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T Seki

Publications and source records attributed to T Seki.

At least 253 records · Page 14Linked to original sources

Three single-strand origins located on both strands of the Streptomyces rolling circle plasmid pSN22.

pSN22 is an 11-kbp, high-copy-number Streptomyces plasmid which replicates via a single-stranded intermediate by the rolling circle replication (RCR) mechanism. We identified an unidirectional single-strand origin (SSO) of pSN22, sso1, where the initiation of second-strand synthesis takes place, located between the spdA and traR genes in a noncoding region which is functional in its natural orientation. The nucleotide sequence of sso1 is similar over 170 bp to the SSOs of the Streptomyces plasmids pIJ101 and pJV1. A previous report described that a 548-bp BglII-SmaI fragment has an SSO activity (ori2; Kataoka et al., Mol. Gen. Genet. 242, 130-136, 1994). To our surprise, we discovered that on pSN22, the SSO in the BglII-SmaI fragment is in the wrong, inactive, orientation and thus cannot be involved in the conversion of the single-stranded pSN22 replication intermediate to the double-stranded form of the plasmid. We revealed that this BglII-SmaI fragment contains two SSO fragments. Secondary structure analysis of these two SSOs showed similarity to the consensus TAGCGT which is conserved in SSOs of RCR plasmids from Staphylococcus and the other several Gram-positive bacteria. Deletion of these hexanucleotide sequences caused loss of SSO activities. Our result shows that two types of SSOs, Streptomyces type and Staphylococcus-like type, can function in Streptomyces lividans.

Base Sequence↗

Disruption of actin cytoskeleton attenuates sulfonylurea inhibition of cardiac ATP-sensitive K+ channels.

Two actin filament-depolymerizing agents, DNase I and cytochalasin D, were used to examine the involvement of the cytoskeleton in the functional interaction between the sulfonylurea receptor (SUR) and the ATP-sensitive K+ (KATP) channels. Isolated rate ventricular cardiomyocytes were studied using open cell-attached patches for single-channel recording. Bath application of DNase I (100 microg/ml) or cytochalasin D (10 microM) stimulated the KATP channel activities (in presence of 30 microM ATP), and these channels became resistant to inhibition by tolbutamide (0.5 mM). After exposure to tolbutamide, the relative NPo value was 0.09 +/- 0.02 in control patches in absence of actin disrupters, and 0.67 +/- 0.22* or 0.65 +/- 0.10*, respectively, in cells treated with DNase I or cytochalasine D (*P < 0.05 vs. control). The inhibitory action of glibenclamide (10 microM) on the KATP channels was also attenuated by DNase I. Thus, the disruption of the actin cytoskeleton attenuates the ability of SUR to inhibit the opening of KATP channels.

Actins↗

Experience with revascularizing renal artery aneurysms: is it feasible, safe and worth attempting?

PURPOSE: We retrospectively evaluated the feasibility and efficacy of surgical revascularization for renal artery aneurysms. MATERIALS AND METHODS: Beginning in 1984, 12 patients with renal artery aneurysm underwent renal revascularization regardless of clinical features. Postoperative results were analyzed regarding split renal function, patency of the revascularized arteries, blood pressure control and surgical complications. RESULTS: Postoperative renal function was stable or improved in all but 1 case and patency in branched arteries was preserved in 86%. Hypertension in 8 patients was cured in 7 (88%), including 2 with renovascular hypertension, and improved in 1 (12%). Complications were minimal with only 1 ureteral stricture that required reoperation. CONCLUSIONS: The majority of renal artery aneurysm cases are amenable to surgical repair. Carefully performed renal revascularization is rewarding in that high blood pressure is better controlled, renal function is improved and the potential risk of rupture is obviated.

Adult↗

The promoter of an androgen dependent gene in the hamster flank organ.

