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Biomedical subjects

K Tokunaga

Publications and source records attributed to K Tokunaga.

At least 217 records · Page 12Linked to original sources
PubMed1997

Evoked potentials in patients with chronic respiratory insufficiency.

P300, somatosensory evoked potential (SEP) and brainstem auditory evoked potential (BAEP) are widely used neurophysiological methods for objectively evaluating cognitive, somatosensory and brainstem auditory functions. We studied the P300, SEP and BAEP in 17 patients with chronic respiratory insufficiency (PaO2:58.2 +/- 7.0 mmHg; mean +/- SD) and 15 age-matched healthy subjects (PaO2: 84.4 +/- 11.3 mmHg). The latency and amplitude of P300, the N9 latency, N9-N13 and N13-N20 interpeak latencies (IPL) in SEP, wave I latency and I-V IPL in BAEP were compared between the patients and controls. The P300 latency, N9-N13 and N13-N20 IPLs in SEP in the patients were significantly prolonged compared to the controls. In contrast, the amplitude of P300, N9 latency in SEP, wave I latency and I-V IPL in BAEP were not significantly different between the patients and controls. These results suggest that chronic respiratory insufficiency influences the cognitive and somatosensory functions, and indicate that there is a selective vulnerability of evoked potentials to this condition.

Aged↗
PubMed1997

Expression of macrophage colony-stimulating factor and its receptor in hepatic granulomas of Kupffer-cell-depleted mice.

In mice administered with liposome-entrapped dichloromethylene diphosphonate, which depletes Kupffer cells, the size and the number of zymosan-induced granulomas in the liver were smaller than in untreated mice. The number of macrophage precursors, as detected by the monoclonal antibodies for macrophage precursors, increased after zymosan injection in both groups of mice, proliferated, and differentiated into macrophages. Expression of macrophage colony-stimulating factor (M-CSF), interleukin-1, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, and interferon-gamma mRNA was enhanced in the stage of granuloma formation in the control mouse liver, whereas it was suppressed in Kupffer-cell-depleted mice. However, M-CSF mRNA expression was increased in the Kupffer-cell-depleted mice to form granulomas in the late stages. In situ hybridization demonstrated the expression of M-CSF mRNA and c-fms mRNA in Kupffer cells and monocyte-derived macrophages in the sinusoid and granulomas. The concentration of M-CSF in serum of zymosan-injected control mice was within normal range, but that of zymosan-treated or untreated Kupffer-cell-depleted mice was markedly elevated at day 1. These findings imply that Kupffer cells are indispensable for granuloma formation and produce various cytokines including M-CSF. The local production and consumption of M-CSF in the liver may play a crucial role in granulomatous inflammation.

Animals↗
PubMed1997

Successful endoscopic injection sclerotherapy with N-butyl-2-cyanoacrylate following the recurrence of bleeding soon after endoscopic ligation for ruptured duodenal varices.

Bleeding from duodenal varices in a 63-yr-old man with alcoholic cirrhosis of the liver was found at endoscopy, and ligation surgery was carried out. Ten months after the operation, bleeding from the duodenal varices occurred and was treated by endoscopic ligation. However, after performing this procedure, bleeding again occurred 1 week later. Hemostasis was finally achieved by endoscopic injection sclerotherapy with N-butyl-2-cyanoacrylate. For the 22 months since the injection, the patient has been free from further bleeding. These results suggest that endoscopic injection sclerotherapy with N-butyl-2-cyanoacrylate was effective in bringing about immediate cessation of the bleeding in duodenal varices and that long-term hemostasis can be expected.

Duodenoscopy↗
PubMed1996

Molecular genetic analysis of variant phenotypes of the ABO blood group system.

