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Biomedical subjects

J Koizumi

Publications and source records attributed to J Koizumi.

At least 19 recordsLinked to original sources
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

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

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

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↗
PubMed1996

Long-term probucol treatment results in regression of xanthomas, but in progression of coronary atherosclerosis in a heterozygous patient with familial hypercholesterolemia.

A 66-year-old male heterozygous familial hypercholesterolemia (FH) patient with significant coronary atherosclerosis has been treated by us with probucol (1000 mg daily) for eight years. This treatment has produced significant reductions in the cholesterol levels of his serum, low density lipoprotein (LDL), and high density lipoprotein (HDL) from 237 +/- 20 mg/dl (mean +/- S.D.) to 156 +/- 15, from 175 +/- 8 to 111 +/- 16 mg/dl, and from 23 +/- 4 to 19 +/- 2 mg/dl, respectively. These reductions have been maintained for eight years. Serum triglyceride levels also decreased, from 220 +/- 54 to 146 +/- 36 md/dl. During this period, marked regression of xanthomas on the eyelids and finger extensor tendons was observed, while thickness of the Achilles tendons was reduced from 21.0 mm to 13.0 mm. On other hand, effort-induced anginal symptoms requiring additional antianginal medication have been noticed, and angiographically-demonstrated coronary atherosclerosis has progressed significantly during these eight years. These observations lead us to suggest that maintaining low levels of HDL cholesterol with probucol, even though resulting in satisfactory reduction of LDL cholesterol and marked regression of xanthomas, appears to be associated with the progression of atherosclerosis in the coronary arteries.

Aged↗
PubMed1996

[Recanalization of dural sinus occlusion following the disappearance of dural arteriovenous fistula: report of a case].

A 73-year-old female was admitted to our hospital because of disturbed consciousness and left-sided motor weakness. Computed tomographic scans demonstrated a hemorrhagic infarction in the right parietal region. Right carotid angiograms showed both the posterior portion of the superior sagittal sinus (SSS) and the entire left transverse sinus simultaneously occluded. Left carotid angiograms revealed an enlarged occipital artery, which had direct communications to the left sigmoid sinus and the superior petrosal sinus. These findings were consistent with dural arteriovenous fistula (D-AVF). The laboratory examinations yieled normal results. The patient was managed conservatively with glyceol and anticonvulsants for four weeks and eventually recovered with complete resolution of hemiparesis. Follow-up angiography carried out 6 weeks later showed the SSS, partially stenotic, but recanalized with no evidence of venous congestion. The D-AVF still remained opacified, but there was a marked reduction in retrograde flow to the sigmoid sinus. Further repeated angiograms obtained at 10 months after the onset confirmed complete recanalization of the SSS and disappearance of the D-AVF. From the timing of the angiographies, we considered that the sinus occlusion was caused by the high arterial flow to the fistula and its disappearance made recanalization of SSS possible.

Aged↗
PubMed1996

[Cholesteryl ester transfer protein (CETP) deficiency and increased HDL cholesterol levels (hyperalphalipoproteinemia)].

Four different CETP gene mutations have been identified as causes of increased levels of HDL cholesterol by us and other investigators; two splice donor site mutations involving intron 14, one missense mutation of D442G in exon 15, and one nonsense mutation of Q309X in exon 10. Two splice donor site mutations are G(+1)-to-A transition (Int14A) and T insertion at +3 position (Int14T), and both mutations result in null phenotype as well as a nonsense mutation. By contrast, the D442G mutation is partially defective in plasma CETP activity. Both Int14A and D442G are common mutations in the general Japanese population with high frequencies of the heterozygotes of 1% and 7%, respectively. Heterozygous CETP deficiency is sufficiently common to explain 5% of the variation in HDL-C level in the general Japanese population, in addition to well-known environmental factors. CETP common mutations may be useful for risk-assessment of coronary heart disease, as a negative and genetic risk factor.

Carrier Proteins↗
PubMed1995

Clinical efficacy of fluvastatin in the long-term treatment of familial hypercholesterolemia.

The long-term clinical efficacy of fluvastatin was assessed in 24 patients with familial hypercholesterolemia over a total treatment period of 104 weeks. Patients received an initial fluvastatin dose of 20 mg/day for 8 weeks, which was increased to 30 mg/day for a further 16 weeks. From week 24, if serum total cholesterol remained > or = 230 mg/dL, the fluvastatin dose could be increased to 40 or 60 mg/day, as necessary. By the end of treatment, 4 patients were receiving 30 mg/day fluvastatin, 1 patient was receiving 40 mg/day, and 19 patients were receiving 60 mg/day. Serum total cholesterol and low density lipoprotein cholesterol (LDL-C) levels showed a significant decrease from baseline at week 104 (total cholesterol, -26.8 +/- 2.4%; LDL-C, -33.1 +/- 3.3%; p < 0.001). The reductions in total cholesterol and LDL-C were dose-related. Statistically significant (p < 0.05) increases in serum high density lipoprotein cholesterol (HDL-C) were observed at week 24 (12.1 +/- 5.0%) and at week 76 (11.0 +/- 3.3%), although the effect was variable. Nevertherless, at the end of treatment the LDL-C: HDL-C ratio showed a 35% reduction from baseline. Changes in triglyceride levels failed to achieve statistical significance, with a reduction from baseline of -13.9 +/- 7.3% at week 104. Changes in apolipoprotein A-I were variable, with statistically significant (p < 0.01) increases observed at week 24 (7.6 +/- 2.3%) and week 76 (8.4 +/- 2.7%). By contrast, a significant reduction from baseline in apolipoprotein B was achieved by week 12 (-15.0 +/- 2.3%; p < 0.001) and was maintained throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Blood pressure change and syncope during leg phlebography].

