were 140 mg/dl, 140 mmHg, 80 mmHg, 180 mg/dl, 120 mg/dl, and 23 kg/m2, respectively. When these cutoff points were used as control criteria, the prevalence of MA was significantly lower in subjects whose risk factor measurements remained under the proposed control criteria for four or more of the six variables. In conclusion, in nonobese NIDDM patients, age, hypertension, and dyslipidemia were found to be risk factors for MA. Duration of diabetes was also demonstrated as an independent risk factor, indicating the close association of deranged glucose metabolism with the pathogenesis of MA in NIDDM patients. It seems to be crucial to control these risk factors for the prevention of MA in NIDDM patients.

Aged↗
PubMed1996

[NGFI-B/nur77 family involved in T-cell apoptosis].

NGFI-B/nur77 is a member of the steroid receptor superfamily. NGFI-B/nur77 and its related genes constitute a family and the NGFI-B/nur77 family consists of three subtypes, named nur77 alpha, nur77 beta, nur77 gamma. We cloned human nur77 beta cDNA, called TINUR. Although NGFI-B/nur77 is essential for TCR-mediated apoptosis in T-cell hybridomas, the reports on nur77 knock-out mice and nur77 dominant negative transgenic mice suggest that there is a functional redundancy among NGFI-B/nur77 family. NGFI-B/nur77 binds to the response element by monomer or heterodimer with retinoid X receptor (RXR). Assuming that 9-cis-retinoic acid (9-cis-RA) inhibits TCR-mediated apoptosis, nur77 may cause apoptosis by monomer in the absence of 9-cis-RA and may inhibit apoptosis by heterodimer with RXR in the presence of 9-cis-RA.

Animals↗
PubMed1996

Role of endogenous cholecystokinin in the regeneration of pancreatic tissue after acute hemorrhagic pancreatitis in rats.

The aim of this study was to investigate the effect of endogenous cholecystokinin (CCK) on pancreatic regeneration after acute hemorrhagic pancreatitis. Acute hemorrhagic pancreatitis was induced in rats by two intraperitoneal cerulein injection (20 micrograms/kg BW) with 5h water-immersion stress once a day for successive 3 days. After the cessation of repetition of acute pancreatitis the rats were treated with successive feeding with 0.1% camostat-containing diet or SC injection of CR-1505 (CCK receptor antagonist, 50 mg/kg BW x 2/day) for 7 days. Zymogen enzymes and protein contents per DNA in pancreatic tissue were significantly higher in rats treated with camostat compared with control rats, and plasma CCK level was elevated. To the contrary, pancreatic regeneration was retarded in the rats treated with CR 1505. It is concluded that endogenous CCK has a trophic effect during regeneration after acute hemorrhagic pancreatitis.

Acute Disease↗
PubMed1996

[Primary macroglobulinemia with t(11;18) (q21;q21)].

This is the first case of primary macroglobulinemia with t(11;18) (q21;q21) reported in the literature. A 77-year-old man was admitted to a hospital in December, 1994, with acute renal failure and pleural effusion. He was treated with prednisolone pulse therapy and his symptoms improved. He was referred to our hospital for further examination. Analysis of blood chemistry revealed macroglobulinemia (IgM-kappa). There were no other findings that would indicate a diagnosis of malignant lymphoma. A complete blood count revealed a hemoglobin level of 8.7 g/dl and a white blood cell count of 5,300/microliters with 11% abnormal lymphoid cells. Immunologic and karyotype analyses revealed that these abnormal cells were positive for IgM-kappa, CD19, and CD20, negative for CD5, and CD10, and had t(11;18) (q21;q21). The bone marrow had also been infiltrated by 8.6% abnormal lymphoid cells. Six other cases with t(11;18) (q21;q21) have been reported including 5 of small lymphocytic lymphoma and 1 of mucosa-associated lymphoid tissue-type lymphoma. The tumor cells in these cases were the same as in our case. Therefore, our report is in agreement with the finding that t(11;18) (q21;q21) might be one of the characteristic chromosomal abnormalities in mature B-lymphoid neoplasms.

