Search PubMedSearch

Biomedical subjects

S Iino

Publications and source records attributed to S Iino.

At least 19 recordsLinked to original sources

[The mechanism of glucose intolerance in patients with Graves' disease].

To investigate the mechanism of glucose intolerance in patients with Graves' disease, a 2-hour oral glucose tolerance test and euglycemic glucose clamp study using Biostator were performed in patients with Graves' disease and control subjects. 80 per cent of the patients showed impaired glucose tolerance. Insulinogenic index in the patients with borderline or diabetic glucose response was lower than that in subjects with normal glucose response. Insulinogenic index was inversely correlated with sigma PG during the test. Despite normal basal plasma glucose concentrations, basal plasma insulin levels in the patients with Graves' disease were higher than in the controls. Using the euglycemic glucose clamp technique, the glucose utilization rate (M value), the metabolic clearance rate of glucose (MCRG) and the insulin sensitivity index (M/I x 100) in the patients with Graves' disease were lower than in the controls. After treatment with antithyroid drug in 3 patients, glucose tolerance completely normalized, and there was a significant increase in the M value and the MCRG and a significant decrease in the metabolic clearance rate of insulin (MCRI) compared to the values before treatment. In the patients with Graves' disease, basal serum glucagon levels were higher than in the controls, and glucagon suppression during insulin infusion was found to be decreased. From these data, it is concluded that the decrease in glucose tolerance in patients with Graves' disease can be explained by 1) the impairment of early insulin release response to rapid intestinal glucose absorption, 2) increased insulin metabolic clearance and 3) hyperglucagonemia.

Adult

[Difference of acute ketone body metabolism between insulin-dependent diabetic and non-insulin-dependent diabetic individuals].

The difference in the acute metabolic change in ketone bodies between patients with insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) was investigated in this study. The subjects employed were 7 patients with IDDM losing residual insulin secretion and 7 patients with NIDDM matched to the former patients for age, body mass index, duration of diabetes, daily insulin dosage, fasting plasma glucose and HbA1c. Blood samples were drawn at 3A.M. and 7A.M. on the same day, and plasma glucose, acetoacetic acid (AcAc), 3-beta-hydroxybutylic acid (3-OHBA), free fatty acid (FFA), glycerol, cortisol and growth hormone (GH) concentrations were determined. Plasma total ketone bodies (AcAc and 3-OHBA), 3-OHBA and FFA concentrations at 7A.M. were significantly higher in the patients with IDDM than in those with NIDDM (p < 0.05), while there were no significant differences in any other parameters at 3A.M. between the patients with IDDM and those with NIDDM. The ratios of 7A.M. value/3A.M. value of total ketone bodies, AcAc and 3-OHBA concentrations were also more significantly elevated in the patients with IDDM than in those with NIDDM. It was observed that the ratio of 3-OHBA was more than 2.0 in all of the patients with IDDM and less than 2.0 in all of the patients with NIDDM, the difference being significant with p < 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Use of anti-peptide antibodies for the design of antigen-specific immune complex assays.

A simple and sensitive method is described for the detection of circulating immune complexes (ICs) in an antigen-specific manner. The method is based on the use of anti-peptide antibodies as solid-phase capture reagents to bind antigen which is complexed to serum antibodies. The bound serum antibody is detected with a labelled second antibody. The method requires that the anti-peptide antibodies bind native protein efficiently, and that the anti-peptide antibodies do not compete with antibodies raised against the native protein which are involved in IC formation. Two anti-peptide antibodies specific for the hepatitis B surface antigen (HBsAg) and the hepatitis B e antigen (HBeAg), which possessed the requisite characteristics, were chosen as models for IC assay development. The solid-phase, anti-peptide based assays efficiently detected HBsAg and HBeAg-containing ICs in preformed antigen/antibody mixtures and in the serum of chronically infected hepatitis B patients.

Amino Acid Sequence

[The possibility of hereditary factors in the susceptibility to diabetic nephropathy in NIDDM].