ABO is clinically the most important blood group system in transfusion medicine and includes many variant phenotypes. To understand the molecular genetic basis of this polymorphic system, we have analyzed genomic DNAs obtained from Japanese individuals possessing variant ABO phenotypes including A2, Ax, Ael, cis-AB, Bx, and Bel. By polymerase chain reaction-single-strand conformation polymorphism (SSCP) and nucleotide sequence analyses, we identified 11 different alleles. These alleles had nucleotide sequences different from those of the previously described 13 different alleles responsible for the common ABO phenotypes. Analysis of the nucleotide sequences of the alleles responsible for those variant phenotypes showed that the amino acid residues at position 266 and 268 may be crucial for transferase specificity, whereas those at positions 214, 216, 223, 291, and 352 may be critical for the activity level. Nine of the 11 alleles, responsible for the A2, Ax, Ael, cis-AB, Bx, and Bel phenotypes, were presumed to be generated from common ABO alleles by single nucleotide mutations such as nonsynonymous substitution, deletion, or insertion. Two other alleles, responsible for the A2 and Ael phenotypes, may have originated by recombination, gene conversionlike events or accumulation of nucleotide substitutions. Our data indicate that different alleles could cause the same ABO variant phenotypes, and that these alleles do not necessarily belong to a single evolutionary lineage.

ABO Blood-Group System↗
PubMed1996

Immunochemical detection of carboxymethylated Apo B-100 in copper-oxidized LDL.

The objective of this study was to detect carboxymethyllysine (CML) moieties in biological materials using immunological methods. We prepared a polyclonal antibody specific to the carboxymethylated protein. The antibody recognizes the CML moiety in protein. Protein-bound carboxymethylcysteine (CMS) is scarcely recognized by the antibody. By use of the antibody, the formation of carboxymethylated apo B in copper-oxidized low density lipoprotein (ox-LDL) was immunochemically confirmed. To clarify the source compounds of carboxymethylation, various aldehyde-modified BSAs were prepared, and their reactivities with the antibody were investigated. Among the aldehyde-modified BSAs used, the glyoxal-BSA adduct showed a strong antigenicity. As far as we know, this is the first report of the detection of the CML moiety in ox-LDL using immunological methods.

Antibodies↗
PubMed1996

Visual demonstration of the organization of the human complement C4 and 21-hydroxylase genes by high-resolution fluorescence in situ hybridization.

We analyzed the gene organization in the complement component C4 and 21-hydroxylase (21OH) gene region of the human major histocompatibility complex using visual mapping of stretched DNA by multicolor fluorescence in situ hybridization (FISH). Normally, this region contains a duplicated 21OH-C4 gene cluster (21OHB-C4B-21OHA-C4A). Duplication and deletion of one or more copies of the 21OH-C4 gene unit are known to occur frequently. Biotin-labeled cDNA of the C4 gene and digoxigenin-labeled cDNA of the 21OH gene were hybridized to decondensed nuclei of peripheral blood lymphocytes obtained from individuals with various 21OH-C4 haplotypes. Hybridization signals of the C4 and 21OH probes were detected with fluorescein isothiocyanate (green) and rhodamine (red), respectively. Two linear green and red signal clusters were observed in each nucleus showing the normal haplotype. Gene duplication and deletion were visualized as addition and deletion of the signal cluster, respectively. The DNA types of the 21OH-C4 region determined by FISH were concordant with the results previously obtained by conventional molecular studies. Our high-resolution FISH technique is found to be useful for screening gene duplications and deletions.

Complement C4↗
PubMed1996

HLA class II alleles in Ainu living in Hidaka District, Hokkaido, northern Japan.

The Ainu people are considered to be the descendants of preagricultural native populations of northern Japan, while the majority of the population of contemporary Japan (Wajin) is descended mainly from postneolithic migrants. Polymorphisms of the HLA-DRB1, DRB3, and DQB1 alleles were investigated in DNA samples of 50 Ainu living in Hidaka district, Hokkaido. Unique features of the Ainu in this study were high incidences of DRB1*1401, DRB1*1406, and a newly described allele, DRB1*1106 (20%, 17%, and 5%, respectively). On the other hand, several common alleles in Wajin (DRB1*1502, 1302, 0803, and 1501) were found at relatively low frequencies (1-2%) in Ainu. Previously DRB1*1406 was described as a characteristic allele of some Native American or northeast Asian ethnic groups, and DRB1*1106 had been found in only two Singapore Chinese and one Korean. Principal component analysis of various populations based on HLA class II allele frequencies places the Ainu population midway between other east Asian populations, including Wajin, and Native Americans. These observations may support the hypothesis that the Ainu people are the descendants of some Upper Paleolithic populations of northeast Asia from which Native Americans are also descended.

Alleles↗
PubMed1996

HLA-A null allele with a stop codon, HLA-A*0215N, identified in a homozygous state in a healthy adult.

A healthy adult having no serologically detectable HLA class I A locus antigens was identified. The parents of the individual are consanguineous. Results of a family study indicated that the individual is homozygous for the B46-Cw1-DR8.1 haplotype, which was shown to be positively associated with A*0207 in our previous study. The HLA-A null individual is healthy and exhibits no apparent immunological abnormality. Total RNAs extracted from peripheral blood were converted to cDNAs. The reverse transcriptase-polymerase chain reaction (PCR) product, which is of the same size as the normally expressed gene, was easily obtained from the cDNAs with HLA-A locus-specific primers. The nucleotide sequence of this null allele (A*0215N) was the same as that of A*0207 except for a single nucleotide substitution which resulted in a stop codon in exon 4. From its nucleotide sequence, a truncated molecule was expected to be produced; however, the immunoprecipitation study failed to detect the predicted product. Genomic DNAs from 29 unrelated individuals who expressed only one HLA-A antigen with HLA-B46, were analyzed by a PCR-sequence-specific oligonucleotide method. None of the samples possessed this stop codon. Therefore, A*0215N is likely to be a rare allele generated by a single point mutation from A*0207.

Adult↗
PubMed1996

Effects of pravastatin on plasma and urinary mevalonate concentrations in subjects with familial hypercholesterolaemia: a comparison of morning and evening administration.

In order to determine whether there is a difference in the effect of the hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor pravastatin on cholesterol synthesis between the morning and the evening, we studied the 24-h profile of mevalonate in plasma and urine in 11 subjects with heterozygous familial hypercholesterolaemia. In study 1, eight subjects with familial hypercholesterolaemia took pravastatin (20 mg) once in the morning, and another 20-mg dose in the evening after a 1-week wash-out period. In study 2, five subjects with familial hypercholesterolaemia took pravastatin (20 mg per day) in the morning on 3 consecutive days and on 3 days in the evening after a 1 day wash-out. Plasma mevalonate concentrations were reduced at 9 h and 5 h after pravastatin administration in the morning and the evening, respectively. Urinary mevalonate excretion was significantly reduced at 4-8 h after pravastatin administration in the morning (51 vs 19 nmol.h-1) and at 4-16 h after pravastatin administration in the evening (56 vs 27 nmol.h-1). Daily urinary mevalonate excretion was equally and significantly reduced by pravastatin in the morning or evening. In conclusion, we found that morning and evening administration of pravastatin caused equal reductions in plasma and urinary mevalonate concentrations.

Administration, Oral↗
PubMed1996

Extensive polymorphism of ABO blood group gene: three major lineages of the alleles for the common ABO phenotypes.

Polymorphism of the ABO blood group gene was investigated in 262 healthy Japanese donors by a polymerase chain reactions-single-strand conformation polymorphism (PCR-SSCP) method, and 13 different alleles were identified. The number of alleles identified in each group was 4 for A1 (provisionally called ABO*A101, *A102, *A103 and *A104 according to the guidelines for human gene nomenclature), 3 for B (ABO*B101, *B102 and *B103), and 6 for O (ABO*O101, *O102, *O103, *O201, *O202 and *O203). Nucleotide sequences of the amplified fragments with different SSCP patterns were determined by direct sequencing. Phylogenetic network analysis revealed that these alleles could be classified into three major lineages, *A/*O1, *B and *O2. In Japanese, *A102 and *B101 were the predominant alleles with frequencies of 83% and 97% in each group, respectively, whereas in group O, two common alleles, *O101 (43%) and *O201 (53%), were observed. These results may be useful for the establishment of ABO genotyping, and these newly described ABO alleles would be advantageous indicators for population studies.

ABO Blood-Group System↗
PubMed1996

Effects of hypothermia during cardiopulmonary bypass and circulatory arrest on sympathetic nerve activity in rabbits.

