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Biomedical subjects

J Koizumi

Publications and source records attributed to J Koizumi.

At least 37 records · Page 2Linked to original sources

[Angiographic findings of hemodialysis access insufficiency].

One hundred forty-six angiographic findings of malfunctioning internal arteriovenous fistulas without any history of interventional procedures were reviewed. Angiographies demonstrated 110 cases of stenosis, 72 of occlusion, 5 of venous varicosity, and 13 of venous aneurysm. Of 182 stenotic lesions, 118 (65%) lesions (74 venous stenoses: 67%; 44 venous occlusions: 61%) were revealed within five centimeters of anastomoses. In 4 of 5 cases of varicosity, proximal venous occlusions were demonstrated. On the other hand, interventional procedures were performed in 81 cases of stenoses and 14 of occlusions in the manner of PTA and fibrinolysis. The initial success rate was 90% in stenotic lesions and 71% in occlusive lesions, not a statistically significant difference. Furthermore, there was no statistically significant difference in initial success rates according to anatomical location and lesion length. Although there was no statistically significant difference according to the angiographic findings of lesions, we would like to emphasize the importance of correct understanding of anatomical changes in the dialysis shunt and of early intervention to improve the initial success rate of PTA.

Adolescent↗

Hyperhomocysteinemia, diabetes mellitus, and carotid atherosclerosis independently increase atherosclerotic vascular disease outcome in Japanese patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease (ESRD) have high mortality from atherosclerotic/atherothrombotic vascular disease (AVD). However, the role of an elevated plasma total homocysteine (tHcy) level as a risk factor is uncertain in ESRD. METHODS: We enrolled 55 ESRD patients in a prospective follow-up study in order to evaluate the prognostic significance of their tHcy levels, common methylenetetrahydrofolate reductase (MTHFR) gene polymorphism, and other atherosclerotic risk factors, in combination with the results of B mode ultrasound for carotid arteries. RESULTS: Mean intima-media thickness of the common carotid artery (CCA-IMT) in ESRD patients was thicker than that in 102 age- and sex-matched healthy controls. Carotid plaque was more frequently present in patients compared with controls, as was calcified plaque more common in patients (p < 0.001). Plasma tHcy levels (mean +/- SD) in patients (39.1 +/- 27.2 nmol/ml) were higher than that (8.8 +/- 2.7 nmol/ml) in controls (p < 0.001). Folic acid was the major determinant of elevated tHcy levels in ESRD patients. During the follow-up period of 31 +/- 3 months, 14 patients had one or more AVD complications, and 10 consequently died from AVD causes. Proportional hazards modeling showed that 5-year intervals of age (relative risk of 2.95, 95% CI 1.62 - 5.37), 10 nmol/ml intervals of tHcy levels (relative risk of 2.31, 95% CI 1.31 - 4.08), and presence of diabetes mellitus (relative risk of 6.62, 95% CI 1.07 +/- 40.8) were independent predictors of future AVD events, and tHcy levels (relative risk of 2.67, 95% CI 1.29 - 5.52) and age (relative risk of 2.10, 95% CI 1.15 - 3.83) were those of AVD mortality. We also found a significant association between carotid plaque prevalence and AVD events (X(2) = 11.6, p = 0.001). CONCLUSION: Hyperhomocysteinemia, diabetes mellitus, and carotid atherosclerosis appeared to contribute independently to increase the risk of AVD outcome in Japanese patients with ESRD.

Adult↗

Effect of common methylenetetrahydrofolate reductase gene mutation on coronary artery disease in familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by primary hypercholesterolemia and premature coronary artery disease (CAD). However, the development of CAD in FH shows considerable interindividual variations. Elevated levels of plasma homocysteine have been recognized as independent risk factors for CAD. A 5,10-methylenetetrahydrofolate reductase (MTHFR) gene mutation (valine [V] was substituted for alanine [A]) has been reported to be associated with elevated levels of plasma homocysteine in mutant homozygotes (i.e., VV). We studied 199 consecutive male heterozygous FH patients, 99 with and 100 without CAD. In the CAD group, genotype VV and V alleles were significantly more frequent than in the non-CAD group (15% vs 7% in genotypes [p = 0.035] and 0.41 vs 0.30 in alleles [p = 0.017]). The mean ages at onset in the CAD group were 50, 51, and 43 years for genotypes AA, AV, and VV, respectively (p <0.05); the age of onset of CAD in genotype VV was significantly lower than in the other 2 genotypes. Kaplan-Meier survivor curves indicated that the development of CAD was significantly accelerated by MTHFR mutation, probably in a gene dose-dependent manner. Furthermore, only MTHFR genotype VV was shown to be an independent predictor of the early onset of CAD in a stepwise multiple regression analysis. The mean plasma homocysteine levels of genotype VV were significantly higher than those of the other 2 genotypes. Thus, the MTHFR mutation appears to accelerate the onset of CAD through elevation of plasma homocysteine levels in male heterozygous patients with FH.