Hamster flank organs are useful for studying androgen-dependent growth of hair follicles and sebaceous glands. A cDNA clone (FAR-17a) was isolated from the hamster flank organ, whose expression was highly sensitive to androgen. The mRNA level of this gene was reduced after castration but reappeared after testosterone treatment. To elucidate the mechanism of expression of this gene regulated by androgen we isolated a genomic clone, from a hamster genomic library, that includes the promoter and upsteam region. The promoter region was used to drive a luciferase reporter gene in Cos 7 cells. This construct was activated five to six times higher over a control plasmid lacking the promoter region. We tested the effects of testosterone by transfection of the reporter plasmid into androgen dependent SC-3 cells. The results showed up to fivefold stimulation after the addition of androgen. The sequence of this promoter region was analyzed and the transcription factor binding sites were predicted. Since no obvious androgen responsive elements were included in the promoter region, we suggest that the stimulation of the reporter construct has to be mediated indirectly by androgen-dependent transcription factor(s).

Amino Acid Sequence↗

Kidney-alone transplantation in diabetic patients with end-stage renal disease.

From January 1989 to December 1995, 5 diabetic patients with end-stage renal disease (1 woman, 4 men) underwent kidney-alone transplantation. The mean age of the recipients at the time of transplantation was 37.4 years (range, 32 to 43). Craft function and glucose tolerance was evaluated for 5 to 72 months after surgery. Postoperative complications were seen in 2 patients; nonspecific subcutaneous infections and an asymptomatic partial allograft infarction. All renal allografts were functioning 1 year after transplantation, with a mean serum creatinine level of 1.10 mg/dL (range, 0.8 to 1.8 mg/dL), and a mean urinary protein level of 17.8 mg/dL (range, 5 to 27 mg/dL). The postoperative daily dose of insulin was higher than the preoperative dose, while the level of glycated hemoglobin (HbA1C) increased after surgery and peaked 6 months after transplantation; 1 year after transplantation it had reverted to the preoperative level. As long as the diabetic complications of the renal allograft recipients are not severe, the short-term survival and the renal function of diabetic patients with end-stage renal disease improves after kidney-alone transplantation, which is still the standard method of treatment in Japan.

Adult↗

Antihypertensive and vasculo- and renoprotective effects of pioglitazone in genetically obese diabetic rats.

Although an improvement of insulin sensitivity has been shown to be a new therapeutic approach for treating diabetes mellitus, details of effects of this treatment on the cardiovascular system and possible renal complications remain unknown. In the present study, we investigated the effects of a thiazolidine derivative, pioglitazone, and examined the insulin-sensitizing action on blood pressure, nephropathy, and vascular changes in genetically obese diabetic Wistar fatty (WF) rats. Pioglitazone (3 mg.kg-1.day-1) was orally administered for 13 wk starting at the age of 5 wk, and the results were compared with those of vehicle-treated WF rats. At the age of 18 wk, vehicle-treated WF rats were associated with mild hypertension, nephropathy with proteinuria histological glomerular injury, and renal arteriolosclerosis in addition to hyperglycemia, hyperinsulinemia, and hyperlipidemia. Treatment with pioglitazone significantly improved glucose and lipid metabolism. In addition, it lowered blood pressure, decreased proteinuria, and prevented glomerular injury, renal arteriolosclerosis, and aortic medial wall thickening, whereas body weight, food intake, sodium balance, and urinary norepinephrine excretion were significantly increased. These results suggest that the insulin-sensitizing agent pioglitazone is effective in correcting not only glucose and lipid metabolism but also cardiovascular and renal complications in non-insulin-dependent diabetes mellitus.

Animals↗

Dexamethasone suppressed gene expression and production of interleukin-10 by human peripheral blood mononuclear cells and monocytes.

Interleukin-10 (IL-10) is known to inhibit T cell-mediated responses. IL-10 has also been shown to play an important pathogenetic role in allergic diseases. Glucocorticoid is known to inhibit the production and gene expression of many cytokines which induce inflammatory reactions. We examined the effect of dexamethasone on the gene expression and production of IL-10 by human peripheral blood mononuclear cells (PBMCs) and monocytes. PBMCs and monocytes from 5 healthy volunteers were incubated with or without dexamethasone for 1 h, then stimulated with 5 micrograms/ml lipopolysaccharide (LPS). Gene expression and production of IL-10 by human PBMCs were detected without stimulation and increased by LPS stimulation. Dexamethasone suppressed the gene expression and production of IL-10 by LPS-stimulated PBMCs in a dose-dependent manner by 41.6 and 61.1% at 10(-6) M, respectively. Also in monocytes, the gene expression and production of IL-10 were detected without stimulation, increased by LPS stimulation, and significantly suppressed by dexamethasone by 53.1 and 61.2% at 10(-6) M, respectively. This suppressive effect on IL-10 gene expression was not so potent compared with its effect on cytokines such as IL-5. The suppression of IL-10 production by glucocorticoid is suggested to be one of the important mechanisms by which glucocorticoids suppress allergic inflammation in the treatment of allergic diseases.

