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Biomedical subjects

Y Uchigata

Publications and source records attributed to Y Uchigata.

At least 73 records · Page 4Linked to original sources
PubMed1989

The immunoglobulin class, the subclass and the ratio of kappa:lambda light chain of autoantibodies to human insulin in insulin autoimmune syndrome.

The immunoglobulin class, subclass and the k:lambda light chain ratio of insulin autoantibodies were determined in the sera of twenty-four patients with insulin autoimmune syndrome. All sera proved to be of the IgG immunoglobulin class but exhibited various IgG1:IgG2:IgG3:IgG4 ratios. The ratio of k:lambda light chain ranged from 1:0.13 to 1:0.75 with the exceptions of two sera that were characterized as IgG1(k) and IgG1(lambda).

Adult↗
PubMed1988

Probing the human B-cell repertoire: isolation of Epstein-Barr virus (EBV)-transformed human B lymphocytes making antibodies with a common idiotope that have different antigen-binding specificities.

Human peripheral B lymphocytes were transformed with Epstein-Barr virus and probed with an antiidiotypic antibody made against a human monoclonal autoantibody. Six cell lines were isolated that produced antibodies bearing a common idiotope. Despite the presence of this common idiotope, the antibodies showed antigen-binding specificities different from that of the parental antibody to which the antiidiotypic antibody was made. By probing Epstein-Barr virus-transformed cells with well-characterized antiidiotypic antibodies, it should now be possible to isolate and determine the frequency of B cells bearing specific idiotopes in the human repertoire and to study the antigen-binding properties of these antibodies.

Antibodies, Viral↗
PubMed1987

Human monoclonal multiple-organ-reactive autoantibodies distinguished by mouse monoclonal anti-idiotypic antibodies: expression of idiotopes in humans with and without autoimmune diseases.

Previously we reported on the production and characteristics of a number of human monoclonal autoantibodies. All of these autoantibodies were of the IgM class and reacted with antigens in multiple organs. In this study we generated IgG murine monoclonal anti-idiotypic antibodies against five human monoclonal autoantibodies, (i.e., MOR-h2, MOR-h3, MOR-h4, CG1, and CG2). These anti-idiotypic antibodies reacted strongly with the corresponding human monoclonal autoantibody, but minimally or not at all with other human monoclonal autoantibodies. By using these anti-idiotypic antibodies as probes, we screened sera obtained from normal individuals and patients with insulin-dependent diabetes mellitus, Hashimoto's thyroiditis, and systemic lupus erythematosus for the expression of idiotopes. Our study showed that the idiotopes recognized by three of the anti-idiotypic antibodies, i.e., anti-CG1, anti-CG2, and anti-MOR-h2, were not expressed, but the idiotopes recognized by two of the anti-idiotypic antibodies, i.e., anti-MOR-h3 and anti-MOR-h4, were expressed in normal individuals. In patients with autoimmune disorders, there was no increase in the expression of the CG1, CG2, and MOR-h2 idiotopes, but 45 and 23% of the patients with systemic lupus erythematosus showed a significant increase in the expression of the MOR-h3 and MOR-h4 idiotopes respectively. These findings show that there is widespread expression in the B cell repertoire of certain autoantibody-associated idiotopes.

Animals↗
PubMed1987

Pancreatic islet cell surface glycoproteins containing Gal beta 1-4GlcNAc-R identified by a cytotoxic monoclonal autoantibody.