Adult↗

Effects of NK-104, a new hydroxymethylglutaryl-coenzyme reductase inhibitor, on low-density lipoprotein cholesterol in heterozygous familial hypercholesterolemia. Hokuriku NK-104 Study Group.

The clinical efficacy of NK-104, a novel and totally synthetic hydroxymethylglutaryl-coenzyme A reductase inhibitor, was assessed in 30 patients (men/women = 15/15, mean age 51 years) with heterozygous familial hypercholesterolemia. After a placebo phase of >4 weeks, NK-104 was given at an initial dose of 2 mg/day for 8 weeks, which was increased to 4 mg/day for a further 8 weeks. As a result of 2 mg/day of NK-104 treatment, mean +/- SD of total and low-density lipoprotein cholesterol levels decreased significantly (p<0.0001) from baseline, namely from 8.80+/-1.38 to 6.11+/-1.09 mmol/L (-31%) and from 6.81+/-1.52 to 4.09+/-1.03 mmol/L (-40%), respectively. They decreased further (p<0.0001) as a result of 4-mg/day administration, to 5.52+/-0.81 mmol/L (-37%) and 3.55+/-0.85 mmol/L (-48%), respectively. Changes in high-density lipoprotein cholesterol levels failed to reach statistical significance. Serum triglyceride levels decreased significantly (p<0.0001) from baseline as a result of 4 mg/day of NK-104, from 1.99+/-1.72 to 1.35+/-0.90 mmol/L (-23%). Serum apolipoprotein B, CII, CIII, and E levels significantly decreased: mean changes from baseline at the end of the study were -41% (p<0.0001), -27% (p<0.0001), -19% (p = 0.002), and -37% (p<0.0001), respectively. On the other hand, apolipoprotein AI and All levels significantly increased as a result of the treatment: + 10% (p = 0.002) and +6% (p = 0.008), respectively. There were no adverse events observed in either clinical or laboratory findings that could be attributed to the treatment. These results suggest that the potency of NK-104 appears to be dose-dependent, and that NK-104 is safe and well tolerated in the treatment of patients with heterozygous familial hypercholesterolemia, and thus also provides a new therapeutic choice for subjects requiring lipid-modifying therapy.

Female↗

Cholesteryl ester transfer protein and atherosclerosis.

Plasma cholesteryl ester transfer protein facilitates the transfer of cholesteryl ester from HDL to apolipoprotein B-containing lipoproteins. Its significance in atherosclerosis has been debated in studies of human population genetics and transgenic mice. The current review will focus on human plasma cholesteryl ester transfer protein research, including TaqIB, 1405V, and D442G polymorphisms. Plasma cholesteryl ester transfer protein has a dual effect on atherosclerosis, depending on the metabolic background. In hypercholesterolaemia or combined hyperlipidaemia, plasma cholesteryl ester transfer protein may be pro-atherogenic and could be a therapeutic target.

Alleles↗

Covered stent implantation by the puncture method for the treatment of a small aneurysm of the common iliac artery.

A method to repair endovascular aneurysms with covered stents has recently been developed. In the present paper, the implantation of a covered stent through a 12Fr sheath by the puncture method for the treatment of an isolated aneurysm of the right common iliac artery is reported. The aneurysm was less than 3 cm in diameter, and computed tomography showed no signs of aneurysm rupture, but the patient nonetheless complained of right lower abdominal pain and constipation. It was decided to implant a covered stent in lieu of surgical repair because it was difficult to prove a causal relationship between the aneurysm and the patient's complaints. Fortunately, after implantation, the symptoms were resolved. In conclusion, it is possible to choose this less invasive type of therapy for the treatment of an isolated iliac artery aneurysm if the patient complains only of general malaise and there are no certain signs of an impending rupture, although surgery should be indicated regardless of aneurysm size.

