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S Kumakura

Publications and source records attributed to S Kumakura.

At least 37 records · Page 2Linked to original sources
PubMed1996

C-Myc and Bcl-2 protein expression during the induction of apoptosis and differentiation in TNF alpha-treated HL-60 cells.

We examined c-Myc and Bcl-2 protein expressions during the induction of apoptosis and differentiation in TNF alpha-treated HL-60 cells using a two-color flow cytometric method. We found that c-Myc protein was rapidly down-regulated in the apoptotic cells while Bcl-2 protein was expressed at relatively high levels. Concomitantly with terminal differentiation Bcl-2 protein was down-regulated in differentiating cells as well as c-Myc protein. We also showed that c-myc antisense oligonucleotides could induce apoptosis in HL-60 cells whereas bcl-2 antisense did not induce apoptosis during the early time of treatment. These results suggest that the down-regulation of c-Myc protein expression is a primary event to induce apoptosis and neither consistent expression of c-Myc protein nor rapid down-regulation of Bcl-2 protein is necessary for the initial processing of apoptosis in HL-60 cells. Furthermore, concomitant down-regulation of c-Myc and Bcl-2 is closely associated with terminal differentiation and apoptotic cell death of HL-60 cells treated with TNF alpha.

Apoptosis↗
PubMed1995

Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes mellitus.

Most patients with non-insulin-dependent diabetes mellitus are resistant to both endogenous and exogenous insulin. Insulin resistance precedes the onset of this disease, suggesting that it may be an initial abnormality. Insulin-receptor kinase activity is impaired in muscle, fibroblasts and other tissues of many patients with non-insulin-dependent diabetes mellitus, but abnormalities in the insulin-receptor gene do not appear to be the cause of this decreased kinase activity. Skin fibroblasts from certain insulin-resistant patients contain an inhibitor of insulin-receptor tyrosine kinase. Here we show that this inhibitor is a membrane glycoprotein, termed PC-1 (refs 10, 11). We find that PC-1 activity is increased in fibroblasts from seven of nine patients with typical non-insulin-dependent diabetes mellitus. In addition, overexpression of PC-1 in transfected cultured cells reduces insulin-stimulated tyrosine kinase activity. These studies raise the possibility that PC-1 has a role in the insulin resistance of non-insulin-dependent diabetes mellitus.

Adult↗
PubMed1995

Elevated ratio of summed serum proinsulin to insulin response after oral glucose load in type 2 diabetes decreases following sulfonylurea treatment.

We showed previously that the disproportionate elevation of serum proinsulin at fasting and after glucose ingestion in Type 2 diabetes is reduced to nearly normal after improvement of glycemic control by diet therapy. In this study, we investigated the effect of sulfonylurea (SU) treatment on serum proinsulin levels and proinsulin/insulin ratio (PI/I) during oral glucose tolerance test in patients with Type 2 diabetes. Thirteen diabetic patients (age 56 +/- 9 years, body mass index 22.4 +/- 1.9 kg/m2, mean +/- SD) were examined by 75 g oral glucose tolerance test (OGTT) before and after glycemic control by SU therapy. Mean interval of two OGTTs was 126 days. Serum proinsulin was measured by the radioimmunoassay using a human proinsulin-specific antiserum. When glycemic control improved after SU therapy (mean fasting plasma glucose 11.5 and 6.0 mmol/l, before and after SU treatment), fasting insulin, proinsulin and PI/I ratio did not change significantly. Insulin response during OGTT markedly increased after SU therapy. Summed value of insulin (sigma I) increased from 634 to 1064 pmol/l after SU (P < 0.01), whereas summed proinsulin (sigma PI) did not change significantly (146 and 159 pmol/l), resulting in a significant decrease in sigma PI/sigma I (23.6-15.1%, P < 0.05). We conclude that the disproportionate elevation of proinsulin during OGTT in patients with Type 2 diabetes can be reduced after glycemic control by SU treatment, chiefly by a selective increase in insulin response.

Administration, Oral↗
PubMed1994

c-myc protein expression during cell cycle phases in differentiating HL-60 cells.

We examined c-myc protein expression in cell cycle phases during differentiation induction of HL-60 cells by flow cytometry using an indirect immunofluorescence method. In exponentially proliferating HL-60 cells, c-myc protein was expressed in a cell cycle dependent manner. During the differentiation induction of HL-60 cells with dimethylsulfoxide (DMSO), c-myc protein was rapidly down-regulated in the G1/0 specific phase prior to the appearance of differentiation associated markers. Our results indicate that c-myc protein functions in the G1/0 specific phase in cellular differentiation, and the rapid down-regulation of c-myc protein in G1/0 phase is closely associated with initial differentiation programs.

