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Biomedical subjects

M Okubo

Publications and source records attributed to M Okubo.

At least 145 records · Page 8Linked to original sources
PubMed1993

Identification of a universal B cell epitope on DNA topoisomerase I, an autoantigen associated with scleroderma.

OBJECTIVE: To investigate the distribution of B cell autoepitopes of human DNA topoisomerase I (topo I), an autoantigen associated with scleroderma. METHODS: A complementary DNA clone, T1B, was used to produce recombinant proteins of topo I as beta-galactosidase fusion proteins. Immunoreactivity to these fusion proteins was then tested in 35 anti-topo I-positive sera from patients with scleroderma, by immunoblotting, enzyme-linked immunosorbent assay, and double immunodiffusion. RESULTS: One epitope was found to be universally recognized by all sera tested. Thirty-two of the samples recognized multiple antigenic regions, but sera from the remaining 3 patients recognized only this universal epitope, and in longitudinal studies of 1 of these 3 patients, the serum recognized only this epitope for more than 2 years, even though multiple, potent, antigenic regions were found on topo I. CONCLUSION: Recognition of multiple epitopes in most patients suggests that the topo I molecule itself would drive the autoimmunity on topo I. However, antigen-driven autoimmunity could not explain the production of the monoreactive anti-topo I antibody seen in the 3 patients. We thus hypothesize that there is a process whereby recognition of the universal epitope by cross-reaction develops into antigen-driven autoimmunity.

Autoantibodies↗
PubMed1993

Analysis of IMP-SPECT in cerebral infarcts.

We performed single photon emission computed tomography with N-isopropyl[123I]-p-iodoamphetamine in 22 normal volunteers (mean age, 68.3 +/- 9.5 years) and 190 patients with unilateral cerebral infarcts (66.1 +/- 11.4 years). We then compared visual and semiquantitative assessment of the left/right ratio of the early images. Cerebral blood flow in the patients with cerebral infarcts was compared with data from normal volunteers. An abnormal left/right ratio was recognized in 110 of 136 (81%) patients in whom X-ray computed tomography (CT) showed an abnormality, while visual inspection revealed abnormalities in only 99 (73%). In 54 patients no abnormality on CT, an abnormal left/right ratio was found in 28 (52%), and visual abnormalities in only 9 (17%). Altogether, the left/right ratio was abnormal in 138 of 190 (73%) patients, and abnormalities were detected visually in 108 (57%). Of 95 patients, 56 (59%) showed markedly larger lesions using the left/right ratio method than with the visual method.

Aged↗
PubMed1993

Relationships among residual beta cells, exocrine pancreas, and islet cell antibodies in insulin-dependent diabetes mellitus.

Quantitative analysis was performed using computerized morphometry on the relationships between residual beta cells, pancreatic exocrine glands, and islet cell antibodies (ICA) in 14 pancreata of insulin-dependent diabetic (IDDM) patients. Both pancreatic exocrine glands and beta cells were markedly reduced in weight in IDDM patients compared with non-insulin-dependent diabetic (NIDDM) patients or nondiabetic controls. beta cells were preserved in six cases and were completely abolished in eight cases. In nine IDDM pancreata weighed at autopsy, the weights of pancreatic exocrine glands in six patients with either no or virtually no residual beta cells (32.3 +/- 1.6 g) were greater than those in three patients with residual beta cells (23.1 +/- 2.5 g, P < .05). Infiltration of lymphocytes positive for leukocyte common antigen (LCA) around the islet was observed in only one case with ICA and residual beta cells. Infiltration of LCA-positive lymphocytes around pancreatic acinar cells was observed in 50% (six of 12) of patients examined. The weight of pancreatic exocrine glands in patients with LCA-positive lymphocyte infiltration (26.2 +/- 2.3 g) was lower than that in patients without this condition (33.2 +/- 2.4 g, P < .05). Pancreatic cytokeratin autoantibodies (PKA) were detected in four of 10 patients examined. In addition, all four ICA-positive patients had residual beta cells, while only one of seven ICA-negative patients had residual beta cells (P = .03).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Serum lipoprotein(a) levels differ in different phenotypes of primary hyperlipoproteinemia.

