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Biomedical subjects

T Kanda

Publications and source records attributed to T Kanda.

At least 235 records · Page 13Linked to original sources
PubMed1998

Interferon induces insulin resistance in patients with chronic active hepatitis C.

AIM/METHODS: To elucidate the metabolic effect of interferon alpha, the following tests were performed on 14 patients with chronic active hepatitis C before and after interferon therapy (6 million units/day for 2 weeks): (1) oral glucose tolerance tests to measure insulin secretion; (2) euglycemic hyperinsulinemic clamp with oral glucose load to measure peripheral and hepatic insulin sensitivity (splanchnic glucose uptake); and (3) measurements of plasma levels of glucoregulatory hormones. RESULTS: The oral glucose tolerance test showed that a 2-week treatment with interferon did not induce apparent change in plasma glucose and insulin profiles. Nevertheless, interferon therapy worsened insulin-mediated glucose uptake in the peripheral tissues by 17% from 44.4+/-3.2 to 37.3+/-3.0 micromol x kg(-1) x min(-1) (p<0.05). Furthermore, interferon therapy significantly decreased splanchnic glucose uptake by 38% from 47+/-2% to 29+/-3% (p<0.01). No changes were noted for plasma glucoregulatory hormones, such as epinephrine, norepinephrine, cortisol and growth hormone, after interferon therapy. CONCLUSIONS: These results indicate that interferon therapy for 2 weeks induces insulin resistance in the splanchnic, as well as peripheral tissues, in patients with chronic active hepatitis C. Therefore, more careful observation may be needed during interferon therapy in subjects with impaired glucose tolerance.

Antiviral Agents↗
PubMed1998

Determination of antipituitary antibody in patients with endocrine disorders by enzyme-linked immunosorbent assay and Western blot analysis.

The identification of pituitary antigens recognized by human antipituitary antibodies (APAs) is important in evaluating the pathophysiology of multiendocrine disorders linked to autoimmune factors. However, there is no convenient method for the quantitative analysis of circulating APAs. This study reports the development of an enzyme-linked immunosorbent assay (ELISA) for the detection of APAs. APAs were measured by ELISA and confirmed by Western blot analysis in sera from patients with endocrine disorders. APAs were detected frequently in patients with autoimmune thyroiditis, insulin-dependent diabetes mellitus (IDDM), or pituitary dwarfism. Circulating APAs were detected in 18% of patients with autoimmune thyroiditis. Confirmation by Western blot revealed positivity for APAs in the serum of 36% of patients with Hashimoto disease and in 29% of patients with Graves disease. Notably, 39% of patients with IDDM were also positive for APAs by ELISA. The identification of APAs by ELISA may be useful in evaluating autoimmune mechanisms involved in patients with multiendocrine disorders.

Adult↗
PubMed1998

Induction of virus-induced IDDM in virus resistant mice without lymphocyte maturation.

The role of lymphocytes in the pathogenesis of viral-induced insulin dependent diabetes mellitus (IDDM) is controversial. To better understand how a virus-induced IDDM depends on the infiltrating lymphocytes, encephalomyocarditis virus (EMCV) was inoculated intraperitoneally into three kinds of mice; virus-susceptible C57BL/6, virus-resistant 129/SV and recombination activity gene-2 (Rag2) knockout 129/SV mice. Pancreatic inflammation and beta cell necrosis were evaluated after EMCV, D variant (10(3) pfu/mouse) inoculation. On post-inoculation day 14, the lethal rates of C57BL/6, 129/SV and Rag2 knockout mice were 52, 10 and 100%, respectively. The blood glucose in Rag2KO mice on day 8 was significantly elevated as compared with 129SV mice (231 +/- 49 vs 169 +/- 32 mg/dl, P<0.05). In situ hybridization demonstrated the EMCV genome in the pancreas of Rag2 knockout and C57BL/6 mice, but not in 129/SV mice. Beta cell necrosis were more severe in Rag-2 knockout mice than in wild type 129/SV mice, but lymphocyte infiltration was less severe than C57BL/6. Pancreas in Rag2 knockout mice infected with virus were affected more severely than the virus-resistant strain of mice. Diabetogenic virus induced IDDM in virus-resistant mice without mature lymphocytes.