Cell Cycle↗
PubMed1993

A favourable effect of long-term alpha-interferon therapy in refractory idiopathic thrombocytopenic purpura.

We successfully treated two patients with refractory idiopathic thrombocytopenic purpura (ITP) with a weekly or monthly administration of alpha-interferon followed by short-course treatment with alpha-interferon. In both cases an increase in platelet count was brought about within 1 week after administration of alpha-interferon and the favourable response in platelet count was sustained over a few years with the weekly or monthly administration of alpha-interferon in the absence of any noticeable side-effects except for fever. So, alpha-interferon therapy seems to be beneficial in some cases of refractory ITP in terms of both remission induction and maintenance therapy.

Aged↗
PubMed1992

Effect of islet amyloid polypeptide (IAPP/amylin) on 2-deoxyglucose uptake in mouse pancreatic acini.

In order to examine the effect of islet amyloid polypeptide (IAPP/amylin), a product of the pancreatic beta cell and a major component of islet amyloid deposits, on exocrine pancreatic function, we studied the effect of rat IAPP amide (IAPP-NH2) on 2-deoxy-D-glucose (2-DG) uptake in isolated mouse pancreatic acini. Mouse pancreatic acini were preincubated for 80 min with various concentrations of IAPP-NH2 (1 nM-1 microM) and [3H]2-DG uptake for 20 min was measured. The full effect of IAPP-NH2 on this function was not immediate but increased linearly with time for up to 80 min of incubation. IAPP-NH2 caused a dose-dependent stimulation of 2-DG uptake by mouse acini; a detectable effect at 10 nM and a maximal effect at 1 microM. In the presence of 1 microM IAPP-NH2, 2-DG uptake increased by 69 +/- 8% above basal (mean +/- SD, n = 6). The results indicate that IAPP-NH2 stimulates glucose uptake in mouse pancreatic acini, and raise the possibility that IAPP-NH2 plays some physiological role in the insuloacinar axis in mouse pancreas.

Amyloid↗
PubMed1991

Additive effect of islet amyloid polypeptide (IAPP/amylin) and insulin on 2-deoxyglucose uptake in mouse pancreatic acini.

The effect of islet amyloid polypeptide (IAPP/amylin) on 2-deoxyglucose (2-DG) uptake was studied in isolated mouse pancreatic acini in the absence or presence of insulin. Synthetic rat IAPP-NH2 caused a dose-dependent stimulation of 2-DG uptake by mouse acini with a half-maximal concentration at 70 nM. The increase in 2-DG uptake by 1 microM IAPP-NH2 or 100 nM insulin was 68% or 60% above basal, respectively. In the presence of both 1 microM IAPP-NH2 and 100 nM insulin, the increase in 2-DG uptake was 145% above basal, indicating that the effects of IAPP-NH2 and insulin on 2-DG uptake were additive. The results suggest that IAPP stimulates glucose uptake in mouse acini probably by a different mechanism from that of insulin.

Amyloid↗
PubMed1991

Hyperinsulinaemia in obesity is not accompanied by an increase in serum proinsulin/insulin ratio in groups of human subjects with and without glucose intolerance.

Serum proinsulin is disproportionately elevated compared to insulin in Type 2 (non-insulin-dependent) diabetes mellitus. We studied the effect of obesity on serum proinsulin with varying degrees of glucose intolerance. Serum proinsulin and insulin were measured during a 75 g oral glucose tolerance test in 73 obese and 74 non-obese subjects with normal, borderline or diabetic-type glucose tolerance. Proinsulin was assayed by a direct radioimmunoassay using proinsulin-specific antiserum. Fasting serum proinsulin and insulin and the summed values of proinsulin and insulin during oral glucose tolerance test were significantly, or tended to be, higher in obese subjects than in those without obesity in each category of glucose tolerance. However, the molar ratio of proinsulin to insulin was nearly the same between obese and non-obese groups with a similar degree of glucose tolerance. On the other hand, the proinsulin/insulin ratio increased progressively with the deterioration of glucose tolerance. We conclude that proinsulin secretion is disproportionately increased in the presence of glucose intolerance but not by obesity itself. Each Beta cell seems to function normally in obese subjects while glucose tolerance remains normal.

Blood Glucose↗
PubMed1991

Effect of new oral antidiabetic agent CS-045 on glucose tolerance and insulin secretion in patients with NIDDM.