Diabetic nephropathy is the most important complication of diabetes, because it is a major cause of morbidity and mortality for diabetic subjects. Since not all subjects with diabetes are at risk of developing this complication, we conducted a study to determine if heredity might be a possible risk factor for diabetic nephropathy in non-insulin dependent diabetes. Twenty-one factors including inheritance of nephropathy and hypertension were investigated in 109 individuals with NIDDM: 50 patients without proteinuria (Group I), 20 patients with intermittent proteinuria (Group II), and 39 patients with continuous proteinuria (Group III) matched for age and duration of diabetes. Of those patients, 55 patients with inheritance of diabetes were also divided into three groups: 29 patients without proteinuria (Group I), 9 patients with intermittent proteinuria (Group II), and 17 patients with continuous proteinuria (Group III). Individuals in Groups II and III has significantly higher frequency of inheritance of diabetic nephropathy than those in Group I, and also individuals with inheritance of diabetic nephropathy had significantly higher frequency of diabetic nephropathy than those without it. Frequency of hypertension, retinopathy and body mass index in the past were significantly higher in subjects in Groups II or Group III than in those in Group I. There were no significant differences between subjects in Groups II and III. These findings suggest that susceptibility to diabetic nephropathy in NIDDM may be hereditary, although hypertension and obesity may also be important risk factors for diabetic nephropathy.

Aged

Time course of hepatitis A virus antibody titer after active and passive immunization.

To investigate the antibody titer necessary to prevent hepatitis A virus infection, either 15 or 7.5 mg/kg of immune serum globulin was injected into 10 antihepatitis A virus negative volunteers and their serum antihepatitis A virus titers were observed for 28 wk. In addition, antibody titers were observed for 96 wk in a phase 1 clinical trial of a hepatitis A vaccine. The two studies were then compared to assess the immunogenicity of the vaccine and the persistence of the antibody. Serum-neutralizing antibody titers that were greater than or equal to 4 (considered as positive) persisted for 18 wk and 14 wk after the injection of 15 and 7.5 mg/kg of globulin, respectively. Hepatitis A virus vaccine recipients showed adequate neutralizing antibody titers, with the groups receiving 1, 0.5 and 0.25 micrograms/dose showing titers of 4(5.5), 4(4.7) and 4(4), respectively, at 18 mo after the third inoculation. These findings suggested that effective blood antibody titers were likely to be retained in the 1.0 micrograms or 0.5 micrograms/dose groups for at least several years. Moreover, the serum antihepatitis A virus titers demonstrated by a modified radioimmunoassay changed in parallel with the neutralizing antibody titers in the volunteers injected with globulin.

Adult

Clinical trial of a lyophilized inactivated hepatitis A candidate vaccine in healthy adult volunteers.

The safety and immunogenicity of a lyophilized inactivated hepatitis A vaccine was tested in healthy adult male volunteers. Thirty-six volunteers, all of whom were negative for antibody to HAV (anti-HAV), were divided into three dosage groups, 1.0, 0.5 and 0.25 micrograms of viral protein, respectively. Each group received a total course of three intramuscular injections at months 0, 1 and 6. Slight side effects were noted after 16 of 99 injections and the occurrence and degree were almost identical to those of other commercial vaccines. On the other hand, all subjects had measurable titres of serum anti-HAV neutralizing antibodies as early as 2 months after the first injection. The mean values of serum anti-HAV neutralizing antibodies at 7 months in the 1.0, 0.5 and 0.25 micrograms dose groups were 64-, 12-, and 9-fold higher, respectively, than those observed at 5 days in five recipients given 7.5 mg kg-1 body weight of immune serum globulin (ISG).

Adolescent

[Interferon therapy of chronic hepatitis].