To investigate the autoimmune pathogenesis of spontaneously occurring diabetes mellitus in BB rats, spleen cells of newly diagnosed diabetic BB rats were fused with mouse myeloma cells. Hybridoma supernatants were screened for antibodies by indirect immunofluorescence and by 51Cr-release assays using the RINm5F rat insulinoma cell line. One clone, E5C2, produced an IgM kappa antibody that was cytotoxic for RINm5F cells, but not for other rat cell lines nor for primary rat islet cells. However, treatment of primary rat islet cells with neuraminidase exposed surface antigens and rendered the cells susceptible to complement-mediated lysis by antibody E5C2. Using immunostaining of glycolipids separated by thin-layer chromatography, hapten inhibition assays with defined carbohydrates, and Western blots, the antigens recognized by E5C2 on RINm5F cells were identified as glycoproteins with molecular weights of 60,000 and 68,000. The antibody recognizes a carbohydrate antigen containing the sequence Gal beta 1-4GlcNAc-R, which on RINm5F cells is predominantly hidden by covalently bound sialic acid. These studies raise the possibility that hidden antigenic determinants on islet cells exposed by a variety of means may be the target of autoimmune attack.

Animals↗
PubMed1983

Effect of poly(ADP-ribose) synthetase inhibitor administration to rats before and after injection of alloxan and streptozotocin on islet proinsulin synthesis.

Nicotinamide (10 mmol/kg) and 3-aminobenzamide (1.25 mmol/kg), poly(ADP-ribose) synthetase inhibitors, were injected intravenously to rats either 30 min before the intravenous administration of 12 mg/kg alloxan or 50 mg/kg streptozotocin ("pretreatment") or 5 min after the administration ("posttreatment"). Fifteen minutes after the injection of the diabetogenic agents, pancreatic islets were isolated from the rats and proinsulin synthesis was determined. Proinsulin synthesis was decreased in islets from rats treated with alloxan or streptozotocin. Pretreatment with poly(ADP-ribose) synthetase inhibitors was found to protect against alloxan- or streptozotocin-induced decrease in proinsulin synthesis. By posttreatment with poly(ADP-ribose) synthetase inhibitors, streptozotocin-induced decrease in proinsulin synthesis was also significantly reversed, whereas the decrease induced by alloxan was not.

Animals↗
PubMed1982

Protection by superoxide dismutase, catalase, and poly(ADP-ribose) synthetase inhibitors against alloxan- and streptozotocin-induced islet DNA strand breaks and against the inhibition of proinsulin synthesis.

We have shown previously that alloxan and streptozotocin, two major diabetogenic agents, cause DNA strand breaks in rat pancreatic islets and stimulate nuclear poly(ADP-ribose) synthetase, thereby depleting intracellular NAD level and inhibiting proinsulin synthesis (Okamoto, H. (1981) Mol. Cell. Biochem. 37, 43-61; Yamamoto, H., Uchigata, Y., and Okamoto, H. (1981) Nature 294, 284-286). In the present study, superoxide dismutase and catalase, scavengers of radical oxygens, were found to protect against islet DNA strand breaks and inhibition of proinsulin synthesis induced by alloxan. The radical scavengers did not affect islet DNA strand breaks or inhibition of proinsulin synthesis induced by streptozotocin. On the other hand, compounds that inhibit islet nuclear poly(ADP-ribose) synthetase were found to protect against alloxan- as well as streptozotocin-induced inhibition of proinsulin synthesis. The poly(ADP-ribose) synthetase inhibitors were ineffective in protection against DNA strand breaks induced by the agents. These results may provide an important clue for elucidating the prevention of insulin-dependent diabetes as well as for understanding the cause of diabetes.

Alloxan↗
PubMed1982

A syndrome of periodic adrenocorticotropin and vasopressin discharge.

An 8-yr-old girl is presented who had periodic attacks of vomiting, psychotic depression, drowsiness, and hypertension (160/110 mm Hg) for a period of 16 months after head injury. At the initiation of the attack, serum ACTH and vasopressin levels were prominently increased (610 pg/ml and 41 microunits/ml, respectively), followed by hypercortisolemia, hyponatremia, and hypoosmolality in plasma. Serum PRL also was elevated (91 ng/ml). Responses of GH and cortisol to insulin-induced hypoglycemia and those of TSH to TRH were reduced. Urinary excretion of epinephrine and norepinephrine were increased, while dopamine (DA) excretion was reciprocally decreased, resulting in a marked elevation of the epinephrine plus norepinephrine to DA ratio during the episodes (0.4-4.5); this was normalized on attack-free days (0.08-0.25). During the attack, the concentration of homovanillic acid, a major metabolite of DA in the brain, also was reduced in cerebrospinal fluids from 70 to 23 ng/ml. The administration of methyl-dopa and reserpine effectively suppressed the recurrence of the episode. Although the exact cause of this syndrome is unknown, a periodic metabolic dysfunction of catecholamine in the central nervous system might be postulated.

