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Biomedical subjects

A Nagasaka

Publications and source records attributed to A Nagasaka.

At least 19 recordsLinked to original sources
PubMed1998

Effects of thyroid hormone on the sorbitol pathway in streptozotocin-induced diabetic rats.

Sorbitol accumulation plays an important role in diabetic complications involving the kidney, nerves, retina, lens and cardiac muscle. To investigate the influence of thyroid hormone on the sorbitol pathway, we studied the effects of thyroid hormone on polyol metabolism in normal and diabetic rats. Rats were divided into three groups: controls, streptozotocin (STZ)-induced diabetic euthyroid rats (DM) and STZ-induced diabetic hyperthyroid (thyroxine-injected) rats (DM+HT). The sorbitol (Sor) concentrations in the kidney, liver and sciatic nerve (2.53+/-0.74, 0.97+/-0.16 and 24.0+/-5.1 nmol/mg protein, respectively) of the DM rats were significantly higher than those (1.48+/-0.31, 0.58+/-0.13 and 3. 1+/-0.6 nmol/mg protein) of the control rats. The Sor concentrations in the kidney and sciatic nerve of the DM+HT rats (1.26+/-0.29 and 9. 40+/-1.2 nmol/mg protein) were significantly lower than those in the DM rats. These values were reduced in the liver, unchanged in the kidney, and increased in the sciatic nerve from the hyperthyroid rats without diabetes. Thyroid hormone reduced the aldose reductase (AR) activities in the kidney, liver and sciatic nerve of the DM rats, and similarly reduced AR in the kidney and liver, but not in the sciatic nerve, of the non-diabetic rats. The sorbitol dehydrogenase (SDH) activities were decreased by thyroid hormone in the kidney and liver but not the sciatic nerve of DM rats. In the non-diabetic rats, this enzyme activity was decreased in liver, but not in kidney or sciatic nerve. A positive correlation between the Sor concentration and AR activity was observed in the kidney and liver but not in the sciatic nerve from control, DM and DM+HT rats. A negative correlation was observed between the Sor concentration and SDH activities in the same organs. These data suggest that thyroid hormone affects the sorbitol pathway, but the detailed mechanism whereby this hormone reduces the sorbitol content (especially in diabetic rats) remains to be clarified.

Aldehyde Reductase↗
PubMed1998

Reduction of activity, but no decrease in concentration, of erythrocyte Cu,Zn-superoxide dismutase by hyperglycaemia in diabetic patients.

Cu,Zn-superoxide dismutase(SOD) activity in erythrocytes is affected by various diseases, including diabetes mellitus (DM). We investigated changes in the Cu,Zn-SOD activity compared to changes in the Cu,Zn-SOD concentration in erythrocytes obtained from patients with Type 2 (non-insulin-dependent) diabetes mellitus. Cu,Zn-SOD activity in erythrocytes was significantly lower in Type 2 DM patients than in healthy non-diabetic subjects. The activity correlated negatively with HbA1c, but not with other indicators of metabolic control, such as fasting blood glucose or plasma cholesterol or triglyceride. However, there was no statistically significant difference in erythrocyte concentration of Cu,Zn-SOD between diabetic and control samples. Concentration did not correlate with enzymatic activity or HbA1c. These findings indicate that the inactivation of Cu,Zn-SOD activity in erythrocytes of Type 2 DM patients by hyperglycaemia may be slow, because there is a negative correlation between the enzyme activities and HbA1c levels, but not fasting blood glucose levels. This is consistent with glycosylation of the active site of Cu,Zn-SOD, without any effect of hyperglycaemia on the concentration of Cu,Zn-SOD.

Adult↗
PubMed1998

Prevalence of mutations in core promoter/precore region in Japanese patients with chronic hepatitis B virus infection.