The current state of interferon (IFN) therapy for chronic hepatitis B and C in Japan is reviewed. The administration of IFN results in induction of 2'-5' oligoadenylate synthetase (2-5AS). 2-5AS produces 2-5A capable of activating a latent RNAase that degrades viral RNA. In patient with chronic hepatitis B, prominent reduction of HBV DNA, HBe antigen and HBs antigens is observed, when IFN is administered. However, the replication of HBV starts again after stopping of IFN administration, because the effects of IFN do not affect HBV DNA which is the origin of replication. On the other hand, HCV is a RNA virus IFN not only suppresses the production of HCV proteins and its pregenome, but also eradicate HCV RNA that is the origin of replication. In around 40% of the patients with chronic hepatitis C, sustained normalization of ALT and negativity of HCV RNA was obtained after IFN therapy under the most satisfactory regimen.

Chronic Disease

[Clinical studies on 3 pairs of monozygotic twin sisters affected by Graves' disease].

Clinical studies were undertaken of three pairs of monozygotic twin sisters affected by Graves' disease. The evidence that the twins were monozygotic was established by similarity in physical appearance, identical blood-group antigens and identical HLA types. All pairs were female, and the evidence of Graves' disease in both members of the pair was observed in 2 out of 3 pairs. In the remaining pair the disease started in the elder sister, but the younger sister still remained in euthyroidism in spite of the presence of diffuse goiter. The disease occurred in the second decade in all the patients, and the interval between the occurrence of the disease in twin sisters was 1 to 4 years. No common specific type of HLA was found among all three pairs, but DR4 was common in two pairs of twin sisters showing positive MCHA test. Serum TRAb was positive in 2 pairs of twin sisters but negative in the remaining one. However, it became positive in the elder sister of the latter pair during the antithyroid treatment. The effect of antithyroid drug treatment was found to be similar in each of the twin sisters, and the serum TRAb moved almost in parallel with serum FT4 level. These results indicate that a genetic factor may be of great importance in the aetiology of Graves' disease, and there was a strong preponderance for it to occur in women and the second decade was the peak age for its occurrence. The common specific type of HLA for all Graves' patients was not found in this study. A strong relationship was observed between Grave's disease and TRAb.

Adult

A high prevalence of antibody to the hepatitis C virus in patients with hepatocellular carcinoma in Japan.

In Japan, hepatocellular carcinoma (HCC) is one of the most prevalent cancers, with a reported fatality rate showing a consistent and significant increase in the last decade. At most, only 25% of HCC cases are positive for the hepatitis B surface antigen (HBsAg). To investigate a potential role for hepatitis C virus (HCV) in the development of HCC, sera from 105 HBsAg-negative HCC patients were collected from five districts of Japan and assayed for antibody to HCV antigen (HCVAb). A large number of these patients (76.2%) were found to be positive for the HCVAb in comparison with the reported prevalence in sera from blood donors (1.1%). A history of blood transfusion was found in 39.6% of the cases positive for HCVAb, which was significantly different to the lower rate (4.7%) observed in HCC patients who were both positive for HBsAg and negative for HCVAb (P less than 0.001).

Blood Transfusion

Interferon therapy for non-A, non-B chronic hepatitis.

We report the results of our study on 8-week consecutive interferon (IFN) treatment for chronic non-A, non-B hepatitis. In the 6 MIU/day group, most cases had continuously normalized alanine-aminotransferase (ALT) levels even after IFN treatment was discontinued. In responders whose ALT levels remained normal, not only the degree of inflammation, as seen from HAI scores, but also liver histopathological features were improved. Moreover, antibody to hepatitis C virus (anti-HCV) titer in responders was continuously decreased. Antiviral effects of IFN were observed by detection of HCV-RNA using the PCR technique. HCV-RNA became negative with IFN treatment, however, in some patients who relapsed after discontinuation of IFN treatment, re-elevation of ALT levels was usually preceded by re-appearance of HCV-RNA.

Alanine Transaminase

Induction of protection level of anti-pre-S2 antibodies in humans immunized with a novel hepatitis B vaccine consisting of M (pre-S2 + S) protein particles (a third generation vaccine).

