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Biomedical subjects

J Koizumi

Publications and source records attributed to J Koizumi.

At least 55 records · Page 3Linked to original sources
PubMed1999

Plasma homocysteine level and development of coronary artery disease.

BACKGROUND: The plasma level of homocysteine is an independent risk factor for atherosclerotic vascular disease. The relationship between plasma homocysteine level and the onset of coronary artery disease (CAD) has not been established. OBJECTIVE: To investigate the relationship between plasma homocysteine level and the age at which CAD was diagnosed. METHODS: Fifty-seven male patients aged < or = 65 years (mean age 53 years) with angiographically proven symptomatic CAD seen consecutively and 138 age-matched male control subjects (mean age 52 years) free from atherosclerotic vascular disease were studied. They were divided into two subgroups, a group of younger subjects (aged < or = 55 years) and a group of older subjects (aged 56-65 years). RESULTS: Plasma homocysteine levels in CAD patients significantly exceeded those of control subjects (means 13.4 versus 10.6 nmol/ml, P = 0.0002). Plasma homocysteine level of subjects in younger CAD group was significantly higher than that of subjects in older CAD group (15.0 versus 11.3 nmol/ml, P = 0.03), and age and logarithmically transformed plasma homocysteine level exhibited a significant negative correlation (r = -0.28, P = 0.03) for subjects in CAD group. Among control subjects, members of our two age subgroups had similar plasma homocysteine levels. Younger CAD patients had significantly higher plasma homocysteine levels than did younger controls (15.0 versus 10.4 nmol/ml, P < 0.0001). However, for older groups there was no significant difference between plasma homocysteine levels in CAD patients and controls (11.3 versus 10.9 nmol/ml). Multiple regression analysis showed that only logarithmically transformed plasma homocysteine level was a significant predictor for age of onset of CAD. CONCLUSION: An elevated level of plasma homocysteine is more important in the development of premature CAD than it is in that of late-onset CAD among men.

Adult↗
PubMed1999

Abetalipoproteinemia caused by maternal isodisomy of chromosome 4q containing an intron 9 splice acceptor mutation in the microsomal triglyceride transfer protein gene.

Uniparental disomy (UPD), a rare inheritance of 2 copies of a single chromosome homolog or a region of a chromosome from one parent, can result in various autosomal recessive diseases. Abetalipoproteinemia (ABL) is a rare autosomal recessive deficiency of apoB-containing lipoproteins caused by a microsomal triglyceride transfer protein (MTP) deficiency. In this study, we describe a patient with ABL inherited as a homozygous intron 9 splice acceptor G(-1)-to-A mutation of the transfer protein gene. This mutation alters the splicing of the mRNA, resulting in a 36 amino acids, in-frame deletion of sequence encoded by exon 10. We analyzed chromosome 4, including MTP gene (4q22-24), using short tandem repeat markers. The proband has only his mother's genes in chromosome 4q spanning a 150-centimorgan region; ie, segmental maternal isodisomy 4q21-35, probably due to mitotic recombination. Nonpaternity between the proband and his father was excluded using 6 polymorphic markers from different chromosomes (paternity probability, 0.999). Maternal isodisomy (maternal UPD 4q) was the basis for homozygosity of the MTP gene mutation in this patient.

Abetalipoproteinemia↗
PubMed1999

[Clinical significance of serum lipoprotein(a) concentration in the elderly with regard to vascular complications and long-term prognosis].

