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Biomedical subjects

Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 73 records · Page 4Linked to original sources

[Bronchial hyperresponsiveness before and after percutaneous transluminal mitral commissurotomy in patients with mitral stenosis].

To study the effects of percutaneous transluminal mitral commissurotomy (PTMC) on bronchial responsiveness to inhaled methacholine in patients with mitral valve stenosis (MS), methacholine inhalation tests and pulmonary function tests were done in 10 patients with MS before and one week after PTMC. The mean log cumulative dose producing a 35% decrease in respiratory conductance (PD35Grs) was significantly higher after PTMC in nine patients in whom PTMC was successful (p < 0.05). There were no significant changes in the results of pulmonary function tests after PTMC. One patient had severe mitral regurgitation after PTMC, and a decrease in PD35Grs. Six of the other nine patients in whom PTMC was successful continued to be hyperresponsive to inhaled methacholine. These data show that bronchial hyperresponsiveness in patients with MS is less severe after PTMC, concomitant with the relief of pulmonary congestion, and they suggest that the remaining bronchial hyperresponsiveness is responsible for peripheral airway narrowing with organic remodeling.

Bronchial Hyperreactivity

[Bronchial hyperresponsiveness and relaxability in patients with mitral stenosis].

To study the differences in bronchial responsiveness to inhaled methacholine and salbutamol between patients with mitral valve disease those with bronchial asthma a bronchial provocation test (Astograph) and pulmonary function tests were done in 25 patients with mitral stenosis (MS) and 18 patients with bronchial asthma (BA). We derived an index of airway reloxability from the effect of salbutamol after precontraction with inhaled methacholine. This index was the change in respiratory conductance (Grs) over time during inhalation of salbutamol (SGrs-d). It was computed as SGrd = delta Grs/delta t. Eighteen patients with MS (72%) showed bronchial hyperresponsiveness (BHR) to methacholine. The MS patients with BHR (MS(+)) had lower values of the ratio of the forced expiratory volume in one second to the forced vital capacity (FEV/FVC) and maximal expiratory flow at 25% of vital capacity (V25) than MS patients without BHR (MS(-)). There was a significant correlation between V25 and the log cumulative dose producing a 35% decrease in respiratory conductance (PD35Grs) in MS(+). The mean log Dmin of MS(+) was significantly higher than that of the patients with BA (0.14 +/- 0.64 log units and -0.30 +/- 0.65 log units, p < 0.05, respectively). The mean log PD35Grs of MS(+) was also significantly higher than that of the patients with BA (1.09 +/- 0.53 log units and 0.45 +/- 0.66 log units, p < 0.01, respectively). Indices of relaxability (SGrs-d and SCrs-d/Grs-d) in MS(+) were significantly lower than in BA patients. Indices of hyperresponsiveness and relaxability were both significantly lower in patients with MS than in patients with BA.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuterol

Inhibition of skin xenograft rejection by depleting T-cell receptor alpha beta-bearing cells without T-cell receptor gamma delta-bearing cells or natural killer cells by monoclonal antibody.

We compared the effects of in vivo administration of the anti-T-cell receptor (TCR) alpha beta monoclonal antibody (mAb) (H57-597) to those of the anti-CD3 mAb (145-2C11), with or without anti-NK1.1 mAb (PK136), on xenogeneic skin graft survival in mice. In anti-TCR alpha beta mAb-treated B6 mice, F344 rat skin grafts survived for about 54 days, whereas in anti-CD3 mAb-treated B6 mice with or without anti-NK1.1 mAb treatment grafts survived about 25 days. In anti-TCR alpha beta mAb-treated B6 mice, TCR alpha beta-bearing T-lymphocyte function was completely abrogated, although TCR gamma delta-bearing T-lymphocyte function was still intact on day 9. In the anti-CD3 mAb-treated mice, the functions of both types of T lymphocytes were completely abrogated. On day 32, when most of the skin xenografts had been rejected in the anti-CD3 mAb-treated mice, the functions of both T lymphocytes had recovered considerably, and could actually respond to F344 antigens. In contrast, the function of TCR alpha beta-bearing cells had only partially recovered in the anti-TCR alpha beta mAb-treated mice. Finally, natural killer (NK) activity in the anti-TCR alpha beta mAb-treated mice was intact on day 32, when rat skin grafts still survived. In contrast, NK activity in the anti-CD3 mAb plus anti-NK1.1 mAb-treated mice did not recover on day 32, when skin xenografts had already been rejected. These results suggest that TCR gamma delta-bearing T cells and NK cells by themselves, at least in the absence of TCR alpha beta-bearing T cells, do not mediate xenogeneic skin graft rejection in mouse/rat combinations.

