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Biomedical subjects

J Koizumi

Publications and source records attributed to J Koizumi.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1993

Autoradiographic localization of CCK-8 binding sites in the rat brain: effects of chronic methamphetamine administration on these sites.

The effects of chronic methamphetamine (MAP) administration (at a dose of 4 mg/kg for 14 days) on [3H]pCCK-8 binding sites in the rat brain were investigated by an in vitro quantitative receptor autoradiographic technique. The number of [3H]pCCK-8 binding sites was significantly reduced in layers III and IV of the medial frontal, anterior, and posterior cingulate cortices, in layers II-IV of the retrosplenial cortex, in layers III-VI of the dorsal insular cortex, and in the reticular nucleus of the thalamus, compared to these numbers in a control group of rats that received physiologic saline. Further, chronic methamphetamine administration led to a significant increase in the number of these binding sites in layer I of the entorhinal cortex. These findings indicate the CCK peptides in the limbic lobe may be closely related to the development of the behavioral changes associated with methamphetamine sensitization. In addition, these results provide supporting evidence for the involvement of the limbic system in the pathophysiology of schizophrenia.

Animals↗
PubMed1993

Rapid detection and prevalence of cholesteryl ester transfer protein deficiency caused by an intron 14 splicing defect in hyperalphalipoproteinemia.

A deficiency of plasma cholesteryl ester transfer protein (CETP) is one of the genetic causes of increased serum high density lipoprotein (HDL)-cholesterol levels (hyperalphalipoproteinemia). A splicing defect (G-->A mutation) at the +1 position of intron 14 of the human CETP gene is a common mutation in the Japanese CETP deficiency. A rapid screening method for the splicing defect by means of primer-specified restriction map modification was described. The frequency of the mutation in hyperalphalipoproteinemia was determined, and its frequency in the general population was estimated. During polymerase chain reaction (PCR) with a modified primer, a novel NdeI restriction endonuclease site was created from the mutated allele in the PCR products, which could be visualized after electrophoresis of the digested products. As a result, 21 of 121 unrelated hyperalphalipoproteinemic subjects with HDL-cholesterol > or = 60 mg/dl (1.55 mmol/l), were found to have the G-->A mutation. Of the 21 individuals, 8 were found to be homozygous for the mutation. Allele frequency of the mutation was 1.5% (1/68), 2.8% (2/72), 7.1% (4/56), and 47.8% (22/46) in the groups with HDL-cholesterol levels of 60-79 mg/dl, 80-99 mg/dl, 100-119 mg/dl, and > or = 120 mg/dl, respectively. Based on the percentage of the area under the computed normal distribution curve of serum HDL-cholesterol, the frequency of the mutated allele in the general population was estimated to be 0.81% from the present results. This rapid detection method facilitates large-scale screening of CETP deficiency caused by the splicing defect. The mutation was frequent in Japanese subjects with hyperalphalipoproteinemia, especially in the group with HDL-cholesterol > or = 120 mg/dl.

Adult↗
PubMed1993

Reduction of lipoprotein(a) by LDL-apheresis using a dextran sulfate cellulose column in patients with familial hypercholesterolemia.

Lipoprotein(a) (Lp(a)) was eliminated by LDL-apheresis using a dextran sulfate cellulose column in 3 homozygous and 10 heterozygous familial hypercholesterolemic patients. Immediately after LDL-apheresis by the LA-15 system (continuous LDL apheresis), there were significant reductions in Lp(a) concentrations (28.6 +/- 11.8 mg/dl (mean +/- S.E.) to 9.6 +/- 5.6 mg/dl (P < 0.01)), and in LDL-cholesterol concentrations (156 +/- 32 mg/dl to 48 +/- 18 mg/dl (P < 0.01)). Immediately following LDL-apheresis, Lp(a) and LDL-cholesterol were reduced by 67.4% +/- 11.6% and 68.3% +/- 11.8%, respectively. The removal of Lp(a) paralleled that of LDL-cholesterol. The reduced levels of Lp(a) nearly returned to baseline within 7 days. In 6 of the heterozygous FH patients the rates of recovery of LDL cholesterol and Lp(a) were calculated, according to Apstein's equation after discontinuing lipid altering drug treatment for 4 weeks. Mean constant k values of LDL cholesterol and Lp(a) were 0.354 (range: 0.136-0.752) and 0.427 (range 0.112-0.933), respectively. The average concentration during the 7 days following LDL-apheresis was calculated. Average reductions were 28% in LDL cholesterol and 18% in Lp(a). Pravastatin treatment, which continued for 4 weeks, significantly decreased LDL cholesterol (P < 0.01); however, before LDL-apheresis pravastatin treatment significantly increased Lp(a) levels (P < 0.05) in a small number (n = 6) of the FH patients, who had been regularly treated with LDL-apheresis. These results suggest that LDL-apheresis using the dextran sulfate cellulose column is an effective treatment to reduce levels of serum Lp(a) and LDL proportionally. This therapy may be of value in the prevention and regression of coronary artery disease in FH patients.

