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Biomedical subjects

T Asano

Publications and source records attributed to T Asano.

At least 631 records · Page 35Linked to original sources

Increased liver glucose-transporter protein and mRNA in streptozocin-induced diabetic rats.

The effect of insulin-deficient diabetic states on the rat liver glucose-transporter (L-transporter isoform) protein and mRNA levels were studied. Rats were injected with 65 mg/kg streptozocin to induce diabetes and were maintained for 10 days and then treated with or without insulin for the next 5 days. The L-transporter isoform with apparent Mr of 55,000 was observed to be increased approximately twofold in the membranes from liver homogenates of diabetic rats compared with control rats when assessed by Western blot analysis with an anti-peptide antibody directed against rat L-transporter isoform. Insulin treatment of diabetic rats decreased the amount of L-transporter isoform protein toward levels observed in nondiabetic rats. Northern blot analysis demonstrated similar alterations in the rat L-transporter isoform mRNA that paralleled the changes observed in the L-transporter isoform protein. The increased levels of the L-transporter isoform protein and mRNA in diabetic rats are in marked contrast to the effects of insulin deficiency in rat adipocytes, which specifically decrease the amount of the adipocyte glucose-transporter isoform protein and mRNA. These results suggest that glucose-transporter isoforms in rat liver and adipocytes are regulated by different mechanisms and that an increased synthesis of the L-transporter isoform may contribute to the increased glucose output that occurs from the liver during insulin deficiency.

Amino Acid Sequence↗

[Simultaneous occurrence of renal cell and transitional cell carcinoma in the same kidney and ureter. A case report].

An unusual case of 2 concurrent primary renal tumors within the same kidney is reported. A 70-year-old woman presented with gross hematuria when she was in the hospital for cerebral infarction. Excretory urography revealed a marked expansion of the right kidney with no renal function. CT scan showed a mass arising from the right kidney, the hydronephrotic right renal pelvis, and a mass in the lower right ureter. Selective renal angiogram showed marked neovascularity of the mass. There was an encasement of the intrarenal artery to the lower pole. Angiographic findings were highly suggestive of a renal cell carcinoma with a second neoplasm in the renal pelvis. Subsequently, the patient underwent right radical nephroureterectomy and partial cystectomy. Section of the removed specimen revealed a 4.0 X 3.8 cm solid tumor confined to the kidney in the upper pole and a transitional cell carcinoma arising from the renal pelvis. In addition, transitional cell carcinoma was present in the distal ureter.

Aged↗

'Radioresistant' CD4-CD8- intrathymic T cell precursors differentiate into mature CD4+CD8- and CD4-CD8+ T cells. Development of 'radioresistant' CD4-CD8- intrathymic T cell precursors.

Using lectin (PNA) and monoclonal antibodies for Pgp-1, IL-2R, H-2k, CD3, and F23.1 (T cell receptor V beta 8), we characterized the 'radioresistant' CD4-CD8- double negative thymocytes at an early stage after 800 rad irradiation. Most of the CD4-CD8- cells on day 8 after irradiation expressed a high level of Thy-1, H-2k, and PNA, while a small proportion of these cells were CD3+ and/or F23.1+. The appearance of Pgp-1 and IL-2R on the 'radioresistant' double negative precursors was also sequentially examined from day 5 to day 9 after irradiation. The double negative thymocytes at day 5 expressed the highest level of Pgp-1 antigens and these cells gradually decreased in number from day 7 to day 9. By contrast, IL-2R was transiently expressed on the double negative cells on the day 7 and 8 after irradiation. These results indicate that progression of thymocyte development occurred within the CD4-CD8- thymocytes after irradiation. We further examined the homing ability of the double negative 'radioresistant' intrathymic T cell precursors to the periphery by intrathymic cell transplantation method. The double negative thymocytes proliferate and differentiate into CD4+CD8+ cells and CD4+CD8- cells but few CD4-CD8+ cells in the thymus, while only CD4-CD8+ cells were detected in the peripheral lymphoid organs 14 days after intrathymic transplantation of the double negative cells in the H-2 compatible Thy-1 congenic mice. These results suggest that the 'radioresistant' intrathymic precursors differentiate and mature in the thymus and migrate to the periphery.

Animals↗

Effects of captopril on urinary excretion of albumin and prostaglandins in patients with diabetic nephropathy.

