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Biomedical subjects

M Okubo

Publications and source records attributed to M Okubo.

At least 127 records · Page 7Linked to original sources
PubMed1995

Glucocorticoid-induced hypertension in the elderly. Relation to serum calcium and family history of essential hypertension.

To explore the syndrome of glucocorticoid-induced hypertension in the elderly, we analyzed the clinical findings from 35 patients aged more than 65 years (12 men, 23 women) who received glucocorticoid therapy. Resting blood pressures (BP) were less than 140/90 mm Hg before glucocorticoid therapy, and patients were apparently disease-free apart from the condition for which glucocorticoid therapy was prescribed. Glucocorticoid-induced hypertension is defined as systolic BP more than 160 mm Hg and/or diastolic BP more than 95 mm Hg after glucocorticoid administration. Glucocorticoid-induced hypertension was seen in 13 patients (37.1%); all patients with hypertension [steroid (glucocorticoid)-induced hypertension (SH(+)) group] received more than 20 mg of prednisolone daily, and BP rose rapidly within a week of commencing glucocorticoid administration. The SH(+) group did not differ significantly in terms of age, heart rate, blood count, plasma biochemistry, plasma renin activity, plasma aldosterone, routine urinalysis, or urinary electrolytes from patients who did not show hypertension [SH(-) group]. However, serum total calcium concentrations were significantly lower in the SH(+) group both before and after 2 weeks of glucocorticoid therapy than in the SH(-) group. Furthermore, the SH(+) group showed a significantly higher percentage of patients with a positive family history of essential hypertension than the SH(-) group. In conclusion, although the detailed mechanisms are as yet uncertain, glucocorticoid-induced hypertension occurs often in elderly patients, and is more common in patients with total serum calcium concentrations lower than the normal range, and/or in those with positive family history of essential hypertension.

Aged↗
PubMed1995

Corticosteroid therapy for ventricular tachycardia in children with silent lymphocytic myocarditis.

OBJECTIVE: The objective of our study was to describe the efficacy of corticosteroids for ventricular tachycardia in four children with structurally normal hearts in whom endomyocardial biopsy revealed histologic changes of lymphocytic myocarditis. PATIENTS: The four patients had unexplained ventricular tachycardia. Three dysrhythmias were sustained, and one was inducible by exercise. Patient ages ranged from 4 months to 12 years. Three of the four patients had no symptoms. In two of them, ventricular tachycardia was identified by mass screening for heart disease. Two patients received oral steroids and two received pulse steroid therapy. RESULTS: In all four patients, significant underlying diseases were not found by noninvasive evaluation. Right ventricular endomyocardial biopsy revealed abnormal histologic findings of chronic lymphocytic myocarditis in all patients. Steroid therapy was effective in all four patients, two of whom received methylprednisolone pulse therapy. CONCLUSIONS: We conclude that unexplained ventricular tachycardia may be the only manifestation of clinically silent myocarditis. Steroid therapy should therefore be considered if conventional antiarrhythmic medication is not effective and histologic findings confirm the presence of lymphocytic myocarditis.

Adolescent↗
PubMed1995

Gold sodium thiomalate selectivity inhibits interleukin-5-mediated eosinophil survival.

Gold sodium thiomalate (GST) has been used for treatment of patients with bronchial asthma. In this study we investigated the effects of GST on interleukin (IL)-5-mediated eosinophil survival in vitro. Blood cells were obtained from patients with bronchial asthma (n = 18). Eosinophils were purified from the blood samples by a Percoll discontinuous method and negative selection of neutrophils. Eosinophils (10(6) cells/ml) were incubated for 96 hours in 10% fetal bovine serum-RPMI 1640 (Nissui Pharmaceutical Co. Ltd., Tokyo, Japan) with various concentrations of recombinant human IL-5 (2 x 10(-9) to 2 x 10(-5) mmol/L) and with GST (0.01 to 100 mumol/L) in 96-well, flat-bottomed microtiter plates at 37 degrees C in a humidified 5% carbon dioxide atmosphere. Eosinophil viability was determined by trypan blue exclusion. IL-5 enhanced eosinophil survival in a dose-dependent manner. Higher concentrations of GST inhibited IL-5-mediated eosinophil survival. Moreover, GST induced apoptosis of eosinophils by antagonizing the effects of IL-5. However, GST did not inhibit IL-3- or granulocyte-macrophage colony stimulating factor-mediated eosinophil survival, suggesting that GST selectivity inhibits IL-5-mediated eosinophil survival. These results suggest that IL-5-mediated eosinophil survival is inhibited by GST and that GST blocks eosinophil apoptosis by IL-5. It is possible that GST may be capable of controlling eosinophil functions regulated by IL-5 in patients with bronchial asthma.