Although syncope attacks such as black-out, faint consciousness, and cold sweat are sometimes experienced during leg phlebography, no study of their incidence and mechanism has been reported. We measured blood pressure noninvasively by using a Finapress with ECG monitor during overall examinations (21 cases, 33 limbs; male 8, female 13) following anamnesis. Age, sex, and past history of drug, syncope, leg phlebography, and other diseases were determined. All examinations were done in the upright position. Three cases (14.3%) and four limbs (12.1%) showed syncope attacks during leg phlebography. Syncope occurred after steps taken for the evaluation of venous return in two limbs, during infusion of contrast medium in one, and after infusion in the other. In all cases, the systolic blood pressure measurement during syncope was below 80 mmHg, and the sudden decrease of both systolic blood pressure (-83.0 +/- 22.0 mmHg) and heart rate (-29.5 +/- 5.0/min) suggested vasovagal reaction as a mechanism of syncope. Other causes of syncope including anaphylaxy, hyperventilation syndrome, seizure, and arrhythmia (except for bradycardia) were not found. There were also significant changes in blood pressure and heart rate in the nonsyncope group during leg phlebography that seemed to trigger vasovagal excitation. Premedication, contrast media, and position might be important factors and should be discussed further.

Adult↗
PubMed1994

Genetic cholesteryl ester transfer protein deficiency caused by two prevalent mutations as a major determinant of increased levels of high density lipoprotein cholesterol.

Genetic determinants of HDL cholesterol (HDL-C) levels in the general population are poorly understood. We previously described plasma cholesteryl ester transfer protein (CETP) deficiency due to an intron 14 G(+1)-to-A mutation(Int14 A) in several families with very high HDL-C levels in Japan. Subjects with HDL-C > or = 100 mg/dl (n = 130) were screened by PCR single strand conformational polymorphism analysis of the CETP gene. Two other mutations were identified by DNA sequencing or primer-mediated restriction map modification of PCR products: a novel intron 14 splice donor site mutation caused by a T insertion at position +3 from the exon14/intron14 boundary (Int14 T) and a missense mutation (Asp442 to Gly) within exon 15 (D442G). The Int14 T mutation was only found in one family. However, the D442G and Int14 A mutations were highly prevalent in subjects with HDL-C > or = 60 mg/dl, with combined allele frequencies of 9%, 12%, 21% and 43% for HDL-C 60-79, 80-99, 100-119, and > or = 120 mg/dl, respectively. Furthermore, prevalences of the D442G and Int14 A mutations were extremely high in a general sample of Japanese men (n = 236), with heterozygote frequencies of 7% and 2%, respectively. These two mutations accounted for about 10% of the total variance of HDL-C in this population. The phenotype in a genetic compound heterozygote (Int14 T and Int14 A) was similar to that of Int14 A homozygotes (no detectable CETP and markedly increased HDL-C), indicating that the Int14 T produces a null allele. In four D442G homozygotes, mean HDL-C levels (86 +/- 26 mg/dl) were lower than in Int14 A homozygotes (158 +/- 35 mg/dl), reflecting residual CETP activity in plasma. In 47 D442G heterozygotes, mean HDL-C levels were 91 +/- 23 mg/dl, similar to the level in D442G homozygotes, and significantly greater than mean HDL-C levels in Int14 A heterozygotes (69 +/- 15 mg/dl). Thus, the D442G mutation acts differently to the null mutations with weaker effects on HDL in the homozygous state and stronger effects in the heterozygotes, suggesting dominant expression of a partially defective allele. CETP deficiency, reflecting two prevalent mutations (D442G and Int14 A), is the first example of a genetic deficiency state which is sufficiently common to explain a significant fraction of the variation in HDL-C in the general population.

Adult↗
PubMed1994

[CETP deficiency].

Four different CETP gene mutations have been reported to be causes of increased levels of HDL cholesterol by us and other investigators; two splice donor site mutations involving intron 14, one missense mutation of D442G in exon 15, and one nonsense mutation of Q309X in exon10. Two splice donor site mutations are G (+1)-to-A transition (Int14A) and T insertion at the +3 position (Int14T), and both mutations result in null phenotype as well as a nonsense mutation. In contrast, D442G mutation is partially defective in CETP activity. Two mutations of Int14A and D442G are common mutations in the general Japanese population with a high frequency of the heterozygotes of 2% and 7%, respectively. Heterozygous CETP deficiency is sufficiently common to explain a significant fraction of the variation in HDL-C level in the general Japanese population.

Carrier Proteins↗
PubMed1994

[Probucol treatment of hyperlipidemia].

Probucol lowers total and LDL cholesterol levels, and also lowers HDL cholesterol levels. Probucol is able to lower cholesterol levels in homozygous patients with familial hypercholesterolemia as well as in heterozygous patients. In heterozygous familial hypercholesterolemia, probucol lowered total cholesterol levels by 22%, LDL-cholesterol levels by 17%, and HDL-cholesterol levels by 40%, respectively. The lowering HDL cholesterol levels by probucol may reflect increased reverse cholesterol transport. Probucol increases cholesteryl ester transfer protein concentration, and diminishes HDL particle size. Probucol has been reported to retard and even regress atherosclerosis in animal models and to diminish tendinous xanthomas in man. Its lowering LDL-cholesterol levels, activation of reverse cholesterol transport process, and antioxidant effects may cause an antiatherogenic action.

Carrier Proteins↗