Animals

[HLA-linked susceptibility to intractable vasculitis syndrome].

Sixty-four patients with Takayasu arteritis, 204 patients with rheumatoid arthritis (RA), 53 patients with systemic lupus erythematosus (SLE) and 64 patients with mixed connective tissue disease (MCTD) in the Japanese population were typed for HLA class II genes at DNA level. The results suggest that susceptibility to Takayasu arteritis is controlled by HLA-B52-DRB1*1502-DRB5*0102-DQA1*0103-DQB1 *0601-DPA1*02-DPB1*0401 haplotype, because the frequency of that HLA haplotype was increased with statistical significance in the patients as compared with that in the healthy controls. On the other hand, the HLA-DRB1*0405-DQA1*0301-DQB1*0401 haplotype was associated with the susceptibility to RA. Susceptibility to SLE and MCTD are controlled by the HLA-DRB1 *1501-DRB5*0101-DQA1*0102-DQB1*0602 haplotype and the HLA-DRB1*0401-DRB4*0101- DQA1*0301-DQB1*0301, haplotype respectively. These observations clearly indicate the presence of HLA-linked disease susceptibility genes to Takayasu arteritis, RA, SLE and MCTD, and the difference in HLA-linked genetic background between these four diseases.

Amino Acid Sequence

[Study on the evaluation of recurrence of HCC and the effect after transcatheter hepatic arterial embolization--fluctuations in AFP values].

To determine the usefulness of alpha-fetoprotein (AFP) in determining recurrence of HCC after interventional angiography (IVA) and to define the relation between AFP and the imaging diagnosis of HCC recurrence, changes in AFP values in 160 patients with hepatocellular carcinoma who were treated by IVA > or = two times were classified into four patterns: A: the AFP value was decreased after the first IVA, increased at recurrence and decreased again after the second IVA; B: the AFP value was unchanged after the first IVA, but increased at recurrence and decreased after the second IVA; C: the AFP value was decreased after the first IVA, but was not increased at recurrence; D: the AFP value showed no change. The frequency of each AFP pattern and the diagnosis of recurrence by AFP were determined. The relation between tumor type and AFP was defined. Pattern A was the most frequently detected. In 62.6%, AFP was increased at recurrence (A and B), and there was a positive correlation between changes in the AFP value and the findings of imaging diagnosis. In another 37.5%, AFP was not increased at recurrence (C and D), and therefore, the diagnosis of HCC recurrence by imaging methods was very important.

Aged

Observations on morphology and electrophysiological properties of the normal and axotomized facial motoneurons in the cat.

The correlation between the morphology of facial motoneurons stained intracellularly with horseradish peroxidase and their physiological parameters was examined in cats following facial nerve section and in cats with intact facial nerve. A certain statistical relationship exists between cell size and excitability in normal neurons. After axotomy, facial neurons showed a slow conduction velocity and a low rheobasic current, but had a normal cell size. Physiological changes include repetitive firing in response to intracellular current injection, reflecting an increase in the excitability in the axotomized neurons.

Animals

Expression of mouse cathepsin L cDNA in Saccharomyces cerevisiae: evidence that cathepsin L is sorted for targeting to yeast vacuole.

