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Biomedical subjects

H Nawata

Publications and source records attributed to H Nawata.

At least 181 records · Page 10Linked to original sources
PubMed1998

Interactive mechanisms among pituitary adenylate cyclase-activating peptide, vasoactive intestinal peptide, and parathyroid hormone receptors in guinea pig cecal circular smooth muscle cells.

Vasoactive intestinal peptide (VIP) causes relaxation of smooth muscle cells via both VIP-specific receptor coupled to nitric oxide synthase and VIP-preferring receptor coupled to adenylate cyclase. Because the mechanism of interaction among VIP, pituitary adenylate cyclase-activating peptide (PACAP), and PTH is still unclear, the characteristics of the receptors for PACAP and PTH in circular muscle cells obtained from the guinea pig cecum were investigated. The effects of an inhibitor of cAMP-dependent protein kinase [cyclic adenosine 3',5'-monophosphorothioate (Rp-cAMPS)], guanylate cyclase inhibitors, antagonists of these peptides, and the selective receptor protection on the relaxing effect produced by PACAP, VIP, and PTH were examined. PACAP-induced relaxation was significantly inhibited by a VIP antagonist, a PTH antagonist, Rp-cAMPS, and an inhibitor of particulate guanylate cyclase. VIP-induced relaxation was significantly inhibited by a PACAP antagonist and a PTH antagonist. PTH-induced relaxation was significantly inhibited by a VIP-specific receptor antagonist and Rp-cAMPS, but not by a PACAP antagonist. A PTH antagonist significantly inhibited a VIP-preferring receptor agonist-induced relaxation. The muscle cells in which cholecystokinin octapeptide and PTH receptors were protected completely abolished the inhibitory responses to VIP and PACAP. The muscle cells in which cholecystokinin octapeptide and VIP or PACAP receptors were protected completely abolished the inhibitory response to PTH. This study shows that PACAP induces relaxation of these muscle cells via both VIP-preferring receptor coupled to adenylate cyclase and PACAP-specific receptor, and that PTH induces relaxation of the muscle cells via PTH-specific receptor coupled to adenylate cyclase. In addition, the results of a selective receptor protection show that PTH does not bind to VIP receptors, and that VIP does not bind to PTH receptor. Therefore, this study first demonstrates the presence of one-way inhibitory mechanisms from the PTH-specific receptor to the VIP-preferring receptor, and from the VIP-specific receptor to the PTH-specific receptor in the mechanisms of interaction between VIP and PTH.

Animals↗
PubMed1998

Diagnosis and staging of pancreatic cancer by endoscopic ultrasound.

The aim of this study was to evaluate the usefulness of and problems associated with endoscopic ultrasonography (EUS) in the diagnosis and pre-operative staging of pancreatic cancer. 96 patients suspected of having pancreatic cancer were pre-operatively examined with EUS. 37 of these 96 patients had pancreatic cancer. Results of the EUS imaging were compared with findings of histology and/or surgery, and the patient's clinical course. The sensitivity and specificity of EUS for diagnosing pancreatic cancer were 89% and 97%, respectively. EUS had excellent sensitivity regardless of tumour size or location. EUS was accurate (90%) in determining tumour size in pancreatic cancers less than 3 cm in maximum diameter, but not for tumours greater than 3 cm (30%). The accuracy of tumour (T) and nodal (N) staging were 64% and 50%, respectively. EUS is a promising method for the early diagnosis and pre-operative staging of pancreatic cancers, but requires further refinement.

Adult↗
PubMed1998

Immunohistochemical study of cytochrome b5 in human adrenal gland and in adrenocortical adenomas from patients with Cushing's syndrome.

Cytochrome b5, a component of the electron transfer system increases the relative activity of 17,20-lyase to 17alpha-hydroxylase of P450c17 in vitro. In the present study, immunohistochemical analysis of cytochrome b5 was performed in the human adrenal gland and in adrenocortical adenomas from patients with Cushing's syndrome. In the human adrenal gland, cytochrome b5 was stained in all three adrenocortical layers but the staining was most remarkable in the zona reticularis. All of the adenomas were composed mainly of compact cells, which exhibited immunoreactive staining for cytochrome b5 as well as for P450c17 and 3beta-hydroxysteroid dehydrogenase (3beta-HSD). The distribution of b5 in the adenomas was correlated with that of P450c17 rather than with that of 3beta-HSD. The immunoreactive staining for cytochrome b5 appeared to be more prominent in the two adenomas that produced relatively high concentrations of adrenal androgens than in adenomas that produced low concentrations of adrenal androgens. These results immunohistochemically support the functional association of b5 with androgen production through interaction with P450c17 and the previous finding that higher concentrations of cytochrome b5 are associated with greater production of adrenal androgens in adrenocortical adenomas from patients with Cushing's syndrome.