Animals↗
PubMed1998

Endothelin converting enzyme inhibitor protects development of right ventricular overload and medial thickening of pulmonary arteries in rats with monocrotaline-induced pulmonary hypertension.

We evaluated the effects of FR901533, endothelin converting enzyme inhibitor, on development of right ventricular overload and medial thickening of pulmonary arteries in rats with monocrotaline-induced pulmonary hypertension. Pulmonary hypertension was induced by a single injection of monocrotaline (80 mg/kg). Twenty-four hours later (day 1), continuous subcutaneous injection of FR901533 (100 mg/kg/day) was started. Right ventricular systolic pressure, mass ratio of right ventricle to left ventricle, right ventricular wall thickness, right ventricular myocardial fiber diameter, percent medial thickness, and percent smooth muscle area in pulmonary arteries were significantly less in rats that received FR901533 than in the control with monocrotaline on day 28. Both immunoreactivities of endothelin-1 in pulmonary arteries and plasma endothelin-1 levels were observed significantly less in rats treated with FR901533 than in the control with monocrotaline. There were significant increased immunoreactivities of endothelin-B receptor in pulmonary arteries in rats that received FR901533 as compared with those in the control with monocrotaline. FR901533 (100 mg/kg/day), protected the development of right ventricular overload and medial thickening of pulmonary arteries in a rat model of pulmonary hypertension.

Animals↗
PubMed1998

Pioglitazone enhances splanchnic glucose uptake as well as peripheral glucose uptake in non-insulin-dependent diabetes mellitus. AD-4833 Clamp-OGL Study Group.

To evaluate the effect of pioglitazone on insulin resistance in non-insulin-dependent diabetes mellitus (NIDDM) patients, a double-blind placebo-controlled trial was carried out with 30 NIDDM patients. Twenty-one subjects, three on diet alone and 18 on sulfonylurea (SU), orally received 30 mg pioglitazone once daily for 12 weeks. Nine subjects, one on diet alone and eight on SU, received a matching placebo once daily for 12 weeks. Euglycemic (5.2 mmol/l) hyperinsulinemic (1200 pmol/l) clamp combined with an oral glucose load (OGL) was performed before and after 3-month treatment with pioglitazone or placebo to determine insulin-stimulated glucose disposal and splanchnic glucose uptake (SGU). No significant differences existed in the patients' characteristics, including age and body mass index, between the two study groups. The pioglitazone treatment increased the mean glucose infusion rate (GIR) prior to OGL from 8.2 +/- 2.2 to 9.2 +/- 2.0 mg/kg.min (mean +/- SD, P = 0.003) and increased the SGU rate from 28.5 +/- 19.4 to 59.4 +/- 27.1% (P = 0.010). The placebo treatment produced no significant changes in either GIR or SGU after treatment. A significant difference (P = 0.042) was observed in change of SGU between the pioglitazone and placebo treatment groups. In conclusion, the results indicate that pioglitazone is effective for ameliorating insulin resistance in NIDDM by enhancing SGU as well as peripheral glucose uptake.

Blood Glucose↗
PubMed1998

Quantitative analysis of GBV-C RNA in liver and serum by strand-specific reverse transcription-polymerase chain reaction.

BACKGROUND/AIMS: Although GB virus C (GBV-C) is frequently detectable in patients with liver diseases, it is not known whether it actually replicates in the liver. Therefore we have quantitatively examined the strand-specific RNA of this virus. METHODS: Fourteen patients (two GBV-C RNA only seropositive, seven both GBV-C RNA and HCV RNA seropositive, and five HCV RNA only seropositive) were examined. Extracted RNAs from sera and liver specimens of these patients were serially diluted and strand-specific RNAs of GBV-C and HCV were quantitatively measured using strand-specific primers by reverse transcription-polymerase chain reaction. RESULTS: Positive-strand GBV-C RNA in serum was detected in all nine GBV-C RNA seropositive cases, and negative-strand RNA was detected in three, uncertain in three, and undetected in three. Positive-strand GBV-C RNA in the liver was detected in seven and undetected in two, while negative-strand RNA in the liver was undetected in eight and uncertain in one. On the other hand, positive-strand HCV RNA was detected in serum from all 12 HCV RNA seropositive patients and negative-strand HCV RNA was detected in one, uncertain in seven, and undetected in four. Positive-strand HCV RNA was detected in the liver from all 12 HCV RNA seropositive patients, and the presence of negative-strand HCV RNA in the liver was confirmed in 10 and uncertain in the remaining two. CONCLUSION: GBV-C is considered to be far less hepatotropic than HCV, and it is suggested that GBV-C might not be replicating in the liver.