Aged↗

Long-term results of percutaneous transluminal angioplasty for hemodialysis shunt insufficiency

Purpose: The purpose of this study was to evaluate the long-term results of percutaneous transluminal angioplasty (PTA) for stenosis and/or occlusion of dialysis shunts. Methods: One hundred thirty-nine stenosed or thrombosed dialysis shunts (99 native fistulae, 37 grafts) in 122 patients were treated by PTA. In 39 cases, additional PTA for restenosis was performed. In total, 230 PTAs were performed (1-10 PTA/shunt). Results: The initial success rate was 86% in cases without occlusion. In contrast, the success rate in cases with occlusion was 53%, significantly worse than in the cases without occlusion. In cases in which initial success was obtained, primary cumulative patency rates at 3, 6, and 12 months were 87%, 60%, and 40%, respectively. With repeat PTA, secondary cumulative patency rates at 3, 6, 12, and 24 months were 96%, 83%, 63%, and 55%, respectively. Patency of native fistulae was better than patency of grafts. There was no significant relationship between the anatomical location of the stenoses and the patency rates. Conclusion: PTA is an effective treatment for shunt stenosis; although primary patency after PTA is not sufficient, repeated PTA increases patency.

Journal Article↗

A case of aortoduodenal fistula occurring after surgery and radiation for pancreatic cancer.

The patient was a 58-year-old woman given curative treatment (pancreatectomy (body and tail) + intraoperative irradiation (25 Gy)) on the basis of a diagnosis of pancreatic carcinoma. Having a favorable postoperative course, she was discharged 24 days after surgery. A week after discharge, she was readmitted for a hemorrhagic gastric ulcer. She was later discharged again on conservative treatment, and followed up at the outpatient clinic, but nine months postoperatively, was readmitted complaining of loss of appetite and abdominal pain. Subsequent tests revealed stricture of the horizontal portion of the duodenum with distension oral to the stricture. Around the celiac artery, the paraaortic lymph nodes were swollen, and a diagnosis of stricture due to recurrent pancreatic carcinoma was made. On the day before bypass surgery was scheduled, the patient vomited blood, so the operation was postponed, conservative treatment such as blood transfusion was administered, and emergency angiography was performed simultaneously. The findings were an aortic pseudoaneurym 1 cm in diameter immediately below the origin of the superior mesenteric artery and between the left and right renal arteries, and a hemorrhage, caused by an aortoduodenal fistula, issuing from the horizontal portion of the duodenum. Hemostasis via a laparotomy was judged difficult, and so an indwelling stent-graft in the aorta was tried to stanch the blood, but without success. Another stent then had to be inserted within the first, thus stopping the flow, but the blood supply to the celiac artery, the superior mesenteric arteries and the renal arteries was impaired, and the patient died about six hours later. Postmortem examination revealed aortoduodenal fistula without recurrence of the carcinoma. The duodenal wall around the fistulous tract showed delayed radiation changes with deep ulceration. The intraoperative radiation may have played an important part in the formation of the fistula.

Aortic Diseases↗

[A case of chronic localized thoracoabdominal aortic dissecting aneurysm].

A rare case of chronic localized thoracoabdominal aortic dissecting aneurysm was surgically treated. The patient was a 76-year-old woman. She was reffered to our hospital because of the abnormality of the chest roentogenogram. Chest CT and aortography revealed localized thoracoabdominal dissecting aneurysm 70 mm in diameter. Patch closure of intimal tear was carried out under partial cardiopulmonary femoro-femoral bypass. The patient discharged on the 23rd post operative day without any complications.

Aortic Dissection↗

[Metallic stent placement for iliac artery occlusive disease].

Since 1991, we have performed stent placement for 35 iliac artery lesions in 31 patients. The etiologic diseases were atherosclerotic in 34 patients and traumatic dissection in one. The indications of placement were total occlusion in 3, late restenosis after angioplasty in 5, dissection in 5, and residual stenosis due to inadequate angioplasty in 21. We also performed direct stent placement for one traumatic dissection. The stents used were Wallstents in 10, Palmaz stents in 14, Strecker stents in 9, and Memotherm stents in 2 lesions. Follow-up was performed clinically or angiographically with measurement of the ankle/arm pressure index. Stent placement was successful in all cases, and relief or improvement of symptoms was achieved. The follow-up period ranged from 6-85 months (mean, 37.3 months). Late stent stenosis or occlusion occurred in 6 cases, among which 4 occluded lesions were successfully recanalized by thrombolytic therapy with angioplasty or second stent placement. In total, the primary patency rates were 88% and 77% at two and four years, respectively, while the secondary patency rates were 94% and 94%. In conclusion, metallic stent placement may offer extended application of intravascular treatment for iliac artery occlusive disease, and good long-term patency rates can be expected.

Adult↗

Surgical treatment of a distal arch pseudoaneurysm and migrated stent-graft after interrupted aortic arch repair.