We examined the frequency and significance of mutations in the core promoter and precore region in 103 Japanese patients with chronic hepatitis B virus (HBV) infection. HBV DNAs from the patients' sera were amplified by polymerase chain reaction and were directly sequenced. A double mutation (T1762 A1764) in the core promoter was frequently observed in the patients regardless of HBeAg status except for asymptomatic carriers with HBeAg. Furthermore, a mutation at nucleotide 1753 from T to C or G was frequently found in anti-HBe positive patients and was often accompanied by the double mutation. The A1896 mutation was found in only about one fourth of the patients with anti-HBe. These data suggest that the patients with chronic liver diseases frequently had a double mutation regardless of HBeAg status and a mutation at nucleotide 1753 might be associated with HBeAg-negative chronic hepatitis B virus infection.

Amino Acid Sequence↗
PubMed1998

Surface expression and release of soluble forms of CD8 and CD23 in CD40- and IL-4-activated mononuclear cells from patients with Graves' disease (GD).

We investigated the effect of T cell-dependent B cell activation on the surface expression and release of the soluble forms of CD8 and CD23 by peripheral blood mononuclear cells (PBMC) obtained from patients with GD, versus patients with Hashimoto's thyroiditis, and normal controls. Incubating the PBMC with anti-CD40 MoAbs and IL-4 increased the soluble CD23 levels in cells from all three groups. An increase in the number of CD23+ cells was observed in the PBMC from the patients with GD, but not in PBMC from Hashimoto's thyroiditis or controls. Less soluble CD8 was released from anti-CD40 antibody and IL-4-stimulated PBMC obtained from patients with GD relative to those from the controls. In addition, the number of CD8+ cells was significantly reduced in stimulated PBMC from the GD patients relative to those from controls. Incubation of PBMC with anti-CD40 antibody plus IL-4 did not affect the proportions of CD4+, CD20+, Fas+ CD4+, and Fas+ CD8+ cells. The addition of T3 to cultured PBMC from controls did not reproduce the changes in CD23+ and CD8+ cells noted in the samples froin GD patients. Thus, T cell-dependent B cell activation, mediated by a CD40 pathway, may reduce the number of CD8+ cells, causing exacerbation of GD.

Adult↗
PubMed1998

Effects of thyroid hormone on catecholamine and its metabolite concentrations in rat cardiac muscle and cerebral cortex.

Clinical and experimental data suggest that thyroid hormone affects the actions of catecholamine (CA). However, the serum or tissue levels of CA during thyroid disorders have not been well defined. Accordingly, we investigated the levels of CA and their metabolites in the cardiac muscle, the cerebral cortex, and the plasma of rats with hyperthyroidism and hypothyroidism versus euthyroid animals. The Neurochem analyzer system (ESA, Inc., Bedford, MA) was used in such determinations. The cardiac muscles of hyperthyroid rats exhibited a 16% decrease in the levels of 1-dopa, 3-methoxytyramine (3-MT) and homovanillic acid (HVA) as compared with those in euthyroid rats. The levels of norepinephrine (NE) in cardiac muscle of these rats increased significantly (5.2-fold) relative to the levels in euthyroid rats. NE was undetectable in the cardiac muscles of the hypothyroid rats. Epinephrine (E) and dopamine (DA) were not detected in the cardiac muscles of the rats with either thyroid disorder. Levels of E and 3,4-dihydroxymandelic acid (DOPEG) were detected only in the cerebral cortex of hyperthyroid rats. The cerebral cortex levels of 3-methyoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC), metanephrine (MN), and homovanillic acid (HVA) were all significantly increased in the hyperthyroid versus the euthyroid rats. The cerebral cortex levels of DA, NE, normetanephrine (NMN), and VMA in the hyperthyroid rats all showed a significant decrease. Levels of NE, NMN, and DOPAC in the cerebral cortex increased significantly in the hypothyroid rats. The level of VMA was undetectable in cerebral cortex of such animals. Data from studies on cardiac muscle and cerebral cortex indicate that the changes in CA and CA metabolites are responsible in part for the cardiovascular and the central nervous system symptoms observed in hyperthyroidism and hypothyroidism.

Animals↗
PubMed1998

Vitamin E and coenzyme Q concentrations in the thyroid tissues of patients with various thyroid disorders.