To investigate the intracellular transport mechanism of lysosomal cathepsin L in yeast cells, we attempted to produce mouse cathepsin L in Saccharomyces cerevisiae by placing the coding region under the control of the promoter of the yeast glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene. Immunoblotting analysis by the use of an antibody specific for rat cathepsin L revealed that the yeast cells carrying the cathepsin L coding sequence produced 39- and 30-kDa products, which correspond to the rat procathepsin L and the single-chain form of mature cathepsin L, respectively. The precursor polypeptide showed sensitivity toward endoglycosidase H treatment. Cell fractionation experiments demonstrated that the processed form of 30-kDa cathepsin L was found to be colocalized to the yeast vacuole with the marker enzyme carboxypeptidase Y in a Ficoll step gradient. In the prepared vacuolar fraction, a considerable amount of cathepsin L was revealed to be cofractionated with the vacuolar membranes. Furthermore, the phase separation experiments with Triton X-114 provide the first evidence showing that the mature form of cathepsin L polypeptide is strongly associated with the vacuolar membranes. Therefore, the present results suggest that the mouse cathepsin L precursor polypeptide is initially synthesized as the proenzyme in the yeast cells and then correctly delivered to the vacuole. During the intracellular sorting pathway, the procathepsin L would undergo the post-translational proteolytic processing step to generate the mature enzyme. Based on these lines of evidence, we propose that cathepsin L is recognized by mechanisms similar to those for the intracellular sorting and processing of vacuolar proteins in the yeast cells.

Animals

Interference with cyclophosphamide-induced skin allograft tolerance by cyclosporin A.

In a murine strain combination identical in H-2 Ag but disparate in minor histocompatibility (H) Ag consisting of C3H/He (C3H; H-2k, Mls-1b) mice as recipients and AKR/J (AKR; H-2k, Mls-1a) mice as donors, a permanent skin allograft tolerance can be achieved by the cyclophosphamide (CP)-induced tolerance system that consists of i.v. injection of donor spleen cells (day -2) and i.p. injection of CP 2 days later (day 0). Such permanent take of allografts in CP-induced tolerant mice was interfered with by intramuscular injection of cyclosporin A (CsA) from day -5 to day -1 and their grafts were rejected by 21 days after grafting. Mls-1a-reactive CD4+V beta 6+ T cells in the periphery, as the indicator to follow the kinetics of donor-reactive T cells, increased on day 0 and day 3 in the C3H mice treated with AKR spleen cells alone, whereas they disappeared rapidly from day 0 to day 3 in CP-induced tolerant mice. When CsA capable of interfering with IL-2 production and T cell proliferation was administered before CP treatment in CP-induced tolerance system, the number of CD4+V beta 6+ T cells in periphery did not increase on day 0 and 3, but increased on day 7 in contrast to the decreased number of those in CP-induced tolerant mice. On day 7, MLR against donor cells was decreased in CP-induced tolerant mice, but maintained in CsA-interfered tolerant mice. These result may indicate that the destruction of donor-Ag-stimulated, proliferating T cells by CP is interfered with by CsA, probably because CsA inhibits the proliferation of donor-reactive T cells at the time of CP treatment. Furthermore, these results also implicate that the protocol for immunosuppression with CsA and antimetabolites has to be designed carefully in clinical transplantation.

Animals

Extraordinarily stable mini-hairpins: electrophoretical and thermal properties of the various sequence variants of d(GCGAAAGC) and their effect on DNA sequencing.

A small DNA fragment having a characteristic sequence d(GCGAAAGC) has been shown to form an extraordinarily stable mini-hairpin structure and to have an unusually rapid mobility in polyacrylamide gel electrophoresis, even when containing 7M urea. Here, we have studied the stability of the various sequence variants of d(GCGAAAGC) and the corresponding RNA fragments. Many such sequence variants form stable mini-hairpins in a similar manner to the d(GCGAAAGC) sequence. The RNA fragment, r(GCGAAAGC) also forms a mini-hairpin structure with less stability. The DNA mini-hairpins with GAAA or GAA loop are much more stable than DNA and RNA mini-hairpins with other loop sequence so far as has been examined. The stability difference between DNA and RNA mini-hairpins may be deduced to the stem structures formed by DNA (B form) and RNA (A form). The stable hairpins consisting of the GCGAAAGC sequence cause strong band compression on the sequencing gel. This phenomenon should be carefully considered in DNA sequencing.

Base Sequence

Solution structure of a DNA-binding unit of Myb: a helix-turn-helix-related motif with conserved tryptophans forming a hydrophobic core.