Adrenocorticotropic Hormone↗
PubMed1982

Maturation of renal and hepatic monodeiodination of thyroxine to triiodothyronine and post-natal changes of serum thyroid hormones in young rats.

Maturational changes of renal and hepatic 5'-monodeiodination of thyroxine (T4) and post-natal changes of serum thyroid hormone levels were investigated in young rats under 35 days of age. Renal T3 generation in the 1-day-old rats was low, rose progressively to a level of more than 200% of the adult rats on days 21 and 28 and declined thereafter. In contrast, hepatic T3 generation increased from an initial low activity to a plateau after 7 days of age, which was 1 1/2 times higher than that of adult rats. Because of the extremely low value of serum T4 in the neonatal period, T3/T4 and rT3/T4 ratios were elevated on day 7. The ratio of rT3/T4 decreased gradually and became stable after 21 days of age, while the T3/T4 ratio increased reciprocally to a peak on days 21 and 28, corresponding to the period of maximal activity of renal T4 monodeiodination. These results indicate that in addition to elevated hepatic T4 monodeiodination, renal conversion of T4 to T3 may play a significant physiological role during the period of enhanced T3 requirement for maturation.

Age Factors↗
PubMed1980

Periodic ACTH discharge.

A 9 1/2-year-old girl is presented who had cyclical attacks of abdominal pain, vomiting, emotional disturbance, and marked weight change for two years. Associated findings were facial plethora, hypertension, transient hyperglycemia and glycosuria, elevated plasma ACTH, cortisol, and urinary 17-OHCS excretion, and low plasma osmolality with hyponatremia. Urinary excretion of catecholamines and porphyrin metabolites was not increased. Between episodes, she showed no abnormal clinical signs or laboratory data. The attacks were effectively suppressed with the administration of chlorpromazine. The disorder appears to be due to the periodic release of excessive ACTH; the cause remains unknown.

Adrenocortical Hyperfunction↗
PubMedDate not supplied

Age of onset and type of Japanese younger diabetics in Tokyo.

The age of onset of diabetes and the type of diabetes were examined in 1408 Japanese patients who were initially diagnosed as having diabetes under the age of 30 and were registered in our Diabetes Center between 1980 and 1989. Of the 1408 patients, 538 (38.2%) had insulin-dependent diabetes mellitus (IDDM) (male/female ratio of 2:3), and 870 (61.8%) had non-insulin-dependent diabetes mellitus (NIDDM) (male/female ratio of 5:4). There were significant differences of the sex ratio in both IDDM and NIDDM. The age at which the numbers in both the IDDM and NIDDM groups were almost equal was 13-14 (26 for IDDM and 23 for NIDDM at 13; 28 for IDDM and 30 for NIDDM at 14). A total of 58% of IDDM patients (22% of all patients) and only 6% of NIDDM patients (4% of all patients) were diagnosed under the age of 14 (P less than 0.01). Of the patients with IDDM, 42% (16% of all patients) were diagnosed over the age of 14, as were 94% of NIDDM (58% of all patients). The percentage of NIDDM cases increased even more over the age of 28, and no NIDDM patients developed diabetes under the age of 9.

Adolescent↗
PubMedDate not supplied

Carotid atherosclerosis in young-aged IDDM associated with diabetic retinopathy and diastolic blood pressure.