Aged↗
PubMed1996

[Two cases of liver scar that was examined by biliary scintigraphy].

36-year-old-female admitted because of jaudice and ascites. T-bil was 18.5 mg/dl and transaminase, ALP, LDH and gamma-GTP was elevated. Ultrasonography (US) showed that right lobe was atrophy and left lobe was swelling. Plain computed tomography (CT) showed right lobe was low density. Magnetic resonance (MR) finding was T1-weighted image of right lobe was low intensity and T2-weighted image was high intensity. Angiography showed right lobe was more stained than left lobe. Histologically, right lobe was massive necrosis. These findings suggested that right lobe was liver scar. Biliary imaging showed right lobe was delayed. A 23-year-old-female admitted because of fever and abdominal tumor. Transaminase was normal, only gamma-GTP was elevated. US, plain CT, enhanced CT, MR imaging finding was as same as that of the first case. Similarily, biliary scintigraphy showed right lobe was delayed. Causes of the two liver scars was not clear, whereas liver scar detected after delivery was rare case.

Adult↗
PubMed1996

[Successful treatment with combination of all-trans retinoic acid (ATRA) and rhG-CSF a relapsed acute promyelocytic leukemia with umbilical tumor].

A 48-year-old female was admitted to our hospital because of pancytopenia and pneumonia in February, 1993. The increase of abnormal promyelocytes with t (15; 17) and PML-RAR mRNA was detected in bone marrow aspirate and a diagnosis of acute promyelocytic leukemia was made. She obtained complete remission after the administration of all-trans retinoic acid (ATRA) and following chemotherapy. Then she received peripheral blood stem cell transplantation in September, 1993. However she noticed a umbilical tumor in June, 1995. Abnormal promyelocytes were demonstrated not only in bone marrow aspirate but also in the umbilical tumor. Because of the poor response to ATRA and development of fever, a side effect of ATRA, G-CSF and prednisolone were administrated together with ATRA. After the combined therapy, umbilical tumor disappeared and she obtained complete remission again. These findings suggest that combined therapy of ATRA and G-CSF is effective to the low responder to ATRA and that combined use of ATRA and prednisolone reduces the side effect of ATRA without diminishing the favorable effect on differentiation.

Drug Therapy, Combination↗
PubMed1996

Secretory protein 7B2 response to oral glucose loading and intravenous glucagon injection in patients with diabetes mellitus.

Serum 7B2 concentrations in control subjects and patients with diabetes mellitus were measured following a 75 g oral glucose load and following intravenous glucagon infusion. In response to oral glucose, serum 7B2 levels increased in the controls (n = 10) and in the diabetic patients (n = 7). The increment of the serum 7B2 level was smaller in the diabetic patients than the controls. During the 75 g oral glucose tolerance test (75g OGTT), serum 7B2 levels were significantly positively correlated with serum C-peptide levels. In contrast, following intravenous glucagon infusion, serum 7B2 levels increased only in diabetic patients treated with oral hypoglycemic agents (n = 20) and did not increase in controls (n = 5): the group having the highest insulin secretion activity in the present study, nor in diet or insulin-treated diabetic patients. No correlation between serum 7B2 levels and serum CPR levels was observed in the intravenous glucagon infusion study. These data suggest that an extra-pancreatic source which produces the observed serum 7B2 increase following oral glucose intake can not be excluded and that 7B2 may not be secreted concomitantly with insulin from the pancreatic beta cell in response to intravenous glucagon injection.

Administration, Oral↗
PubMed1995

cDNA cloning of a NGFI-B/nur77-related transcription factor from an apoptotic human T cell line.

A human T lymphoid cell line, PEER, dies by apoptosis in the presence of PMA and calcium ionophore. A new gene, TINUR, was cloned from apoptotic PEER cells. The expression of the TINUR gene is induced within 1 h after the cross-linking of the T cell Ag receptor complex. TINUR belongs to the NGFI-B/nur77 family of the steroid receptor superfamily and is an orphan receptor. TINUR binds to the same DNA sequence as NGFI-B/nur77. We also propose that the NGFI-B/nur77 family can be classified into two subtypes.