Blotting, Northern↗

Gene expression of endothelial type isoform of nitric oxide synthase in various tissues of stroke-prone spontaneously hypertensive rats.

Nitric oxide (NO) has been suggested to play important roles in the pathophysiology of various cardiovascular diseases. This study tested the hypothesis that an attenuated biological action of NO in hypertension is attributed to a change in the gene expression of NO synthase (NOS), a key enzyme involved in NO formation. The expression level of mRNA of endothelial type NOS (NOS-III) was determined in stroke-prone spontaneously hypertensive rats (SHR-SP/Izm) and Wistar Kyoto rats (WKY/Izm) by ribonuclease protection assay using a partial clone as probe. NOS-III mRNA was expressed ubiquitously in various tissues of WKY/Izm and SHR-SP/Izm either at 5 wk or 13 wk of age. There was no significant difference in the tissue expression of NOS-III mRNA between the two strains at either age. The intensity and localization of the hybridization signal for NOS-III mRNA in the heart of SHR-SP/Izm did not differ from those in the heart of WKY/Izm. These results suggest that the attenuated biological action of NO implied in genetically hypertensive rats is not attributed to an abnormality at the level of NOS-III mRNA expression in the tissues, although lack of an increase in NOS-III gene expression, despite the hypertensive hemodynamic stress, may modify the blood pressure in hypertension.

Animals↗

Left ventricular hypertrophy is more prominent in patients with primary aldosteronism than in patients with other types of secondary hypertension.

We determined functional and morphological changes of the heart by 2-dimensional and pulse Doppler echocardiography in 20 patients with primary aldosteronism and compared the results with those in 50 healthy normotensive subjects, 12 patients with Cushing's syndrome, 9 patients with pheochromocytoma, and 47 patients with essential hypertension. All hypertensive groups had greater left ventricular mass indexes than did the normotensive group (76.9 +/- 17.2 g/m2). Despite similar age distribution, blood pressure during antihypertensive treatment, and duration of hypertension, the primary aldosteronism group had a significantly greater left ventricular mass index (152.5 +/- 42.5 g/m2) than did the Cushing's syndrome (103.4 +/- 37.5 g/m2), pheochromocytoma (122.4 +/- 28.5 g/m2), and essential hypertension (101.4 +/- 32.8 g/m2) groups. The left ventricular posterior wall thickness and interventricular septal wall thickness were significantly greater in the hypertensive groups than in the normotensive group and also significantly greater in the primary aldosteronism group than in any of the other hypertensive groups. By contrast, there were no significant differences among the four hypertensive groups in any variable of systolic or diastolic function of the heart. The results suggest that left ventricular hypertrophy is more pronounced in patients with primary aldosteronism than in patients with other forms of hypertension. It is therefore important to echocardiographically evaluate cardiac hypertrophy as a risk factor of morbidity and mortality in patients with this low renin hypertension.

Adrenal Gland Neoplasms↗

Apolipoprotein E Sendai (arginine 145-->proline): a new variant associated with lipoprotein glomerulopathy.

Lipoprotein glomerulopathy (LPG) is a novel disease characterized by proteinuria, lipoprotein thrombi in the glomeruli, and increased concentration of plasma apolipoprotein (apo) E. It is believed that a genetic disorder of apo E may be present and associated with the disease. Three patients with LPG were examined in this study. The patients' DNA sequences were analyzed, and a nucleotide G to C point mutation in exon 4 of the apo E gene was confirmed in each patient. This missense mutation denotes amino acid substitution of the proline residue for arginine residue at position 145 of apo E. This variant (apo E Sendai) may cause a marked molecular conformational change of the apo E. These findings suggest that a novel variant is etiologically related to LPG.

