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Biomedical subjects

T Kamada

Publications and source records attributed to T Kamada.

At least 235 records · Page 13Linked to original sources
PubMed1995

A case of non-insulin dependent diabetes mellitus with antiinsulin antibody: effect of subcutaneous injection of human recombinant insulin-like growth factor-I.

We saw a 57-yr-old female non-insulin dependent diabetes mellitus (NIDDM) patient with antiinsulin antibody, in whom insulin-like growth factor-I (IGF-I) was shown to be effective as a blood glucose-lowering agent. Due to the presence of the antibody, the patient suffered from postprandial hyperglycemia and frequent hypoglycemia, which were uncontrollable even by multiple insulin injection therapy. In contrast to insulin injection (0.24 IU/kg body wt) which showed a delayed glucose-lowering effect, subcutaneous injection of recombinant human IGF-I (0.05-0.1 mg/kg body wt) caused a quick fall in plasma glucose levels. Prolongation of the glucose-lowering effect of "rapid-acting" insulin frequently caused subsequent hypoglycemia in this patient, but the effect of IGF-I seemed to have disappeared within the first three hours.

Diabetes Mellitus, Type 2↗
PubMed1995

Angiotensin II stimulates interleukin-6 release from cultured mouse mesangial cells.

Interleukin-6 (IL-6) is a multifunctional cytokine exerting a wide variety of biologic responses, including cell proliferation. Recently, IL-6 has been known to play a role in the pathogenesis of mesangial proliferative glomerulonephritis. IL-6 is now recognized as an autocrine growth factor for glomerular mesangial cells, and various inflammatory mediators have been shown to promote IL-6 release from mesangial cells. However, little is known about the noninflammatory stimuli of IL-6 release from mesangial cells. In this study, it was hypothesized that angiotensin II (AngII) is one of the noninflammatory mediators of IL-6 release in mesangial cells, and the effects of AngII on IL-6 release and mRNA expression in cultured mouse mesangial cells (CMMC) were investigated. It was demonstrated that AngII (10(-7) M or higher) caused IL-6 release and mRNA accumulation in CMMC. IL-6 release was detected at 4 h and reached a plateau at 8 h after the addition of AngII, whereas IL-6 mRNA expression peaked at 4 h. The effects of AngII on IL-6 release and gene expression were completely blocked by the AngII receptor type 1 (AT1 receptor) antagonist CV-11974. AngII and IL-6 were both shown to stimulate DNA synthesis in CMMC, and the blockade of IL-6 signaling with anti-IL-6 receptor antibody abolished the enhanced DNA synthesis induced by AngII. These results raise a possibility that the growth-promoting effect of AngII on mesangial cells is at least partially mediated by IL-6 released from mesangial cells.

Angiotensin II↗
PubMed1995

Association of angiotensin I-converting enzyme gene polymorphism with susceptibility to antiproteinuric effect of angiotensin I-converting enzyme inhibitors in patients with proteinuria.

The antiproteinuric effect of angiotensin I-converting enzyme (ACE) inhibitors in patients with renal diseases of various origins has been well recognized. However, individual responses regarding the degree of decrease in urinary protein excretion appear to vary considerably. The mechanism underlying this variable response to ACE inhibitors has not been clarified yet. A possible role of ACE gene insertion/deletion (I/D) polymorphism in the responsiveness to antiproteinuric effect of ACE inhibitors is examined. Thirty-six patients with proteinuria (23 men and 13 woman; mean age, 47 +/- 13 yr) were studied. These patients were classified into two groups on the basis of the percent decrease in their urinary protein excretion: the effective group, those with a decrease in proteinuria (18 patients, -64 +/- 19%) and the noneffective group (18 patients, +13 +/- 40%). A 287-base pair (bp) I/D polymorphism in the ACE gene was examined by polymerase chain reaction. The allelic frequencies of the ACE gene were I/D = 0.53/0.47 in the effective group and I/D = 0.81/0.19 in the noneffective group. The difference in the allelic frequencies between the two groups was significant (chi 2 = 6.25, P = 0.0114 < 0.05). Furthermore, the difference in the responsiveness of proteinuria to ACE inhibition between genotype II versus genotype ID + DD was statistically significant (chi 2 = 4.05, P = 0.0442 < 0.05). There was no significant difference between the two groups with regard to initial urinary protein level, blood pressure, renal function, and daily sodium intake. The genetic susceptibility to the antihypertensive effect of ACE inhibitors was also studied, but no significant relation was observed. This study suggests the association of ACE gene I/D polymorphism with the antiproteinuric efficacy of ACE inhibitors in patients with proteinuria.