Amino Acid Sequence↗
PubMed1995

An E box element is required for the expression of the ad4bp gene, a mammalian homologue of ftz-f1 gene, which is essential for adrenal and gonadal development.

Ad4BP, also known as SF-1, is a cell type-specific transcription factor regulating all the steroidogenic P-450 genes. Recently, the targeted disruption of the mouse ftz-f1 gene encoding Ad4BP/SF-1 has established its essential function in both adrenal and gonadal development and sexual differentiation. As an initial step toward understanding its role in the cascade of gene activations necessary for the differentiation of the steroidogenic tissues and the sex differentiation of the gonads, we isolated and characterized the rat ad4bp gene. A sequence analysis of the ad4bp gene revealed that another nuclear factor ELP was also transcribed from the same gene by alternative promoter usage and splicing. The promoter of the ad4bp gene showed activities in the steroidogenic cells such as Y-1 adrenocortical cells and I-10 testicular Leydig cells when examined by transient transfection assays. Using deletion analysis and site-directed mutagenesis, we identified a cis-element at the position from -82 bp to -77 bp in the 5'-upstream region. The cis-element was identical to the consensus E box element, which is the binding site for the basic-helix-loop-helix proteins. Gel mobility shift analyses revealed the amount of a binding factor to this E box in the nuclear extract prepared from the rat testes attained a maximal level 1 week after birth and then decreased dramatically thereafter, and only trace amounts were detected in adult rats. In contrast, the binding factor in the ovaries attained a maximal level just after birth and kept its level thereafter. These dimorphic expressions of the binding factor to the E box correlated well with those of Ad4BP, and thus suggested that the expression of Ad4BP, and thus suggested that the expression of Ad4BP is transcriptionally regulated through this E box element.

Adrenal Cortex↗
PubMed1995

[A case of primary hypothyroidism with pituitary enlargement and abnormal secretion of growth hormone and prolactin].

A case of primary hypothyroidism accompanied by pituitary enlargement and pituitary dysfunction is documented. A 27-year-old woman was admitted to our hospital for further examination of pituitary enlargement. Endocrinological examination revealed that she had primary hypothyroidism. Her TSH level in serum was elevated to more than 300 microU/ml. She also had pituitary dysfunction such as hypersecretion of prolactin in response to TRH and paradoxical rise of GH to glucose load. Serum antibodies against the pituitary gland were negative. Magnetic resonance imaging (MRI) examination showed an enlarged pituitary gland extending to supraseller cistern, which was homogeneously enhanced after Gadolinium-DTPA treatment. Treatment with 50-100 micrograms of levothyroxine sodium normalized her thyroid function and secretion of GH and prolactin. In addition, periodic MRI examination demonstrated a gradual decrease in the size of the pituitary gland after the treatment. The above clinical course indicates that pituitary enlargement in this patient occurred as a result of primary hypothyroidism. The mechanism of the abnormal secretion of TSH, GH and prolactin secondary to primary hypothyroidism was discussed.

Adult↗
PubMed1995

Inhibition of intercellular communication via gap junction in cultured aortic endothelial cells by elevated glucose and phorbol ester.

Gap junctional intercellular communication (GJIC) is important in coordinating the cells in maintaining tissue homeostasis and in regulating signal transmission. We examined the effect of elevated glucose on GJIC activity in cultured bovine aortic endothelial cells. GJIC activity was assessed by quantitating the transfer from cell to cell of directly microinjected fluorescent dye molecules. GJIC was activated in the subconfluent monolayer. In this condition, exposing the cells to elevated glucose (400 mg/dl) for 24 hrs significantly inhibited GJIC activity, as compared with low glucose (100 mg/dl). This inhibition of GJIC activity induced by elevated glucose was mimicked by addition of 12-O-tetradecanoylphorbol-13-acetate and was restored by addition of staurosporin (10(-8)M), a PKC inhibitor. These results suggest that inhibition of GJIC activity induced by elevated glucose probably through activation of PKC may be involved in the vascular endothelial cell dysfunction associated with diabetes.