3-Hydroxysteroid Dehydrogenases↗
PubMed1998

Nur77, a member of the steroid receptor superfamily, antagonizes negative feedback of ACTH synthesis and secretion by glucocorticoid in pituitary corticotrope cells.

Nur77 is a member of the steroid receptor superfamily and is known to be expressed in animals under stress. We studied the role of nur77 in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis during the stress response using a murine pituitary corticotrope cell line, AtT-20. Corticotropin-releasing hormone (CRH), a stress mediator in the HPA axis, induced the expression of nur77 transiently in AtT-20 cells. Gel shift assay showed that nur77 bound to negative glucocorticoid responsive element (nGRE) in the promoter of the human proopiomelanocortin (POMC) gene and the formation of the nur77-nGRE complex increased after treatment of the cells with CRH. Negative GRE is known to be necessary for the negative regulation by glucocorticoid of the POMC gene expression. In stable transformants of AtT-20 cells expressing a human homolog of nur77, NAK-1, at a high level, glucocorticoid-mediated inhibition of both POMC mRNA induction and ACTH secretion was significantly lower than that in the NAK-1-non-expressing cells (P < 0.001). These results strongly suggest that nur77 antagonizes the negative feedback effect of glucocorticoid on the synthesis and secretion of ACTH in pituitary corticotropes. This suggests that nur77 plays an important role in the pituitary gland in the biological adaptation to overcome stress.

Adaptation, Physiological↗
PubMed1998

A rare case of 46,XX true hermaphroditism with hidden mosaicism with sex-determining region Y chromosome-bearing cells in the gonads.

The sex-determining region Y chromosome (SRY) triggers testis determination. We report a 46,XX true hermaphrodite who had ambiguous genitalia at birth. A laparotomy at one year of age revealed this patient to have a testis on the right side and an ovotestis on the left side. By polymerase chain reaction analysis no SRY was detected in the DNA from the leukocytes but it was found in the DNA from the ovotestis. The hidden mosaicism with the Y-bearing cells in the gonads is likely the cause of the dual gonads in this patient.

Adult↗
PubMed1998

Retroperitoneal Castleman's disease of the hyaline vascular type presenting arborizing calcification.

Castleman's disease (CD) usually manifests as a solitary mediastinal tumor and only rarely as an isolated retroperitoneal mass. In the latter instances it is difficult to distinguish radiographically from other retroperitoneal masses. We report a 22-year-old female patient with retroperitoneal CD of the hyaline vascular type presenting with arborizing calcification. This characteristic calcification pattern is considered unique to CD, and is useful in diagnosis when present.

Adult↗
PubMed1998

High glucose induces alteration of gap junction permeability and phosphorylation of connexin-43 in cultured aortic smooth muscle cells.

Gap junction is thought to have a crucial role in maintaining tissue homeostasis. We examined the effect of a high glucose level on gap junctional intercellular communication (GJIC) activity in cultured vascular smooth muscle cells (VSMCs) using the fluorescent dye transfer method. After a 48-h incubation with 22 mmol/l glucose (high glucose level), GJIC activity of VSMCs was significantly reduced compared with incubation with 5.5 mmol/l glucose (normal glucose level) (P < 0.05). Treatment of the cells with 12-O-tetradecanoylphorbol-13-acetate (TPA; 5 x 10(-8) mol/l), a protein kinase C (PKC) activator, for 1 h also reduced GJIC activity (P < 0.01). In addition, treatment of the cells with calphostin C, a specific PKC inhibitor, for 3 h completely restored the GJIC activity inhibited by the high glucose level. Western blot analysis showed that connexin 43 (Cx43), which is the major functional protein of gap junction, is present in multiphosphorylated forms: a nonphosphorylated form (P0) and phosphorylated forms (P1, P2, and P3). Incubation of VSMCs with a high glucose level significantly increased the density ratio of P3/P0 compared with a normal glucose level (P < 0.05). Similarly, treatment of the cells with TPA significantly increased the P3/P0 ratio compared with controls (P < 0.01). In addition, the increase in the P3/P0 density ratio induced by a high glucose level was restored to the control level by both staurosporine and calphostin C. These results suggest that the high glucose level induced the inhibition of GJIC activity in cultured VSMCs through excessive phosphorylation of Cx43, mediated by PKC activation. This may contribute to the development of the macroangiopathy associated with diabetes.

Animals↗
PubMed1998

Heterogeneous induction of apoptosis in colon cancer cells by wild-type p53 gene transfection.