Adult↗
PubMed1995

Apoptotic cell death triggered by nitric oxide in pancreatic beta-cells.

Nitric oxide (NO) is believed to be an effector molecule that mediates interleukin (IL)-1 beta-induced destruction and dysfunction of pancreatic beta-cells. We have demonstrated that both exogenous NO and NO generated endogenously by IL-1 beta brought about apoptosis of isolated rat pancreatic islet cells as well as pancreatic beta-cell tumor-derived cell line HIT. This apoptosis was characterized by cleavage of DNA into nucleosomal fragments of 180-200 bp and morphologically by nuclear shrinkage, chromatic condensation, and apoptotic body formation. The IL-1 beta-induced internucleosomal DNA cleavage occurred in a time- and dose-dependent manner. Actinomycin D, cycloheximide, and nitric oxide synthase inhibitors inhibited the DNA cleavage, which was correlated with the amount of NO produced, indicating that NO produced by HIT cells themselves could mediate the apoptosis. Furthermore, in the presence of tumor necrosis factor (TNF)-alpha, large amounts of NO were produced by IL-1 beta and DNA cleavage occurred more noticeably, although TNF-alpha alone did not generate NO. Streptozotocin (STZ), a diabetogenic reagent containing a nitroso moiety, also released NO and induced internucleosomal DNA cleavage in HIT cells. These results suggest that NO-induced internucleosomal DNA cleavage is an important initial step in the destruction and dysfunction of pancreatic beta-cells induced by inflammatory stimulation or treatment with STZ.

Amino Acid Oxidoreductases↗
PubMed1995

1,5-Anhydro-D-glucitol evaluates daily glycemic excursions in well-controlled NIDDM.

OBJECTIVE: To evaluate the usefulness of plasma 1,5-anhydro-D-glucitol (1,5-AG) as a possible marker for daily glycemic excursion, we measured plasma 1,5-AG, HbA1c, fasting plasma glucose (FPG) level, and daily excursion of glycemia, from which the M-value (after Schlichtkrull) was calculated as an index of daily glycemic excursion. RESEARCH DESIGN AND METHODS: The subjects were 76 patients with well-controlled non-insulin-dependent diabetes mellitus (NIDDM) treated with diet therapy only (diet, n = 17), oral hypoglycemic agents (OHA, n = 28), conventional insulin therapy (CIT, n = 16), or multiple insulin injection therapy (MIT, n = 15). RESULTS: HbA1c values were similar among all the groups (diet, 6.9 +/- 0.6; OHA, 7.2 +/- 0.5; CIT, 7.1 +/- 0.6; MIT, 7.2 +/- 0.5%). The MIT group showed a significantly higher 1,5-AG concentration (11.5 +/- 5.3 micrograms/ml), a significantly lower M-value (9.2 +/- 5.2), and little risk of hypoglycemia ( < 4 mmol/l) and hyperglycemia ( > 10 mmol/l) (1.3 +/- 1.1 times/24 h) compared with the CIT group (6.9 +/- 3.3 micrograms/ml, 15.7 +/- 8.9, 2.2 +/- 1.6 times/24 h, respectively). Insulin doses (22.4 +/- 4.5 vs. 22.0 +/- 8.9 U/day), FPG (6.6 +/- 2.2 vs. 7.4 +/- 2.4 mmol/l), and HbA1c concentrations were not significantly different between the CIT and MIT groups. M-values significantly correlated with 1,5-AG concentrations (r = 0.414, P < 0.05), but not with HbA1c concentrations. CONCLUSIONS: The findings suggest that the plasma 1,5-AG concentration can be a useful index of the daily excursion of blood glucose, especially in patients with well-controlled NIDDM.