Apoptosis↗
PubMed1995

Renal dysfunction in multiple myeloma.

This study aims to determine the clinical factors that may affect renal function and patient survival in 82 multiple myeloma patients. The patients were divided into 3 groups according to their renal function during the initial 8 weeks after diagnosis: Group I, 54 patients with serum creatinine (S-Cr) < 177 mumol/L; Group II, 11 with S-Cr > or = 177 mumol/L and receiving no dialysis; Group III, 17 undergoing dialysis treatment. Clinical status at diagnosis, subsequent renal function and patient survival were compared. Bence Jones proteinuria (BJP) was found in all patients in Groups II and III, compared to 67% of patients in Group I (p < 0.05, I vs II or III). Hypercalcemia, hyperuricemia and intravenous administration of contrast medium, together with BJP each constituted independent risk factors of renal dysfunction. The incidence of hypercalcemia in Group II was significantly higher than in the other 2 groups. Patient survival was 26.8 +/- 23.7 months in Group I, 8.1 +/- 10.3 in II and 12.1 +/- 16.6 in III (p < 0.05, I vs II or III). Renal function and patient survival depended on the initial renal function. Renal function was likely compromised in the presence of BJP.

Female↗
PubMed1995

Prospective study of lipoprotein(a) as a risk factor for atherosclerotic cardiovascular disease in patients with diabetes.

OBJECTIVE: To assess whether lipoprotein(a) [Lp(a)] is a risk factor for atherosclerotic cardiovascular disease in diabetes. RESEARCH DESIGN AND METHODS: We studied 221 patients with non-insulin-dependent diabetes mellitus (NIDDM) without diabetic complications who were followed for 2.2-3.1 years. Their serum Lp(a) levels were semiquantified by a rapid electrophoretic method that accurately discriminates high from low serum Lp(a) at the 20 mg/dl level. RESULTS: Seven of 105 diabetic patients with a high serum Lp(a) experienced a clinical event related to atherosclerotic cardiovascular disease. This incidence was significantly higher than that of the 110 diabetic patients with a low serum Lp(a). The logistic regression analysis revealed that Lp(a) was an independent risk factor for the event. CONCLUSIONS: Lp(a) is a significant risk factor for atherosclerotic cardiovascular disease in NIDDM.

Adult↗
PubMed1994

Clonotype analysis of peripheral blood T cells and autoantigen-reactive T cells from patients with mixed connective tissue disease.

T cells that recognize autoantigens may play a central role in the autoimmune response. We have previously shown that autoantigen-reactive T cells (CD4+) to U1-small nuclear ribonucleoprotein A were found in the PBMC of patients with systemic lupus erythematosus or mixed connective tissue disease. To reveal clonotypes of such T cells that spread to the periphery, T cell clonal accumulations and their TCR-beta chain variable gene usages in fresh PBMC from eight patients with mixed connective tissue disease were analyzed by a new method of single strand conformation polymorphism applying to TCR gene detection. The results revealed that the numbers of accumulated T cell clones (mean: 24.3 clones) were greater than the numbers of clones detected in healthy donors (mean: 4.0 clones). Frequently used V beta genes in these accumulated T cell clones were V beta 1, 3, 4, 5.2, 14, and 16. After the stimulation for these samples with the soluble recombinant U1-small nuclear ribonucleoprotein A protein, proliferative T cell responses were observed. We found that T cell clones expressing more restricted TCR V beta genes (1, 3, 5.2, and 14 families) accumulated in vitro. These results suggest that autoantigen-reactive oligoclonal T cell accumulations are present in the peripheral blood from systemic autoimmune disease patients.

Amino Acid Sequence↗
PubMed1994

Characteristics of porcine coronary artery endothelial cells in culture: comparison with aortic endothelium.

In the present study we compared the characteristics of porcine coronary artery endothelial cells in culture with the characteristics of aortic endothelium. Morphologically, coronary artery endothelial cells were larger than aortic endothelial cells. Under basal culture conditions, both coronary artery and aortic endothelial cells secreted significant amounts of prostacyclin and endothelin-1. The outstanding findings is that coronary artery endothelial cells secreted larger amounts of endothelin-1 than aortic endothelial cells. Immunofluorescence staining revealed that individual endothelial cells synthesize both substances. This comparative study provides important evidence indicating that the characteristics of coronary artery endothelial cells differ from those of aortic endothelial cells.