Adult↗
PubMed1998

Streptococcus pyogenes hospital-acquired infection within a dermatological ward.

Seventeen strains of Streptococcus pyogenes were isolated from 17 patients in the Dermatological Ward of Gunma University Hospital in Japan between June 1994 and March 1995. Of these 17 strains, 14 were isolated from the pus of skin infections, two from blood, and one from ascitic fluid. The strains showed the same minimum inhibitory concentrations; 4 mg/L of minomycin, 4 mg/L of ofloxacin and 16 mg/L of fosfomycin. T-antigen typing of the strains indicated they were T11 type. The restriction endonuclease digestion patterns of chromosomal DNA from the 17 strains were all identical. The vinyl sheet covering the bed on which the patients were treated was found to be contaminated with S. pyogenes. This strain showed identical characteristics to the strains derived from the patients. These results suggest that S. pyogenes was transmitted to patients in the Dermatological Ward from the surface of the vinyl sheet covering the bed.

Bedding and Linens↗
PubMed1998

Cloning of two Bombyx homologues of the Drosophila rosy gene and their relationship to larval translucent skin colour mutants.

To clone the Bombyx xanthine dehydrogenase (XDH) gene as a dominant marker for silkworm transgenesis, we performed nested reverse transcriptase-polymerase chain reaction (RT-PCR) using embryonic mRNA and primers designed from the conserved region of Drosophila and rat XDH genes. Sequencing of amplified 180 bp fragments showed that two different sequences were present in the fragments. Since both possessed striking similarity to XDH genes of other organisms, we considered these to be portions of silkworm XDH genes and designated them BmXDH1 and BmXDH2. Subsequently we cloned separately the entire region of the two cDNAs by PCR using phage DNA of an embryonic cDNA library and sequenced them. The two cDNAs were around 4 kb in size and possessed complete open reading frames. The deduced amino acid sequences of the two BmXDHs were very similar to each other and to those of other organisms. The expression pattern of wild-type larvae basically followed the tissue specificity of the enzyme and no significant difference was observed between the two XDH genes. The expression of both genes was detected in the XDH-deficient mutants, oq and og, but non-synonymous substitutions were specifically detected in the BmXDH1 of the oq mutant. In addition, a length polymorphism of the second intron of the BmXDH1 co-segregated with the oq translucent phenotype, suggesting that deficiency in BmXDH1 is the cause of the oq translucent phenotype.

Amino Acid Sequence↗
PubMed1998

Impaired expression of brain natriuretic peptide gene in diabetic rats with myocardial infarction.

Accordingly, we induced streptozotocin diabetes in rats and evaluated the effects of ligating the coronary artery to produce myocardial infarct by analyzing hemodynamics and the expression of brain natriuretic peptide (BNP) messenger (m) RNA. Eight-week diabetic rats and age-matched nondiabetic rats underwent ligation of the coronary artery for 1 week. Left ventricular end-diastolic pressure (LVEDP) was not statistically different between diabetic rats (15+/-6 mmHg) and nondiabetic rats (13+/-9 mmHg) 1 week after coronary ligation, size of infarct, systolic blood pressure were also similar in both groups after coronary ligation. The BNP mRNA/beta-actin mRNA ratio in right ventricle of nondiabetic rats with MI was increased to 350+/-60%, however, in diabetic rats with MI, that was slightly increased to 200+/-50% (P < 0.01). The level of BNP mRNA in the left ventricle of diabetic rats with MI was not increased significantly (120+/-30% versus that in diabetic rats without MI), although that in left ventricle of nondiabetic rats with MI was increased to 280+/-40% versus nondiabetic rats without MI (P < 0.01). Cardiac BNP synthesis in diabetic rats completely reverted to control levels after insulin therapy.

Animals↗
PubMed1998

In vitro construction of pseudovirions of human papillomavirus type 16: incorporation of plasmid DNA into reassembled L1/L2 capsids.