To determine whether young patients with IDDM already have atherosclerosis and what factors would relate to atherosclerosis, we examined the intimal-medial thickness (IMT) of the common carotid artery by ultrasonography. Subjects were 29 young patients with IDDM (aged 17-39 years, duration 4-31 years) without manifest macroangiopathy and 13 healthy controls of comparable age (22-29 years). The carotid artery IMT of young patients with IDDM were significantly higher than those of controls (0.60 +/- 0.09 vs. 0.46 +/- 0.02 mm, P < 0.0001). The levels of IMT significantly correlated to diastolic blood pressure (r = 0.45, P < 0.02), and were higher in those with proliferative retinopathy than those without retinopathy (0.66 +/- 0.09 vs. 0.55 +/- 0.08 mm, P < 0.02). The levels of IMT showed no significant correlation to the attained age, duration of IDDM, HbA1c, systolic blood pressure, and cholesterol level. These findings suggest the usefulness of this examination for the early detection of diabetic macroangiopathy, and point to a close relationship between microangiopathy and macroangiopathy in IDDM.

Adolescent↗
PubMedDate not supplied

Changes of albumin concentrations in the first morning urine according to age and sex in 2990 healthy children and adults.

This study was performed to clarify the changes in urinary albumin excretion according to age and sex in healthy subjects, for the appropriate judgment of microalbuminuria in insulin-dependent diabetes mellitus (IDDM). Concentrations of albumin in the first morning urine from 2990 healthy individuals (1713 males, 1277 females) aged from 6 to 39 years were measured by turbidimetry immunoassay. Reference values of the concentrations for each age group were obtained from the 95% confidence limits from the distribution simulated by the chi 2-test (k = 1). Reference values were 1.3-2.2 mg/dl in children aged 6-11 years. Values for females increased significantly from 22 mg/dl at age 11 years to 3.9 mg/dl at age 12 years (P < 0.0001) and those of males increased gradually from 1.7 mg/dl at age 11 years to 3.9 mg/dl at age 16 years. There were significant differences between males and females at the ages of 12 (P < 0.0001), 13 (P < 0.0001), and 14 (P < 0.0007). After 17 years, the values decreased from 3.9 mg/dl to 3.3 mg/dl in females, and to 2.9 mg/dl in males. We conclude that reference values of urinary albumin excretion change according to age and sex, which should be taken into consideration in the assessment of diabetic nephropathy in IDDM.

Adolescent↗
PubMedDate not supplied

Development of diabetic nephropathy in Japanese patients with insulin-dependent diabetes mellitus: Tokyo Women's Medical College epidemiologic study.

To clarify the development of diabetic nephropathy in Japanese insulin-dependent diabetes mellitus (IDDM), 373 patients with IDDM who had no proteinuria at the first visit to our Diabetes Center were evaluated. The incidence of persistent proteinuria increased rapidly between 10 and 19 years of diabetes duration, and only a few new cases occurred thereafter. Patients whose ages at onset of IDDM were 9-17 years (n = 167) and 18-29 years (n = 90) had rapid development of persistent proteinuria compared to the 0 to 8-year group (n = 116) (p < 0.02 and p < 0.003, respectively). Females (n = 233) developed persistent proteinuria to a greater extent until 24 years of diabetes duration than males (n = 140) (p = 0.17). Development of proteinuria did not vary according to calendar year of diagnosis of IDDM or diabetes duration at the first visit. Renal insufficiency (serum creatinine of 2.0 mg/dL or greater) followed the onset of proteinuria; 60% of the patients with the onset of IDDM between 1951 and 1969 developed renal insufficiency 10 years after the onset of proteinuria, whereas 30% of patients with the onset of IDDM after 1970 developed this condition. Development of renal insufficiency did not vary according to sex, age at onset of IDDM, or age at onset of proteinuria. Renal failure requiring dialysis therapy occurred within 4 years after renal insufficiency. In conclusion, development of diabetic nephropathy in Japanese IDDM exhibits three stages. The onset of proteinuria appears to be influenced by age at onset of IDDM and sex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