To clarify the different roles of free radical scavenging systems in various thyroid disorders, we measured the levels of alpha-, beta-, and gamma-tocopherols and coenzyme Q in the thyroid tissues of patients with thyroid tumors and Graves' disease using high-performance liquid chromatography. The levels of alpha-tocopherols and gamma-tocopherols in the thyroid tissue of patients with papillary carcinoma and the level of gamma-tocopherol in the thyroid tissue of patients with malignant lymphoma were elevated compared with those in normal thyroid tissues. The level of coenzyme Q was reduced in the thyroid tissue of patients with Graves' disease and follicular and papillary thyroid carcinomas. These findings imply that vitamin E and coenzyme Q as scavengers play some role in thyroid follicular cell hyperfunction or dysfunction.

Graves Disease↗
PubMed1998

Utility of measuring serum parathyroid hormone-related protein concentration in leukemic patients with hypercalcemia for assessing disease status.

OBJECTIVE: To evaluate serum parathyroid hormone-related protein (PTHrP) as a marker of hypercalcemia in leukemic patients. DESIGN AND METHODS: We measured the serum levels of PTHrP, lactate dehydrogenase (LDH) and calcium in three patients with hypercalcemia due to leukemia. RESULTS: Serum levels of PTHrP, LDH and calcium were elevated at admission in all patients, and these levels were reduced to within the normal range after chemotherapy. However, normalization of serum PTHrP concentration occurred more rapidly than normalization of serum LDH levels after chemotherapy. The increase in serum PTHrP concentration accompanied leukemic cell proliferation and preceded the increases in serum LDH and calcium. Serum LDH concentration increased, but serum PTHrP concentration did not after administration of granulocyte colony-stimulating factor. CONCLUSION: These findings suggest that serum PTHrP may be a more useful marker than serum LDH or calcium in assessing the status of leukemic patients with hypercalcemia.

Biomarkers↗
PubMed1998

[Relationship between mitral valve echo score and hemodynamic variables in patients with mitral stenosis].

Mitral valve echo score has been proposed as a predictor or of the outcome of balloon mitral valvotomy in patients with mitral stenosis. The relationship between mitral echo score and the hemodynamic variables was evaluated. In 41 patients with pure mitral stenosis (nine men and 32 women, aged 57.9 +/- 9.4 years), mitral echo score was estimated from two-dimensional echocardiographic findings, and mitral valve area was measured by planimetry on the two-dimensional short-axis view. Apex phonocardiography and continuous-wave Doppler echocardiographic recording of transmittral flow were simultaneously performed to measure left atrial/left ventricular mean transmittral pressure gradient, pressure half-time and (Q-1)-(2-OS) interval. Linear regression analysis revealed that both mitral echo score and mitral valve area were significantly correlated with mean transmittral gradient (r = 0.522, p = 0.0005 and r = -0.651, p < 0.0001, respectively), pressure half-time (r = 0.491, p < 0.005 and r = -0.757, p < 0.0001) and (Q-1)-(2-OS) interval (r = 0.551, p < 0.0005 and r = -0.487, p < 0.005, respectively). Mitral echo score has a significant correlation with hemodynamic variables, which were comparable to but slightly different from mitral valve area, in patients with mitral stenosis.

Adult↗
PubMed1997

Recombinant human TSH receptor expressed in E. coli.

We expressed the extracellular domain (20-408 aa, (T) of human TSH receptor (TSHR) in E. coli to detect TSHR autoantibodies (TRAb) and, moreover, we expressed the two portions (20-218 aa (5') and 217-408 aa (3')) of the extracellular domain thought to distinguish thyroid stimulating antibodies (TSAb) from blocking antibodies (TSBAb), using pGEX.3X as the expression vector. Using Western blotting analysis of the sera from patients with autoimmune thyroid disease, sera from Graves' patients and patients with idiopathic myxedema who had TSBAb reacted with the fusion protein (T), but none of the control sera reacted with it. We further evaluated whether or not the positive sear for T recognized fusion proteins (5') or (3'). The sera from Graves' patients reacted with both fusion proteins (5') and (3'). The sera from patients with idiopathic myxedema did not react with either of fusion proteins (5') or (3'). These findings suggest that these recombinant TSHR proteins could be used as antigens to detect TRAb, and differentiate TSABb from patients with idiopathic myxedema.