Lack of permissive and productive cell cultures for the human papillomaviruses (HPVs) has hindered the study of virus-neutralizing antibodies and infection. We developed a cell-free system generating infectious HPV16 pseudovirions. HPV16 L1/L2 capsids, which had been self-assembled in insect cells (Sf9) expressing virion proteins L1 and L2, were disassembled with 2-mercaptoethanol (2-ME), a reducing agent, and reassembled by removal of 2-ME in the presence of a beta-galactosidase expression plasmid. Plasmid DNA purified together with the reassembled capsids was resistant to DNase I digestion. The reassembled pseudovirions mediated DNA transfer to COS-1 cells, as monitored by induced beta-galactosidase activity. Transfer was inhibited by anti-HPV16 L1 antiserum but not by antisera against L1s of HPV6 and HPV18. Construction in vitro of HPV pseudovirions containing marker plasmids would be potentially useful in developing methods to assay virus-neutralizing antibodies and to transfer exogenous genes to HPV-susceptible cells.

Animals↗
PubMed1998

Inhibitory effects of apple polyphenol on induced histamine release from RBL-2H3 cells and rat mast cells.

The anti-allergic activities of polyphenol fractions extracted from immature fruits of apple (Rosaceae, Malus sp.) were evaluated by in vitro assays. A crude apple polyphenol (CAP) fraction, which had been obtained from the juice of immature apples by reverse-phase column chromatography, was further purified by LH-20 column chromatography to obtain an apple condensed tannin (ACT) fraction consisting of linear oligomeric epicatechins from the dimer to pentadecamer. ACT strongly inhibited the release of histamine from rat basophilic leukemia (RBL-2H3) cells stimulated by the antigen-stimulation and from rat peritoneal mast cells stimulated by compound 48/80. The IC50 values for histamine release were 30 micrograms/ml and 25 micrograms/ml, respectively. ACT also inhibited hyaluronidase activity and the increase in intracellular free calcium concentration in RBL-2H3 cells stimulated with the antigen. These results suggest that ACT affected early signal transduction including the calcium influx.

Animals↗
PubMed1998

Decreased basal production of nitric oxide in patients with heart disease.

STUDY OBJECTIVES: The pathophysiologic role of nitric oxide (NO) released in the lung is not well understood. To determine whether the production of endogenous NO is correlated with any hemodynamic parameters, we measured the amount of NO released from the lung tissue of patients with heart disease. METHODS: Twenty patients (14 with ischemic heart disease, 4 with dilated cardiomyopathy, and 2 with mitral stenosis) and 16 normal control subjects were enrolled in the study. We measured exhaled air samples by using a method developed in our laboratory. The NO release rate from the lungs was calculated from the amount of exhaled NO and the duration of the exhalation. RESULTS: The rate of NO release was significantly lower in the patients with moderate-to-severe heart failure (New York Heart Association [NYHA] II or III) than in those with mild heart failure (NYHA I) or in normal control subjects. The rate of NO release was positively correlated with the cardiac index (r=0.50, p<0.05), and was negatively correlated with either the systemic (r= -0.58, p<0.01) or pulmonary vascular resistance (r=-0.45, p<0.05). In the patients with moderate-to-severe heart failure, the amount of NO released and the oxygen tension in the pulmonary artery were significantly lower compared with those parameters in patients with mild heart failure. CONCLUSIONS: Results suggest that the basal production of endogenous NO in the lung tissue of patients with heart failure is impaired, perhaps leading to the elevated pulmonary vascular tone seen in patients with moderate-to-severe heart failure.

Adult↗
PubMed1998

Studies on circulating anti-pituitary antibodies in NIDDM patients.

The clinical significance of anti-pituitary antibodies (APA) was examined by enzyme-linked immunosorbent assay (ELISA) in individuals with non-insulin dependent diabetes mellitus (NIDDM). Serum samples were obtained from 150 NIDDM patients and 45 normal subjects. Urinary C-peptide (U-CPR) was also measured for the NIDDM patients. APA-positive serum was incubated with porcine pancreas, liver, kidney, or spleen powder and analyzed by immunoblot. The prevalence of APA was found to be significantly (P<0.05) higher in NIDDM patients (24.7%) than in the controls (6.7%) by ELISA. The index values for APA were inversely related to the levels of U-CPR (P<0.005). The levels of U-CPR were significantly (P<0.0001) lower and the prevalence of insulin deficiency was significantly (P<0.05) higher in NIDDM patients who were APA positive than in those who were APA negative. The presence of APA may therefore be related to reduced secretion of insulin in NIDDM patients. In Western blot analysis, preincubation of APA-positive sera with porcine pancreas powder prevented recognition of the 22-kD protein (APA). The possibility of a common autoantigenicity in the pancreas and the pituitary was indicated.