OBJECTIVE: To study the effects of CS-045, a newly developed thiazolidine analogue, on glucose tolerance and insulin response to oral glucose load in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Nineteen NIDDM patients (mean +/- SD age 48.9 +/- 9.4 yr) whose previous glycemic control on diet and/or sulfonylurea (SU) therapy was judged stable but unsatisfactory (greater than 7.8 mM) were selected for this study. CS-045 (400 mg/day p.o.) was given alone or together with the previous SU drugs for 12 wk. A 75-g oral glucose tolerance test (OGTT) was performed before and after CS-045 treatment. RESULTS: The following results were found after CS-045 treatment. 1) Fasting plasma glucose (FPG) and HbA1c decreased (n = 19, FPG, 11.0 +/- 2.4 vs. 8.4 +/- 2.7 mM [before vs. after], P less than 0.001; HbA1c, 8.0 +/- 1.1 vs. 7.4 +/- 1.3%, P less than 0.005), and glucose tolerance markedly improved. 2) Fasting insulin (immunoreactive insulin [IRI]) and insulin response during OGTT decreased (n = 19, fasting IRI, 77.4 +/- 49.8 vs. 56.5 +/- 24.6 pM [before vs. after], P less than 0.05; area under the curve of IRI, 540.3 +/- 350.5 vs. 426.4 +/- 216.3 pM.h, P less than 0.05). CONCLUSIONS: CS-045 is effective in improving glucose tolerance without stimulation of insulin secretion in NIDDM, suggesting an effect in improving insulin sensitivity.

Blood Glucose↗
PubMed1991

Antiarrhythmic and cardiovascular profiles of the fused indole compound (3aR,12R,12aR,12bS)-12-amino-2,3,3a,4,11,12,12a,12b-octahydro-10-hydrox yisoquino [2,1,8-lma]carbazol-5(1H)-one hydrochloride 1.5 hydrate.

Antiarrhythmic and cardiovascular profiles of a fused indole compound, (3aR,12R,12aR,12bS)-12-amino-2,3,3a,4,11,12,12a,12b -octahydro- 10-hydroxyisoquino [2,1,8-lma]carbazol-5(1H)-one hydrochloride 1.5 hydrate (RS-2135, CAS 133775-36-7), were investigated in anesthetized dogs. Class I antiarrhythmic agents such as disopyramide, lidocaine, mexiletine and flecainide were used as reference compounds. RS-2135 exerted more potent antiarrhythmic activity than reference compounds against ouabain-induced arrhythmias in dogs. The onset of action was slow, but the duration of action was longer than with the other compounds tested. The agent suppressed the conduction in the atrium, A-V node and ventricle more markedly than the reference compounds. RS-2135, however, did not change blood pressure and heart rate at a dose 5 times the dose for antiarrhythmic activity and decreased cardiac contractility to a lesser extent than the reference compounds.

Animals↗
PubMed1990

Inhibitory effect of indomethacin farnesil, a novel antiinflammatory prodrug, on carrageenin-induced inflammation in rats.

Antiinflammatory effects of indomethacin farnesil (IMF), a novel prodrug of indomethacin, was examined after both oral and local administration. In the air pouch carrageenin-induced inflammation, an oral dose of IMF exerted dose dependent inhibitory effects on the accumulation of inflammatory exudate fluid and the migration of leukocytes into the exudate. Both the increased vascular permeability and the prostaglandin E2 levels in the exudate fluid were reduced by IMF. Significant levels of free indomethacin were detected in the pouch fluid. In spite of the inability of IMF to inhibit prostaglandin synthesis in a cell free cyclooxygenase system, IMF injected locally inhibited carrageenin paw edema, and the inhibitory effect was comparable to that of indomethacin itself. When injected locally into the paw together with carrageenin, 14C-IMF was effectively converted to its active metabolite, indomethacin. The indomethacin concentration in the paw tissue was comparable to that of indomethacin injected paws with the same molar dose of free indomethacin.

Animals↗
PubMed1989

Role of bradykinin in exudative reactions of inflammation in rats.

This study was done with the aid of experimental models of inflammation provoked in air pouch, which was made subcutaneously on the back of rats, by applying a carrageenin solution or a suspension of kaolin in a carboxymethylcellulose solution as an irritant. Bradykinin in the inflammatory sites, determined by an enzyme immunoassay method, were comparatively high in the earliest stage of inflammation in both the models and responsible for the exudative reactions. With the passage of time, i.e. within 20 min in the case of kaolin and 120 min in carrageenin, tissue kininase entered the inflammatory site and reduced bradykinin to a very low level, though bradykinin was still being generated very actively. In this later stage, bradykinin collaborates with prostaglandin to bring about a significant increase in the vascular permeability.