To examine the effects of wild-type (wt)-p53 gene transfer on cancer cell growth and apoptosis induction, we transduced human wt-p53 cDNA into three colon cancer cell lines either with or without a mutation of the p53 gene using the HVJ-cationic liposome method. Wt-p53 gene transfer, thus, induced an apparent growth arrest in all cell lines, but its enhancement of the apoptotic rate varied (from about 4 to 70 times). The simultaneous doxorubicin treatment was able to enhance growth arrest and the apoptosis induction rate. These findings suggest that wt-p53 gene transfer using HVJ-cationic liposomes seems to be a potentially effective therapeutic strategy, however wt-p53 gene transfer still appears to be more effective in combination with other cytotoxic treatments.

Apoptosis↗
PubMed1998

Preoperative staging of colorectal cancer by a 15 MHz ultrasound miniprobe.

BACKGROUND: Our objective was to examine the accuracy of a 15 MHz ultrasound miniprobe in the pre-operative staging of colorectal cancer by assessing the depth of tumor infiltration and involvement of pericolonic lymph nodes. METHODS: Thirty-three patients with colorectal cancer who underwent ultrasonography with a miniprobe were studied prospectively. The results of this imaging were compared with the histologic findings of the resected specimens. RESULTS: The accuracy of the miniprobe for depth of invasion (T category) was 82% (27 of 33) for all tumors, 76% (13 of 17) in pT1 cases, and 88% (14 of 16) in pT2 to pT4 cases. The accuracy of the miniprobe for nodal staging (N category) was 87% (26 of 30) overall. The sensitivity was 63% (5 of 8), the specificity was 95% (21 of 22), the positive predictive value was 83% (5 of 6), and the negative predictive value was 88% (21 of 24). CONCLUSIONS: The miniprobe is an accurate method for the preoperative TN staging of colorectal cancer. We recommend its preoperative use because the results may influence the surgical approach.

Aged↗
PubMed1998

Thiol compounds rescue growth inhibition by retinoic acid on HTLV-I (+) T lymphocytes; possible mechanism of retinoic-acid-induced growth inhibition of adult T-cell leukemia cells.

We demonstrated significant growth inhibition by retinoic acid (RA) of HTLV-I (+) T-cell lines (ATL-2 and HUT102), but not HTLV-I (-) T-cell lines (MOLT-4 and Jurkat). We hypothesized that the mechanism of growth inhibition by RA depends on an imbalance in redox potential. To examine the effect of exogenous thiol compounds for the growth of HTLV-I (+) T-cell lines by RA, HTLV-I (+) T-cell lines were cultured with several thiol compounds (thioredoxin, L-cystine, and GSH), following addition of 13-cis RA or ATRA, respectively, in cultured with thiol free medium. Unexpectedly, thiol compounds alone did not restore growth inhibition of HTLV-I (+) T-cell lines. However, when those cells were preincubated with thiol compounds for 24 hours, no growth inhibition by 13-cis RA or ATRA was observed. These results suggest that thiol compounds are associated strongly with sensitivity to RA of HTLV-I (+) T cells, but not of HTLV-I (-) T cells and that thiol compounds serve an important role on HTLV-I (+) T cells.

Cell Division↗
PubMed1998

[Functional role of nur77 family in T-cell apoptosis and stress response].

Nur77 is an orphan member of the steroid receptor superfamily (nuclear receptor). Nur77 family consists of three subtypes and the subtypes show functional redundancy. Nur77 family plays an important role in the apoptotic process of negative selection of T-cells. Moreover, nur77 seems to play a pivotal role in the hypothalamic-pituitary-adrenal axis (HPA axis) during stress response. Nur77 antagonizes the negative feedback effect on the production and secretion of ACTH by glucocorticoid in corticotrope cells of the pituitary gland.

Adrenocorticotropic Hormone↗
PubMed1998

[Pathogenesis of androgen insensitivity syndrome].

Androgen plays an important role in male sexual differentiation and the defect of androgen action mainly due to androgen receptor abnormality causes androgen insensitivity syndrome (AIS). The number of the reports of AR gene mutations is AIS reaches more than 250, including structural mutations such as gene deletion and single base mutations. The intriguing characteristics of the single amino acid substitutions by single base mutations are that they tend to occur in restricted areas and on restricted bases, and that the same mutation sometimes shows phenotypic variation even among the family members. In addition, in some AIS cases, neither androgen binding abnormality nor AR gene mutation is detected. In these cases, other factors which take part in transcriptional activation by AR might be affected.

Androgen-Insensitivity Syndrome↗
PubMed1998

[An autopsy case of rhino-orbito-cerebral mucormycosis associated with multiple cranial nerve palsy and subsequent subarachnoid hemorrhage].