Recently the beneficial effects of captopril (angiotensin-converting-enzyme inhibitor) on diabetic nephropathy, especially proteinuria, have been reported by some investigators. The mechanism whereby proteinuria is reduced, however, have not been clarified yet. The present study was undertaken to evaluate the effects of captopril on urinary albumin excretion in relation to urinary prostaglandins (PGs) excretion in patients with non-insulin-dependent diabetes mellitus (NIDDM). Captopril (37.5 mg/day) was orally administered to 13 diabetic patients for an eight-week period. A single administration of captopril (12.5 mg) was performed in the same patients. The spot urine samples were collected in the early morning and 2 hr after the single administration of captopril. The albumin index (mg/gram-creatinine) was markedly decreased in eight patients (Group A) within four weeks, but no decrease was found in five patients (Group B). Furthermore, in Group A, by the single administration of captopril urinary excretions of 6-keto-PCF1 alpha (a stable metabolite of PGI2) and PGE2 were significantly (p less than 0.05) increased while urinary TXB2 (a stable metabolite of TXA2) excretion did not change significantly. The urinary 6-keto-PGF1 alpha/TXB2 ratio, which is significantly (p less than 0.05) low in diabetic patients was significantly (p less than 0.01) increased up to the normal value in Group A. In Group B, however, there were no significant changes in urinary PGs excretion. These results suggest that captopril enhances the production of intrarenal vasodilatory PGs such as PGI2 and PGE2, which may be deeply involved in the reduction of intraglomerular capillary pressure and urinary protein excretion in diabetic patients.

6-Ketoprostaglandin F1 alpha↗

[Aging of nervous system and S-100 proteins].

Recently, the human gene encoding the beta subunit of S-100 protein (S-100 beta) has been mapped on the long arm of chromosome 21 (21q, 22), where the locus of Down's syndrome (DS) is present. We determined the concentrations of S-100 proteins (alpha and beta) together with Cu/Zn-superoxide dismutase (SOD), a well-known marker protein of chromosome 21, in the blood samples of patients with Down's syndrome by means of sensitive immunoassay methods. S-100 beta and SOD concentrations in blood plasma and lymphocyte fractions of the patients were enhanced, while S-100 alpha concentrations in the same samples showed levels similar to those of control subjects. These results indicate that the gene-dosage effect of S-100 beta is expressed in patients with trisomy of chromosome 21. Concentrations of several proteins related to nervous tissues (S-100 alpha, S-100 beta, SOD, alpha-enolase, gamma-enolase, and G-proteins, Go alpha, Gi2 alpha G beta) in the brains of rats aged 2 to 30 months and in the human cerebral cortices obtained at autopsy were immunoassayed. It was found that S-100 beta concentrations in rat brains increased with age solely in the cerebral cortex, but there was little increase or decrease in the levels of SOD and other proteins. S-100 beta levels in human cerebral cortices showed a tendency similar to those of rat cerebral cortices; S-100 beta concentrations in the aged cerebral cortices were significantly higher than those of young adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[The alpha subunits of the GTP-binding proteins, Go and Gi2 in lung cancer].

The alpha subunits of the GTP-binding proteins, Go and Gi2, in sera, tissues, and pleural effusions have been studied, using an enzyme immunoassays system. The Gi alpha concentrations were found increased in the pleural effusions of patients with a small cell lung cancer, as compared to patients with a nonsmall cell lung cancer. Both GTP-binding proteins, however, were not elevated in the sera of patients with a lung cancer. Thus, an evaluation of the amount of Go alpha in the pleural effusion is thought to be a useful tumor marker of small cell lung cancers, elevating the specificity of a combination assay with other markers, NSE or CKBB.

Adenocarcinoma↗

Functional consequences of the right ventricular isolation procedure.

The right ventricular free wall was surgically isolated from the remainder of the heart in eight dogs to evaluate the functional consequences of this procedure. Each dog was instrumented with ultrasonic dimension transducers in the right and left ventricular free walls, intracavitary micromanometers, and pulmonary artery flow probes. Volume loading and vena caval occlusions were performed to assess diastolic compliance and systolic function. Right ventricular unstressed myocardial segment length increased from 14.2 +/- 0.7 to 15.0 +/- 0.8 mm (p less than 0.5). There was an accompanying significant postoperative loss of right ventricular diastolic compliance (p less than 0.005). Regional right ventricular systolic function and regional left ventricular diastolic compliance and systolic function were preserved after the procedure. Postoperatively, when the right ventricular free wall was not paced and left silent, right ventricular stroke work decreased from 7.0 +/- 0.8 to 2.7 +/- 0.5 gm-m/m2 (p less than 0.05). These data demonstrate that the diastolic compliance of the right ventricular free wall decreases significantly after right ventricular isolation. However, there were no changes in regional right ventricular systolic or regional left ventricular function. The isolated right ventricular free wall contributes significantly to postoperative cardiac performance.

Animals↗

[Steroid withdrawal in renal transplant recipients].