Previous studies have indicated that serum lipoprotein(a) [Lp(a)] levels are mostly under genetic control. We have attempted to determine whether serum Lp(a) levels differ in different phenotypes of primary hyperlipoproteinemia (HL). A total of 129 subjects with HL (three with type I, 43 with familial hypercholesterolemia [FH], 17 with type IIa [non-FH], 11 with type IIb, six with type III [E2/2], 44 with type IV, and five with type V) and 18 normolipidemic controls were included in the study. Thirty-two FH subjects were being treated with hypolipidemic agents, but none of the other subjects were receiving any medication. Fasting blood samples were collected for determination of both serum lipid and Lp(a) levels. Lp(a) level was measured by enzyme-linked immunosorbent assay. The 18 controls had serum Lp(a) concentrations of 18.0 +/- 14.5 mg/dL (mean +/- SD), and four of them had high serum Lp(a) levels (> or = 25 mg/dL). Serum Lp(a) concentrations in FH subjects tended to be higher than in the controls (30.5 +/- 25.0 mg/dL), and the incidence of high Lp(a) levels in FH subjects was significantly higher than in the controls (51% v 22%, P < .01). There was no difference between serum Lp(a) levels of FH subjects depending on whether they were receiving medication. In contrast, most of the subjects with selective hypertriglyceridemia had very low serum Lp(a) levels (1.5 +/- 0.7, 8.1 +/- 8.3, and 3.5 +/- 5.3 mg/dL in type I, IV, and V, respectively; P < .01 v controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Mechanisms of aluminum fluoride- and insulin-stimulated p33 mRNA accumulation in rat hepatoma cells: involvement of a G protein and kinase action and demonstration of effects on mRNA turnover.

The insulin signalling pathway to control nuclear p33 gene expression was examined. An AlF4-stimulated pertussis toxin-insensitive G protein was shown to be involved. The action of AlF4- was completely blocked by deferoxamine. Insulin action was markedly stimulated in the presence of AlF4-. cAMP and diacylglycerol concentrations were examined as possible regulators but no increases were detected. The effects of AlF4- and of insulin were completely inhibited by the general kinase inhibitor H-7. A second calcium calmodulin protein kinase inhibitor, W-7, had no detectable effect. Insulin and AlF4- were shown to stabilize p33 mRNA.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

High-dose 15-deoxyspergualin monotherapy surpasses methylprednisolone in its therapeutic effect on advanced lupus nephritis in New Zealand black/white F1 hybrid mice, and low-dose combination may be synergistic.

To compare the therapeutic effect of 15-deoxyspergualin with that of methylprednisolone on advanced lupus nephropathy of New Zealand black/white F1 hybrid (B/W) mice, and also to study the possible synergistic effect of both drugs, B/W mice were heminephrectomized at 32 weeks of age, and were divided into six groups. Each group of mice was treated with 50 microliters phosphate-buffered saline (PBS), 3 mg/kg methylprednisolone, 20 mg methylprednisolone, 0.6 mg DSP, 6 mg DSP, or with 3 mg methylprednisolone plus 0.6 mg DSP, s.c., four times per week for 8 weeks. Urine and blood samples (by tail vein venipuncture), as well as renal tissue specimens, were taken at 32 and 40 weeks of age. The degree of proteinuria, and serum anti-DNA activity (by ELISA) were determined. Renal specimens were evaluated with light- and immunofluorescence (C3)-microscopy, the degree of pathological changes being semi-quantitated and expressed as total light-microscopy (LM) and immunofluorescence (IF) scores. The survival rate at 40 weeks of age was significantly elevated in 0.6 mg DSP, 6 mg DSP, and methylprednisolone + DSP groups of mice compared with the control group. The appearance rate of significant post-treatment proteinuria was comparable among all groups. The difference (post-treatment titre--pretreatment titre) of serum anti-DNA activity in the 6 mg DSP and methylprednisolone + DSP groups were significantly less, while that of the 3 mg methylprednisolone group was greater compared with the control level. As for the total LM score, the levels significantly decreased in the 6 mg DSP, methylprednisolone + DSP and 3 mg methylprednisolone groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

15-Deoxyspergualin "rescue therapy" for methylprednisolone-resistant rejection of renal transplants as compared with anti-T cell monoclonal antibody (OKT3).

A randomized trial with OKT3, an anti-T cell monoclonal antibody or with 15-deoxyspergualin against methylprednisolone-resistant rejection crisis was performed in 25 posttransplant patients immunosuppressed with prednisolone and cyclosporine. At least temporary reversal of rejection was observed in 58.3% of patients treated with 15-deoxyspergualin. This reversal rate may be quite comparable to 61.5% seen in patients treated with OKT3. Adverse effects with 15-deoxyspergualin were related to bone marrow suppression, while those with OKT3 were pyrexia, gastrointestinal symptoms, and herpes infection. In contrast to OKT3, which may act by modulating T cell surface antigen, 15-deoxyspergualin may be effective somewhere in the later stages of the rejection cascade.

Adult↗
PubMed1993

Immunogenetic and clinical characterization of slowly progressive IDDM.