Biomarkers↗
PubMed1995

[A study of osteopenia in elderly diabetic patients].

It is well known that IDDM cases can be complicated with osteopenia, but most of these results were reported using single photon absorptiometry. There have been few reports of diabetic osteopenia using dual energy X-ray absorptiometry (DXA), a method that is excellent for precise bone mineral measurement. Osteoarthritis and osteophytes of unknown origin in the lumbar vertebrae are often observed in elderly NIDDM patients. In this study, we examined the clinical characteristics of decreased bone mineral density (BMD) and whether anteroposterior (AP) scanning of the lumbar vertebrae (L2-L4) provides sufficient informations concerning osteopenia in elderly diabetic patients. The study was performed using DXA, which can quantify regional BMD throughout the body. The BMD in the total body and that in the lumbar vertebrae were measured by DXA (Lunar Co.) in 68 diabetics over age 60, 33 males and 35 females, mean age 68 +/- 8 yr, (mean +/- SD) and in 94 middle-aged diabetics (40 to 59), 56 males and 38 females, mean age 51 +/- 4 yr. The percentage of decrease in regional BMD in diabetic patients differed significantly by age and gender. The BMD in the head and spine especially decreased after menopause in women. However, the BMD of the leg and spine did not decrease with age in men. When the BMD of the lumbar vertebrae was plotted against the Y axis and the BMD in the total body against the X axis, the slope of the curve showed a greater increase in elderly diabetics than that in middle aged diabetics (1.8 vs 1.5) suggesting the BMD in the lumbar vertebrae has been overestimated.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1995

Gene expression of N-acetylglucosaminyltransferases III and V: a possible implication for liver regeneration.

N-acetylglucosaminyltransferases III and V (GnT-III and -V) are key enzymes in the synthesis of the branches of asparagine-linked oligosaccharides. Although their messenger RNAs (mRNAs) are expressed in various rat tissues, they are not detected in normal rat liver. Expression of the GnT-III and -V mRNAs, however, increased in regenerating liver after two-thirds partial hepatectomy compared with sham-operated rats. The enzymatic activities of GnT-III and -V increased in proportion to mRNA expression. To determine which type of cells in the liver have high activities of these glycosyltransferases, hepatocytes and nonparenchymal cells were separated by means of a two-step collagenase perfusion technique. GnT-III activity was only detected in nonparenchymal cells of normal rat liver. However, during liver regeneration, GnT-III activity increased and thus was also detectable in hepatocytes. GnT-V activity was detected in both types of cells. These data were supported by reverse transcription-polymerase chain reaction results. Although the mechanism underlying the induction of these glycosyltransferases is unknown, lectin blot analysis showed that oligosaccharides in many glycoproteins, including hepatocyte growth factor, a major growth factor associated with liver regeneration, were newly synthesized during liver regeneration. This is the first report on the expression of glycosyltransferases during liver regeneration and suggests that there are different mechanisms involved in regulation of the genes of GnT-III and -V during liver regeneration.

Animals↗
PubMed1995

Nitric oxide synthase protects the heart against ischemia-reperfusion injury in rabbits.