Animals↗
PubMed1994

Dynamic changes of accumulated T cell clonotypes during antigenic stimulation in vivo and in vitro.

It has not been known how T cell clones respond to antigenic stimulation. We applied reverse transcription polymerase chain reaction and subsequent single-strand conformation polymorphism (SSCP) analysis to monitor the kinetics of accumulated T cell clonotypes with respect to the TCR beta chain. Before exposure to an antigen, peripheral blood lymphocytes from healthy individuals exhibited smears with SSCP, indicating a heterogeneous T cell population. However, some bands were demonstrated within the smears, each corresponding to a distinct clonal accumulation. The majority of the accumulated clones were CD8+ and were stably detected over 1 year in the same individual. Next it was demonstrated that a number of clonal accumulations appeared in a diverse population after an acute infection in vivo or in cell culture with an antigen in vitro. The accumulations in vivo were demonstrated in both the CD4+ and CD8+ subsets, the latter having the longer duration of response after stimuli. On the other hand, in vitro culture with purified protein derivative induced expansions of a number of CD4+ clones throughout the culture, while CD8+ clones were shown to be induced later. There was no preferential usage of particular V beta genes in these clonotypes. Stimuli by more simple peptides could also induce clonal expansions of T cells. Therefore, with our novel experimental system, we could monitor the kinetics of T cell clonotypes induced by an antigen. This method may be applied to analyses of T cell clonality in many kinds of immune responses.

Adult↗
PubMed1994

A multi-centre study of the efficacy and safety of pravastatin in hypercholesterolaemic patients with non-insulin-dependent diabetes mellitus.

A multi-centre, non-randomized clinical study of 12-months' duration was performed in 112 patients with hyperlipidaemia associated with non-insulin-dependent diabetes mellitus to evaluate the clinical efficacy and tolerability of pravastatin and to assess its effect on glycaemic control. Patients were eligible for this trial if they fulfilled the following criteria; a high plasma total cholesterol level greater than 220 mg/dl associated with stable glycaemic control for at least 3-months' observation period. On entry, patients received 10 mg pravastatin per day (5 mg twice daily) for 12 months. Clinical efficacy was evaluated in 108 patients. The results showed that pravastatin induced a significant decrease in serum cholesterol level mainly with LDL-cholesterol. Total cholesterol levels were decreased significantly from 275 +/- 3 mg/dl to 222 +/- 4 mg/dl within 3 months of the start of treatment, and LDL-cholesterol decreased from 192 +/- 4 mg/dl to 137 +/- 4 mg/dl. After 12 months' treatment, total cholesterol and LDL-cholesterol levels were 216 +/- 4 mg/dl (p < 0.001) and 137 +/- 5 mg/dl (p < 0.001), respectively. HDL-cholesterol levels were increased from 51 +/- 2 mg/dl to 56 +/- 2 mg/dl at 3 months (p < 0.001) and 55 +/- 2 mg/dl at 12 months (p < 0.01). Triglyceride concentrations were also decreased from 173 +/- 11 mg/dl to 156 +/- 13 mg/dl at 3 months and 137 +/- 10 mg/dl at 12 months (p < 0.01). Fasting plasma glucose and glycated haemoglobin levels were not affected by pravastatin. Adverse events observed in 5 cases were always mild and reversible. These results indicate a clinical usefulness of pravastatin with high compliance in patients with hyperlipidaemia associated with non-insulin-dependent diabetes mellitus.

Adult↗
PubMed1994

Pharmacokinetics of RK-28 (a new radiosensitizer) and pharmaceutical design of a suppository form using rats.

The pharmacokinetics of RK-28, a new hypoxic cell radiosensitizer, was studied in rats following its intravenous, intraportal, oral, and rectal administration. The pharmaceutical design of an RK-28 suppository form was also examined. After intravenous injection, RK-28 was rapidly removed from the plasma (biological half-life of 17 min) and its area under the curve (AUC) was proportional to the amount of RK-28 administered. The absolute bioavailability of RK-28 was 59.7% for intraportal administration and 36.9% for oral administration. Following oral administration of RK-28, it seems likely that specific acid-catalyzed decomposition of RK-28 takes place in the stomach and then the absorbed RK-28 undergoes first-pass metabolism in the liver. When "solidified RK-28 suppository," made by solidifying molten RK-28, was inserted into the rectum, hepatic first-pass metabolism could be avoided substantially. The resulting absolute bioavailability of RK-28 increased to 75%. Furthermore, "RK-28 emulsion suppository," prepared by emulsifying RK-28 with 1-hexadecanol and hydrogenated castor oil (HCO 60) at 80 degrees C, showed a plasma concentration-time curve very suitable for radiation therapy; the maximum plasma concentration was attained 30 min after rectal administration and then decreased within a short period. Administration of "RK-28 emulsion suppository," resulted in an absolute bioavailability of 76%.

