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S Kono

Publications and source records attributed to S Kono.

At least 145 records · Page 8Linked to original sources
PubMed1994

Immunohistochemical localization of plasminogen activator inhibitor type 1 in human brain tumors.

We investigated the immunohistochemical localization of plasminogen activator inhibitor type 1 (PAI-1) in surgical specimens of 41 human intracranial tumors. Malignant tumors (7 glioblastoma multiforme, 5 anaplastic gliomas, 4 malignant meningiomas, and 9 metastatic tumors) showed consistently stronger PAI-1 immunohistoreactivity than benign or low-grade tumors (5 low-grade gliomas, 8 benign meningiomas, and 3 Schwannomas). Strong PAI-1 positivity was confined to glomeruloid-shaped proliferative vessels seen in high-grade gliomas and metastatic tumors. Blood vessels near necrotic foci and some zones of necrosis also showed strong PAI-1 positivity. PAI-1 localizes in the vascular basement membrane and perivascular connective tissue, while endothelial cells themselves show weak positivity. None of the specimens showed PAI-1 reactivity within the tumor cells per se. Localization of PAI-1 in proliferating vessels suggests that PAI-1 may be involved in angiogenesis.

Brain Neoplasms↗
PubMed1994

Obesity and adenomatous polyps of the sigmoid colon.

The relation between obesity and adenomatous polyps of the sigmoid colon was investigated in male self-defense officials who received a retirement health examination at three hospitals of the Self-Defense Forces in Japan between January 1991 and December 1992. Body mass index (BMI) and waist-hip circumference ratio (WHR) were used as indices of obesity. A total of 228 adenoma cases and 1484 controls with normal sigmoidoscopy were identified in 2228 men: cases having small adenomas (< 5 mm in diameter) and those with large adenomas (5 mm or greater) numbered 115 and 102, respectively. Smoking, alcohol use, physical activity, rank, and hospital were controlled for by multiple logistic regression analysis. BMI and WHR were classified into four levels using the 30th, 60th, and 90th percentiles of each distribution in the control as cut-off points. There was a significant two-fold elevation in the overall adenoma risk among men at the highest BMI level (> or = 26.95) compared with those at the lowest level (< 22.48), but the risk did not linearly increase: a similar increase was also noted for large adenomas. While WHR was only weakly related to the overall adenoma risk, the risk of large adenomas progressively increased with increasing levels of WHR; odds ratio (OR) 2.9 (95% confidence interval (CI) 1.4-5.9) for the highest (> or = 0.958) versus lowest (< 0.878) levels. BMI was not materially associated with adenoma risk after additional adjustment for WHR, but a positive association between WHR and large adenomas was independent of BMI: OR 3.4 (95% CI 1.5-7.6) for the highest versus lowest levels. These findings suggest that obesity is associated with an increased risk of colon adenomas, probably with adenoma growth.

Adenoma↗
PubMed1994

A novel substrate for insulin-sensitive serine/threonine kinase in intact cells.

We have studied insulin-stimulated threonine phosphorylation of cellular proteins by immunoblotting and immunoprecipitation using antiphosphothreonine antibody (anti-P-Thr). A 50-kilodalton protein (p50) was found to be greatly phosphorylated on threonine residues upon insulin stimulation in intact rat hepatoma cells (Fao) and Chinese hamster ovary cells overexpressing human insulin receptor (CHO-HIR). Insulin induced threonine phosphorylation of this protein in a dose-dependent manner, with an ED50 of 3-6 x 10(-9) M. The 50-kilodalton phosphoprotein (pp50) was detectable 20 min after exposure of the cells to insulin, and phosphorylation reached a maximum after 90 min. Immunoprecipitation of pp50 with anti-P-Thr required extraction of the cellular proteins with sodium dodecyl sulfate and dithiothreitol, and subcellular fractionation of the cells revealed that pp50 is present in the membrane fraction, implying that pp50 is a protein integrated into the membrane component in the cells. Tryptic phosphopeptide mapping of the pp50 was distinct from that of the insulin receptor beta-subunit. Phosphoamino acid analysis of the pp50 demonstrated that insulin increased phosphorylation, mainly of threonine and moderately of serine, whereas pp50 did not contain phosphotyrosine. Cycloheximide, a protein synthesis inhibitor, did not affect the insulin-induced appearance of pp50 in the cells. pp50 was not detectable in A431 cells and KB cells stimulated by epidermal growth factor. These data suggest that p50 is a novel endogenous substrate for insulin-sensitive serine/threonine kinase in intact cells.