The role of nitric oxide (NO) in myocardial ischemia-reperfusion injury is still controversial. To determine the role of NO in the propagation of myocardial injury in a coronary artery occlusion-reperfusion model, we examined the effect of a competitive NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), with and without L-arginine, on the size of the infarct resulting from coronary artery occlusion (30 min) followed by reperfusion (48 hr) in rabbits. L-NAME (300 micrograms/kg, as a bolus, and 100 micrograms/kg/min, i.v.) with and without L-arginine (30 mg/kg, as a bolus, and 10 mg/kg/min, i.v.) was administered immediately before coronary occlusion to 60 min after reperfusion. The infarct size in the L-NAME-treated rabbits (75.1% +/- 5.0%, n = 7), assessed as a percentage of infarcted region/ischemic region, was significantly larger than that of control rabbits (51.2% +/- 7.4%, n = 7; P < .05). The increase in infarct size was significantly attenuated by the treatment with L-NAME and L-arginine (62.0% +/- 4.0%, n = 7). However, the infarct size for the treatment with L-NAME and D-arginine (76.7% +/- 5.7%, n = 6) did not differ from that in the L-NAME-treated rabbits. There was no significant difference in the infarct size between L-arginine-treated (60.1% +/- 7.3%, n = 6) and control rabbits. Rate-pressure products, as an index of myocardial oxygen consumption, were comparable in all the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1995

The significance of immunoglobulin M antibody response to hepatitis C virus core protein in patients with chronic hepatitis C.

The significance of immunoglobulin (Ig) M antibody to hepatitis C virus core protein (IgM anti-HCV core) was studied in 41 patients with chronic hepatitis C virus (HCV) infection diagnosed by the polymerase chain reaction (PCR). IgM anti-HCVcore was tested with a solid-phase enzyme-linked immunoassay. The results were correlated with clinical features, liver histology findings evaluated by the histological activity index, and virological features such as genotypes and viremic levels assessed by a branched DNA assay. IgM anti-HCVcore was found in 29 (71%) patients, and its occurrence was only related to viremic levels. A significant relationship was observed between viremic levels and IgM anti-HCVcore cut-off index (rs = .42, P < .01). Of the eight low viremic (branched DNA-negative) patients, only two (25%) tested positive for IgM anti-HCVcore with a low cut-off index of < 3, whereas 27 (82%) of the 33 highly viremic (branched DNA-positive) patients had IgM anti-HCVcore (P < .01). After a 28-week interferon-alpha course (IFN-alpha), sustained aminotransferase normalization after therapy withdrawal was achieved by only two (13%) of the 16 patients with IgM anti-HCVcore cut-off index > 3 compared with 11 (44%) of the 25 patients with that < 3 (P < .05). IgM anti-HCVcore cut-off index decreased after therapy in patients who cleared the virus in sera but increased again after reappearance of viremia. These findings suggest that IgM anti-HCVcore may serve as a simple serological indicator of active virus replication and have relevance to the outcome of antiviral therapy.

Adult↗
PubMed1995

Hepatitis C viral quasispecies in hepatitis C virus carriers with normal liver enzymes and patients with type C chronic liver disease.

Hepatitis C virus (HCV) has been reported to conform to a quasispecies nature, which is most evident in hypervariable regions of the putative envelope 2 domain. The aim of this study was to determine the relationship between the nucleotide complexity and diversity of hypervariable region 1 and various stages of the carrier states. The subjects studied were 20 HCV carriers with normal alanine aminotransferase (ALT) levels, 50 patients with chronic hepatitis who showed elevated ALT levels, 22 with cirrhosis, and 24 with hepatocellular carcinoma. The quasispecies complexity was analyzed by means of polymerase chain reaction-mediated single strand conformation polymorphism (PCR-SSCP). The value of nucleotide diversity was calculated by PCR cloning and sequencing. The number of SSCP bands ranged from 1 to 7, with no significant differences in the mean numbers among the stages of HCV infection. There was no correlation between the amounts of serum HCV RNA and the numbers of SSCP bands. No significant difference was found in the values of nucleotide diversity between carriers with normal ALT levels (mean, 6.6 x 10(-2) per site) and patients with chronic hepatitis (7.7 x 10(-2). These findings suggest that the quasispecies complexity of hypervariable region 1 is independent of the stage of chronic HCV infection.

Adolescent↗