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T Saruta

Publications and source records attributed to T Saruta.

At least 91 records · Page 5Linked to original sources
PubMed2000

Mapping of four simple sequence repeat (SSR) markers on rat chromosome 4.

We previously reported that several markers on rat chromosome (Chr) 4 cosegregated with the occurrence of cerebral stroke and brain edema in stroke-prone spontaneously hypertensive rats (SHRSP). To obtain insights into the positional candidate genes for stroke susceptibility in this region, we mapped four genes, Taurine transporter (Tau), tumor necrosis factor receptor (Tnfr), GABA transporter (Gat1) and glucose transporter-3 (Glut3) genes, using newly developed simple sequence repeat (SSR) markers on rat Chr 4. We isolated the SSRs for the genes either by screening a rat genomic library or by searching the GenBank database. By linkage analysis using two sets of backcrosses, Gat1 and Tnfr were mapped in the region associated with stroke, while Taut was located distant from the region. The Glut3 locus was also assigned to rat Chr 4 using a rat x mouse hybrid clone panel. These results indicated that the Tnfr, Gat1 and Glut3 genes were good positional candidates for the stroke susceptibility in SHRSP, suggesting that further evaluation of these genes by functional studies could prove useful.

Animals↗
PubMed2000

The effects of calcium channel blockers on nuclear factor kappa B activation in the mesangium cells.

It has been reported that calcium channel blockers (CCBs) have an inhibitory action on cell growth and transcriptional changes induced by cytokines and hormones. In this study, we examined the effects of CCBs on nuclear factor kappa B (NFkappaB), which plays a key role in the intracellular signaling of various growth factors and cytokines. The activity of NFkappaB was determined by luciferase assay with the transfection of the reporter gene, which has six NFkappaB-recognizing sequences in the upstream of herpes simplex virus thymidine kinase promoter. In cultured human mesangial cells, increased intracellular calcium concentration by calcium ionophore, A23187, showed a stimulatory effect on the phorbor 12-myristate 13-acetate (PMA)-induced activation of NFkappaB, while L-type calcium channel agonist, Bay K 8644, did not have any significant effects on either basal or PMA-stimulated activity of NFkappaB. At a higher concentration (10 microM), nifedipine, verapamil, or efonidipine showed an inhibitory effect on the activation of NFkappaB by PMA and A23187, while at a lower concentration (1 microM), only efonidipine showed a significant inhibitory effect. From these results, we conclude that CCBs have an inhibitory effect on NFkappaB via the independent pathway of an L-type calcium channel and that the potency of this effect is variable among L-type calcium channel blockers.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2000

IgG1 is the dominant subclass of antibody against glutamic acid decarboxylase among type 1 diabetes in Japanese.

Autoantibody against glutamic acid decarboxylase (GADA) is a highly sensitive predictor of insulin-dependency in adult diabetic patients as well as young individuals. A considerable number of diabetics who do not reach the insulin-dependent stage have this antibody. Recently, type 1 diabetes has been thought to be caused by T helper 1 (Thl)-type autoimmunity based on studies in non-obese diabetic mice, but it is still difficult to investigate antigen-specific T-cell function in human type 1 diabetes. We therefore assessed an IgG subclass assay for GADA, which should reflect T-helper function against GAD. Sera from 14 type 1 diabetic patients positive for GADA by radioligand binding assay were tested for the IgG subclass of GADA. The assay was based on an enzyme-linked immunosorbent assay, which showed a good correlation with radioligand binding assay. The sera of all but one of the 14 type 1 diabetic patients (93%) were positive for the IgG1 subclass of GADA. The IgG2 and IgG3 subclasses of GADA were also detected in one diabetic patient each who were also positive for IgG1. The IgG4 subclass was not detected in any of the sera we tested. We concluded that IgG1 is the dominant subclass of GADA in Japanese type 1 diabetic patients.

Adolescent↗
PubMed2000

Risk factors associated with persistent postoperative hypertension in Cushing's syndrome.