Animals↗
PubMed1994

Epidemiology of gallbladder polyps: an ultrasonographic study of male self-defense officials in Japan.

The prevalence and risk factors of gallbladder polyps diagnosed by ultrasonography were investigated in 2739 male self-defense officials who received a retirement health examination at the Self-Defense Forces Fukuoka Hospital, Japan, between October 1986 and December 1990. Excluding 38 men whose gallbladder had been removed previously, 143 men were found to have gallbladder polyps. The overall prevalence of gallbladder polyps was 5.3%. The relation between gallbladder polyps and smoking, alcohol use, body mass index, glucose tolerance, and serum lipids was examined in 137 men with stoneless polyps and 2495 normal subjects. Whereas smoking tended to be inversely associated with gallbladder polyps, none of the other lifestyle and clinical variables were related to this condition. Thus the reported risk factors of gallstones had no relation to gallbladder polyps.

Alcohol Drinking↗
PubMed1994

Plasminogen activator inhibitor-1 in the pathogenesis of delayed radiation damage in rat spinal cord in vivo.

The pathophysiology of radiation-induced damage to the central nervous system (CNS) is poorly understood. Preliminary data suggest that fibrinolytic inhibitors are involved in the development of necrosis. In this study, cervical spinal cord irradiation was studied in 90 rats by measuring plasminogen activator inhibitor (PAI)-1 on Days 2, 7, 30, 60, 90, 120, 130, or 145 after irradiation. Paralysis due to radiation necrosis developed in all animals kept alive for 140 to 150 days. Assay of PAI-1 was by Western blot, enzyme-linked immunosorbent assay (ELISA), and complex formation with 125I-labeled urokinase. No PAI-1 was detected in normal spinal cord tissue or in irradiated spinal cord up to Day 90. However, PAI-1 was detected at Day 120 and was marked by elevated ELISA levels at the time of paralysis. Western blot showed detectable PAI-1 (51 kD) at Day 120 and very significant levels at the time of paralysis. Complex formation with 125I-labeled urokinase was also detected at Day 120 with similar results. Immunohistochemical studies showed that PAI-1 was highly concentrated within and immediately adjacent to zones of necrosis at 145 days and was absent in normal tissue. This study adds considerable weight to the proposal that PAI-1 is closely associated with the pathogenesis of CNS radiation necrosis.

Animals↗
PubMed1994

Fatherhood and distal adenomas of the large bowel: a study of male self-defense officials in Japan.

Parity has been studied extensively as a risk factor for colorectal cancer but has not been definitively shown to be associated with altered risk. In a few studies, risk of colorectal cancer in childless men has been compared to risk in men with children, but results have not been consistent. We analyzed the association of fatherhood with risk of colorectal adenomas in male self-defense officials (ages 49-55) in Japan. The study participants received a preretirement health examination including flexible sigmoidoscopy at Self-Defense Forces hospitals in Japan from January 1991 through December 1992. The examinations identified 265 cases with rectal or sigmoid adenomas and 1480 controls with normal examinations up to 60 cm from the anus. Data on marital status, number of children, long-term work assignment away from wife and children, and other lifestyle variables were obtained by means of a self-administered questionnaire prior to physical examination. Multiple logistic regression analysis assessed the risk of adenomas in relation to number of children, marital status, long-term work assignment away from family, and military rank, with adjustment for cigarette smoking, alcohol intake, dietary variables, body mass index, and recreational physical activity. In this relatively homogeneous group, more than 98% of both cases and controls were currently married, and more than 93% had children. The adjusted odds ratio for the association of adenomas with fatherhood was 0.4 (95% confidence interval, 0.2-0.8). Marital status and work assignment away from the family were not associated with adenoma risk. These findings suggest that colorectal adenomas and perhaps cancer risk may be associated with childlessness in men.

Adenoma↗
PubMed1994

Relationship of alcohol consumption and smoking to plasma cortisol and blood pressure.