Antibodies, Blocking↗
PubMed1997

Alteration of platelet aggregation in patients with thyroid disorders.

To determine whether Graves' disease or primary hypothyroidism influence platelet function, we evaluated platelet aggregation in the platelet-rich plasma (PRP) from such patients. Platelet aggregation induced by adenosine diphosphate (ADP) in blood obtained from patients with untreated Graves' disease was significantly lower than normal, whereas that in patients with untreated primary hypothyroidism was relatively increased. The magnitude of platelet aggregation induced by collagen in both groups of patients resembled that induced by ADP. However, significant differences were evident between the two diseases (P < .05). In addition, we observed a significant inverse correlation between the extent of platelet aggregation and plasma levels of thyroid hormones (triiodothyronine [T3], thyroxine [T4], and free T3). Platelet aggregation returned to normal when the euthyroid condition was obtained in the patients following administration of antithyroid drugs or thyroid hormone. The findings are consistent with the possibility that thyroid hormones influence platelet aggregation partly via inhibition of myosin light-chain kinase (MLCK).

Adenosine Diphosphate↗
PubMed1997

Changes in free radical scavengers and lipid peroxide in thyroid glands of various thyroid disorders.

To clarify whether the changes of free radicals and its scavengers are induced by thyroid disorders, we measured levels of free radical scavengers and checked O2 radical generating systems in the human thyroid gland. Thyroid specimens from patients with Graves' disease, follicular adenoma, and papillary and follicular carcinomas contained significantly higher concentrations of xanthine oxidase (XOD) and gluthathione peroxidase (GSH-PX), compared to those in the normal thyroid tissue. Catalase concentration was significantly lower in thyroid specimens from patients with Graves' disease and significantly lower in thyroid specimens from patients with follicular adenoma, compared to those in the normal thyroid tissue. Cu/Zn superoxide dismutase (Cu/Zn SOD) concentration was significantly lower in the specimens from follicular adenoma and papillary carcinoma and Mn SOD concentration was significantly higher in the specimens from papillary carcinoma than those in the normal thyroid tissue. The lipid peroxide concentration, expressed as malondialdehyde (MDA) concentration, was significantly higher in the specimens from papillary carcinoma than those in the normal thyroid tissue. These findings suggest that the levels of free radicals are increased and are scavenged and catalyzed in the thyroid of Graves' disease, whereas free radicals and lipid peroxide are not completely scavenged in papillary carcinoma tissues, suggesting that these substances affect some role in cell function of thyroid tumors.

Adenocarcinoma, Follicular↗
PubMed1997

Differential flotation centrifugation study of hepatitis C virus and response to interferon therapy.

Hepatitis C virus (HCV) appears to circulate in various forms such as native virion, immune complexes, and nucleocapsids during chronic infections. To determine the association of the physicochemical properties of HCV and its response to interferon therapy in patients with chronic hepatitis C, we examined pretreatment serum samples from 43 patients with HCV RNA who had received interferon therapy, using differential flotation centrifugation in a NaCl solution with a density of 1.063 g/ml. After centrifugation, the ratio of HCV RNA in the top and bottom fractions was determined by the polymerase chain reaction and expressed as T/B. Patients with a sustained response to IFN therapy were found to have higher T/B ratios than transient responders who relapsed after treatment (P < 0.01) and nonresponders (P < 0.01). With regards to HCV genotypes, patients with genotype 1b had higher T/B ratios in the sustained response group than in the nonsustained response groups (P = 0.001), but patients with genotype 2 had a similar distribution of T/B among the 3 response groups (not significant). These findings indicate that the physicochemical properties of HCV affect the effectiveness of interferon therapy, particularly in patients with genotype 1b.

Adult↗
PubMed1996

Nucleotide sequences of the hepatitis C virus core region in patients without anti-core antibody.

