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Biomedical subjects

M Okubo

Publications and source records attributed to M Okubo.

At least 109 records · Page 6Linked to original sources
PubMed1996

Lipoprotein(a) is an independent risk factor for multiple cerebral infarctions.

In an attempt to ascertain whether Lp(a) is a risk factor for multiple cerebral infarctions (MCI), we have studied 83 patients with proven MCI and 39 subjects without MCI by computed tomography (CT). Seventy-one patients with non-insulin-dependent diabetes mellitus (NIDDM) were included: 52 with and 19 without MCI. Serum Lp(a) levels were significantly higher in patients with MCI than in subjects without MCI. There were no differences in serum Lp(a) levels between NIDDM and non-diabetic patients with MCI. The logistic regression analysis revealed that Lp(a) and hypertension were independent risk factors for the cerebral event. The current study demonstrated that Lp(a) and hypertension are significant risk factors for multiple cerebral infarctions.

Aged↗
PubMed1996

A novel missense mutation (Asn5-->Ile) in lecithin: cholesterol acyltransferase (LCAT) gene in a Japanese patient with LCAT deficiency.

We identified a novel missense mutation in the lecithin:cholesterol acyltransferase gene in a new case of lecithin:cholesterol acyltransferase (LCAT) deficiency. The patient was a 64-year-old diabetic Japanese male who showed an extremely low level of serum high-density lipoprotein-cholesterol, corneal opacities, anemia, and proteinuria. Both the patient's LCAT activity and mass were markedly low. DNA sequence analysis of the LCAT gene showed an A-to-T transition at base 97 in exon 1, and predicted a change in asparagine to isoleucine at the 5th amino acid of the protein. Restriction analysis of polymerase chain reaction-amplified DNA using Ase I showed that the patient was homozygous for this mutation. Our results suggested that asparagine 5 was an important amino acid and substitution with isoleucine caused marked reduction of LCAT activity and mass, resulting in LCAT deficiency.

Amino Acid Sequence↗
PubMed1996

Insulin stimulates protein synthesis of glycogen synthase in rat hepatoma H4 cells associated with acceleration of translation rate.

To assess the regulatory mechanism of insulin action on the biosynthesis of glycogen synthase under long-term control, we investigated post-transcriptional and post-translational regulation by insulin of glycogen synthase in rat hepatoma H4 cells. Glycogen synthase protein gradually increased in response to insulin and peaked at 6 h during a 24-h insulin incubation (185% of the control), corresponding with the second peak of glycogen synthase activation measured by the activity ratio (low glucose 6-P/high glucose 6-P). The effect of insulin on synthesis of glycogen synthase protein was assessed by measuring the incorporation of [35S]-methionine into the enzyme protein during a 6-h insulin incubation. The amount of [35S]-methionine incorporation into glycogen synthase was increased in response to insulin with time, and peaked at 4 h (250% of the control). The degradation of glycogen synthase examined by measuring the rate of reduction of [35S]-methionine for 6 h after the tracer incubation for 12 h was not affected by insulin. The results indicate that (a) insulin induces glycogen synthase activity by accumulating the enzyme protein due to stimulation of protein synthesis rather than inhibition of protein degradation and (b) insulin-reduced stability of glycogen synthase mRNA is caused by acceleration of the translation rate.

Amino Acid Sequence↗
PubMed1996

Hypertriglyceridemia and low HDL cholesterol in Japanese patients with NIDDM.

Diabetes is frequently associated with the combination of hypertriglyceridemia and low HDL cholesterol level, a known risk factor for cardiovascular disease. We evaluated the frequency of elevated serum triglyceride and the reduced HDL cholesterol levels in Japanese male NIDDM patients. Hypertriglyceridemia (>1.69 mmol/l) and low HDL cholesterol level (<0.91 mmol/l) were frequently found in Japanese male (NIDDM patients (30.4 and 14.2%, respectively). The combined abnormality, i.e., hypertriglyceridemia with concomitant low HDL cholesterol level, was more common in patients with poor glycemic control. We observed that inpatient diet therapy markedly reduced serum triglyceride but serum HDL cholesterol did not change significantly. This is in marked contrast to primary hypertriglyceridemia, in which HDL cholesterol level generally increases in parallel with a reduction in serum triglyceride level. We discuss the defective removal of triglyceride-rich lipoproteins and ineffective HDL production caused by lipoprotein lipase (LPL) deficiency. We also discuss possible correction of this combined abnormality by certain maneuvers that increase LPL activity.

Adult↗
PubMed1996

Dose-dependent effect of niceritrol on plasma lipoprotein-a.