An enzyme-linked immunosorbent assay (ELISA) for anti-pre-S2 antibodies was developed by the use of both recombinant yeast-derived S and M (pre-S2 + S) protein particles as antigens. By this ELISA was determined the amount of both human and chimpanzee anti-pre-S2 antibodies produced by a new type of yeast-derived hepatitis B (HB) vaccine (TGP-943, subtype adr), which consists of modified M protein particles. In seven randomly selected human individuals who were vaccinated intramuscularly with 10 micrograms (as a protein) TGP-943 three times (0, 4th and 24th week), a detectable level of anti-pre-S2 antibodies was found to be rapidly elicited at 4th or 8th week after the first vaccination. The protective level of anti-pre-S2 antibodies in humans was tentatively assessed by comparing the anti-pre-S2 antibody titres in the vaccinated human individuals with that in chimpanzees which produced only anti-pre-S2 antibodies to tolerate well against the challenge by 1000 chimpanzee infectious units of HBV (subtype ayw). From this assessment, it was speculated that all human individuals tested had already acquired the protective level of anti-pre-S2 antibodies at 4th or 8th week after the first vaccination with TGP-943.

Animals

Antibody to the hepatitis C virus in acute hepatitis and chronic liver diseases in Japan.

In a 6-month follow-up study of acute hepatitis in Japan, 31 out of 41 (75.6%) cases of post-transfusion non-A and non-B hepatitis (NANB-PTH) and 14 out of 40 (35.0%) cases of sporadic non-A non-B hepatitis (NANB-SPO) were found to be positive for antibody to the hepatitis C virus (HCVAb). After 12 months of follow-up, 30 cases (81.1%) became chronic among 37 HCVAb positive acute NANB hepatitis cases. This figure shows a significantly higher rate of chronicity as compared with HCVAb negative acute NANB hepatitis. The prevalences of HCVAb in hepatitis B surface antigen (HBsAg) negative cases of chronic hepatitis and liver cirrhosis were 76.3% (200/262) and 66.7% (106/159), respectively, which were significantly different from the values of 5.1% (13/255) and 10.6% (13/123) observed in HBsAg positive cases. Of chronic liver disease cases positive for HCVAb, 45.8% (152/332) had a history of blood transfusion, in contrast to the value of 3.7% (13/352) observed in HBsAg positive cases of chronic liver disease that were negative for HCVAb.

Enzyme-Linked Immunosorbent Assay

Large molecular form of serum HBeAg in chronic hepatitis B virus infection: relation to liver cell damage.

We have separated circulating HBeAg into small and large molecular forms by agarose gel electrophoresis and analyzed the relationship between the two forms and other clinical features of chronic hepatitis B, especially in regard to liver cell damage. The large HBeAg accounted for 7.3% +/- 3.4% of serum HBeAg in 9 subjects with normal liver histological findings or nonspecific reactive hepatitis, 38.0% +/- 27.8% in 32 patients with chronic persistent hepatitis and 65.6% +/- 23.3% in 21 patients with chronic active hepatitis (p less than 0.01). A positive correlation was seen between the height of aminotransferase elevations and the percentage of large HBeAg. Three patients who progressed from histologically normal liver or nonspecific reactive hepatitis to chronic active hepatitis had dramatic increases in the percentage of large HBeAg. The finding that the presence of large HBeAg in serum correlated with the severity of hepatitis suggests that HBeAg may play an important role in determining the degree of liver injury in chronic hepatitis B.

Adolescent

Purification and characterization of a novel intracellular acid proteinase from the plasmodia of a true slime mold, Physarum polycephalum.