Adolescent↗
PubMed1993

Delusional depression and suicide.

During the 12-year period of retrospective observation, 38 cases of 93 major depressive inpatients were delusional and the remainders were nondelusional. We evaluated the differences on several variables, especially about suicide, between the two groups. The mean age at the onset of illness of delusional depressive patients was higher than that of nondelusional ones. The incidence of psychomotor retardation was lower in the former group than in the latter. The frequency of suicidal ideation and suicidal attempts were higher in the former group than the latter. The suicidal methods in the delusional depressives tended to be more active and violent than those in nondelusional depressives and were supposed to have a twofold mortality than those in the nondelusional ones. We discussed this high rate of suicides of delusional depression from the viewpoint of disinhibition of psychomotor retardation, chronicity, partial affinity of delusional depressives to schizophrenics and neuroendocrinological perspective.

Adult↗
PubMed1993

CNS changes in DRPLA with dementia and personality changes: CT, MR and SPECT findings.

CNS changes in a case of DRPLA associated with dementia and personality changes were observed by CT, MR and SPECT. Brain CT and MR of the patient revealed progressive cortical atrophy which was recognized in parallel with the clinical course of the progression of dementia and personality changes. SPECT using 123I-iodoamphetamine (IMP) disclosed a diffuse low perfusion of the cerebral cortex, especially in the frontal and temporal lobes. These findings suggest that the dementia and personality changes in this case might be concerned with a dysfunction of the cerebral cortex.

Adult↗
PubMed1993

Abdominal aortic aneurysms in familial hypercholesterolemia--case reports.

Familial hypercholesterolemia (FH) is a genetic disease characterized by high serum cholesterol levels and premature coronary atherosclerosis. Hypercholesterolemia is one of the factors promoting the arteriosclerotic process and is a major cause of aortic aneurysm. Few data are available, however, about abdominal aortic aneurysms (AAAs) in patients with FH. In this study, the clinical and angiographic characteristics of AAAs found in patients with FH were investigated. Thirty-one cases (23 men, 8 women, aged fifty +/- fourteen years) were examined by coronary angiography, thoracic and abdominal aortography, and clinical data. Abdominal aortography detected abdominal aneurysms in 8 cases (26%), all of whom were men, including 4 cases (50%) that were complicated by diabetes mellitus. The abdominal aneurysm patients manifested severe coronary atherosclerosis, severe abdominal aortic irregularity, and higher blood pressure than the nonaneurysm FH patients. These findings suggest that AAAs are an important and prevalent feature in FH, especially in men with diabetes mellitus and high blood pressure.

Adult↗
PubMed1993

[A case of food-dependent exercise-induced anaphylaxis associated with repeated episodes of syncope].

This report describes a patient with food-dependent exercise-induced anaphylaxis (FEA). A 25-year-old female has had three episodes of syncopal attack associated with urticaria in the past two years: the attacks have been developed by exercise after taking meals made of wheat flour. She has an allergic predisposition to metals. No abnormal findings were observed in the routine work up for syncope including, ECG, 24-hour Holter ECG, UCG, tilt table test, and EEG examinations. A provocative test for FEA was performed. It included food (sandwich) intake followed by exercise. The serum histamine concentration was elevated to a three times higher than the control value after the provocation. Accordingly, she was diagnosed as FEA and advised not to take wheat flour prior to physical exercise. No syncopal episode has been observed during the 16 months since the diagnosis.

Adult↗