Administration, Oral↗
PubMed1994

Preparation and evaluation of suppositories for RK-28 (a new radiosensitizer) using rabbits.

The pharmacokinetics of RK-28 [1-(4-hydroxy-2-butenoxy)methyl-2-nitroimidazole], a new hypoxic cell radiosensitizer, was studied following intravenous, oral, and rectal administration to rabbits. After an oral administration of RK-28 solution, the plasma concentration of RK-28 was considerably lower than that after intravenous administration through all time periods, and the absolute bioavailability was a mere 4.2%. It was presumed that a specific acid-catalized decomposition of RK-28 progressed in the stomach, and also, the absorbed RK-28 suffered first-pass effects in the liver. In contrast, the absolute bioavailability following the rectal administration of a solidified RK-28 suppository preparation was significantly increased in comparison with that obtained by other administration routes. Also, RK-28 emulsion suppositories were prepared by emulsifying various amounts of the drug with 1-hexadecanol and hydrogenated castor oil (HCO 60) at 80 degrees C, and these were administered into the rabbit rectum. The resulting absolute bioavailability was 91% for the RK-28 emulsion suppository and 86.9% for an RK-28 emulsion suppository containing small amounts of Eudispert hv. These values were better than those in rats. The rectal administration of the RK-28 emulsion suppository containing small amounts of Eudispert hv showed a preferable plasma concentration-time pattern that reflects on radiation therapy.

Administration, Oral↗
PubMed1994

Neglect in three dimensions.

OBJECTIVES: Neglect in vertical and radial directions is rarely evaluated systematically in patients with brain damage. METHOD AND RESULTS: Using the line bisection task, we confirmed that some patients with unilateral brain damage manifest vertical or radial spatial neglect. In fact, patients with severe left horizontal neglect tend to have severe vertical neglect. CONCLUSION: Because vertical and radial neglect may affect the ability to perform functional daily activities, occupational therapists need to address the existence of vertical and radial neglect when evaluating and training patients with brain damage.

Aged↗
PubMed1994

[Apolipoprotein (a)].

Apo (a) consists of multiple tandem repeat of kringle 4, which resembles a counterpart of plasminogen. Plasma Lp (a) levels are genetically determined primarily by alleles at the apo (a) gene. Apo (a) shows size heterogeneity on the analysis of the protein and the mRNA. Pulse field gel electrophoresis revealed that size heterogeneity is largely due to different numbers of kringle 4-encoding sequences in the apo (a) gene. The cloning of apo (a) gene and identification of the 5'-flanking promoter region provide tools to study the regulation of apo (a) gene. The development of transgenic mice expressing human apo (a) offered a good model for understanding of atherosclerosis associated with elevated plasma levels of Lp (a).

Animals↗
PubMed1994

[Clinical characteristics of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) in adult].

Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) were originally described as separate disease entities. Recently, HUS and TTP have been considered a single disease, because of the identical microangiopathic lesion. In the present study, we investigated the clinical and histological characteristics of HUS/TTP. Eleven patients with a definite diagnosis of HUS/TTP were found from a cohort of adult patients who were admitted to Kitasato University Hospital in the past two decades. Their clinical and histological characteristics were retrospectively analyzed. All of the 11 patients with HUS/TTP were sporadic and non-diarrheal cases with a mean age of 49 years +/- 10. Preceding episodes of flu-like syndrome and the administration of mitomycin C were observed in 3 and 5 patients, respectively. On admission, two of 10 patients with renal dysfunction required dialysis treatment, while none developed nephrotic syndrome. Six patients showed CNS manifestation, such as consciousness disturbance and convulsion. Three patients with severe hypertension did not show consciousness disturbance. As for the final outcome, 6 patients recovered and the remaining 5 died. Two died after 60 hospital days. In the histopathological investigation, renal biopsy specimen showed narrowing of the capillary loops in the glomeruli due to swelling of the endothelial cells, double contour of the glomerular basement membrane, or mesangial cell necrosis and sclerosis. In the autopsy specimen, internal organ infarction with fibrin thrombi in small arteries was observed in multiple organs, such as brain, kidneys, hearts, lungs, jejunum, liver, pancreas, adrenal glands and pituitary gland. A circumferential myocardial infarction with hyaline thrombi in the medial layer of myocardium was characteristic of HUS/TTP. In conclusion, microangiopathic lesions with infarction spread widely throughout various organs in HUS/TTP. Involvement of internal organs, not to mention kidneys and brain, is lethal and their prognosis remains poor.