We report an autopsy case of 53-year-old male with poor controlled diabetes mellitus and hepatocellular carcinoma who developed rhino-orbito-cerebral mucormycosis. Initial complaints were epistaxis and headache followed by a sudden blindness, the 2nd through 7th cranial nerve palsy and diabetes inspidus. Laboratory data revealed that he had liver cirrhosis due to hepatitis C virus infection and diabetes mellitus. Head CT and MRI showed no significant findings. Eleven days after the onset, he died of subarachnoid hemorrhage. The postmortem examination revealed severe infiltration of numerous mucors in the sphenoid sinus, cavernous sinus and bilateral internal carotid arteries. Severe granulomatous vasculitis was seen in the cavernous portion of the bilateral internal carotid arteries. Thus, we considered that this case had been caused by the infiltration of mucors to the cavernous sinus, resulting in the obstruction of ophthalmic arteries. Rupture of the right internal carotid artery was seen at the branching portion of the ophthalmic artery, demonstrating the cause of his death. We would like to emphasize that rhino-orbito-cerebral mucormycosis should be ruled out if we examine a nondiagnostic case of diabetes mellitus or immunosuppressed disease associated with rapid multiple cranial nerve palsy following the orbital symptoms.

Abducens Nerve↗
PubMed1997

[Phe21]big endothelin-1(18-34) and [Ala31]big endothelin-1(18-34) inhibit the human endothelin-converting enzyme-1 (ECE-1) expressed in CHO-K1 cells in a different fashion.

Endothelin-converting enzyme-1 (ECE-1) is one of the most important enzymes to convert big endothelin-1 (big ET-1) to ET-1. To identify the inhibitors of ECE-1, we examined the effects of variously substituted analogues of big ET-1 on ECE-1 activity using solubilized membranes prepared from human ECE-1-expressed CHO-K1 cells. Among the big ET-1 analogues tested, [Phe21]big ET-1(18-34) and [Ala31]big ET-1(18-34) exhibited a significant inhibition of ECE-1. A kinetic analysis revealed [Phe21]big ET-1(18-34) to be a competitive inhibitor (Ki=20.6 microM) and [Ala31]big ET-1(18-34) to be a noncompetitive inhibitor (Ki=35.6 microM). These results not only support the concept that ECE-1 recognizes big ET-1 both at the P1 position and at the C-terminal region but also revealed that these two regions are recognized by this enzyme in a different manner.

Animals↗
PubMed1997

Differential expression of PPAR gamma1 and gamma2 isoforms in human adipose tissue.

One of the essential factors for adipogenesis, peroxisome proliferator activated receptor gamma (PPAR gamma), is classified into two isoforms, gamma1 and gamma2 encoded by a single PPAR gamma gene. To examine the mode of expressions of both the PPAR gamma1 and gamma2 isoforms in human adipose tissue, we cloned a partial cDNA of the human PPAR gamma2 (hPPAR gamma2) from a human adipose tissue cDNA library. The sequence encoded an additional 28 amino acids amino-terminal to the first ATG codon of hPPAR gamma1. The simultaneous quantitation of hPPAR gamma1 and gamma2 mRNA in subcutaneous or visceral (mesenteric) fat tissue from 10 different individuals was performed by an RNase protection assay and revealed a relatively higher expression of gamma1 than gamma2 in all specimens examined.

Adipose Tissue↗
PubMed1997

Effects of retinoids on the production of tumour necrosis factor-alpha and nitric oxide by lipopolysaccharide-stimulated rat Kupffer cells in vitro: evidence for participation of retinoid X receptor signalling pathway.

Kupffer cells play important roles in the development of liver injury by producing cytokines and free radicals. In consequence inhibition of these inflammatory mediators will be one of the targets for treating liver diseases. Retinoids modulate a wide variety of functions of monocytes/macrophages. Cellular effects of retinoids are mediated by two families of nuclear receptors, retinoic acid receptors (RARs) and retinoid X receptors (RXRs). We examined the effects of several kinds of natural and synthetic retinoids on the production of tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) by LPS-stimulated rat Kupffer cells in vitro. Of the various retinoids tested, 9-cis-retinoic acid (9-cis-RA) and Ro 13-6307 which are agonists of both RARs and RXRs, suppressed the production of TNF-alpha and NO in a concentration-dependent fashion, whereas three types of RAR-selective agonists, Ro 13-7410, Ro 40-6055 and Ro 19-0645 did not show any effect. Furthermore, the RAR alpha antagonist, Ro 41-5253, did not prevent the effects induced by 9-cis-RA. The results suggest that these effects of 9-cis RA and Ro 13-6307 were induced by the RXRs-dependent signalling pathway.

Animals↗