A 13-year-old girl, who had undergone a modified Blalock-Park operation using an equine pericardial patch for a type A aortic arch interruption at 10 days of age, and patch repair of a ventricular septal defect at 1 year, presented with recurrent stenosis of the aorta. She underwent balloon angioplasty which resulted in a pseudoaneurysm at the distal suture line of the patch. Endovascular stent-grafting was employed. Soon after placement, the stent-graft had migrated into the distal portion of the descending aorta. The distal aortic arch and proximal descending thoracic aorta were replaced with a prosthetic graft. The migrated stent-graft was removed. The operation was performed through an anterior approach under hypothermic circulatory arrest and selective cerebral perfusion. The postoperative course was uneventful. The migration was likely caused by the limited ability to bend the stent-graft to match the curvature of the arch, the stiffness of the scarred equine pericardial patch, and the shape of the aorta.

Adolescent↗

Multi-effective properties of homogentisic acid revealed in reactions with human hemoglobin and human erythrocytic hemoglobin.

Homogentisic acid (HGA) causes oxidation of human oxyhemoglobin and reduction of methemoglobin. The rate of oxidation of oxyhemoglobin by HGA is greatly accelerated in the presence of myo-inositol hexakis-phosphate (P6-inositol) or superoxide dismutase (SOD), but is inhibited in the presence of catalase. The reduction rate of methemoglobin by HGA is accelerated in the presence of P6-inositol but is greatly inhibited in the presence of SOD. It is suggested that the semiquinone and quinone form of HGA and oxygen radicals may be involved in the mechanism of oxido-reductive reactions of human hemoglobin with HGA. In addition, a new anodic hemoglobin found by isoelectric focusing electrophoresis was produced during the reaction of oxyhemoglobin with HGA. When human erythrocytes were exposed to HGA for several hours at 37 degrees C (pH 7.4), the anodic oxyhemoglobin (HGA-modified hemoglobin) and its half met-form hemoglobin [(alpha3+beta2+)2 of HGA-modified hemoglobin] were produced in significant amounts. HGA-modified hemoglobin was stably purified and showed increased oxygen affinity, absence of titratable sulfhydryl groups, and the absorption spectrum of normal oxyhemoglobin. Our results demonstrate that HGA shows multiple effects on human hemoglobin and erythrocytic hemoglobin, which is consistent with the evidence that HGA is involved in various pathological conditions such as arthritis and carcinogenesis in humans.

Erythrocytes↗

Cloning and expression of the gene encoding thermostable poly(3-hydroxybutyrate) depolymerase.

The gene encoding extracellular poly(3-hydroxybutyrate) depolymerase from a thermophilic poly(3-hydroxybutyrate)-degrading bacterium, strain HS, was cloned and intracellularly expressed in Escherichia coli. The gene was found to consist of 1485-bp nucleotide sequence coding for a 22-amino-acid signal peptide and a 473-amino-acid mature protein. Phylogenetic analysis and domain structure showed that the enzyme was clustered with type II PHB depolymerases. The gene was expressed in E. coli under the control of the tac promoter. A 46-kDa protein was detected in the cell extract by SDS-PAGE. The N-terminal sequence of the protein agreed with that of the original enzyme. The crude enzyme was able to degrade PHB particles at 70 degrees C.

Journal Article↗

Early Lung Cancer Action Project: overall design and findings from baseline screening.

BACKGROUND: The Early Lung Cancer Action Project (ELCAP) is designed to evaluate baseline and annual repeat screening by low-radiation-dose computed tomography (low-dose CT) in people at high risk of lung cancer. We report the baseline experience. METHODS: ELCAP has enrolled 1000 symptom-free volunteers, aged 60 years or older, with at least 10 pack-years of cigarette smoking and no previous cancer, who were medically fit to undergo thoracic surgery. After a structured interview and informed consent, chest radiographs and low-dose CT were done for each participant. The diagnostic investigation of screen-detected non-calcified pulmonary nodules was guided by ELCAP recommendations, which included short-term high-resolution CT follow-up for the smallest non-calcified nodules. FINDINGS: Non-calcified nodules were detected in 233 (23% [95% CI 21-26]) participants by low-dose CT at baseline, compared with 68 (7% [5-9]) by chest radiography. Malignant disease was detected in 27 (2.7% [1.8-3.8]) by CT and seven (0.7% [0.3-1.3]) by chest radiography, and stage I malignant disease in 23 (2.3% [1.5-3.3]) and four (0.4% [0.1-0.9]), respectively. Of the 27 CT-detected cancers, 26 were resectable. Biopsies were done on 28 of the 233 participants with non-calcified nodules; 27 had malignant non-calcified nodules and one had a benign nodule. Another three individuals underwent biopsy against the ELCAP recommendations; all had benign non-calcified nodules. No participant had thoracotomy for a benign nodule. INTERPRETATION: Low-dose CT can greatly improve the likelihood of detection of small non-calcified nodules, and thus of lung cancer at an earlier and potentially more curable stage. Although false-positive CT results are common, they can be managed with little use of invasive diagnostic procedures.