Aged↗

A protein kinase inhibitor H-7 induces process extrusion in fetal rat thyroid C-cells in vitro.

Calcitonin-producing cells (C-cells) are endocrine cells derived from the neural crest. We examined the effects of three types of protein kinase inhibitors on the induction of neuronal phenotypes in the rat thyroid C-cells in vitro. In a primary culture of 16-day-old fetal rat thyroid glands, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7, 25-75 microM) induced both process extrusion and expression of highly polysialylated neural cell adhesion molecule (NCAM) in the C-cells. These effects of H-7 were completely prevented by okadaic acid, a potent protein phosphatase inhibitor. In contrast to H-7, selective inhibitors for cyclic nucleotide-dependent protein kinases such as N-(2-guanidinoethyl)-5-isoquinolinesulfonamide hydrochloride (HA1004, 25-200 microM) and N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89, 0.25-20 microM) failed to induce process extrusion or the expression of highly polysialylated NCAM in fetal rat C-cells. In cultured C-cells of adult origin, H-7 failed to induce marked process elongation or the expression of highly polysialylated NCAM. These results suggest that the morphological plasticity of the fetal C-cells depends upon the degree of phosphorylation of some proteins, and that the plasticity of adult C-cells are more restricted than that of fetal origin.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Antinuclear antibodies in children with chronic nonspecific complaints.

Children who are chronically complaining nonspecific symptoms such as headache, fatigue, abdominal pain, and low grade fever are commonly seen in daily pediatric outpatient clinics. Some of them are unable to go to school and are diagnosed as school refusal by physicians or educational staff. On the other hand, there are children who do not fulfill any criteria of collagen diseases and whose anti-nuclear antibodies (ANA) are found to be positive. Some of these children have chronic nonspecific complaints. We prospectively studied the prevalence of ANA in children who visited a pediatric outpatient clinic because of chronic nonspecific complaints. Surprisingly, 74 out of 140 symptomatic children (52.4%) were positive for ANA, while only 5 out of 82 healthy control children (6.1%) were positive (p < 0.0001). 39 of 74 ANA positive patients (52.1%) have low ANA titers < or = 1:80, nevertheless 36 patients (47.9%) have high ANA titers > or = 1:160. ANA fluorescent patterns were homogeneous and speckled in 75.3%, speckled in 17.6% and others in 6.8%. ANA positive patients tended to have general fatigue and low grade fever, while gastrointestinal problems such as abdominal pain and diarrhea and orthostatic dysregulation symptoms were commonly seen in ANA negative patients. Children who were unable to go to school more than 1 day a week were seen significantly more in ANA positive patients than in negative patients. Autoantibody analysis using Western immunoblot revealed that 26 out of 63 ANA positive sera (41.3%) had antibodies to the 62 kD protein which had not been previously noticed. These data suggest that autoimmune mechanism may play a role in childhood chronic nonspecific symptoms. We therefore propose a new disease entity of the autoimmune fatigue syndrome in children. When chronically complaining children visit a pediatric out-patient clinic, immunological approaches should be considered before they are discriminated as school refusal or having psychogenic disorders.

Abdominal Pain↗

[Clinical evaluation of donor renal artery reconstruction in kidney transplantation].

UNLABELLED: This retrospective study describes the experience of arterial reconstruction of donor kidney in our institute since 1982. MATERIALS AND METHODS: Of total 56 living related kidney transplantations 15 required renal arterial reconstruction or ligation of donor kidneys. Renal arterial reconstruction was employed for 11 cases (end to side anastomosis [4 cases], conjoined anastomosis [3], hypogastric artery graft interposition [3], other [1], while simple ligation was employed for 4. Bench surgery with microsurgical techniques was employed for the repair. Elective surgery was done for preoperatively defined multiple renal arteries [10] and aneurysm [1], while imperative surgery for intraoperatively detected accessory arteries [2] and surgical injuries [2]. Postoperative patency of arteries and renal function (GFR) and evaluated by 99mTc-DTPA renoscintigraphy. RESULTS: The mean total ischemic time of reconstructed cases was 135 min., while that of ligated ones was 67 min. None of them required hemodialysis due to acute tubular necrosis. Postoperative graft arterial patency was impaired in 2 of 11 reconstructed cases (18%), while it was impaired in 3 of 4 ligated cases (75%). Two failure attempts of arterial reconstruction cases were all imperative ones. Postoperative GFR of the graft was well preserved in all cases. CONCLUSION: We conclude that (1) Ligation and imperative surgery tend to be associated with renal infarction, although it does not affect GFR. (2) Renal artery reconstruction was highly successful in preserving renal mass (or normal cortical image), albeit longer ischemic time than simple ligation. (3) Considering importance of preserved nephron mass in clinical renal transplantation every attempt should be made to repair the donor arterial anomalies when expected (elective) or found (imperative). (4) Thorough preoperative evaluation of donor renal arteries is mandatory.