To elucidate the clinical significance of lipoprotein(a) [Lp(a)] in the elderly, 48 patients with Lp(a) of 35 mg/dl or more [the high Lp(a) group] and 97 patients with Lp(a) less than 20 mg/dl [the low Lp(a) group] were enrolled to investigate their outcome for five years. At registration, they were all examined by brain computerized tomography (CT) for cerebrovascular diseases, B-mode ultrasonography (US) for carotid lesions, ECG for myocardial ischemia, and Doppler arteriography for the ankle pressure index (API). They were followed up completely to study survival rates, cause of death, and morbidity rates of vascular events, including occurrence of stroke, myocardial infarction, and aortic aneurysm as well as progression of the stage in arteriosclerosis obliterans. The mean age of the high Lp(a) group was 78.1, whereas that of the low Lp(a) group was 76.8. Baseline clinical findings revealed no difference in age or gender between the two groups, although a previous history of stroke, abnormal CT and US findings, and low API were more frequent in the high Lp(a) group than in the low Lp(a) group. In the high Lp(a) group [vs. the low Lp(a) group], 18 patients (vs. 21 patients) died within five years, which resulted in a cumulative mortality rate of 37.5% (vs. 21.6%) and an annual mortality rate of 9.4% (vs. 4.8%). Based on log-rank analysis, the survival rate of the high Lp(a) group was significantly lower than that of the low Lp(a) group. The most common causes of death were vascular events and pneumonia, more than half of them were aspiration pneumonia complicated with stroke. Ten patients in the high Lp(a) group had vascular events (vs. 8 patients). The morbidity rate of vascular events, most of which were cerebral infarction, was higher in the high Lp(a) group (annual morbidity rate 5.5%) than in the low Lp(a) group (1.8%). These findings suggested that serum Lp(a) concentration, genetically determined and remaining consistent throughout life, had influenced vascular wall damage over a long time with age, therefore, a high Lp(a) level might promote atherothrombosis. In the elderly, therefore, high Lp(a) level, resulting in symptomatic vascular lesions with organ dysfunction, is a distinct and independent poor prognostic risk factor.

Aged↗
PubMed1999

[A case of mediastinal myelolipoma].

Myelolipoma is a benign tumor composed of mature adipose tissue and hematopoietic tissue. It was mainly found in the adrenal grand, but there have been reports of extra-adrenal locations. Only 7 cases of mediastinal myelolipoma have been reported ever. We have experienced a case of mediastinal myelolipoma surgically resected from a 55-year-old-man. He has visited our department because of chest pain. Chest X-ray showed typical pneumothorax, but abnormal mediastinal shadow was remarked. Chest CT showed a well circumscribed mass with fat and soft-tissue attenuation in posterior mediastinum. Lung bullectomy and mediastinal tumor resection under VATS was performed. A blue-red tumor 4 cm in diameter was resected en bloc. Pathological examination showed its composition of mature adipose tissue and hematopoietic tissue. Diagnosis was extra-adrenal myelolipoma. No recurrent nor abnormality was found in 8 months since surgery.

Endoscopy↗
PubMed1999

Coronary ectasia in familial hypercholesterolemia: histopathologic study regarding matrix metalloproteinases.

A 39-year-old male heterozygous familial hypercholesterolemia patient with marked ectasia over the entire coronary artery tree had been treated with several kinds of lipid-lowering single or combined drug therapies using clofibrate, compactin, cholestyramine, probucol, and pravastatin, and LDL-apheresis. During the 19-year follow-up, he suffered myocardial infarction three times and some of the ectatic coronary segments became enlarged, others narrowed, and one of them occluded in spite of the treatment. At the age of 58, he died after a fourth cardiac attack and subsequent cardiogenic shock. The autopsy indicated that his three coronary arteries showed diffuse ectatic changes and the largest lumen diameter of the left anterior descending artery was 25 mm, of the circumflex artery 12 mm, and of the right coronary artery 13 mm. The ectatic artery wall was not thick and the major part of the lumen was occupied by organized thrombi. Microscopic examinations showed that the larger the diameter of the lumen, the more severe the structural damage of the intima and tunica media and the larger the number of infiltrated cells, including lymphocytes, macrophages, and plasma cells. Immunoreactivity against matrix metalloproteinase (MMP)-1, and MMP-2 was observed in smooth muscle cells, macrophages, lymphocytes, and endothelial cells of the vasa vasorum or neovasculature. MMP-9 immunoreactivity was also localized in intimal foamy macrophages and round cells (macrophages and lymphocytes) of the media and adventitia. MMP-1 increased with the lumen diameter of the ectatic arteries. The ratio of immunoreactivity against both MMP-2 and MMP-9 to that against tissue inhibitor of metalloproteinase (TIMP)-2 also increased with the lumen diameter, but it no longer increased when the diameter was over 10 mm. These observations suggest that the MMP-TIMP system appears to play a significant role in the development of coronary ectasia

Adult↗
PubMed1998

Long-term efficacy of low-density lipoprotein apheresis on coronary heart disease in familial hypercholesterolemia. Hokuriku-FH-LDL-Apheresis Study Group.