The role of plasma cortisol in the relationship of alcohol consumption and smoking with BP was investigated in a study of 297 Japanese men, aged 50-54 years, who were not receiving antihypertensive agents. They were admitted to the Self-Defense Forces Fukuoka Hospital between January and June 1992 for a detailed pre-retirement health examination. A history of alcohol consumption and cigarette smoking were determined from a self-administered questionnaire. The plasma level of cortisol and BP were determined in the morning of the first admission day. While the plasma level of cortisol was positively related to systolic and diastolic BP, cortisol levels did not vary substantially with alcohol consumption. Both BP and plasma cortisol levels were lower among current smokers than nonsmokers. The lower BP observed among current smokers was ascribed in part (about 20-30%) to the plasma cortisol levels. While the cortisol levels may contribute the lower BP among current smokers, the data did not support its role in mediating the alcohol-BP relationship.

Alcohol Drinking↗
PubMed1994

[The significance of portal infusion chemotherapy for prevention of recurrence in residual liver after hepatectomy for metastases from colorectal cancer].

We performed portal infusion chemotherapy using a reservoir for prevention of recurrence in residual liver after hepatectomy for metastases from colo-rectal cancer. To study the usefulness of portal infusion chemotherapy, the period from hepatectomy to recurrence in residual liver was investigated by three treatment groups for H2 cases; (a) a group of systemic chemotherapy, (b) a group of arterial infusion chemotherapy and (c) a portal infusion chemotherapy group. Treatment in (a) group was for 204 +/- 98.2 days (n = 6), in (b) group for 343.0 +/- 238.3 days (n = 8) and in (c) group for 961.0 +/- 1,172.4 days (n = 5). There was no statistically significant difference in the three groups, but (c) group had a better result in recurrence in residual liver. As for prevention of recurrence in residual liver after re-hepatectomy, there was no significant difference in the three groups, but (c) group had the longest survival.

Aged↗
PubMed1994

Elevated levels of plasminogen activators in the pathogenesis of delayed radiation damage in rat cervical spinal cord in vivo.

The pathophysiology of the cellular basis of radiation-induced demyelination and white-matter necrosis of the central nervous system (CNS) is poorly understood. Preliminary data suggest that tissue damage is partly mediated through changes in the proteolytic enzymes. In this study, we irradiated rat cervical spinal cords with single doses of 24 Gy of 18 MV photons or 20 MeV electrons and measured the levels of plasminogen activators at days 2, 7, 30, 60, 90, 120, 130 and 145 after irradiation, using appropriate controls at each time. Fibrin zymography revealed fibrinolytic bands representing molecular weights of 68,000 and 48,000 in controls and irradiated samples; these bands increased significantly at days 120, 130 and 145 after irradiation. Inhibition of these enzymatic bands with specific antibodies against tissue-type plasminogen activator (tPA) and amiloride, an inhibitor for urokinase plasminogen activator (uPA), confirmed that these bands were tPA and uPA. Enzymatic levels quantified by densitometry showed a twofold elevation in the levels of tPA and more than a tenfold increase in uPA after 120 days' irradiation. Activity of uPA was increased threefold by day 2 and increased steadily with time compared to nonirradiated control samples. Enzyme-linked immunosorbent assay (ELISA) also showed a threefold increase in the tPA content in the extracts of irradiated rat cervical spinal cords at days 120, 130 and 145. This study adds additional information to the proposed role of plasminogen activators in the pathogenic pathways of radiation damage in the CNS.

Animals↗
PubMed1993

Sweet syndrome in patients with solid tumors.