Animals↗
PubMed1988

HLA DR antigens in adult-onset and juvenile-onset Japanese insulin-dependent diabetic patients.

In order to discover the HLA DR antigens linked to Japanese insulin-dependent diabetes (IDDM), and to relate them to the clinical features, HLA DR antigens were examined in 75 IDDM patients including 56 adult-onset cases. Among the tested HLA DR antigens, 4, w9 and w13 were significantly more frequent in IDDM (55%, 47% and 27% respectively). The relative risk was 1.71 for DR4, 2.81 for DRw9 and 4.74 for DRw13. DR2 was significantly less frequent and the relative risk was 0.14. The distribution of DR antigens did not differ between juvenile-onset and adult-onset IDDM, males and females, or cases with and without thyroid autoantibodies. Homozygotes for DRw9 were, but those for DRw13 and DR4 were not more frequent than expected by a random combination. Heterozygotes for DR4 and w9 were less frequent while other heterozygotes for high-risk antigens were as frequent as expected. 97% of IDDM had either DR4, w9 or w13. In conclusion, HLA DR4, w9 and w13 were significantly increased in patients with both juvenile- and adult-onset IDDM. There was no surplus increase in the frequency of IDDM patients with two high-risk HLA DR antigens, more than expected from random combination of each of these DR antigens. Clinical features did not differ among IDDM patients with each of these three antigens.

Adult↗
PubMed1988

Effect of bromelain on kaolin-induced inflammation in rats.

The effects of stem bromelain on the plasma kallikrein system, bradykinin levels and plasma exudation at the inflammatory site were examined in rats with a kaolin-induced inflammation of an air pouch. Bromelain (5, 7.5 mg/kg) caused a dose-dependent decrease of bradykinin levels at the inflammatory site and a parallel decrease of the prekallikrein levels in sera. Plasma exudation was also reduced dose dependently. Bradykinin-degrading activity in sera was elevated after treatment with bromelain, although it was unchanged in the pouch fluid. These data indicate that bromelain inhibits plasma exudation through inhibiting the generation of bradykinin at the inflammatory site via depletion of the plasma kallikrein system.

Animals↗
PubMed1988

Nature of kininase activity in the exudate in kaolin-induced inflammation of the air pouch type in rats.

Experimental inflammation was induced by injection of a suspension of kaolin in carboxymethylcellulose solution into a subcutaneous air pouch preformed on the back of rats. Endogenous bradykinin generated in the inflammatory pouch declined quickly unless kininase inhibitors were administered into the pouch. Bradykinin injected into the pouch brought about no significant increase in plasma exudation in the pouch unless kininase inhibitors were administered simultaneously. Although kininase I and II activities were present in normal rat serum, kininase II rather than kininase I was mainly responsible for the degradation of bradykinin in rat serum. In the pouch challenged with the kaolin suspension and vehicle, kininase II originating from the pouch wall tissue played a predominant role in the degradation of bradykinin while the role of kininases derived from the blood and inflammatory cells was minor.

Animals↗
PubMed1988

Role of bradykinin in the vascular permeability response induced by carrageenin in rats.

1 Bradykinin in carrageenin-induced inflammatory pouch fluid was measured by an enzyme immunoassay method. 2 The bradykinin showed a single peak in the 30-60 min period after the challenge and then decreased quickly, and there was a correlation between the bradykinin level and exudation of fluorescein-labelled bovine serum albumin in the first 60 min period. 3 Captopril (an inhibitor of kininase II) elevated both the bradykinin level in the inflammatory pouch fluid and vascular permeability, while DL-2-mercaptomethyl-3- guanidinoethylthiopropanoic acid (an inhibitor of kininase I) had no effect. 4 Soybean trypsin inhibitor (SBTI) inhibited the vascular permeability response in parallel with the decrease in the bradykinin level. 5 A bradykinin-degrading activity appeared in the pouch fluid within 1 h after the challenge and increased with time. 6 In the period of 3.5-4 h, bradykinin levels were suppressed below the sensitivity limit of the assay, i.e. 0.07 nm ml-1, in spite of active generation. This was because degradation of bradykinin was very rapid in this late stage. Nevertheless, bradykinin still played a definite role in sustaining a high level of vascular permeability response in the late stage in conjunction with prostaglandins.

Animals↗