Familial hypercholesterolemia (FH) is characterized by severe hypercholesterolemia and premature coronary heart disease (CHD). The lower the plasma cholesterol level, the more likely it is that CHD can be prevented or retarded; aggressive cholesterol-lowering therapies may be indicated for FH patients with CHD. This study describes the long-term (6 years) safety and efficacy of intensive cholesterol-lowering therapies with low-density lipoprotein (LDL) apheresis in heterozygous FH patients with CHD. One hundred thirty heterozygous FH patients with CHD documented by coronary angiography had been treated by cholesterol-lowering drug therapy alone (n=87) or LDL apheresis combined with cholesterol-lowering drugs (n=43). Serum lipid levels and outcomes in each treatment group were compared after approximately 6 years. Both treatment groups had significant reductions in serum cholesterol, LDL cholesterol, and high density lipoprotein cholesterol levels. LDL apheresis significantly reduced LDL cholesterol levels from 7.42+/-1.73 to 3.13+/-0.80 mmol/L (58%) compared with group taking drug therapy, from 6.03+/-1.32 to 4.32+/-1.53 mmol/L (28%). With Kaplan-Meier analyses of the coronary events including nonfatal myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, and death from CHD, the rate of total coronary events was 72% lower in the LDL-apheresis group (10%) than in drug therapy group (36%) (p=0.0088). It is concluded that LDL-apheresis is effective as treatment of CHD in FH heterozygotes, and may become the therapy of choice in severe types of FH.

Aged↗
PubMed1998

Clinical efficacy and safety of cerivastatin in the treatment of heterozygous familial hypercholesterolemia.

Patients with heterozygous familial hypercholesterolemia are at especially high risk of premature coronary artery disease and usually require aggressive long-term lipid-lowering drug therapy to decrease plasma low-density lipoprotein (LDL) cholesterol concentrations to normal levels. In the present study, the lipid-lowering effects of cerivastatin in combination with cholestyramine and probucol were investigated in 20 patients with heterozygous familial hypercholesterolemia over a 20-week treatment period. After an initial 4-week treatment with once-daily 0.2 mg cerivastatin, serum total cholesterol and LDL cholesterol levels had decreased by a significant 22% and 25%, respectively (p <0.01). The addition of 8 g/day cholestyramine or 1 g/day probucol to ongoing cerivastatin therapy produced further significant reductions in total cholesterol of 16% and 16%, respectively, and in LDL cholesterol of 22% and 15%, respectively (p <0.01), over the 12-week combination therapy period. The potent lipid-lowering effects of combined treatment were accompanied by excellent toleration of study drugs. Only 2 patients experienced gastrointestinal side effects associated with cholestyramine therapy. There was no evidence of any abnormalities in creatine phosphokinase in either treatment group and only 2 patients exhibited minor increases in hepatic transaminases. This study has shown that cerivastatin can be safely combined with either cholesytramine or probucol to provide a safe and highly effective hypolipidemic treatment regimen for patients with heterozygous familial hypercholesterolemia.

Adult↗
PubMed1998

Low-density lipoprotein receptor genotype-dependent response to cholesterol lowering by combined pravastatin and cholestyramine in familial hypercholesterolemia.

We compared the effects of cholesterol-lowering therapy on 2 patient groups genetically defined as heterozygous for familial hypercholesterolemia (FH), 5 with a deletion of exon 15 (FH(Tonami-1)), and 7 with a point mutation at codon 664 (FH(Kanazawa-2)). There were significant differences in both serum and low-density lipoprotein cholesterol reductions between the 2 groups after combination therapy with pravastatin and cholestyramine, and the overall effect of genotype on serial changes in both was significant.

Adult↗
PubMed1998

Enzyme immunoassay for cholesteryl ester transfer protein in human serum.

We developed a new simple sandwich-type enzyme immunoassay to measure cholesteryl ester transfer protein (CETP) mass in human serum. In assay validation, Intra- and Inter-assay coefficients of variation were 2.7 to 5.7% and 2.2 to 12.2%, respectively. There was no cross-reactivity with various lipoproteins (apo A-I, apo A-II, apo B, apo C-III). A good correlation between CETP mass and CETP activity (n = 46, correlation coefficient = 0.88) was observed. This assay provided a specific and reproducible method for measuring CETP mass in samples. The average value of CETP in the normal sera of 41 males was 1.8+/-0.6 microg/ml (mean+/-S.D.) and that of 37 females was 2.0+/-0.5 microg/ml. In the study of patients with the CETP gene mutation (Int 14A and D442G), our results on the value of plasma CETP mass reflected to genetic CETP deficiency. In conclusion, this assay for CETP mass in human serum may be a useful tool for clinical investigations involving lipid metabolism related to disease.