The DNA-binding domain of the c-myb protooncogene product consists of three imperfect tandem repeats of 51 or 52 amino acids, each of which contains three conserved tryptophans, spaced 18 or 19 amino acids apart. The structure of the third repeat, which is essential for sequence-specific DNA binding, has been determined by NMR with distance geometry calculation. It includes three well-defined helices (residues 149-162, 166-172, and 178-187) maintained by a hydrophobic core that includes the three conserved tryptophans, together with two histidines. Helices 2 and 3 form a structure related to but distinct from a canonical helix-turn-helix motif. In particular, the turn between these helices is one amino acid longer than the corresponding turn in bacterial repressors and homeodomains and contains a proline residue. In addition, the architecture of the three helices is different from those of homeodomains and DNA-binding domains of bacterial repressors. Based on the present structure, the binding mode of Myb repeat 3 with a specific DNA is also discussed.

Amino Acid Sequence

Synaptic inhibition of accessory motoneurons evoked by stimulation of the trigeminal nerve in the cat.

Stimulation of the trigeminal nerve produced polysynaptic inhibitory postsynaptic potentials (IPSPs) in accessory motoneurons of the cat. This contrasts with the observation that dorsal cervical motoneurons responded with EPSPs to trigeminal stimulus. Stimulation of the rostral part of spinal trigeminal nucleus elicited di- or polysynaptic IPSPs in accessory motoneurons. Transection of the anterior funiculus at the upper cervical cord selectively abolished the IPSPs. The IPSPs were antagonized by systematically administrated strychnine but not bicuculline.

Accessory Nerve

Afferent projections in the spinal accessory nerve to the facial motoneurons of the cat.

Stimulation of the accessory nerve evoked polysynaptic excitatory postsynaptic potentials (EPSPs) in the facial nucleus (FN) neurons of anesthetized cats. From the experiments with severance of C1-C3 dorsal roots, it is suggested that accessory afferents enter the brainstem through the accessory nerve. It was also found that stimulation of the solitary tract nucleus produced exclusively monosynaptic EPSPs in the FN neurons and the afferent volleys are most likely to be relayed at the solitary tract nucleus.

Accessory Nerve

Accelerated declining tendency of human T-cell leukemia virus type I carrier rates among younger blood donors in Kumamoto, Japan.

The annual age- and sex-specific human T-cell leukemia virus type I carrier rate of blood donors in Kumamoto, Kyushu, Japan from 1986 to 1990 revealed that the carrier rates of all the age groups below 50 years declined linearly in both sexes (P less than 0.005). Furthermore, the annual declining rates relative to the carrier rates of 16-19-year-old and 20-29-year-old males were higher than those of all of the older males (P less than 0.02), and all female age groups below 50 years had higher relative declining rates than 50-64-year-old females (P less than 0.05). Although several factors, such as a notification program at obstetric clinics, methodological and technical improvement of the assays, wider knowledge of human T-cell leukemia virus type I infection in the latter years, and immigration of individuals from a nonendemic area, might cause an absolute decline of the carrier rate of the blood donors, these factors could not explain the acceleration of the relative declining rate among younger donors. Therefore, this acceleration represents the tendency of the general population.

Adolescent

Genetic control of nonresponsiveness to hepatitis B virus vaccine by an extended HLA haplotype.

We previously reported evidence for a statistical association between the serologically determined HLA-Bw54, DR4 and DRw53 alleles and the non-immune responsiveness to hepatitis B virus surface antigen (HBsAg) in the Japanese population. To identify the locus and allele within the HLA region associated with the nonresponsiveness to HBsAg, serological HLA typing, DNA typing of HLA-DQ and DP alleles using amplified HLA genes and sequence-specific oligonucleotide probes, and restriction fragment length polymorphism (RFLP) analysis of the fourth component of complement (C4) genes were performed in healthy unrelated Japanese vaccinees who were immunized subcutaneously three times with plasma-derived HBsAg vaccine. In nonresponders to HBsAg, the frequencies of HLA-Bw54 cross-reactive epitope group (CREG); (Bw54, Bw55, Bw56 and other Bw22), C4 RFLP (6.5 kb + 12.0 kb), DR4, DRw53 and DQw4 (DQA1*0301-DQB1*0401) were increased and the frequencies of HLA-DR1, DRw6 and DQw1 were decreased as compared with those in healthy unrelated controls. Further analysis revealed that the coexistence of HLA-Bw54CREG and DR4-DRw53-DQw4 (DQA1*0301-DQB1*0401) was associated with the nonresponder group, whereas, donors positive for exclusively either Bw54 CREG or DR4-DRw53-DQw4 (DQA1*0301-DQB1*0401) were not associated with the nonresponder group. Because there is a strong linkage disequilibrium between HLA-Bw54CREG, C4 RFLP (6.5 kb + 12.0 kb) and HLA-DR4-DRw53-DQw4 (DQA1*0301-DQB1*0401) in the Japanese population, the extended HLA-Bw54CREG-C4 RFLP (6.5 kb + 12.0 kb)-DR4-DR-w53-DQw4 (DQA1*0301-DQB1*0401) haplotype may well control nonimmune responsiveness to HBsAg. This extended HLA haplotype controls nonresponsiveness as a dominant genetic trait because all ten heterozygotes and two of three probable homozygotes of this extended HLA haplotype were nonresponders.

