PubMed Health⌕ Search

Biomedical subjects

Kozo Hashimoto

Publications and source records attributed to Kozo Hashimoto.

At least 37 records · Page 2Linked to original sources
PubMed2005

Expression of type 1 corticotropin-releasing hormone (CRH) receptor mRNA in the hypothalamic paraventricular nucleus following restraint stress in CRH-deficient mice.

Previous studies have demonstrated that various types of stress increase type 1 corticotropin-releasing hormone (CRH) receptor (currently abbreviated to CRF1 receptor) mRNA in the hypothalamic paraventricular nucleus (PVN) of rats, but not mice. This study investigated whether different sensitivities of glucocorticoid-mediated negative feedback effects can explain this species difference in stress-induced PVN CRF1 receptor mRNA expression. First, the CRF1 receptor mRNA level in the PVN of CRH knockout (KO) mice during acute restraint stress was compared with that in wild-type (WT) mice. Consistent with previous findings, WT mice showed no induction of CRF1 receptor mRNA in the PVN following acute restraint, regardless of normal hypothalamic-pituitary-adrenocortical responses. In contrast, CRF1 receptor mRNA in the PVN of CRH KO mice was increased following 2 h of restraint. Since the response of tyrosine hydroxylase (TH) mRNA in the locus coeruleus (LC) to restraint was similar between CRH KO and WT mice, it is unlikely that enhanced noradrenergic input into the PVN was responsible for the CRF1 receptor mRNA induction in CRH KO mice. Second, to determine whether CRH KO per se or a low corticosterone response to stress is required to induce CRF1 receptor mRNA expression in the PVN in mice, the response of adrenalectomized WT mice was examined. Acute restraint increased the CRF1 receptor mRNA level in the PVN of adrenalectomized WT mice, similar to the case for CRH KO mice. TH mRNA in the LC showed similar increases in sham and adrenalectomized WT mice. These results indicate that PVN CRF1 receptor mRNA is much more sensitive to glucocorticoid-mediated negative feedback in mice than in rats, such that a normal increase in plasma corticosterone during stress can mask CRF1 receptor mRNA induction in the PVN of mice.

Adrenalectomy↗
PubMed2005

Type 1 diabetes developed in a type 2 diabetic patient with severe insulin resistance.

We report a 38-year-old female with severe insulin resistance who developed type 1 diabetes after being diagnosed with type 2 diabetes. At the initial examination, BMI was 31.8 kg/m(2) and HbA1c 10.8%. Her insulin secretion was sufficient (urinary CPR 80 microg/day) and the GAD antibody was negative. Following treatment with insulin and glimepiride, HbA1c decreased to 6.3%, though diabetic control deteriorated after 1 year (HbA1c, 11.0%) and her body weight was reduced in a short period, from 78 to 67 kg. Re-examination revealed that the GAD antibody was high (1870 U/mL, normal <1.5) and the anti-islet cell antibody positive, and insulin secretion decreased (urinary CPR 18 microg/day). Further, a hyperinsulinemic-euglycemic cramp study using an artificial pancreas showed that the patient had severe insulin resistance [glucose infusion rate 1.8 mg/(min kg); normal, 7.4+/-2.4 (mean+/-S.D.)]. An HLA-analysis showed that she was a homozygote of haplotype DRB1*0901-DQB1*0303. In spite of strict insulin therapy, glucose control was not improved. Pioglitazone could not be used because of side effects, however, metformin was effective for glucose control. The accumulation of case reports of patients with type 1 diabetes and insulin resistance is important for studying the relationship between the onset of the disease and insulin resistance, and for developing an effective treatment strategy.

Adult↗
PubMed2005

Immune thrombocytopenic purpura associated with rheumatoid arthritis: case report.

A 54-year-old Japanese woman was diagnosed with rheumatoid arthritis (RA) in 1995 on the basis of symmetric effusive polyarthritis, morning stiffness, and strongly positive rheumatoid factor. She had received low-dose prednisolone, indomethacin, methotrexate (MTX), and cyclophosphamide (CPA), at least, over 4 years before the current admission and showed partial improvement of polyarthralgia. In November 2002, she suddenly developed thrombocytopenia (platelet count was 0.3 x 10(4) mm(-3)) with purpura and was diagnosed with immune thrombocytopenic purpura (ITP). As she had refractory ITP, the administration of pulsed high-dose dexamethasone (DEX) therapy was started, resulting in the complete remission of ITP. The present paper reports that pulsed high-dose DEX therapy was useful for the treatment of refractory ITP associated with RA.