The aim of the present study was to assess the long-term results of adrenalectomy and to evaluate potential risk factors for the persistence or recurrence of hypertension. Forty-five patients with Cushing's syndrome caused by benign cortisol-producing adrenocortical adenomas were evaluated before and for a period of 1 year after surgical cure. When the patients were classified into two groups according to whether their preoperative BP was more (HBP group) or less (NBP group) than 140/90 mmHg, the BP level was found to be continuously higher in the HBP group than in the NBP group during the year after surgery. This finding suggests that the preoperative BP level in Cushing's syndrome may be a determinant factor for persistent hypertension after surgery (P<0.05). In addition, a correlation was found between postoperative BP level and duration of hypertension (P<0.05), but no relationships were found between postoperative BP levels and other factors, including age, BMI, tumor size, serum cortisol, aldosterone, potassium, total cholesterol, or glucose levels. The above findings indicate that intensive control of preoperative BP to maintain it below 140/90 mmHg with antihypertensive medication is a very important means of improving prognosis for postoperative BP. Immediate diagnosis and surgical treatment to reduce the duration of hypertension are also crucial for the long-term BP prognosis.

Adrenalectomy↗
PubMed2000

Expression and regulation of BCL-2 family genes in human adrenocortical adenomas in comparison with adrenal hyperplasia of Cushing's disease.

The significance of increases in the expression of apoptosis-suppressing genes such as bcl-2 and mcl-1/EAT in human adrenal tumors has not yet been fully elucidated. Furthermore the roles of these genes in cell proliferation may involve interaction with steroidogenesis in the tumors via intracellular second messengers. Cyclic AMP (cAMP) caused human adrenocortical H295R cells to overexpress hCYP17 resulting in hypersecretion of cortisol. At the same time, however, expression of bcl-2, which has a cAMP response element (CRE), was not affected. Furthermore, in vivo Bcl-2 protein analysis showed its down-regulation in adrenal hyperplasia of Cushing's disease despite ACTH stimulation. Exogenous addition of glucocorticoid did not affect the expression of bcl-2 family genes. Expressions of Mcl-1/EAT and Bax did not differ markedly among human adrenal glands affected by various pathologies. In conclusion the down-regulation of Bcl-2 in Cushing's disease did not agree with no induction of this gene by cAMP in H295R cells, suggesting that expression of Bcl-2 protein was not regulated mainly by cAMP-protein kinase (PKA) pathways in human adrenal hyperplasia.

Adenoma↗
PubMed2000

Transcriptional regulation of steroid receptor coactivator-1 (SRC-1) in glucocorticoid action.

Diverse mechanisms of steroid receptor action have been clarified in recent years, as a consequence of the discovery of multiple coactivators. Among them, steroid receptor coactivator-1 (SRC-1) is a member of the p160 coactivator families, which are 160 kDa proteins that interact with steroid receptors in a hormone-sensitive manner. Since coactivators function as transcriptional power boosters, subtle changes in coactivator expression levels in certain cells markedly change of receptor-mediated transcriptional activity. Expression of the glucocorticoid receptor (GR) has been shown to be autoregulated in glucocorticoid action, i.e., GR is downregulated by its cognate ligand, indicating that this autoregulation of GR may protect target cells against excessive hormone action. In the present study, we examined whether coactivator expression levels are also regulated by glucocorticoids. Among several coactivators, the SRC-1 mRNA level was downregulated by dexamethasone treatment in rat tissues, such as liver, heart, kidney, stomach, and cerebrum, in vivo. We also demonstrated dexamethasone-mediated downregulation of SRC-1 mRNA and its protein levels in rat renal mesangial cells in vitro. These results suggest that ligand-mediated downregulation of SRC-1 is crucial in the physiology of glucocorticoid action.

Animals↗
PubMed2000

Orphan receptors COUP-TF and DAX-1 as targets in disordered CYP17 expression in adrenocortical tumors.