Adult

Tumor necrosis factor and endotoxin in the pathogenesis of liver and pulmonary injuries after orthotopic liver transplantation in the rat.

This study examines whether tumor necrosis factor and endotoxin are involved in the pathogenesis of primary nonfunction of graft and pulmonary complication after orthotopic liver transplantation. Livers from Lewis rats were stored for either 1 or 4 hr in ice-cold Euro-Collins solution (1-hr storage and 4-hr storage group, respectively). Subsequently, donor livers were implanted orthotopically. In some experiments, anti-tumor necrosis factor antibody was administered intravenously before and immediately after the surgery into animals that received livers stored for 4 hr. Blood samples for the measurement of tumor necrosis factor and endotoxin were collected by way of an indwelling catheter placed in the suprahepatic vena cava. Serum tumor necrosis factor was elevated at all time points studied postoperatively in rats of the 4-hr storage group; however, tumor necrosis factor was not detected in the serum in the 1-hr storage group. Endotoxin was also elevated significantly in the serum of the former group compared with levels in the serum of the latter group. The peak value of endotoxin occurred 1 hr earlier than that of tumor necrosis factor, suggesting that the rise in endotoxin stimulated release of tumor necrosis factor. The histological study of livers stored for 4 hr showed substantial hepatocellular degeneration 24 hr after surgery, whereas hepatocellular damage was minimal in the 1-hr storage group. Serum ALT levels 24 hr after the operation in the 1-hr and 4-hr storage groups were 169 +/- 46 IU/L and 374 +/- 41 IU/L (mean +/- S.E.M., p less than 0.05), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase

Allele-specific expression of the cytoplasmic exon of HLA-DQB1 gene.

The beta chain of the HLA-DQ molecule is shorter by eight amino acid residues than other major histocompatibility complex class II beta chains due to elimination of the fifth exon coding for part of the cytoplasmic domain. This elimination is caused by one base substitution in the splice acceptor site of the exon. We found that two HLA-DQB1 alleles, DQB1*0503 and DQB1*0601, did not have this substitution, and the exon was utilized in these two alleles. However, two forms of HLA-DQB mRNA, with or without exon 5, were generated in Epstein-Barr virus-transformed cell lines homozygous for DQB1*0503 or DQB1*0601, indicating alternative mRNA splicing. The alternative splicing of DQB1*0601 mRNA was also found in peripheral blood lymphocytes and L cell transfectants. To investigate the functional relevance of the allele-specific long cytoplasmic tail of HLA-DQ beta chain, we developed three types of L cell transfectants expressing exclusively the HLA-DQw6 molecules with short cytoplasmic tail, long cytoplasmic tail, or both forms of the beta chain, and used them as antigen presenting cells for streptococcal cell wall antigen-specific T cell lines. These three types of transfectants could function almost equally well as antigen presenting cells. It was thus demonstrated that both forms of HLA-DQ beta chain, with or without eight amino acid residues coded for by the exon 5, can be associated with the HLA-DQ alpha chain, be expressed on the cell surface, and function as restriction molecules in antigen recognition by the CD4+ T cells.

Alleles

Intracranial cavernous angioma in the 1st year of life and a review of the literature.

Three cases of symptomatic cavernous angioma occurring in the 1st year of life are presented. All three patients were treated with radical extirpation. Postoperatively, two of them improved, but the third died due to cerebral herniation secondary to recurrence of bleeding of the lesion. The clinical characteristics of cavernous angioma in the 1st year of life are briefly discussed and a review of the literature presented, including 16 previous cases operated on directly.

Brain Neoplasms