Anti-Inflammatory Agents↗
PubMed2005

Pioglitazone prevents reactive hypoglycemia in impaired glucose tolerance.

A 42-year-old woman with hypoglycemic symptoms that occurred several hours after a meal visited our hospital. The hypoglycemic symptoms appeared when she was 37 years old, and her plasma glucose level had been assessed as less than 60 mg/dL when she experienced the symptoms. One year before, she had been diagnosed with reactive hypoglycemia by 75 g-oral glucose tolerance test (OGTT), which showed a normal glucose tolerance (NGT) pattern, and had begun taking an alpha-glucosidase inhibitor and nutritional treatment. A 75 g-OGTT on admission showed hypoglycemia at 240 min after glucose loading, excessive insulin secretion and an impaired glucose tolerance (IGT) pattern. A euglycemic-hyperinsulinemic clamp study demonstrated decreased insulin sensitivity. Therefore, we suspected that she had reactive hypoglycemia associated with insulin resistance and treated her with 15 mg/day pioglitazone. Her hypoglycemic symptoms completely disappeared after treatment with pioglitazone; insulin sensitivity in a euglycemic-hyperinsulinemic clamp study improved. Another 75 g-OGTT revealed that the excessive insulin secretion and hypoglycemia at 240 min after glucose loading had disappeared, and glucose tolerance was normalized from an IGT pattern to an NGT pattern. Thus, we believe that pioglitazone is effective for reactive hypoglycemia and aggravated glycemic metabolism associated with insulin resistance.

Adult↗
PubMed2005

Suppressive effects of iron on TGF-beta1 production by renal proximal tubular epithelial cells.

BACKGROUND: TGF-beta1, which is one of the profibrogenic cytokines, is considered essential for both the tubulointerstitial fibrosis found in chronic kidney diseases and the repair of tissue damage in acute renal injury. Iron plays an important part in inflammatory damage since it supplies cytotoxic hydroxyl radicals. The aim of the present study was to examine the direct effects of iron on TGF-beta1 production and the expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative stress, by human renal proximal tubular epithelial cells (RPTEC). METHODS: Using human RPTEC, TGF-beta1 expression was studied by immunohistochemical staining, ELISA and RNase protection assays. 8-OHdG expression was evaluated by immunohistochemical staining. RESULTS: Ferric iron suppressed both TGF-beta1 secretion and mRNA expression, and enhanced 8-OHdG expression in RPTEC in a dose-dependent manner. Desferrioxamine, an iron chelator, eliminated the suppressive effect of ferric citrate on TGF-beta1 production. CONCLUSIONS: The results suggest that iron may delay the repair of kidney injury during the acute inflammatory phase via a reduction in TGF-beta1 production by RPTEC. Iron chelation may therefore be a useful strategy in the treatment of inflammatory kidney diseases.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2005

An extra-adrenal abdominal pheochromocytoma causing ectopic ACTH syndrome.

We report a 55-year-old woman with ectopic adrenocorticotropin (ACTH) secretion caused by extra-adrenal pheochromocytoma. The patient presented with a 6-month history of hypertension and diabetes mellitus. Her serum and urinary cortisol levels were extremely high and dexamethasone failed to suppress the cortisol secretion. Her plasma ACTH levels were also elevated (>300 pg/mL) and irresponsive to corticotropin-releasing hormone (CRH) or metyrapone administration. Gel filtration analysis of the patient's plasma detected the existence of large molecular weight ACTH being eluted with a major peak of authentic 1-39 ACTH. Abdominal computed tomographic scan and magnetic resonance imaging revealed a 5-cm paraganglioma located underneath the left kidney, in which (123)I-MIBG tracer specifically accumulated. Bilateral adrenal glands were diffusely enlarged. After surgical removal of the paraganglioma, the patient's clinical symptoms improved and biochemistry normalized including plasma ACTH, urinary free cortisol, and urinary catecholamines. Subsequent histologic evaluation of the transected paranglioma tissue revealed ACTH, synaptin, and chromogranin-A histologically immunostaining. Culture of primary cells collected from the resected paraganglioma demonstrated of in vitro production of ACTH, noradrenaline, and adrenaline. This is the first report of ectopic ACTH syndrome induced by an extra-adrenal abdominal paraganglioma.