Autoantibodies↗
PubMed1998

Bilateral coronary ostial stenosis and aortic regurgitation due to syphilitic aortitis.

Coronary ostial stenosis in otherwise normal coronary vessels, is a rare complication of syphilitic aortitis, and most of the cases are found at autopsy. We report here a case in which bilateral coronary ostial stenosis and aortic regurgitation due to syphilitic aortitis was diagnosed; coronary artery bypass graft and aortic valve replacement were then performed. The macroscopic finding and the histopathological examination of the ascending aorta revealed the presence of syphilitic aortitis. It is important to note that syphilis is one of the causes of coronary ostial stenosis in young adults associated with aortic regurgitation.

Adult↗
PubMed1998

Effect of troglitazone on microalbuminuria in patients with incipient diabetic nephropathy.

OBJECTIVE: Although some studies have suggested a direct action of troglitazone on vascular cells, its effects on diabetic vascular diseases have not been reported. We therefore investigated the effect of troglitazone on microalbuminuria in patients with incipient diabetic nephropathy. RESEARCH DESIGN AND METHODS: A total of 30 patients with type 2 diabetes associated with microalbuminuria (urinary albumin-to-creatinine ratio [ACR] [milligrams per gram creatinine] ranging from 30 to 300 mg/g creatinine) were studied. They were randomly divided into two groups: patients treated with metformin (500 mg/day, n = 13) or with troglitazone (400 mg/day, n = 17) for 12 weeks. ACR, lipid profile, blood pressure, glycated hemoglobin, and plasma glucose during meal-load tests were measured every 4 weeks. RESULTS: Anthropometric indices (BMI and percent fat), lipid profile, and blood pressure did not change with either treatment. Fasting and postmeal glucose levels decreased similarly in the two groups. Decrements in glycated hemoglobin were greater in the metformin group at 4 and 8 weeks after the initiation of treatment (P < 0.05). Troglitazone reduced ACR (median [25-75th percentiles]) from 70 (49-195) to 40 (31-90) mg/g creatinine at 4 weeks (P = 0.021) and maintained these reduced levels throughout the treatment period (8 weeks: 35 [26-68], P = 0.007; 12 weeks: 43 [26-103], P = 0.047). Metformin did not change ACR throughout the 12 weeks. CONCLUSIONS: Troglitazone ameliorated microalbuminuria in diabetic nephropathy. Furthermore, our findings suggest that troglitazone has some effects on vascular cells other than lowering plasma glucose levels. Troglitazone might be useful for diabetic angiopathy, including nephropathy and coronary artery disease.

Aged↗
PubMed1998

Impaired expression of atrial natriuretic peptide in diabetic rats with myocardial infarction.

We evaluated the effects of myocardial infarction (MI) on the hemodynamics and the expression of atrial natriuretic peptide (ANP) mRNA in rats with streptozotocin-induced diabetes. Eight weeks after streptozotocin injection, the diabetic rats and age-matched nondiabetic controls underwent coronary artery ligation. One week later, the left ventricular end-diastolic pressure, systolic blood pressure, infarct size, and serum ANP levels did not differ significantly between the diabetic and nondiabetic rats. Compared with control animals without MI, the atrial ANP/beta-actin mRNA ratio in rats with MI was increased to 195% in diabetic animals and 213% in nondiabetic animals. In the left ventricle, however, the ANP/beta-actin mRNA ratio in diabetic animals with MI was increased to only 131% compared with control animals, whereas the corresponding increase in nondiabetic animals was 240% (p<0.05). Thus, the modulation of ANP mRNA expression after MI was impaired in the left ventricle, but not in the atria, of diabetic rats. A reduced myocardial expression of ANP could increase the morbidity and mortality associated with cardiovascular disorders in patients with diabetes.

Animals↗