The clinically important side effects of long-term steroid use are well known. We report the results of complete steroid withdrawal in 7 living-related renal transplants in HLA-identical (3) or one-haplotype match (4) recipients initially treated with azathioprine (5) or cyclosporine (2), and steroids. After the end of the second year, steroids were stopped if renal function was normal (serum creatinine below 2.0 mg/dl) and if no alterations were seen on renal biopsy. In 1 patient steroid had to be discontinued because of the complications of steroid immunosuppression. The study population consisted of 7 patients with a mean age of 32.4 years. The sex distribution was 6 males and 1 female. All patients had received a minimum of 3 blood transfusions prior to transplantation. Steroid was discontinued 34.0 +/- 18.1 months posttransplant. Oral azathioprine or cyclosporine were employed for long-term maintenance immunosuppression. Six patients (86%) have remained continuously off steroids for 52.2 +/- 50.5 months (range 4-150) with stable renal function. The mean serum creatinine was 1.1 +/- 0.4 mg/dl at the most recent follow-up. Reinstitution of steroid was required in 1 patient (14%) for rejection (36 months after steroid withdrawal). Thus, steroid withdrawal was successful in 6 of 7 patients. In HLA-identical recipients, all are currently steroid-free. In haplo-matched patients, 75% are steroid independent. Discontinuation of steroid resulted in a decrease in serum cholesterol concentration from 246 +/- 41 to 204 +/- 25 mg/dl (P less than 0.003). We conclude that steroid withdrawal may be accomplished in selected patient without increasing the rate of graft loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Absorption of tetrahydropyranyl adriamycin administered intravesically immediately after transurethral resection of bladder carcinoma].

Absorption of tetrahydropyranyl adriamycin (THP) administered immediately after transurethral resection of bladder carcinoma (TUR-Bt) has not been reported. In this study, we have examined the absorption of THP and the systemic toxicity in the early post-TUR period. Of 21 patients with bladder carcinoma, 10 had a solitary tumor and 11 multiple tumors. Twenty mg THP in 40 ml of sterile water was intravesically administered on days 1, 3, 5, 7, 14 and 28, and then every 4th week. The THP solution was retained for 2 hours. The blood THP concentration was measured 30 minutes and 2 hours after the intravesical administration on days 1, 7 and 28. No systemic side effects were observed. Thirteen of the 38 (34%) samples contained a detectable level (more than 1 ng/ml) of THP on the post-TUR-Bt on day 1, 8, of 42 (19%) on day 7, and 3 of 18 (17%) on day 28. Altogether, 24 of the 98 (24%) samples contained more than 1 ng/ml THP. The highest blood THP level was 23 ng/ml on day 1. The differences between frequency of detection of blood THP in the samples at 30 minutes and 2 hours were not statistically significant. The difference between average concentration of blood THP of patients with solitary and multiple tumors also was not significant. These results indicate that intravesical THP administration starting within 24 hours after TUR-Bt can not result in significant systemic absorption of THP, and the systemic toxicity can be avoided.

Absorption↗

[Effect of high dose etoposide, adriamycin, cisplatin (EAP) therapy with autologous bone marrow transplantation in gastric cancer].

A clinical usefulness of high dose EAP therapy with autologous bone marrow transplantation for gastric cancer was investigated. Three patients with advanced gastric cancer (one recurrent and 2 inoperable) with measurable lesions were treated with high dose EAP therapy consisting of VP-16 1200 mg/m2, ADM 80 mg/m2 and CDDP 80-120 mg/m2, and then 1 x 10(7)/kg of cryopreserved autologous bone marrow cells were transfused intravenously. All patients were recovered from aplastic period without any severe complications. Measurable lesions, namely, stenosis of prepyloris lesion, lymph node metastasis and invasion into pancreas in 3 patients with gastric cancer were reduced or diminished. It seemed that high dose EAP therapy with autologous bone marrow transplantation was safe and an useful strategy, especially for advanced gastric cancer.

Adult↗

[Surgical treatment of postinfarction left ventricular free wall rupture--experience of 12 cases including 2 successful repairs of acute (blow out) rupture].

Left ventricular free wall rupture (LVFWR) complicating myocardial infarction is still a lethal complication. Although there have been reports of successful repair of LVFWR, most of them were of subacute type in which main symptom was cardiac tamponade and the surgical repair was undertaken several hours after the onset of rupture. Between March, 1984 and June, 1987. We treated 12 cases of LVFWR surgically, thoracotomy and open drainage in 2 cases, thoracotomy and direct closure of rupture in 8 cases, median sternotomy and patch closure of rupture in 2 cases. We used cardiopulmonary bypass (CPB) only in 3 cases, because most of the cases except two developed electromechanical dissociation abruptly, requiring an emergency thoracotomy and there was no time for establishing CPB. In the cases of electromechanical dissociation, cardiopulmonary resuscitation and an emergency thoracotomy were performed simultaneously. There were three early survivors (greater than 30 days) by emergency thoracotomy and direct closure of rupture and one survivor (double rupture case) by patch closure on CPB. We believe that acute type of LVFWR in which initial symptom is electromechanical dissociation without any preceding symptoms can be rescued by emergency thoracotomy and direct closure of rupture with no aid of CPB if rupture is a small tear of anterior or lateral left ventricle. For this purpose, prompt diagnosis is mandatory and this is possible by two dimensional echocardiogram even during cardiopulmonary resuscitation.