Lipoprotein-a, Lp(a), is a variant form of low density lipoprotein (LDL) that contains apolipoprotein-a, whose structure has 75-85% homology with plasminogen. Elevated plasma levels of Lp(a) are considered to be one of the independent risk factors for cardiovascular disease. We studied the effects of niceritrol, a nicotinic acid derivative, on plasma Lp(a) levels in 72 patients with hypercholesterolaemia. The dose of niceritrol was increased every 4 weeks, from 750 to 1500 and then to 2250 mg day-1. The final dose was adjusted to obtain a plasma cholesterol level less than 5.69 mmol l-1. Niceritrol led to significant decreases in plasma levels of median Lp(a), from 16.1 mg dl-1 (interquartile intervals, 8.7 to 32.8) to 11.1 mg dl-1 (interquartile intervals, 6.6 to 21), the mean reduction rate being 17.6%. In the group with pretreatment Lp(a) levels of over 20 mg dl-1, Lp(a) decreased by 10.0, 22.0 and 31.8% at the doses of 750, 1500, and 2250 mg day-1, respectively. In the group with levels less than 20 mg dl-1, only the dose of 2250 mg day-1 was effective in the reduction of Lp(a). The results suggest that the reduction of Lp(a) was dependent on the dose of niceritrol and on the pretreatment level of Lp(a). In conclusion, niceritrol is effective, in a dose-dependent manner, for reducing Lp(a) levels.

Aged↗
PubMed1996

Enhancement of lymphokine-activated killer cell cytotoxicity implicated in the increased expression of surface adhesion molecules on tumor cells treated with anticancer agents.

We investigated mechanisms underlying lymphokine-activated killer (LAK) cell cytotoxicity in terms of intensity of expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte-function-associated antigen-3 (LFA-3) on Daudi and KATO-III cells treated with cis-diamminedichloroplatinum (II) (CDDP) and mitomycin-C (MMC). Enhancement (mean, 49.8%) of ICAM-1 or LFA-3 in mRNA and protein expression on treated tumor cells was found by flow cytometry, slot-blot RNA analysis, and reverse transcription-polymerase chain reaction (RT-PCR). Increases in adhesion and cytotoxicity of LAK cells to treated tumor cells were 10.1% and 17.7%, respectively. Results suggested that increased ICAM-1 or LFA-3 expression by low-dose CDDP or MMC binds LAK cells to tumor cells, helping to kill tumor cells. Thus, LAK cell therapy with anticancer agent pretreatment could be useful for treatment of cancer patients.

Antibodies, Monoclonal↗
PubMed1996

Increased serum concentrations of pro-gastrin-releasing peptide in patients with renal dysfunction.

BACKGROUND: Gastrin-releasing peptide has a prominent role as a tumour marker in the diagnosis of small-cell lung carcinoma. This study was designed to assess the validity of a newly developed enzyme-linked immunosorbent assay (ELISA) for pro-gastrin-releasing peptide in patients with renal and systemic diseases. METHODS: Pro-gastrin-releasing peptide concentrations in sera from normal subjects and patients with small-cell lung carcinoma, diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, chronic glomerulonephritis, or undialysed or dialysed chronic renal failure were measured with the TND-4 Kit, a newly developed ELISA for pro-gastrin-releasing peptide. RESULTS: All of the patients with normal renal function, whether they had diabetes mellitus (n=16), rheumatoid arthritis (n=10), systemic lupus erythematosus (n=12) or chronic glomerulonephritis (n=14), had serum pro-gastrin-releasing peptide concentrations less than 46 ng/l, the upper limit in normal subjects. In contrast, 14 or 16 patients (88%) with small-cell lung carcinoma, who had normal renal function, and 25 of 26 (96%) patients with chronic renal failure on haemodialysis had serum pro-gastrin-releasing peptide concentrations greater than 46 ng/l. The highest serum pro-gastrin-releasing peptide levels in patients with chronic renal failure, before and after initiating haemodialysis were 183 and 290 ng/l respectively. Ten of 16 (63%) small-cell lung carcinoma patients had serum pro-gastrin-releasing peptide concentrations greater than 290 ng/l, the highest level in haemodialysed patients. Serum pro-gastrin-releasing peptide concentrations were also elevated in patients with chronic glomerulonephritis or diabetes mellitus when their serum creatinine concentrations were greater than 120 micromol/l. And, there was a significant correlation, y=23.5+0.15x(n=22, r=0.82, P<0.001),between serum pro-gastrin-releasing peptide (y, in ng/l) and serum creatine (x in micromol/l) concentrations in those patients with renal dysfunction. The correlation between serum pro-gastrin-releasing peptide and serum urea nitrogen concentrations was likewise significant. CONCLUSIONS: The evaluation of patients as to their renal functional state may be mandatory when serum pro-gastrin-releasing peptide levels are to be applied as one of the diagnostic tools for small-cell lung carcinoma or as a marker monitoring their clinical course.

Adult↗
PubMed1996

Donor leukocyte transfusions and discontinuation of immunosuppressants to achieve an initial remission after allogeneic bone marrow transplantation in a patient with primary refractory acute leukemia.