OBJECTIVE: To examine the clinical and immunogenetic heterogeneity of IDDM. RESEARCH DESIGN AND METHODS: We divided 207 IDDM patients into groups based on the interval from clinical onset to initiation of insulin therapy: group A (< 3 mo, acute clinical-onset group, n = 134), group B (3-12 mo, intermediate group, n = 31), and group C (> or = 13 mo, slowly progressive group, n = 42). Immunogenetic and clinical markers were compared between group A and group C. RESULTS: The mode age of onset was higher in group C (52 yr) than group A (10 yr). Group C had a higher prevalence of islet cell antibodies (42.9%, 18 of 42) than group A (25.4%, 34 of 134, P = 0.05). Serum C-peptide immunoreactivity assayed by radioimmunoassay in response to a 100-g oral glucose tolerance test was significantly higher in group C than in group A. Group C patients were also more likely to have a family history of NIDDM (26.1%, 11 of 42) among their first-degree relatives than group A patients (11.2%, 15 of 134, P = 0.039). The prevalences of family history of IDDM and endocrine autoimmune diseases were not different between groups C and A. The frequency of complications of endocrine autoimmune disease was not different between group A (6.7%, 9 of 134) and group C (2.3%, 1 of 42). Significant associations with two class I major histocompatibility complex antigens (HLA-A24 and -Bw54) and one class II antigen (HLA-DR4) were observed in group A. Group A patients were associated with three diabetogenic HLA-DQ haplotypes including DQA1*0301-DQB1*0401, DQA1*0301-DQB1*0302, and DQA1*0301-DQB1*0303. In contrast, group C lacked the association with class I antigens, although HLA-DR4 and HLA-DQA1*0301-DQB1*0401 were more common in this group than in control subjects. CONCLUSIONS: These results indicate that the clinical subtype with slowly progressive course (slowly progressive IDDM) has distinct findings including late-age onset, high prevalence of islet cell antibodies, preserved beta-cell function, and high family history of NIDDM. An additive effect of class I and class II major histocompatibility complex antigens is suggested as an explanation for the acute clinical manifestations and more severe beta-cell destruction in group A patients.

Adolescent↗
PubMed1993

[A study of crossed cerebellar diaschisis on 123I-IMP SPECT images and its redistribution phenomenon].

Crossed cerebellar diaschisis (CCD) is interpreted as a functional deactivation, presumably caused by a loss of excitatory or inhibitory afferent inputs on the corticopontocerebellar pathway and others. A redistribution phenomenon (RD) is usually observed in the contralateral cerebellum with CCD on delayed images of 123I-IMP SPECT. This phenomenon was analyzed in a view point of rCBF measurement in 24 patients with brain tumor, infarction and so forth. Regional CBF was measured by the microsphere method with 123I-IMP and a delayed-to-early counts ratio (D/E ratio) was used. As a result, there was no relation between rCBF and the D/E ratio in the cerebellum, which means that RD is occurred by other factors except for rCBF in the cerebellum. Regional CBF and the D/E ratio in the contralateral and ipsilateral cerebellum was 46.3 ml/100 g/min, 1.01 and 57.0 ml/100 g/min, 0.86, respectively. These results mean that the high activity of IMP gradually decreased in the ipsilateral cerebellum, while, the low activity in the contralateral cerebellum was almost stable, and the difference of both activity reduced after 5 hours and RD was observed on the delayed image. The data indicate that retention mechanism of IMP and vascular permeability are not affected in the cerebellum with CCD.

Adolescent↗
PubMed1992

Accumulation of multiple T cell clonotypes in the synovial lesions of patients with rheumatoid arthritis revealed by a novel clonality analysis.

T cell activation in the characteristic synovial lesions of rheumatoid arthritis may play a major role in the pathogenesis of this autoimmune disease. Analysis of T cell clonal diversity in these sites remains equivocal. Using the PCR and subsequent single-strand conformation polymorphism analysis it is possible to assess the degree of junctional diversity in the TCR with minimal selection bias. Concentrating on the beta-chain of the TCR, a paucity of clonotypic T cell expansion is demonstrated in the peripheral blood of healthy individuals. After polyclonal stimulation in vitro (with concanavalin A or phytohemagglutinin) this pattern does not change. In contrast, some T cell clonotypes appear following in vitro stimulation with purified protein derivative. Analysis of the peripheral blood, synovial fluid, and synovial tissue of patients with rheumatoid arthritis indicated many dominant T cell clonotypes. These data argue for a clonally diverse T cell response in the affected tissues of rheumatoid arthritic subjects.

Arthritis, Rheumatoid↗
PubMed1992

Neuropeptide Y inhibits beta-adrenergic agonist- and vasoactive intestinal peptide-induced cyclic AMP accumulation in rat pinealocytes through pertussis toxin-sensitive G protein.