Adult↗

[One-stage-bilateral adrenalectomy by thoracoabdominal approach for bilateral large pheochromocytomas in men type IIa. A case report].

We experienced a case of MEN type 2a with bilateral and large pheochromocytomas. A 39-year-old man was admitted to the previous hospital with complaints of paroxysmal headache. hypertension and diabetes mellitus. Radiographic imagings showed thyroid tumors in both lobes and bilateral adrenal tumors. Thyroid tumors were histologically proved to be medullary thyroid carcinoma by needle biopsy and systemic investigations revealed an excessive secretion of plasma and urinary cathecholamines which suggested the presence of pheochromocytoma. The patient was diagnosed as MEN type 2a. He was admitted to our hospital for the treatment of bilateral adrenal tumors for which we performed one-stage bilateral adrenalectomy by thoracoabdmonal approach. Both adrenal tumors were histologically confirmed as pheochromocytoma. The patient's postoperative course was uneventful. He underwent uneventful total thyroidectomy approximately 2 months after bilateral adrenalectomy. Even in bilateral and large pheochromocytomas, one-stage bilateral adrenarectomyenables safe postoperative managements. We concluded that the thoracoabdominal approach is feasible in the patients with huge and cranially spreading adrenal tumor, which gives us a wide operative field for easy vascular control.

Adrenal Gland Neoplasms↗

[Treatment of West syndrome: present and future perspectives].

The efficacy and side effects of various antiepileptic drugs (AEDs), especially pyridoxine, ACTH and valproate sodium (VPA), in the treatment of West syndrome were reviewed. ACTH remains to be the most effective treatment for West syndrome. However, there are significant adversive effects with prolonged ACTH therapy. The efficacy of pyridoxine at the dose of 40-50 mg/kg/day is less encouraging, but there are no serious adversive effects, as opposed to ACTH. Some reports have indicated the possible efficacy of VPA in regular, large (40-100 mg/kg/day) and very high (100-300 mg/kg/day) doses. However, in patients under the age of 2 years, monotherapy using VPA in lower doses should be employed to minimize the risk of VPA-induced adversive effects, such as fatal hepatic toxicity. Consequently, a safer and more effective treatment is required. We have reported a pilot study on combination therapy with high-dose pyridoxine phosphate (40-50 mg/kg/day) and low-dose ACTH (0.01 mg/kg/day) in 25 children with West syndrome, mainly on the basis of neurochemical analysis of the ictal epileptic spasms. The response rate was similar to those achieved with high-dose ACTH, but a quicker cessation of spasms was obtained with the combination therapy than ACTH monotherapy. Transient increases in liver enzymes occurred in 50%, but none of the patients developed more serious side effects. Further study is required to determine the efficacy of this combination therapy.

Adrenocorticotropic Hormone↗

[Emergency coronary artery bypass grafting using the internal thoracic artery graft after percutaneous transluminal coronary angioplasty in a patient with left main coronary artery disease associated with acute myocardial infarction].

A 66-year-old woman suffering acute myocardial infarction developed cardiogenic shock during urgent coronary angiography, which demonstrated a subtotal occlusion of the left main coronary artery and the triple-vessel coronary artery disease. The patient survived, after prompt percutaneous transluminal coronary angioplasty for the left main coronary artery disease, followed by emergency triple-vessel coronary artery bypass grafting using the internal thoracic artery graft for the left anterior descending artery. Postoperative angiography demonstrated well patent bypass grafts with good preservation of left ventricular function.

Aged↗