CYP17 gene transcription is activated by SF-1 binding to a cyclic AMP-responsive sequence within the promoter region of the gene, and its transcription is inhibited by COUP-TF binding to the sequence. Another orphan receptor, DAX-1, is shown to act as a suppressor of SF-1-mediated transcription. We examined the expression level of these orphan receptors in adrenocortical tumors and compared the results with CYP17 expression. CYP17 was highly expressed in cortisol-producing adenomas, whereas COUP-TF and DAX-1 expression levels were very low. In deoxycorticosterone-producing adenomas, on the other hand, CYP17 expression was extremely low, whereas DAX-1 was highly expressed and SF-1 expression was slightly decreased. In conclusion, the reciprocal expression of CYP17 and the transcriptional repressors COUP-TF and DAX-1 indicates that these orphan receptors have a pathophysiologic role in the excessive hormone production in cortisol- and deoxycorticosterone-producing adrenocortical tumors.

Adrenal Cortex Neoplasms↗
PubMed2000

A 35-year-old man with cerebral hemorrhage and pheochromocytoma: the second brain-dead organ donor in Japan.

A 35-year-old man was brought into the emergency room of Keio University Hospital by ambulance because of a sudden onset of coma. His Glasgow Coma Scale was 3 and his blood pressure 150/100 mmHg. CT scanning revealed a subcortical hemorrhage 8 cm in diameter. His respiration deteriorated rapidly, and an emergency craniotomy was performed for hematoma removal and cerebral decompression. Postoperatively the patient remained in a deep coma (GCS = 3) requiring respiratory support. The family presented an organ donor card previously signed by the patient, and brain death was confirmed in accordance with Japan's transplant law. As a result of two tests conducted six hours apart brain death was confirmed on the 5th postoperative day. With the family's consent, the donor's heart, kidneys and skin were removed for organ transplantation to be performed in other institutions. An autopsy was performed after the removal of the organs and skin. An extensive subgaleal hemorrhage was found in the left cerebral hemisphere, and microscopic examination revealed extensive necrosis with karyolysis of neuronal cells, but no viable neuronal cells were found in the cerebrum. The brain stem was marked by edema, hemorrhage, infarction necrosis and neuronal cell loss. The cerebellum was swollen and congested and showed autolysis of the granular layer. These findings suggested brain death syndrome with respirator brain. Other autopsy findings included a huge pheochromocytoma in the right adrenal gland, bilateral bronchopneumonia, liver congestion and fatty metamorphosis with four cavernous hemangiomas, and mild chronic lymphocytic thyroiditis. This patient was the second brain-dead organ donor and the first brain-dead patient to undergo postmortem examination in Japan.

Adrenal Gland Neoplasms↗
PubMed2000

Blood pressure reduction associated with preservation of renal function in hypertensive patients with IgA nephropathy: a 3-year follow-up.

BACKGROUND: The relative importance of hypertension in the progression of renal failure is well understood. Recently, several studies have provided evidence that antihypertensive therapy enhances renal survival. However, the specific antihypertensive drug regimens that are most effective in generating such long-term effects remain controversial. PATIENTS AND METHODS: Forty-nine hypertensive IgA nephropathy (IgAN) patients (39 +/- 7 years old, serum creatinine 1.1 +/- 0.2 mg/dl) with proteinuria received antihypertensive therapy with angiotensin-converting enzyme inhibitors (ACEi: 2.5-10 mg of benazapril daily) and calcium channel blockers (CCBs: 2.5-10 mg amlodipine daily) for 3 years. The patients' blood pressures in group one were controlled below 140/85 mmHg by increases in their first drug dose or by addition of the second drug in group 1. Blood pressures for patients in group 2 were controlled using the same two options, except to levels below 130/70 mmHg. Patients within the two groups were selected and controlled with regard to sex, age, and serum creatinine. The renal protective effects of each protocol were evaluated in terms of reductions in creatinine clearance. After 3 years of the above outlined blood pressure control regimens, the reductions in creatinine clearance were compared. RESULTS: Creatinine clearances decreased in group 1 patients (from 85.7 +/- 2.4 ml/min to 72.9 +/- 2.4 ml/min, p < 0.05). On the other hand, creatinine clearance remained essentially unchanged for patients in group 2 (from 87.2 +/-4.7 ml/min to 85.9 +/- 5.9 ml/min). Although creatinine clearance in both groups was almost the same at the start of study, there was a significant difference between them by the conclusion of the study (p < 0.05). Proteinuria and hematuria did not change significantly throughout the study and there were no significant differences in these respects between these two corresponding groups. There were no significant differences between the groups with reference to side-effects or complications. CONCLUSION: These data provide evidence that reducing blood pressure has protective renal effects in cases of mild renal insufficiency with hypertension in IgA nephropathy.