BACKGROUND: Sweet syndrome (acute febrile neutrophilic dermatosis) may occur as a cutaneous paraneoplastic syndrome. This condition has been associated with hematologic malignancies and, to a lesser extent, with solid tumors. METHODS: The authors report two patients with malignancy-associated Sweet syndrome: a 66-year-old man in whom the onset of Sweet syndrome preceded the diagnosis of an adenocarcinoma of unknown primary by 3 months and a 69-year-old woman in whom a workup after the appearance of Sweet syndrome skin lesions revealed an unsuspected recurrent squamous cell carcinoma of the larynx. The authors review the reports of the other 39 patients with solid tumor-associated Sweet syndrome that have been published in the world literature. RESULTS: The most common malignancies were carcinomas of the genitourinary organs (37%), breast (23%), and gastrointestinal tract (17%). Typical clinical features and laboratory findings in these patients included tender erythematous plaques located on the upper extremities (97%); elevated erythrocyte sedimentation rate (95%); anemia (83%); fever (79%); and neutrophilia (60%). The symptoms and lesions of Sweet syndrome resolved after treatment with corticosteroids, potassium iodide, or colchicine. Sweet syndrome preceded the initial diagnosis of cancer or the detection of asymptomatic metastatic, persistent, or recurrent tumor, or a hematologic malignancy (in an individual with a previously diagnosed solid tumor) in 61% of the patients. In the other 39% of patients, diagnosis of Sweet syndrome followed the development of a solid tumor. CONCLUSION: The search for a neoplasm of the genitourinary organs and breast cancer in women and a gastrointestinal tract carcinoma in men should be emphasized in the evaluation for a solid tumor in patients with Sweet syndrome without a prior diagnosis of malignancy.

Adenocarcinoma↗
PubMed1993

Anti-phosphoserine and anti-phosphothreonine antibodies modulate autophosphorylation of the insulin receptor but not EGF receptor.

We examined the effect of anti-phosphothreonine and anti-phosphoserine antibodies on insulin receptor autophosphorylation. These antibodies did not affect insulin binding activity of the receptor. These antibodies, however, inhibited insulin-stimulated autophosphorylation of insulin receptor, while did not affect EGF-stimulated autophosphorylation of EGF receptor. The inhibition was reversed by adding large amounts of phosphoserine or phosphothreonine. These data suggest that phosphoserine and phosphothreonine on insulin receptor play an important role in insulin-induced conformational change of the receptor.

Animals↗
PubMed1993

Decreased levels of glia-derived nexin/protease nexin I in irradiated rat spinal cord in vivo.

The pathophysiology of the cellular basis of radiation induced demyelination and white matter necrosis of the Central Nervous System (CNS) is poorly understood. There have been no previous studies that have shown the effect of irradiation on glia-derived nexin. In this study, rats were given cervical spinal cord irradiation, and glial derived nexin or protease nexin I (GDN/PNI) was measured on days 2, 7, 30, 60, 120, 130, and 145 after irradiation. The level of GDN/PNI significantly decreased after irradiation compared to levels in control spinal cord, and there was no detectable levels of GDN/PNI by the time paralysis developed. This study adds considerable weight to the proposal that GDN/PNI has an important role in the pathogenesis of CNS radiation damage.

Amyloid beta-Protein Precursor↗
PubMed1993

Effects of ML-9 on insulin stimulation of glucose transport in 3T3-L1 adipocytes.

Treatment of 3T3-L1 adipocytes with insulin resulted in activation of 2-deoxyglucose transport activity and translocation of glucose transporters (GLUT4 and GLUT1) from the cytoplasmic space to the plasma membrane. ML-9 (a myosin light chain kinase inhibitor) inhibited insulin stimulation of 2-deoxyglucose transport activity by 80% at 100 microM (IC50 = 27 microM) without affecting 2-deoxyglucose transport activity in the basal state. The inhibition was independent of extracellular Ca2+ concentration and almost fully reversible at 40 microM ML-9. ML-9 did not inhibit insulin-stimulated tyrosine phosphorylation of 95-kDa protein in the wheat germ agglutinin-purified preparation and of 95- and 160-kDa proteins in intact cells. However, ML-9 inhibited insulin-induced translocation of both GLUT4 and GLUT1 in a dose-dependent manner. The dose-response curves were similar to those observed for the inhibition of insulin stimulation of 2-deoxyglucose transport activity. Neither insulin nor ML-9 affected the phosphorylation state of both heavy and light chains of myosin. Therefore, it seems likely that ML-9 inhibits the insulin-induced translocation of glucose transporters at a step beyond the insulin receptor kinase activity by a mechanism different from that affecting phosphorylation of the myosin light chain. Phosphorylating activity of microtubule-associated protein 2 and myelin basic protein was stimulated by insulin, and this stimulation was not affected by ML-9. ML-9, however, inhibited the phosphorylating activity in vitro and insulin stimulation of the phosphorylating activity of ribosomal protein S6 in intact cells in a dose-dependent manner similar to that observed for the inhibition of insulin stimulation of glucose transport. These results suggest that mitogen-activated protein kinase may be one of the constituents in intracellular insulin signaling to the glucose transport system.