An acid proteinase was purified to apparent homogeneity from the plasmodia of a slime mold, Physarum polycephalum, by a combination of detergent extraction, acid precipitation, and column chromatographies on DEAE-Sephadex, hydroxylapatite, CM-Sephadex, and Sephadex G-100. The enzyme was shown to be composed of two polypeptide chains (a 31-kDa heavy chain and a 23-kDa light chain) cross-linked by disulfide bond(s). The NH2-terminal amino acid sequence of the heavy chain was determined to be Ala-Gly-Val- Asp-Gly-Tyr-Ile-Val-Pro-Tyr-Val-Ile-Phe-Asp-Leu-Tyr-Gly-Ile-Pro-Tyr and that of the light chain to be Ala-Glu-Pro-Pro-Ile. The heavy chain contained carbohydrate moiety composed of mannose, glucosamine, fucose, and glucose. The enzyme was optimally active at pH 1.7 toward hemoglobin as a substrate. Among the proteinase inhibitors tested only diazoacetyl-D,L-norleucine methyl ester, a typical aspartic proteinase inhibitor, inhibited the acid proteinase in the presence of cupric ions. It was insensitive to the other typical aspartic proteinase inhibitors, pepstatin A and 1,2-epoxy-3-(p-nitrophenoxy)propane. The enzyme hydrolyzed Lys-Pro-Ile-Glu-Phe(4-NO2)-Arg-Leu at the Phe-Phe(4-NO2) bond, but could not hydrolyze another synthetic pepsin-substrate, N-acetyl-L-phenylalanyl-3,5-diiodo-L-tyrosine. The enzyme showed a unique substrate specificity toward oxidized insulin B chain. The major cleavage sites were the bonds Gly8-Ser9, Leu11-Val12, Cya19-Gly20, and Phe24-Phe25, and the Gly8-Ser9 bond was most susceptible. These results indicate that the enzyme is a novel type of intracellular acid proteinase with a unique substrate specificity.

Amino Acid Sequence

[The clinical course of Hashimoto's thyroiditis during a 5 year observation period in relation to the change in thyroid function and the titers of the antithyroid antibody].

In order to discover whether or not thyroid function in patients with Hashimoto's disease will move toward hypothyroidism with age, we investigated the thyroid function and antithyroid antibody titers at the initial examination and 5 years later in 181 patients with goitrous Hashimoto's thyroiditis. Pregnant patients and those within 1 year of the postpartum period were excluded. The thyroid function was assessed before medication or at least one month after stopping it. At the initial examination, 52% (94 cases) of the cases were euthyroid, 24% (44 cases) were subclinically hypothyroid and 24% (43 cases) were hypothyroid. It was not observed whether the incidence of hypothyroidism tended to be greater in older patients or in patients with longer duration of illness. Five years later, 68% of euthyroid patients at the initial examination remained in euthyroid state, 18% had become subclinically hypothyroid, and 9% were hypothyroid. The thyroid function was not evaluated in 5% of the patients because they were under treatment with 1-thyroxine. In the patients with subclinical hypothyroidism at the initial examination, 30% had become euthyroid, 23% remained subclinically hypothyroid, 32% had become hypothyroid and 16% were not evaluated. Thirty percent of the patients with hypothyroidism at the initial examination had become euthyroid, 7% were subclinically hypothyroid, 28% remained hypothyroid and 35% were not evaluated. The higher the titer of TGHA, the higher the percentage of hypothyroidism at the first examination. A similar but much stronger tendency was observed in the patients with a higher titer of MCHA. In the patients with a higher titer of TGHA, the number of hypothyroid patients approximately doubled after 5 years, although such a tendency was not observed in the patients with a higher titer of MCHA. In patients with persistent hypothyroidism, the age was significantly higher, the serum concentration of T3 lower and the titer of TGHA at the initial examination and MCHA 5 years later higher than in the patients with transient hypothyroidism. The titer of MCHA was significantly decreased 5 years later in patients with transient hypothyroidism. From these results, it is indicated that in patients with goitrous hypothyroidism, the incidence of hypothyroidism was higher in the cases with high titers of antithyroid antibody than in those with low titers, and that in the patients with transient hypothyroidism, the age was lower, the serum level of T3 higher and the titer of TGHA lower than in the cases with permanent hypothyroidism.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult