Biomedical subjects

Y Koda

Publications and source records attributed to Y Koda.

At least 37 records · Page 2Linked to original sources

PubMed2000

An Alu-mediated large deletion of the FUT2 gene in individuals with the ABO-Bombay phenotype.

Recently, we have found an allelic deletion of the secretor alpha(1,2)fucosyltransferase (FUT2) gene in individuals with the classical Bombay phenotype of the ABO system. The FUT2 gene consists of two exons separated by an intron that spans approximately 7 kb. The first exon is noncoding, whereas exon 2 contains the complete coding sequence. Since the 5' breakpoint of the deletion has previously been mapped to the single intron of FUT2, we have cloned the junction region of the deletion in a Bombay individual by cassette-mediated polymerase chain reaction. In addition, the region from the 3' untranslated region of FUT2 to the 3' breakpoint sequence has been amplified from a control individual. DNA sequence analysis of this region indicates that the 5' breakpoint is within a free left Alu monomer (FLAM-C) sequence that lies 1.3 kb downstream of exon 1, and that the 3' breakpoint is within a complete Alu element (AluSx) that is positioned 1.5 kb downstream of exon 2. The size of the deletion is estimated to be about 10 kb. There is a 25-bp sequence identity between the reference DNA sequences surrounding the 5' and 3' breakpoints. This demonstrates that an Alu-mediated large gene deletion generated by unequal crossover is responsible for secretor alpha(1,2)fucosyltransferase deficiency in Indian Bombay individuals.

3' Untranslated Regions↗

PubMed2000

Embolotherapy for venous impotence: use of ethanol.

PURPOSE: To evaluate the usefulness of embolotherapy with ethanol for the treatment of venous impotence. MATERIALS AND METHODS: Twenty-three patients with venous impotence underwent embolotherapy. The diagnosis of venous impotence was made by means of pharmacocavernosometry and cavernosography. After exposure of the deep dorsal penile vein, a intravenous catheter was inserted directly into the deep dorsal penile vein and advanced into just front of the preprostatic plexus. Fifty percent ethanol was injected through the catheter and the endpoint of the procedure was determined based on results of venography immediately after injection. The procedure was finished when lack of venous leakage was confirmed. RESULTS: In all patients, the deep dorsal penile vein was successfully exposed surgically, the sclerosing agent successfully injected, and the endpoint successfully achieved. Immediate clinical therapeutic effect (restoration of erection) was obtained in 20 cases (87%). No severe complications were observed during or after the procedure. The follow-up period was 6-50 months. Long-term therapeutic effect was confirmed for 18 of 23 patients (78%). CONCLUSION: The authors' findings suggest that this treatment had satisfactory short-term and long-term clinical results and that longer follow-up is necessary to confirm its safety.

Adult↗

PubMed2000

A fatal case of hyperthermia due to tricyclic antidepressant intoxication.

We report here an autopsy case of a 49-year-old woman with depression who died of hyperthermia, probably due to amitriptyline intoxication. She was found dead in bed with several empty amitriptyline pill containers. Her rectal temperature was 41.5 degrees C approximately 3 hours after death. Plasma levels of amitriptyline and nortriptyline were 0.51 and 0.74 mg/l, respectively. Possible mechanisms of fatal hyperthermia are discussed.

Journal Article↗

PubMed1999

Effects of physical inactivity on aortic distensibility in visually impaired young men.

To assess the effects of inordinate physical inactivity on the distensibility of the aorta we measured aortic pulse wave velocity (APWV) and estimated physical activity index (PAI) by a 7-day total activity recall in visually impaired subjects. A group of 12 blind students (blind group) and 28 sighted male students, including 14 runners (runner group) and 14 sedentary subjects (sedentary group), participated in this study. There were no significant differences in body height, body mass, or blood pressure among the three groups. The PAI of the blind group [310 (SD 330) kcal x week(-1)] was significantly lower than that of the runner group [6300 (SD 1920) kcal week(-1), P < 0.0001] and the sedentary group [810 (SD 780) kcal x week(-1); P < 0.05]. The PAI of the runner group (P < 0.0001) was significantly higher than that of the sedentary group. The APWV and APWV index (standardized APWV for diastolic blood pressure: APWVI) of the runner group [5.22 (SD 0.42) m x s(-1) and 5.54 (SD 0.57) m x s(-1) P < 0.01, respectively] were significantly lower than those of the sedentary group [5.88 (SD 0.51) m x s(-1) and 6.16 (SD 0.48) m x s(-1)]. The APWV and APWVI of the blind group [5.29 (SD 0.49) m x s(-1) and 5.40 (SD 0.60) m x s(-1) P < 0.01, respectively] were significantly lower than those of the sedentary group, but there was no significant difference in the values of the APWV and APWVI between the blind and runner groups. These results would suggest that increased physical activity provides subjects with a distensible aorta, as does the inordinately decreased physical activity in the blind.

Adult↗

PubMed1999

The fusion gene at the ABO-secretor locus (FUT2): absence in Chinese populations.

The fusion gene (se(fus)) is a null allele of the secretor type alpha (1, 2) fucosyltransferase gene (FUT2) and was first found in a Japanese population. It has not yet been reported in any other ethnic population. In the present study, we investigated the distribution of the fusion gene of the FUT2 locus in five populations from three ethnic groups in East Asia. The fusion gene was found in two additional Japanese populations with a high frequency (0.0551 in Okinawa and 0.0792 in Akita) and, for the first time outside Japan, in a Korean population, at a very low frequency (0.0063 in Seoul). In contrast, we found no fusion gene in two Chinese populations. These findings showed that the FUT2 fusion gene was ubiquitous in Japanese, but was rare in neighboring populations, suggesting that the FUT2 fusion gene had emerged from within the Japanese. Additionally, a new null allele with a C-to-T substitution at nucleotide 658 was found in one individual native of southern China.

ABO Blood-Group System↗

PubMed1999

Myocardial "elektive disseminierte Parenchymnekrose" revisited.

A 43-year-old man was found to show cardiac arrest during overnight detention in a police station. The autopsy revealed no abnormality other than a fatty liver on gross examination. Microscopic examination of the heart showed typical disseminated hypoxemic foci of necrosis with hemorrhaging but without infiltration of inflammatory cells, which Büchner, about 60 years ago, proposed as a sign of acute coronary insufficiency without acute coronary occlusion due to massive hemorrhage. However, the disseminated focal hemorrhagic necrosis of microscopic size found in the present study appears to be one of early signs of ischemia in the heart muscle and to occur frequently at silent ischemic heart attacks during daily life.

Journal Article↗

PubMed1999

Functional analysis of the 5'-flanking region of FTA for expression of rat GDP-L-fucose:beta-D-galactoside 2-alpha-L-fucosyltransferase.

The tissue-specific and species-specific expression of the ABH antigens is well known among vertebrate species and it is regulated by the alpha(1,2)fucosyltransferase that forms the H antigen, a precursor of the A and B antigens. To investigate the mechanisms governing the tissue-specific and species-specific expression of this alpha(1,2)fucosyltransferase, we characterized the gene structure, including the promoter region, of FTA, a rat orthologous homolog of human FUT1 that encodes the H alpha(1, 2)fucosyltransferase and is responsible for the expression of the ABH antigens on human red blood cells. Northern blot and 5'-RACE analyses suggested that at least two forms of FTA mRNA (2.9 and 2.6 kb), which use alternative transcription start sites, are present in the cancer cell lines RCN-9 (rat colon cancer) and PC12 (rat pheochromocytoma), whereas only the 2.6 kb form was detected in normal colon, stomach and pancreas. Transcriptional activity of the 5'-flanking sequence, which contains three putative Sp1-binding sites, but lacks both TATA and CAAT boxes, was examined. Transient transfection experiments of promoter-reporter gene constructs showed high promoter activity in RCN-9, PC12 and human colon cancer (WiDr) cell lines, weak activity in human vascular endothelial (ECV304) cells and no activity in human erythroleukemia (HEL) cells. The results suggest that the 5'-flanking region of FTA contains a tissue-specific promoter. Deletional analysis of the 5'-flanking sequence revealed regions containing cell-type-specific positive acting element(s) and negative regulatory element(s), which are related to the promoter activity.

5' Untranslated Regions↗

PubMed1999

Allelic diversity of the human plasma alpha(1,3)fucosyltransferase gene (FUT6).

The 1080-bp coding region of the human plasma alpha(1,3)fucosyltransferase gene (FUT6) was sequenced in a total of 161 individuals (322 chromosomes) drawn from three populations, involving 56 Africans (Xhosa), 52 European-Africans of South Africa, and 53 Japanese. In addition to six reported base substitutions, eleven new base substitutions and a single base insertion were found in the coding region of the FUT6. Eleven functional and four null alleles were encountered, of which 10 alleles were novel alleles identified in this study. Two null alleles have been identified previously, whereas two novel null alleles, which contained a single base (cytosine) insertion at nucleotide 499, were found in a Xhosa population. The allelic distributions of FUT6 were different among these three populations. The heterozygosity of FUT6 was 0.860, 0.699, and 0.632, in Xhosa, European-African (South Africa), and in Japanese populations, respectively. The extensive DNA sequence diversity of the FUT6 may be suitable for application as a tool in genetic studies for modern human evolution.

Alleles↗

PubMed1999

Lipoprotein(a) is a predictor for cardiovascular mortality of hemodialysis patients.

BACKGROUND: Although hemodialysis (HD) patients have been associated with elevations in serum lipoprotein(a) [Lp(a)] levels, relatively little has been published on the link between Lp(a) and the risk for atherosclerotic cardiovascular death in HD patients. METHODS: Lipoprotein(a) was measured in 390 HD patients. The relationship between Lp(a) and mortality (overall and cardiovascular) was determined during 28 months of prospective follow-up. RESULTS: Hemodialysis patients demonstrated Lp(a) concentrations that were approximately two times as high as that of healthy controls (median, 16 vs. 8 mg/dl, P < 0.001; mean, 22.9 vs. 12.1 mg/dl, P < 0.01). Lp(a) showed a significant correlation between albumin, total cholesterol, low-density lipoprotein cholesterol, and C-reactive protein. The high-Lp(a) group [Lp(a) > or = 30 mg/dl] showed significantly higher mortality than the low-Lp(a) group [Lp(a) < 30 mg/dl] in a Kaplan-Meier survival analysis (P < 0.05). Multiple logistic regression analysis demonstrated albumin, age, and diabetic state as significant risk factors for overall death. However, if confined to atherosclerotic cardiovascular death, Lp(a) (P < 0.01), age, and diabetic state were the only independent contributors. CONCLUSIONS: Lp(a) is an independent risk factor for atherosclerotic cardiovascular death in Japanese patients receiving chronic dialysis therapy.

Age Factors↗

PubMed1999

Hepatic microcirculatory changes induced by hepatic artery embolization in rats: original investigation.

RATIONALE AND OBJECTIVES: To evaluate the effects of hepatic artery embolization (HAE), hepatic microcirculatory changes induced by HAE were assessed quantitatively in rats. METHODS: Using in vivo microscopy, the blood-flow velocity (BFV) through terminal portal venules (TPVs) and terminal hepatic venules (THVs) was measured during HAE with gelatin sponge powder (GSP), iodized oil (Lipiodol, 0.1, 0.2, and 0.4 mL/kg), or 0.1 mL/kg Lipiodol followed by GSP. RESULTS: After HAE with GSP, BFV through TPVs decreased significantly, but BFV through THVs did not decrease. After HAE with Lipiodol (0.2 and 0.4 mL/kg), BFV through TPVs decreased significantly, but BFV through THVs did not. After HAE with Lipiodol followed by GSP, BFV through both TPVs and THVs decreased significantly. CONCLUSIONS: Neither GSP nor Lipiodol adversely affects hepatic microcirculation when administered alone; however, HAE with a combination of Lipiodol and GSP does adversely affect hepatic microcirculation.

Animals↗

PubMed1999

Improvement of myocardial fatty acid metabolism through L-carnitine administration to chronic hemodialysis patients.

The concentration of carnitine, which is essential to fatty acid metabolism, can decrease markedly in patients on long-term hemodialysis coincident with life-threatening cardiac damage. However, administration of L-carnitine improves the myocardial function of these patients. To evaluate the underlying events of this phenomenon, we used recently developed technology, (123)I-labeled beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) myocardial scintigraphy, as a test of myocardial fatty acid metabolism. Our results showed that the free carnitine concentration (19.2 +/- 6.5 micromol/l) was lower in 11 chronically dialyzed patients than in 8 healthy controls (49.3 +/- 7.7 micromol/l, p < 0. 0001). Additionally the heart to mediastinal ratio (H/M) of BMIPP was higher for these patients than for the controls (1.91 +/- 0.19 vs. 1.52 +/- 0.24, p < 0.005), and the patients' washout rate (WOR) of BMIPP was lower (17.2 +/- 6.0 vs. 22.8 +/- 4.2%, p < 0.05). After L-carnitine was administered orally to the patients at doses of 1 g/day for 1 month and 0.5 g/day for the following month, the concentration of free carnitine in their sera increased to 85.4 +/- 27.0 micromol/l (p < 0.0001). Although the H/M ratio did not change (1.89 +/- 0.20) with this treatment, their WOR increased to 21.9 +/- 6.6% (p < 0.001), similar to that of controls. The left ventricular end-diastolic dimension and left ventricular fractional shortening remained unchanged, as shown by echocardiography. The results presented here denote that a carnitine deficiency in chronically hemodialyzed patients disrupts their myocardial fatty acid metabolism, which is improved by L-carnitine supplementation.

Carnitine↗

PubMed1999

Presence of H type 3/4 chains of ABO histo-blood group system in serous cells of human submandibular gland and regulation of their expression by the secretor gene (FUT2).

We have investigated by immunochemistry the distribution of H Type 3/4 chains of the ABO histo-blood group system in human submandibular gland using a monoclonal anti-H MBr1 antibody specific for H Type 3/4 chains, and have found the expression of H Type 3/4 chains was mainly in the serous cells. Serous cells from secretors were stained by MBr1 but not by anti-A and anti-B antibodies, whereas serous cells from nonsecretors exhibited a negative reaction with MBr1. Mucous cells were not stained by MBr1. Only a few striated duct cells showed a weak reaction with anti-H MBr1. These results suggested that the H Type 3/4 chains were distributed predominantly in the serous cells of the human submandibular gland and that secretor Type alpha(1,2)fucosyltransferase (Se enzyme) controlled the synthesis of H Type 3/4 chains in vivo. Saliva also contained H Type 3/4 chains, which were controlled by the secretor gene (FUT2). The differences in the distributions of H Type 1, H Type 2, and H Type 3/4 chains of the ABO histo blood group system in the submandibular gland are discussed.

ABO Blood-Group System↗

PubMed1999

Association between plasma homocysteine concentration and carotid atherosclerosis in hemodialysis patients.

Accelerated atherosclerosis is a major risk for uremic patients undergoing long-term hemodialysis. Because hyperhomocysteinemia may influence this condition, 168 such patients were examined for a possible association between plasma total homocysteine concentration (tHcy) and conventional cardiovascular risk factors. Generalized atherosclerosis was indicated by excessive intimal-medial wall thickness (IMT) of the extracranial carotid artery as measured by B-mode ultrasonography. The results documented tHcy in these patients of 33.0+/-16.9 micromol/L, a significantly higher amount than that of healthy subjects (11.0+/-3.1 micromol/L, p<0.0001). The patients' carotid maximum IMT was 1.79+/-1.16 mm. In multiple regression analyses with forward elimination procedure, carotid maximum IMT was clearly related to age (r = 0.417, p<0.0001), systolic blood pressure (r = 0.262, p = 0.0043), smoking (r = 0.177, p = 0.0076), duration of hemodialysis (r = 0.083, p = 0.0045), and tHcy (r = 0.195, p = 0.0021). These 5 factors accounted for 36.0% of the variation in carotid maximum IMT. Factors determined as unrelated were male gender, diastolic blood pressure, body mass index, total and HDL cholesterol, triglyceride, lipoprotein(a), uric acid, calcium, inorganic phosphate, and parathyroid hormone. Therefore hyperhomocysteinemia, along with advanced age, systolic hypertension and smoking aggravates atherosclerosis in chronic uremic patients.

Age Factors↗

PubMed1999

Lewis (FUT3) genotypes in two different Chinese populations.

The allelic frequencies of the alpha (1,3/4)fucosyltransferase gene (FUT3) in two different Chinese populations (138 individuals in Shenyang and 154 in Guangzhou) were investigated using PCR-RFLP and nucleotide sequencing methods. The common alleles in the Oriental population, Le (wild type allele), le59,508 (with the mutations at nucleotide (nt) 59T-->G and nt 508G-->A) and le59,1067 (with the mutations at nt 59T-->G and nt 1067T-->A) were encountered, and also the rare alleles, le1067 (with the mutation at nt 1067T-->A) and Le59 (with the mutation at 59T-->G), were observed in these Chinese populations. In addition, the common allele in Caucasians, le202,314 (with the mutations at nt 202T-->C and nt 314C-->T), was found in the Oriental population for the first time. The allelic frequencies of the Le, Le59, le59,508, le59,1067, le202,314, and le1067, were 0.750, 0.011, 0.145, 0.054, 0.036, and 0.004 in the Shenyang population and 0.675, 0.026, 0.14, 0.123, 0.026, and 0.010 in the Guangzhou population, respectively. The presence of the alleles containing either the 59 mutation (Le59) or the 1067 mutation (le1067) suggested that the allele le59,1067 may have originated by recombination between them.

Asian People↗

PubMed1998

Changing transcription start sites in H-type alpha(1,2)fucosyltransferase gene (FUT1) during differentiation of the human erythroid lineage.

Recent studies have suggested that at least three transcription-initiation sites were present in the human H-type alpha(1,2)fucosyltransferase gene (FUT1). In the present study, we have investigated these transcription start sites of FUT1 in undifferentiated leukemic cells (K562) that have erythroid characteristics, in erythroleukemia cells (HEL), and in bone marrow cells. K562 cells used exclusively exon 1 as the start site. While HEL cells used mainly exon 2 as the start site, the major start site for bone marrow cells was within exon 7. In addition, we investigated the transcription start site(s) in vascular endothelial cells (ECV304) as an example of mature cells and found that the start site was predominantly within exon 7. The promoter activities were found in the 5' flanking regions of these three start sites after transfection of constructs with luciferase reporter gene into K562 and HEL cells. These findings suggested that the transcription start sites of FUT1 changed during differentiation of the erythroid lineage and that the tissue-specific and stage-specific expressions of the FUT1 were regulated by three distinct promoters. We also found that the 5' flanking region of exon 2 (intron 1) consisted of repetitive sequences (chromosome 19-specific 37-bp minisatellite repeats, Alu sequence and long terminal repeat) and that the start site of exon 2 was within the long terminal repeat. Thus, these repetitive sequences may play a role in the expression of the FUT1.

Base Sequence↗

PubMed1998

Five novel missense mutations of the Lewis gene (FUT3) in African (Xhosa) and Caucasian populations in South Africa.

Five novel missense mutations, viz., C304 A, T370 G, G484 A, G667 A, and G808 A, in the Lewis gene (FUT3) were detected in African (Xhosa) and Caucasian individuals in South Africa. These single base substitutions may result in changes in amino acid residues from Gln102 to Lys in the 304 mutation, Ser124 to Ala in the 370 mutation, Asp162 to Asn in the 484 mutation, Gly223 to Arg in the 667 mutation, and Val270 to Met in the 808 mutation. Out of the five novel mutations identified in this investigation, four new alleles (le484,667, le484,667,808, Le304, and Le370) were determined in the Xhosa population and two new alleles (le202,314,484 and Le304) in the Caucasian population. The determination of alpha(1,3/1,4)fucosyltransferase activity, after transfection of plasmids containing the new alleles into COS7 cells, suggested that alleles le484,667 and le484,667,808 encoded an inactive enzyme, and that alleles Le304 and Le370 encoded a functional enzyme. In addition, we also examined the incidence of five common alleles, Le59, le59,508 le59,1067, le202,314, and le1067 in two populations by the polymerase chain reaction/restriction fragment length polymorphism method and compared differences in the allele frequencies of FUT3 among three ethnic groups (Orientals, Africans, and Caucasians).

Alleles↗

PubMed1998

Extensive polymorphism of the FUT2 gene in an African (Xhosa) population of South Africa.

The human secretor type alpha(1,2)fucosyltransferase gene (FUT2) polymorphism was investigated in Xhosa and Caucasian populations of South Africa by polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. Six new base substitutions were found in the coding region of FUT2. A single base (C) deletion at nucleotide 778, which led to a frame shift and produced a stop codon at codon 275, was responsible for the enzyme inactivation. Three nonsynonymous base substitutions, A40G (lle14Val), C379T (Arg127Cys), and G481A (Asp161Asn), and two synonymous base substitutions, A375G (Glu125) and C480T (His160), were also identified in functional alleles. As a result, seven new alleles, Se40, Se481, Se40,481, Se357,480, Se357,379,480, Se375, and se357,480,778 were identified. Population studies revealed that an allele containing a nonsense mutation G428A (Trp143stop) (se428) was the common null allele in both Xhosa and Caucasian populations, whereas an allele containing a missense A385T (Ile129Phe) mutation (se357,385), which is the common null allele in Orientals, was found to be absent from both populations. The heterozygosity rates of FUT2 genotypes were as high as 0.75 in the Xhosa population and 0.65 in the Caucasian population. Therefore, the extensive polymorphism and race specificity of the FUT2 gene make it suitable for application as a new tool in genetic studies of modern human evolutionary history.

Alleles↗

PubMed1998

Significance of each of three missense mutations, G484A, G667A, and G808A, present in an inactive allele of the human Lewis gene (FUT3) for alpha(1,3/1,4)fucosyltransferase inactivation.

Recently, we found three novel missense mutations, G484A (Asp162Asn), G667A (Gly223Arg), and G808A (Val270Met), present in a Lewis-negative allele (le484,667,808) from an African (Xhosa) population. To define the relative contribution of each of the three mutations in the le484,667,808 allele for inactivation of the FUT3-encoded enzyme, we made chimeric FUT3 containing each of the three mutations. A transient expression study indicated that COS7 cells transfected with the FUT3 construct containing the G484A mutation expressed the Lewis antigen and had about 20% enzyme activity as compared with COS7 cells transfected with the wild type FUT3 allele, whereas COS7 cells transfected with the FUT3 construct containing either the G667A mutation or the G808A mutation did not express the Lewis antigen and showed no detectable alpha(1,3/1,4)fucosyltransferase activity. These results suggest that the G667A and/or the G808A missense mutations of FUT3 alleles are responsible for the inactivation of the FUT3-encoded enzyme.

Alleles↗