Adult↗
PubMed1994

Exocrine pancreatic ductograms in insulin-dependent diabetes mellitus.

OBJECTIVES: To examine the prevalence of abnormal pancreatic ductograms in patients with insulin-dependent diabetes mellitus (IDDM) and to determine the clinical characteristics of those patients. METHODS: Pancreatic exocrine morphology was studied by endoscopic retrograde pancreatography (ERP) in 43 patients with IDDM, 12 patients with islet cell antibody (ICA)-positive non-insulin-dependent diabetes mellitus (NIDDM), and 22 patients with ICA-negative NIDDM. RESULTS: ERP revealed a significantly higher prevalence of abnormal pancreatic ducts (dilation and stenosis, tortuosity, obstruction, and intraductal calculi) in the patients with IDDM (17/43, 40%) than in the patients with ICA-negative NIDDM (2/22, 9%, p = 0.018). IDDM patients who slowly progressed to insulin dependency more than 13 months after the onset of diabetes had a higher frequency of abnormal pancreatic ducts (13/22, 59%) than those who needed insulin therapy within 12 months after the onset (4/21, 19%, p = 0.016). There was no difference in duration of diabetes between the two groups. ICA-positive NIDDM patients also had a higher frequency of abnormal pancreatic ducts (7/12, 58%) than ICA-negative NIDDM patients (2/22, 9%, p = 0.0074). CONCLUSIONS: These results indicate that a high proportion of IDDM patients who have prolonged histories of non-insulin dependency with ICA suffer pancreatic exocrine impairment. A similarity between IDDM with a slowly progressive clinical course and fibrocalculous pancreatic diabetes seen in tropical countries also was suggested.

Autoantibodies↗
PubMed1993

Characterisation of the binding of [3H]FR115427, a novel non-competitive NMDA receptor antagonist, to rat brain membranes.

The binding of [3H]FR115427 ([3H](+)-1-methyl-1-phenyl-1,2,3,4- tetrahydroisoquinoline) to rat cortical synaptosomal membranes was investigated. Binding was optimal at pH 7.4-8.0, and temperature had little effect on specific binding. Binding reached equilibrium within 30 min at 25 degrees C, and was reversible in the presence of excess unlabelled FR115427. [3H]FR115427 bound to a single population of non-interacting sites with an affinity of 45.4 +/- 3.9 nM, and a binding site density of 9.12 +/- 0.52 pmol/mg protein. The affinities of other N-methyl-D-aspartate (NMDA) receptor channel blockers for [3H]FR115427 binding sites were consistent with binding to a similar site to that occupied by dizocilpine. Binding was potentiated by L-glutamate and glycine with EC50 values of around 80 nM. In the presence of L-glutamate (10 microM), specific binding was increased 4-fold, whilst addition of glycine (10 microM) increased specific binding 2-fold. FR115427 exhibited marked stereoselectivity; (+)-FR115427 has 100-fold higher affinity than (-)-FR115427. This ligand may therefore be useful for the pharmacological investigation of the NMDA receptor ion channel.

Animals↗
PubMed1993

Detection and epitope analysis of autoantigen-reactive T cells to the U1-small nuclear ribonucleoprotein A protein in autoimmune disease patients.

T cells that recognize autoantigens might play an important role in autoimmune diseases. To analyze "autoantigen-reactive T cell" in patients with an autoimmune disease, a human lymphocyte proliferation assay using soluble recombinant autoantigens has been conducted. PBMC from mixed connective tissue disease and SLE patients who possessed anti-U1-small nuclear ribonucleoprotein (snRNP) A autoantibodies responded to a recombinant U1-snRNP A protein. In contrast, PBMC from healthy subjects or autoimmune disease patients not possessing anti-U1-snRNP A autoantibodies did not show such responses. In addition, this proliferative response was inhibited by anti-CD4 mAb. Limiting dilution analyses revealed that the autoantigen-reactive T cells exist in relatively high frequency (1 of 4,065 to 1 of 23,256) in the mixed connective tissue disease patients. Moreover, by T cell epitope mapping, the T cell epitope area was found to be located in the C-terminus of the U1-snRNP A protein, overlapping the B cell epitope area that has been reported. These findings suggest the presence of autoantigen-reactive T cells in such patients, and when these T cells are activated, they may play a central role in the autoantibody generation.

Amino Acid Sequence↗