Alkaloids↗
PubMed1995

The antiobesity effect of dehydroepiandrosterone in castrated or noncastrated obese Zucker male rats.

Although antiobesity effect of dehydroepiandrosterone (DHEA) has been reported in rats, it remains unclear whether the effect is brought about by itself or mediated by sex steroids converted from DHEA in gonads. In the present study, to clarify this point, the effect of DHEA on growth in obese Zucker male rats was reevaluated under two conditions: with or without castration. Castration did not affect the pattern of growth curve of obese Zucker male rats. Three-months treatment of castrated Zucker rats with 0.3% DHEA in the diet resulted in dramatic decrease of body weight gain in comparison to DHEA-untreated and castrated rats. The degree of antiobesity effect of DHEA in castrated rats was almost same as that observed in non-castrated rats. These results suggest that DHEA exerted its antiobesity effect by itself rather than through conversion to testosterone in testis.

Animals↗
PubMed1995

Spontaneous resolution of hypertrophic cranial pachymeningitis.

A 36-year-old woman presented suffering from severe headache and diploia. Magnetic resonance imaging showed a diffuse thickening of the cranial dura mater which was enhanced by gadolinium-DTPA. Two months later, an improvement of the clinical symptoms and a spontaneous resolution of the dural thickening were noted. Hypertrophic cranial pachymeningitis and other diseases causing diffuse dural thickening are discussed.

Adult↗
PubMed1995

Natural killing activity is associated with progression of gastric cancer.

Previously, we proposed a new analysis of natural killing activity, in which an individual effector/target cell ratio was employed for comparison according to the peripheral number of effector cells. In 51 patients with gastric cancer, the activity was studied using that modified analysis. Natural killing activity was activated in patients with early cancer, where tumor-cell invasion was restricted to the mucosa or the submucosa, even though in well-differentiated adenocarcinoma with invasion of the mucosa alone, the activity remained at the level of controls. In contrast, the activity in advanced cancer, where tumor cells infiltrated beyond the submucosa, came to be inactivated as the cancer progressed. These facts suggest that natural killing activity in patients with gastric cancer is closely associated with tumor invasion and that reactive activation of the activity against tumor is induced, at least, in some patients with early stage.

Adenocarcinoma↗
PubMed1995

New chronic pancreatitis model with diabetes induced by cerulein plus stress in rats.

To establish a new experimental model of chronic pancreatitis (CP) with diabetes, we investigated pancreatic endocrine function, blood flow, and histopathology in CP induced by repetition of cerulein injection plus water immersion stress in rats. CP rats were treated with water immersion stress for 5 hr and two intraperitoneal injections of 20 micrograms/kg body weight of cerulein once a week for 16 weeks. In the CP group, pancreatic contents of protein, amylase, elastase, and lipase significantly decreased to 64, 38, 23, and 68% of the control group, respectively. In oral glucose tolerance test (glucose 2 g/kg body wt), blood glucose level in the CP group was 212.1 +/- 97.8 mg/dl (mean +/- SD) at 30 min and was significantly higher than the control group (126.3 +/- 15.4 mg/dl)(P < 0.05). Two of seven rats in the CP group showed an obvious diabetic insulin in the CP group was 640.1 +/- 148.7 pM, significantly lower than in the control group (1133.4 +/- 242.0 pM)(P < 0.001). However, insulin content in the pancreas was 12.37 nmol/pancreas). In CP rats, winding and dilatation of surface blood vessels and gland atrophy were evident. Marked fibrosis, fatty changes, and destruction of lobular architecture were also demonstrated microscopically, although the structure of each pancreatic islet was preserved and each islet was fully stained with anti-insulin antibody. In the CP group, pancreatic blood flow by the hydrogen gas-clearance method was 197.6 +/- 33.0 ml/min/100 g, which was significantly less than the control group (276.2 +/- 19.1 ml/min/100 g) (P < 0.001). Thus, we conclude that the CP model induced by cerulein plus stress is a new CP model with diabetes in rats, in which the glucose tolerance was impaired without loss of insulin reserve.

Amylases↗