Adult↗
PubMed1998

Correlation between magnetic resonance imaging and histopathology of an amputated forearm after an electrical injury.

A 53-year-old man sustained a 50 Hz, 60 kV electrical injury. The current flowed between his right hand and both feet. There was necrosis of the distal portion of the right forearm, and the fourth and fifth toes on the right foot. The skin on the amputated right upper extremity appeared normal except for an ulcer in the antecubital fossa and some blister scars. However, most of the muscles of the arm at the elbow were necrosed and partially replaced by fatty tissue or fibrosis. These necrotic areas corresponded to minimally increased signal intensities on T1-weighted MRI, and high signal intensities on T2-weighted images. MRI may be employed to predict amputation level after electrical injury.

Adult↗
PubMed1998

Hepatic perfusion changes after transcatheter arterial embolization (TAE) of hepatocellular carcinoma: measurement by dynamic computed tomography (CT).

We observed the hemodynamic changes at the level of the hepatic parenchyma induced by transcatheter arterial embolization (TAE) for hepatocellular carcinoma in 22 patients. TAE was performed by administration of a mixture of iodized oil, adriamycin, and mitomycin C, followed by injection of gelatin sponge particles (1-mm pieces). Perfusion measurements (arterial and portal) were done by dynamic computed tomography (CT). Arterial perfusion was increased two to six days after TAE (0.146 +/- 0.073 ml/min/ml, P < 0.0002) compared with that before TAE (0.064 +/- 0.039), but decreased again one month after TAE (0.086 +/- 0.038). Portal perfusion was decreased two to six days after TAE (0.541 +/- 0.180, P < 0.001) compared with that before TAE (0.733 +/- 0.263) and was grossly unchanged one month after TAE (0.651 +/- 0.214). We suspected that these perfusion changes were due to acute inflammatory responses. Quantification of tissue perfusion by dynamic CT was useful for studying hemodynamic changes after TAE.

Aged↗
PubMed1998

Isolation and chemical composition of the sheath of Sphaerotilus natans.

A sheathed bacterium, Sphaerotilus natans, was cultured with vigorous shaking in a medium containing peptone. Then the biomass was harvested and treated with lysozyme, sodium dodecyl sulfate, and protease. With treatment, 1.6 mg of sheaths was obtained from 15 mg of biomass. For the preparation of sheaths of high purity, cultivation must be in the absence of glucose with sufficient aeration to prevent poly(3-hydroxybutyrate) accumulation. Carbohydrate (54.1%), protein (12.2%), and lipid (1-3%) were detected in the sheaths by colorimetric reactions and solvent extraction. Gas-liquid chromatography showed glucose and galactosamine to be present in the molar ratio of 1:4. The most abundant amino acids in the sheath protein were glycine (49.2 mol%) and cysteine (24.6 mol%). The sheaths were resistant to agents that reduce disulfide bonds (dithiothreitol and 2-mercaptoethanol) and to protease. However, sheathes were degraded completely by hydrazine, and a heteropolysaccharide composed of glucose and galactosamine (1:4) was released. The weight-average molecular weight of the polysaccharide was estimated to be 1.2 x 10(5) by gel filtration chromatography with a low-angle laser-light scattering photometer and a rotation index detector. A ladder of 1.5-kDa peptides separable by sodium dodecyl sulfate gel electrophoresis was obtained by partial hydrolysis of sheaths, suggesting the sheath protein has repeating units of 1.5 kDa.

Amino Acids↗
PubMed1998

Evaluation of portal pressure by splenic perfusion measurement using dynamic CT.

OBJECTIVE: The purposes of this study were to determine if splenic perfusion measurements obtained using dynamic CT are useful in the evaluation of portal hypertension. MATERIALS AND METHODS: Forty-four patients with chronic liver disease (29 men and 15 women, 49-81 years old) and 38 control subjects (17 men and 21 women, 21-79 years old) underwent dynamic CT of the spleen. Regions of interest were drawn on images of the spleen and aorta, and splenic perfusion was calculated by dividing the peak gradient of the splenic time-attenuation curve by the peak aortic CT measurement increase. In 11 patients with chronic liver disease and three patients with normal livers, we measured the wedged hepatic vein pressure (WHVP) of the right or right accessory hepatic vein to estimate portal vein pressure. RESULTS: Splenic perfusion was less in patients with chronic liver disease (0.894 +/- 0.324 ml/min) than in the control group (1.299 +/- 0.429 ml/min; p < .0001). We found a significant negative correlation between splenic perfusion and WHVP (r = .741; p = .0024). CONCLUSION: A significant decrease in splenic perfusion in patients with chronic liver disease negatively correlated with WHVP. Measurement of splenic perfusion may be useful in the evaluation of portal hypertension.