OBJECTIVES: Little is known about the effect of hypothermia on neural regulation. We investigated the effects of hypothermia during cardiopulmonary bypass (CPB) on control of renal (RSNA) and lumbar sympathetic nerve activity (LSNA), and plasma catecholamine levels. METHODS: We directly measured RSNA (n = 14) and LSNA (n = 6) during CPB in anesthetized rabbits. CPB was performed via cannulae in the aortic root for arterial perfusion and the right atrium for venous drainage. Systemic hypothermia was induced by core cooling. RSNA and LSNA were recorded at the nasopharyngeal temperature of 37, 30, 24, and 18 degrees C and after rewarming up to 37 degrees C while keeping mean arterial pressure at 70 mmHg by altering perfusion flow. Other variables such as blood gases or electrolytes were kept constant. RESULTS: RSNA at the temperature of 30, 24, and 18 degrees C significantly decreased by 91, 97, and 95% from control (37 degrees C), respectively. LSNA decreased by 18, 57, and 89% from control as well. The decreases in RSNA at 30 and 24 degrees C were greater than those in LSNA (P < 0.05). At 18 degrees C both RSNA and LSNA nearly disappeared. Circulatory arrest for 20 min during hypothermia at 18 degrees C caused no increase in RSNA while it increased LSNA. Plasma catecholamine levels at 18 degrees C were not different from those at 37 degrees C. Rewarming to 37 degrees C increased RSNA and LSNA by 321 and 92% from control (37 degrees C before cooling), respectively (P < 0.01). CONCLUSIONS: Hypothermia progressively decreased and rewarming markedly increased sympathetic nerve activity, but the effects of hypothermia on RSNA and LSNA were not uniform.

Animals↗
PubMed1996

Identification and DNA typing of two Cw7 alleles (Cw*0702 and Cw*0704) in Japanese, with the corrected sequence of Cw*0702.

Two alleles encoding HLA-Cw7 antigens, tentatively called C7J1 and C7J2, have been identified in Japanese using a PCR-SSCP method. The nucleotide sequence of full-length C7J1 cDNAs showed a high degree of homology to the reported Cw*0702 sequence except in exon 1. We then resequenced the allele carried by the cell line JY in which Cw*0702 was first identified, according to a request from the WHO Nomenclature Committee. The results revealed complete identity between the corrected Cw*0702 sequence and the C7J1 sequence. On the other hand, the C7J2 sequence was completely identical to the reported Cw*0704 sequence. Sequences specific for Cw*0702 and Cw*0704 were confirmed using PCR-RFLP and PCR-SSO methods. Moreover, association analysis with other HLA locus alleles showed positive associations of Cw*0702 with HLA-B7, -B39, and -B67 and of Cw*0704 with HLA-B70 in Japanese.

Alleles↗
PubMed1996

HLA-B40, B18, B27, and B37 allele discrimination using group-specific amplification and SSCP method.

We developed a system for discriminating HLA-B40, B18, B27, and B37 alleles using a two-step PCR method followed by SSCP analysis. Fragments (0.8 kb) including exon 2, intron 2, and exon 3 were amplified in the first PCR. We used two sets of primers, one specific for HLA-B60-related alleles and the other specific for HLA-B61-related, B18, B27, and B37 alleles. No amplifications of other class I genes or pseudogenes were observed. In the second PCR, exon 2 and exon 3 were amplified separately, using diluents of the first PCR products as templates. HLA-B61-related, B18, B27, B37, and B60-related alleles were clearly discriminated in the SSCP analysis of the second PCR products. In a population study in which B61 alleles were analyzed, B*4003 was detected in two Japanese individuals in addition to two B61 alleles previously reported to occur in Japanese, B*4002 and B*4006. The relative frequencies of B*4002, B*4006, and B*4003 in Japanese were 58, 35, and 6%, respectively. The individuals having B*4003 are the first non-South Americans in whom this allele has been detected. The SSCP banding patterns of 18 HLA-B60-positive Japanese population samples were identical to those of a B*40012 sample for both exon 2 and exon 3. We also demonstrated that the B37 allele occurring in some Japanese is B*3701.

Alleles↗