We present a female patient who received an allogeneic bone marrow transplantation for primary refractory Philadelphia-positive acute biphenotypic leukemia. Since leukemic blasts were persistently present in peripheral blood and bone marrow, in spite of the evidence for engraftment of male donor hematopoiesis, we performed donor leukocyte transfusions and discontinued immunosuppression. An initial complete remission was obtained 15 weeks after allogeneic bone marrow transplantation, and lasted for 24 weeks. We concluded that the prominent mechanism for the eradication of the refractory leukemic clone in the patient was the graft-versus-leukemia effect.

Adult↗
PubMed1995

Mechanism of balloon angioplasty in children with arterial stenosis assessed by intravascular ultrasound and angiography.

Fifteen patients were examined before and immediately after balloon angioplasty with a 4.3F, 30 MHz rotational tip intravascular ultrasound system. In 12 (80%) patients, 13 procedures could be analyzed because of sufficient image quality. The lesions for intravascular ultrasound (IVUS) study consisted of pulmonary arterial stenosis in 4 patients, Blalock-Taussig shunt stenosis in 3, coarctation of the aorta in 2, subclavian artery stenosis in 1, renal artery stenosis in 1, and ductus arteriosus in 1. Three distinctive morphologic types were identified: Group I had arterial stretching (3 patients); group IIa had superficial tearing (3); group IIb had deep intimal-medial tearing (5); group III had dissection (2). In the narrowest site, minimal and maximal luminal diameters, luminal area before and after balloon angioplasty were 3.5 +/- 1.8 mm vs 4.5 +/- 2.5 mm, 4.1 +/- 2.1 mm vs 5.4 +/- 3.5 mm, and 49.8 +/- 30.2 mm vs 88.3 +/- 45.2 mm2, respectively. The recoil value of group IIb with appropriate balloon angioplasty was approximately 0.3. IVUS may be an useful modality for evaluating the morphologic mechanism of dilatation after balloon angioplasty.

Adult↗
PubMed1995

Relationship between insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus: beta-cell function, islet cell antibody, and haptoglobin in parents of IDDM patients.

To examine the relationship between non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM), we studied beta-cell function, HLA type, and serologic markers of IDDM and NIDDM in the parents of IDDM patients. Fifty-two parents of 33 IDDM patients were examined in terms of islet-cell antibody (ICA) status, haptoglobin phenotype, HLA type, and insulin responses during an oral glucose tolerance test (OGTT). Twenty-seven parents were prospectively evaluated for up to 113 months. They were divided into the following three groups based on pattern of ICA positivity during the follow-up period: group 1, persistently positive ICA (n = 4); group 2, fluctuating ICA (n = 7); and group 3, persistently negative ICA (n = 16). Twenty-three percent (12 of 52) of the parents of IDDM patients had NIDDM, and 12% (six of 52) of the matched controls did. The prevalence of ICA in the parents (11 of 52, 21%) was greater than in normal controls (one of 112, P < .01). Diabetic parents tended to show a higher prevalence of ICA (six of 12, 50%) than nondiabetic parents (six of 40, 15%; P = .06). ICA-positive parents showed higher glucose levels and lower insulin responses than ICA-negative parents. Three of four parents in group 1 slowly progressed to an insulin-dependent state during 25 +/- 3 months of follow-up evaluation. Parents in group 2 and group 3 did not show any changes in glucose levels or insulin responses during the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Effect of administering calcium carbonate to treat secondary hyperparathyroidism in nondialyzed patients with chronic renal failure.

We administered calcium carbonate orally to determine its safety and efficacy in treating nondialyzed patients with mild to moderate renal failure and secondary hyperparathyroidism. Twenty patients with chronic renal failure (creatinine clearance levels ranging from 7.9 to 42.7 mL/min) participated in this study. After a 6-month control period, 3 g calcium carbonate was administered daily for 6 months. We studied the effect for another 6 months after discontinuation of the regimen. We found that serum-intact parathyroid hormone was suppressed from 183 +/- 149 pg/mL to 85 +/- 61 pg/mL (P < 0.05) by treatment. This suppression was achieved with no increase in serum concentrations of 1,25(OH)2D3. Serum phosphorus levels decreased from 3.4 +/- 0.7 to 3.0 +/- 0.7 mg/dL (P < 0.01) and Ca2+ concentration increased significantly from 2.40 +/- 0.12 mEq/L to 2.57 +/- 0.08 mEq/L (P < 0.001) at 6 months. These changes were reversed after the 6-month period of withdrawal from calcium carbonate. Deterioration of renal function was not exacerbated by the therapy. Calcium carbonate administration also suppressed the serum concentrations of alkaline phosphatase and osteocalcin, indicating that improvement of hyperparathyroid bone disease is possible without a vitamin D3 supplement at an earlier stage of renal failure. Thus, administration of 3 g oral calcium carbonate daily was highly effective in treating secondary hyperparathyroidism in patients with mild to moderate renal failure.

Administration, Oral↗