Acute Disease↗

Purification and identification of two pertussis-toxin-sensitive GTP-binding proteins of bovine spleen.

Two alpha subunits of GTP-binding proteins were purified from bovine spleen membranes. Both proteins were ADP-ribosylated by pertussis toxin in the presence of beta gamma subunits. The major protein had a molecular mass of 40 kDa and its immunological reactivity and fragmentation pattern by limited proteolysis were identical with those of the alpha subunit of Gi2. The minor protein had a molecular mass of 41 kDa and its partial amino acid sequences completely matched with those predicted from human and rat Gi3 alpha cDNAs.

Amino Acid Sequence↗

Identification of lung major GTP-binding protein as Gi2 and its distribution in various rat tissues determined by immunoassay.

Antisera were raised in rabbits against the 40-kDa alpha subunit of bovine lung GTP-binding protein, which were identified as the alpha subunit of Gi2 (Gi2 alpha) by the analysis of the partial amino acid sequence. Antibodies were purified with a Gi2 alpha-coupled Sepharose column and then were passed through a Gi1 alpha-coupled Sepharose column to remove antibodies reactive also with 41-kDa alpha. Purified antibodies reacted with Gi2 alpha, but not with Gi1 alpha, Gi3 alpha, or Go alpha in an immunoblot assay. A sensitive enzyme immunoassay method for the quantification of Gi2 alpha was developed by using these purified antibodies. The assay system consisted of polystyrene balls with immobilized antibody F(ab')2 fragments and the same antibody Fab' fragments labeled with beta-D-galactosidase from Escherichia coli. The minimal detection limit of the assay was 1 fmol, or 40 pg. Samples from various tissues were solubilized with 2% sodium cholate and 1 M NaCl, and the concentrations of Gi2 alpha were determined. Gi2 alpha was detected in all the tissues examined in the rat. The highest concentration was found in platelets and leukocytes when the data were expressed as picomoles per milligram of protein. The spleen, lung, and cerebral cortex contained relatively high levels of Gi2 alpha. In the bovine brain, Gi2 alpha was distributed almost uniformly among the various regions. The concentrations of Gi2 alpha were constant in the rat brain throughout ontogenic development, in contrast with those of Go alpha which were markedly increased with age.

Amino Acid Sequence↗

Endothelin and the production of cerebral vasospasm in dogs.

We attempted to determine whether or not endothelin (ET) plays a physiological role in cerebral vasospasm. ET (10(-11) - 3 x 10(-8) M) induced a concentration-dependent contraction in isolated canine basilar arteries. Intracisternal injection of 10 to 1,000 pmol ET into dogs induced a dose-dependent decrease in the basilar artery diameter, as measured angiographically on the 1st day. On the 3rd day after the injection of ET (10 pmol), the diameter of the basilar artery had diminished to 76% of the value seen in the control. There were no effects on blood pressure or heart rate. Thus, ET seems to be a potent constrictor of cerebral arteries in vivo, and these effects are long-lasting.

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

Rabbit brain glucose transporter responds to insulin when expressed in insulin-sensitive Chinese hamster ovary cells.

Transfection of Chinese hamster ovary cells with the expression vector containing rabbit brain HepG2-type glucose transporter cDNA resulted in a dramatic over-expression (approximately 10-fold) of glucose transporter as assessed by either immunoblotting with antipeptide antibody against rabbit brain glucose transporter or photoaffinity labeling with [3H]cytochalasin B. 2-Deoxyglucose uptake was also increased 4-fold in the transfected cells, while no increase in transport activity or transporter amount was observed in cells that were transfected with the expression vector alone without glucose transporter cDNA. Significantly, insulin (10(-7) M) increased 2-deoxyglucose uptake in both control and transfected cells, but the increased amount of the transported 2-deoxyglucose by insulin in the transfected cells was 4.2-fold greater than that in control cells, indicating that the expressed rabbit brain HepG2-type glucose transporter responded to insulin. In addition, we have recently demonstrated that the HepG2-type glucose transporter exists in rat adipocytes and responds to insulin in a fashion similar to a majority of other types of glucose transporters (Oka, Y., Asano, T., Shibasaki, Y., Kasuga, M., Kanazawa, Y., and Takaku, F. (1988) J. Biol. Chem. 263, 13432-13439). In contrast, insulin did not stimulate glucose transport activity in HepG2 cells or IM-9 lymphocytes that have a significant amount of the HepG2-type glucose transporter. Thus, the results in this study further support the notion that insulin regulation of glucose transport activity depends on a tissue-specific signaling mechanism.

Affinity Labels↗