Aged↗

The subcellular localization of SF2/ASF is regulated by direct interaction with SR protein kinases (SRPKs).

Serine/arginine-rich (SR) proteins play an important role in constitutive and alternative pre-mRNA splicing. The C-terminal arginine-serine domain of these proteins, such as SF2/ASF, mediates protein-protein interactions and is phosphorylated in vivo. Using glutathione S-transferase (GST)-SF2/ASF-affinity chromatography, the SF2/ASF kinase activity was co-purified from HeLa cells with a 95-kDa protein, which was recognized by an anti-SR protein kinase (SRPK) 1 monoclonal antibody. Recombinant SRPK1 and SRPK2 bound to and phosphorylated GST-SF2/ASF in vitro. Phosphopeptide mapping showed that identical sites were phosphorylated in the pull-down kinase reaction with HeLa extracts and by recombinant SRPKs. Epitope-tagged SF2/ASF transiently expressed in COS7 cells co-immunoprecipitated with SRPKs. Deletion analysis mapped the phosphorylation sites to a region containing an (Arg-Ser)8 repeat beginning at residue 204, and far-Western analysis showed that the region is required for binding of SRPKs to SF2/ASF. Further binding studies showed that SRPKs bound unphosphorylated SF2/ASF but did not bind phosphorylated SF2/ASF. Expression of an SRPK2 kinase-inactive mutant caused accumulation of SF2/ASF in the cytoplasm. These results suggest that the formation of complexes between SF2/ASF and SRPKs, which is influenced by the phosphorylation state of SF2/ASF, may have regulatory roles in the assembly and localization of this splicing factor.

Glutathione Transferase↗

Opposite effects on serum cholesteryl ester transfer protein levels between long-term treatments with pravastatin and probucol in patients with primary hypercholesterolemia and xanthoma.

Long-term effects of pravastatin and probucol on serum cholesteryl ester transfer protein (CETP) and xanthoma/xanthelasma size were compared. Twenty-three patients with primary hypercholesterolemia and xanthoma/xanthelasma, including 11 patients with heterozygous familial hypercholesterolemia, were treated with pravastatin (20 mg/day) or probucol (1000 mg/day) for 24 months. Serum CETP levels were measured by sandwich ELISA. In 11 patients (six men and five women, 55 +/- 2 [SE] yr) treated with pravastatin, serum cholesterol levels decreased from 262 +/- 13 to 229 +/- 13 mg/dl during the 24-month treatment period (P = 0.05). Serum HDL cholesterol levels were not changed. Serum CETP levels decreased from 2.5 +/- 0.2 to 2.0 +/- 0.2 microg/ml (-21%, P = 0.002). By contrast, in 12 patients (four men and eight women, 57 +/- 4 year) treated with probucol, serum cholesterol levels did not significantly decrease from 236 +/- 11 to 207 +/- 13 mg/dl. Serum HDL cholesterol levels decreased from 44 +/- 2 to 30 +/- 2 mg/dl (P = 0.009). Serum CETP levels increased from 2.3 +/- 0.1 to 2.8 +/- 0.2 microg/ml (+23%, P = 0.02). Xanthelasma regression was found in two of four patients (50%) each treated with pravastatin and probucol, respectively. In contrast, Achilles' tendon xanthoma regressed in four of five patients (80%) treated with pravastatin, but only in two of five patients (40%) treated with probucol. Patients with xanthoma/xanthelasma regression after 2 years treatment had higher baseline levels of serum CETP than those without regression (2.7 +/- 0.2 microg/ml [n = 9] versus 2.1 +/- 0.2 microg/ml [n = 7], P = 0.05). Serial changes in serum CETP levels during treatment with pravastatin and probucol were discordant, but not related to the degree of xanthoma regression. However, higher level of serum HDL3 cholesterol was an independent factor in the smaller size of Achilles' tendon xanthoma at baseline. In addition, higher levels of serum HDL3 triglyceride on lipid-lowering therapy (6 months) appear to be a common predictor of regression of Achilles' tendon xanthoma in the treatment with either pravastatin or probucol.

Achilles Tendon↗