Aged↗
PubMed1997

Characterization of the transposition pattern of the Ac element in Arabidopsis thaliana using endonuclease I-SceI.

We have investigated physical distances and directions of transposition of the maize transposable element Ac in Arabidopsis thaliana. We prepared a transferred DNA (T-DNA) construct that carried a non-autonomous derivative of Ac with a site for cleavage by endonuclease I-SceI (designated dAc-I-RS element). Another cleavage site was also introduced into the T-DNA region outside dAc-I-RS. Three transgenic Arabidopsis plants were generated, each of which had a single copy of the T-DNA at a different chromosomal location. These transgenic plants were crossed with the Arabidopsis that carried the gene for Ac transposase and progeny in which dAc-I-RS had been transposed were isolated. After digestion of the genomic DNA of these progeny with endonuclease I-SceI, sizes of segment of DNA were determined by pulse-field gel electrophoresis. We also performed linkage analysis for the transposed elements and sites of mutations near the elements. Our results showed that 50% of all transposition events had occurred within 1,700 kb on the same chromosome, with 35% within 200 kb, and that the elements transposed in both directions on the chromosome with roughly equal probability. The data thus indicate that the Ac-Ds system is most useful for tagging of genes that are present within 200 kb of the chromosomal site of Ac in Arabidopsis. In addition, determination of the precise localization of the transposed dAc-I-RS element should definitely assist in map-based cloning of genes around insertion sites.

Journal Article↗
PubMed1997

Clinical characteristics of double heterozygotes with familial hypercholesterolemia and cholesteryl ester transfer protein deficiency.

Coronary heart disease (CHD) in familial hypercholesterolemia (FH) may be modified by genetic and/or environmental factors. We described the effect of the cholesteryl ester transfer protein (CETP) gene on CHD in heterozygous FH caused by low density lipoprotein receptor (LDL-R) gene mutation. In 288 unrelated Japanese subjects with heterozygous FH, the allele frequency of an intron 14 G(+1)-to-A mutation (Int14 A) and a missense mutation in exon 15 (Asp442 to Gly, D442G) was 0.3 and 3.0%, respectively. HDL-C levels (1.55 +/- 0.08 mmol/l) in FH patients with heterozygous CETP deficiency were higher than those (1.19 +/- 0.08 mmol/l) in FH without CETP deficiency (P < 0.03), while LDL-C levels in FH with CETP deficiency were moderately reduced. However, two FH patients with CETP deficiency suffered myocardial infarction, and six patients had effort angina pectoris and/or coronary atherosclerosis. No difference in the score of coronary stenosis index (CSI) was found in FH with/without CETP deficiency, although CSI was inversely correlated with HDL-C levels (P < 0.05). Thus, the effect of increased HDL-C levels caused by partial deficiency of CETP is insufficient to prevent CHD in FH.

Adult↗
PubMed1997

Catalytically inactive lecithin: cholesterol acyltransferase (LCAT) caused by a Gly 30 to Ser mutation in a family with LCAT deficiency.

Plasma lecithin:cholesterol acyltransferase (LCAT) plays an important role in early steps of reverse cholesterol transport, i.e., cholesterol efflux from peripheral tissues and cholesterol esterification in HDL. However, structural and functional relationships of LCAT have not been fully elucidated. We described a missense mutation of Gly 30-to-Ser in a patient with classical LCAT deficiency. The proband was homozygous for the mutation and had a very low level of HDL cholesterol (2 mg/dl), with a half of normal LCAT mass (2.75 micrograms/ml), but no detectable or very low LCAT activity in endogenous and exogenous substrate assays. Both his mother and sister were heterozygous for the mutation, and had slightly decreased levels of HDL cholesterol (34 and 36 mg/dl, respectively). Transient expression study using COS cells indicated that mutant cDNA produces similar amounts of media protein as compared to wild type, but no detectable LCAT activity. The missense mutation may result in a near-native conformation without large effects on cellular secretion but a catalytically defective protein. Thus, the N-terminal domain appears crucial for enzymatic activity, in addition to the catalytically active consensus sequence of Gly179 to Gly183 and a putative sterol binding domain of Glu154 to Lys173.

Animals↗