Second-generation assays for detection of hepatitis C virus (HCV) infection that include reactivity of antibodies to core, NS3, NS4 are used because of their high sensitivity. Among these antibodies, anti-core antibody seems to be the most sensitive. However, there are some patients without anti-core antibodies, although HCV RNA is detectable by reverse transcription-polymerase chain reaction and branched DNA assay. The mechanism for the absence of anti-core antibody on its own is unclear. We therefore determined the nucleotide and deduced amino acid sequences of the core region obtained from two anti-core antibody-negative patients with HCV RNA (genotype 1b) and compared them with those of four anti-core antibody-positive patients and a previously reported sequence. Amino acids spanning 1-47, which seemed to exist in major B cell epitopes, were found to be completely conserved among these patients. Furthermore, the predictive binding motif to HLA DR4 (a.a 81-90) was completely conserved in both of the anti-core antibody-negative patients. There were various mutations in the residual amino acids spanning 49-108, but specific mutations could not be found in anti-core antibody-negative patients. These data indicate that the absence of anti-core antibody in two patients is not due to the presence of some formerly unknown viral variants, but due to a possible defect in the host's immune system.

Amino Acid Sequence↗
PubMed1996

Changes in hepatitis C virus quasispecies and density populations in patients before and after interferon therapy.

Some chronic hepatitis C patients show sustained response to interferon (IFN) therapy despite viremia. This condition seems to be related to the density populations of hepatitis C virus (HCV) [Kanto et al. (1995): J Med Virol 46:230-237]. To investigate further the relationship between alanine aminotransferase (ALT) levels after IFN therapy and the HCV density populations, we undertook differential flotation centrifugation of HCV and single strand conformation polymorphism targeted the hypervariable region (HVR) of E2 glycoprotein, which seems to be related to the density populations. Sera were obtained serially from 12 patients who had undergone IFN therapy (six sustained responders with viremia, six nonresponders). During the follow-up after interferon therapy, the HVR heterogeneities changed in 9 of the 12 patients. The remaining three patients whose heterogeneities did not changed persistently showed normal ALT. The changes in HVR heterogeneities were less pronounced in the sustained responders with viremia than in nonresponders; however, their density populations were prominently high in both responders. In two cases, changes in HVR heterogeneities and increase in low-density virion were observed before the hepatitis flare-up. These data indicate that HVR quasispecies show more relation to ALT levels after IFN therapy than HCV density populations and that the changes in the HVR sequences and HCV density populations may be associated with ALT elevation in some patients.

Adult↗
PubMed1996

Short stature due to growth hormone deficiency associated with Cushing's disease and ulcerative colitis.

We report a rare case of Cushing's disease associated with ulcerative colitis in a patient primarily treated with growth hormone due to short stature. At the age of fifteen years, the patient had a short stature due to GHD and was treated with the extracted GH for a short period. At the age of twenty-one years, his body weight gradually increased and, based on the results of several tests, he was diagnosed with Cushing's disease and GHD was observed in our patient. The excess secretion attenuation of pituitary hormones with reduced secretion periods as well as the relation between ulcerative colitis and elevated plasma cortisol concentrations is briefly discussed in this paper.

Adult↗
PubMed1996

A case of myocarditis associated with IDDM.

We report a case of diabetic ketoacidosis (DKA) complicated by acute myocarditis, which was confirmed by cardiac biopsy. A 26-year-old man was hospitalized with severe DKA. On admission, nonspecific ST-T change was noted on the electrocardiogram (ECG). The patient's levels of creatine phosphokinase (CPK) and glutamic oxaloacetic transaminase were slightly elevated, but he did not complain of chest discomfort or symptoms of heart disease. On the first day after admission, ST-T elevation was noted on ECG during treatment of DKA. By cardiac angiography and cardiac biopsy, coronary heart disease was ruled out and postmyocarditic change was histologically confirmed. An episode of upper respiratory viral infection before the onset of acute diabetes suggested that the patient suffered from viral-induced myocarditis and consequent development of IDDM. This possibility was confirmed by the clinical course of ECG change, with elevated CPK and lactate dehydrogenase and a slightly elevated antibody titer for echovirus.

Adult↗