ACTH Syndrome, Ectopic↗
PubMed2005

Effect of pitavastatin on transactivation of human serum paraoxonase 1 gene.

Hepatic hydroxymethyl glutary coenzyme A HMG-CoA reductase inhibitors (statins) have various anti atherosclerosis pleiotropic effects that are independent of cholesterol reduction. Human serum paraoxonase 1 (PON1) is associated with high-density lipoprotein (HDL) and inhibits the oxidative modification of low-density lipoprotein (LDL). We investigated the effects of statins on PON1 gene transcription using a reporter gene assay. Promoter activity of the PON1 gene was estimated by measuring luciferase activity of plasmids with a PON1 promoter region transfected into human hepatoma HepG2 cells and human embryonic kidney (HEK) 293 cells. Pitavastatin, simvastatin, and atorvastatin each significantly increased PON1 promoter activity, and the transactivation by pitavastatin was abrogated by mevalonic acid and farnesyl pyrophosphate (FPP), however, not by geranylgeranyl pyrophosphate. Further, PON1 promoter activity was enhanced by farnesyl transferase inhibitor (FTI), but not by geranylgeranyl transferase inhibitor (GGTI). PON1 gene transcription has been reported to be dependent on Sp1 and the transactivation by pitavastatin was completely abrogated by mithramycin, an inhibitor of Sp1. Our results suggest that pitavastatin activates transcription of the PON1 gene through the FPP pathway, which may play an important role in the anti atherosclerotic effects of statins.

Alkyl and Aryl Transferases↗
PubMed2005

Periodic secretion of adrenocorticotropin in a patient with Cushing's disease manifested during pregnancy.

We report the case of 19-year-old woman with cyclical Cushing's disease, in whom plasma adrenocorticotropin (ACTH) was secreted periodically after her first pregnancy. Since the 33rd week of pregnancy, hypertension and proteinuria became clinically remarkable. She gave normal birth at 36th week of pregnancy; however she continued to gain body weight even after delivery and developed typical Cushingoid features. Her ACTH secretion lacked normal daily fluctuation but exhibited periodic change during 1-year observation, showing 119 pg/ml, 34.6 pg/ml and 115 pg/ml at the 4th, 7th and 13th months after delivery. Plasma ACTH levels were increased by corticotropin releasing hormone and metyrapone, while low-dose dexamethasone suppressed cortisol secretion. Gel filtration analysis of the patient's plasma detected big ACTH molecules being eluted with a peak of authentic 1-39 ACTH. Cranial magnetic resonance imaging revealed a 1-cm pituitary mass in right cavernous sinus. The pituitary tumor was removed by transsphenoidal surgery at 13th month after delivery and was pathologically compatible with ACTH-producing pituitary adenoma by immunohistochemistry. This case includes clinically rare subsets of Cushing's syndrome showing periodic ACTH secretion and aberrant ACTH molecules.

Adenoma↗
PubMed2005

Effect of 17beta-estradiol on tumor necrosis factor-alpha-induced cytotoxicity in the human peripheral T lymphocytes.