3T3 Cells↗
PubMed1993

Specific activity of phosphatidylinositol 3-kinase is increased by insulin stimulation.

We investigated whether phosphatidylinositol 3-kinase (PI3K) is phosphorylated and whether its specific activity is increased by insulin stimulation in vivo using Fao cells and antibodies raised against the 85 kDa subunit of PI3K, insulin-receptor substrate-1 (IRS-1), and phosphotyrosine (pTyr). PI3K activity was detected in the immunoprecipitate produced with anti-PI3K at a basal state. The activity was increased 2-3-fold by insulin stimulation, although the protein concentration of kinase in the anti-PI3K immunoprecipitates was the same before and after insulin stimulation. Both anti-pTyr and anti-IRS-1 antibodies immunoprecipitated the kinase activity only after insulin stimulation. After the first immunoprecipitation with anti-pTyr, the supernatant was immunoprecipitated once more with anti-PI3K. PI3K activity in the second immunoprecipitate revealed little difference between the basal and insulin-stimulated states, suggesting that most of the insulin-activated portion of PI3K was precipitated by anti-pTyr. Both IRS-1 and the insulin-receptor beta-subunit (95 kDa) were phosphorylated on tyrosine residues by insulin stimulation and immunoprecipitated with anti-pTyr. However, phosphorylation of neither subunit of PI3K (85 kDa or 110 kDa) was detectable in the immunoprecipitate produced with anti-pTyr. The 185 kDa pTyr-containing protein was immunoprecipitated with anti-PI3K after insulin stimulation, although there was little phosphorylation of the 85 kDa protein. pTyr in the 110 kDa protein immunoprecipitated with anti-PI3K was below detectable levels. These results indicate that the specific activity of PI3K is increased by insulin stimulation without detectable tyrosine phosphorylation of PI3K itself in Fao cells. The majority of the insulin-activated portion of PI3K is associated with pTyr-containing proteins including IRS-1, which suggests that this is important for activation of PI3K by insulin.

Animals↗
PubMed1993

Preparation of anti-phosphoserine and anti-phosphothreonine antibodies and their application in the study of insulin- and EGF-induced phosphorylation.

We prepared antibodies against phosphoserine (P-Ser) and phosphothreonine (P-Thr) by immunizing rabbits with P-Ser or P-Thr conjugated to bovine serum albumin. The antibodies (anti-P-Ser and anti-P-Thr) were purified using P-Ser or P-Thr affinity columns. Anti-P-Thr was highly specific for P-Thr, while anti-P-Ser showed weak cross-reactivity with P-Thr. We showed that these antibodies can immunodetect serine/threonine phosphorylated insulin and epidermal growth factor (EGF) receptors and several proteins which are phosphorylated on serine/threonine residues in response to insulin or EGF stimulation. The antibodies will certainly provide a good tool for discovering novel kinases and substrates involved in signal transduction.

Animals↗
PubMed1993

Serum lipids and left-sided adenomas of the large bowel: an extended study of self-defense officials in Japan.

In the on-going study of men retiring from the Self-Defense Forces in Japan, we previously reported that serum total cholesterol was not related to colorectal adenomas but that men with low levels of serum high-density lipoprotein (HDL) cholesterol had an elevated adenoma risk. We examined whether the previous observation was reproducible in a different set of data accrued subsequently in the study. Serum total cholesterol, HDL-cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides were compared between 138 cases of colorectal adenomas at the depth of 60 cm or less from the anus and 909 controls with normal sigmoidoscopy in the period from October 1988 to December 1990. There was virtually no relation between adenoma risk and any of the serum lipids studied with or without adjustment for smoking, alcohol use, and body mass index. In the analysis combining the earlier and present data, however, men with large adenomas (> or = 10 mm, n = 25) tended to have lower levels of total cholesterol and LDL-cholesterol compared with controls (n = 1,612); adjusted mean differences were -0.21 mmol/l (P = 0.24) and -0.26 mmol/l (P = 0.13), respectively. These findings are inconclusive, but hypocholesterolemia may be associated with the growth of colorectal adenoma.

Adenoma↗