Adult↗
PubMed2000

Mild renal dysfunction is associated with insulin resistance in chronic glomerulonephritis.

BACKGROUND: Insulin resistance is associated with advanced and moderate chronic renal failure (CRF). However, insulin resistance in chronic glomerulonephritis (CGN) before onset of frank renal dysfunction is not fully evaluated. We attempted to investigate the association of insulin resistance with mild renal dysfunction and with abnormal calcium homeostasis. PATIENTS AND METHODS: Eighteen young, lean non-diabetic male patients with biopsy-proven CGN (age 30 +/- 7 years, body mass index 23.0 +/- 2.5 kg/m2) were enrolled. Insulin sensitivity was estimated by the glucose infusion rate (M value) during euglycemic hyperinsulinemic clamping for 60 to 120 min. Calcium-related parameters including intracellular calcium concentrations ([Ca2+]i) in platelets were also measured. Renal function was normal or slightly impaired (serum creatinine, 1.0 +/- 0.2 mg/dl; glomerular filtration rate (GFR), 68 to 131 ml/min/1.48 m2). We divided subjects into an insulin-sensitive (IS) group (M value > 7.3 mg/kg/min, the overall mean) and an insulin-resistant (IR) group (M value < 7.3 mg/kg/min). RESULTS: During a 75 g oral glucose tolerance test, the plasma glucose concentration at 120 min after glucose loading and the immunoreactive insulin concentration at 60 min were significantly higher in the IR group. GFR was notably lower in the IR group than in the IS group (p = 0.0003), and was significantly correlated with insulin sensitivity (p < 0.02, r = 0.58). The basal [Ca2+]i was significantly higher in the IR than in the IS group (39 +/- 9 vs. 30 +/- 9 nM, p < 0.05). CONCLUSION: Mild renal dysfunction and elevated basal [Ca2+]i are associated with insulin resistance in CGN.

Adult↗
PubMed1999

Caspase activity is required for nephrogenesis in the developing mouse metanephros.

Programmed cell death is a mechanism through which organisms get rid of unwanted cells and is thought to be an important process in organogenesis. Although large-scale cell death is observed in the developing kidney, the precise roles of cell death in kidney organogenesis remain to be elucidated. To address this question, we prevented cell death in metanephric explants by applying caspase inhibitors. Administration of caspase inhibitors (Z-D-CH2DCB and Ac-DEVD-CHO) effectively prevented the cell death that is normally observed in nondifferentiating mesenchymal cells. Both ureteric bud branching and nephrogenesis were prevented by caspase inhibition. Our results suggest that caspases are crucial in kidney organogenesis and cell death in the nondifferentiating mesenchyme.

Animals↗
PubMed1999

Endothelin ET(A) receptor antagonist reverses the inhibitory effect of platelet-derived growth factor on cytokine-induced nitric oxide production.

Cytokines and cytokine-induced nitric oxide (NO) play important roles in inflammatory glomerular diseases, and both platelet-derived growth factor and transforming growth factor-beta inhibit cytokine-induced NO production. In this study, we demonstrated that a selective endothelin ET(A) receptor antagonist, BQ-485 (Hexahydro-1H-azepinylcarbonyl-Leu-D-Trp-D-Trp-OH), reversed the inhibitory effect of platelet-derived growth factor on cytokine-induced NO production, but not that of transforming growth factor-beta. Our findings suggest a difference between the inhibitory mechanisms of platelet-derived growth factor and transforming growth factor-beta on cytokine-induced NO production.

Animals↗