We determined the effect of 17beta-estradiol on tumor necrosis factor alpha (TNF-alpha)-induced cytotoxicity in human peripheral T lymphocytes (T cells) using lactate dehydrogenase assay. Treatment with 17beta-estradiol (1-100 nM) for 24 h showed dose-dependent reduction of TNF-alpha-induced cytotoxicity in T cells. To further evaluate the mechanism of 17beta-estradiol on TNF-alpha-induced cytotoxicity in T cells, we identified estrogen receptor (ER) protein in T cells using immunocytochemistry and used the pure ER antagonist ICI 172,780. ERalpha immunoreactivity was clearly observed in T cells. ERbeta immunoreactivity was also detected in some T cells. ICI 172,780 (10(-7) M) alone did not affect cytotoxicity in T cells, however, ICI 172,780 (10(-7) M) completely abolished 17beta-estradiol cytoprotective effects in T cells. TNF-alpha tended to increase nuclear factor kappaB (NF-kappaB) protein levels in nuclear extracts but it did not reach statistical significance by Western blotting. In contrast, NF-kappaB protein levels in nuclear extracts followed by TNF-alpha with 17beta-estradiol treatment were significantly increased compared with NF-kappaB protein levels in untreated group. NF-kappaB blocker pyrrolidinedithiocarbamate (PDTC) (10(-4) M) alone did not affect cytotoxicity in T cells. In contrast, PDTC (10(-4) M) completely abolished 17beta-estradiol cytoprotective effects in T cells. Caspase -3/-7 activity was significantly increased followed by TNF-alpha, and 17beta-estradiol treatment significantly reduced the increment. The present studies suggest the protective effect of 17beta-estradiol on TNF-alpha-induced cytotoxicity through ERs in T cells and that NF-kappaB activation and caspase suppression may be involved in the mechanism.

Adult↗
PubMed2005

[Persistent apnea in an obese patient with myotonic dystrophy].

We report a case of a 35-year-old woman with myotonic dystrophy and severe obesity of BMI 43.3 who showed persistent apnea at emergence after ovarian resection. The patient received an iv induction with minimum dose of propofol and vecuronium 3 mg. Anesthesia was maintained with propofol, 50% nitrous oxide and 50% oxygen mixture and epidural anesthesia. Additional vecuronium 0.5 mg was administered twice. Surgery was performed uneventfully within 130 minutes and iv propofol was discontinued. The patient awoke promptly after termination of nitrous oxide but no spontaneous breathing appeared with end-tidal CO2 of 60 mmHg. Because she could obey the order to breathe, the endotracheal tube was removed 40 minutes after discontinuation of propofol. Spontaneous breathing at the rate of 17 x min(-1) started soon after extubation. We assume that this apnea was caused by breath holding. Whether this breath holding is specific to myotonic dystrophy or not, anesthesia for patients with this disease requires careful attention for perioperative respiratory management.

Adult↗
PubMed2004

Regulation of human glucocorticoid receptor gene transcription by Sp1 and p53.

The human glucocorticoid receptor (hGR) gene has several GC boxes in the promoter 1C region. We studied the effects of Sp1 and p53 on promoter 1C in HepG2 and HEK293 cells using luciferase (Lu) reporter assay. The results showed that the first GC box upstream of the transcription site activated the hGR promoter and over-expression of Sp1 obviously enhanced the activity. A mutant Lu-hGR vector, whose first GC box was defective, lost promoter activity nearly completely. Further, over-expression of p53 strongly suppressed the stimulating effect of Sp1 on hGR promoter activity. We concluded that Sp1 activates the hGR gene promoter, at least in part, by acting on the first GC box in promoter 1C, while p53 suppresses the transactivation by Sp1. These phenomena, demonstrated in cultured cells, may be important for the expression of hGR in vivo.

Carcinoma, Hepatocellular↗
PubMed2004

Increased amount of the angiotensin-converting enzyme (ACE) mRNA originating from the ACE allele with deletion.

The insertion/deletion (I/D) polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene is involved in the development of cardiovascular diseases. We compared the ACE mRNA expression originating from the allele with a deletion (D allele) and that from the allele with an insertion (I allele) in human white blood cells from ID heterozygotes. We identified the mRNA from the I allele by using the G2215A polymorphism that lies in exon 15 and that was linked to the I/D polymorphism. RNA samples were obtained from 12 healthy heterozygotes of both I/D and G2215A, and every insertion was shown to be linked to 2215G. ACE mRNA was amplified by the reverse transcription/polymerase chain reaction (RT-PCR) method with an end-labeled antisense primer. The PCR products were digested with HaeII and separated by electrophoresis, and the relative radioactivities of the 2215A and 2215G bands were measured on an auto-image analyzer. The results showed that, in every cases, the intensity of the 2215A product (D allele origin) was higher than that of the 2215G product (I allele origin). The mean ratio of 2215A to 2215G was 1.79 (1.11-2.62). Thus, the D allele leads to higher expression of the ACE mRNA and may affect the renin-angiotensin system in local regions.

Adult↗