The effects of neuropeptide Y (NPY) on pineal gland cyclic AMP (cAMP) accumulation were investigated using dispersed pinealocytes from rats. NPY inhibited the intracellular cAMP accumulation stimulated by isoproterenol and norepinephrine in a dose-dependent manner during a 10-min incubation of pinealocytes. NPY (1 x 10(-7) M) also inhibited vasoactive intestinal peptide (VIP)- and cholera toxin-induced cAMP accumulation. The inhibitory effect of NPY on isoproterenol-induced cAMP accumulation was completely abolished by a 5-h pretreatment of pinealocytes with 1 microgram/ml of pertussis toxin (PT). These results suggest that NPY participates in modulation of cAMP production in the rat pineal gland through PT-sensitive G protein. Yohimbine, an alpha 2-adrenergic antagonist, blocked NPY inhibition of isoproterenol-stimulated cAMP accumulation. On the other hand, the alpha 2-adrenergic agonist clonidine by itself did not affect cAMP accumulation stimulated by isoproterenol but significantly potentiated NPY action. The present study demonstrates that NPY inhibits beta-adrenergic or VIPergic stimulation of the pineal gland cAMP accumulation. The inhibitory effect of NPY is mediated through PT-sensitive G protein. Our results also suggest that NPY exerts its action to affect alpha 2-adrenoceptor function.

Adrenergic beta-Agonists↗
PubMed1992

Effect of 15-deoxyspergualin on lupus nephropathy in New Zealand black/white F1 mice.

Fourteen-week-old female New Zealand B/W F1 mice were treated subcutaneously with 15-deoxyspergualin (DSP) at 0.3 mg-6.0 mg/kg body weight, 4 times/week. They were sacrificed at 36 weeks of age to determine the minimal effective dose as well as the lowest maximally effective dose without toxicity of DSP required to suppress the development of nephropathy. The life span of the animals was significantly prolonged with 0.6 mg/kg or more DSP. Additionally, glomerular (immuno)histological improvement of the kidney at 36 weeks was observed with 0.6 mg/kg DSP, although a higher dose was required to lower serum anti-DNA activity or to decrease proteinuria. In addition, DSP produced a decrease of L3T4+ splenocytes without affecting the number of Lyt 2+ cells, while the level of IL-2 generated in vitro was somewhat elevated. It may be concluded that DSP has a therapeutic range within an order of ten, but its exact mechanism of immunosuppression remains to be determined.

Animals↗
PubMed1992

Intermediate-term results of balloon valvuloplasty for isolated and complicated pulmonary valve stenosis.

UNLABELLED: The purpose of this study is to report our experience regarding the acute and intermediate-term results of balloon pulmonary valvuloplasty (BPV) in various types of congenital pulmonary valve stenosis. METHODS AND RESULTS: Twenty-four consecutive patients with a median age of 6.6 years (ranging from 1 month to 24 years old) underwent BPV between January 1988 and September 1991. These patients were divided into 2 groups; Group 1 consisting of 13 patients with isolated pulmonary valve stenosis, and Group 2 consisting of 11 patients with complicated pulmonary valve stenosis (supravalvular, subvalvular, valved conduit and post-right ventricular outflow reconstruction). Mean peak systolic pressure gradients from the right ventricle to the pulmonary artery were as follows: In group 1, 48 +/- 21 (mean +/- SD) mmHg before BPV, 18 +/- 8 mmHg immediately after BPV and 13 +/- 5 mmHg at the longest follow-up based on catheterization or Doppler echocardiographic studies. The gradients in group 2 were 65 +/- 28 mmHg before BPV, 46 +/- 25 mmHg immediately after BPV and 47 +/- 21 mmHg at the longest follow-up. CONCLUSIONS: BPV provides both acute and intermediate-term gradient relief in patients with isolated pulmonary valve stenosis. In complicated pulmonary valve stenosis, on the other hand, the effect of BPV was unsatisfactory and appears to depend on the mechanism of associated obstruction. Therefore accurate evaluation of the anatomy of associated obstruction in the pulmonary valve region is needed to determine that BPV is indicated.

Adolescent↗
PubMed1992

Abnormalities of pulmonary function in patients with non-insulin-dependent diabetes mellitus.

To examine the possible association between the vascular complications of diabetes and changes in pulmonary function, we performed pulmonary function tests including assessment of the diffusing capacity (%DLco) in 80 patients with non-insulin-dependent diabetes mellitus (45 males and 35 females) without overt lung or heart disease. The mean age of the subjects was 57.9 years and the mean duration of diabetes was 10.8 years. The %DLco decreased significantly as the duration of diabetes increased (r = -0.38, p less than 0.01), and the same relationship was also observed in non-smoking subjects (N = 37). The reduction in %DLco was greater in patients with diabetic microangiopathy (especially nephropathy) and in those treated with insulin. Other pulmonary function tests (%VC, FEV1.0, PaO2 and PaCO2) showed no relationship to the duration of diabetes, the degree of microangiopathy or the type of treatment. These results suggest that diabetic microangiopathy may play an important role in the decrease of %DLco.

Aged↗