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Biomedical subjects

Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 55 records · Page 3Linked to original sources
PubMed2001

Calcification and degeneration characteristics of the Biocor no-react bovine internal mammary artery (BIMA) - in vivo evaluation in a sheep model.

OBJECTIVE: The No-React process for biomaterials was suggested to prevent calcification and degeneration. We examined in vivo in a chronic sheep model the performance of a Biocor bovine internal mammary artery (BIMA) graft after No-React processing. METHODS: 'No-React' processing consists of aldehyde cross-linkage following a detoxification process with multiple physical variables and incubation with surfactant. Biocor BIMA No-React treated grafts have been interposed in the carotid artery in seven sheep with a Dacron graft as control. Grafts were explanted after 3 or 6months and were grossly examined, by X-ray, histology, transmission and scanning electron microscopy, and atomic absorption spectrophotometry. RESULTS: In the BIMA, good healing was found with a smooth intimal surface, minimal inflammatory reaction, and a well preserved ultrastructure. Calcification increased progressively. In the Dacron grafts, a fibrous covering the inner surface and infiltration with fibroblasts, histiocytes and macrophages was noted. Calcium content was stable. CONCLUSION: Calcification increased progressively in Biocor BIMA No-React grafts. Minimal inflammatory changes, a smooth inner surface and well preserved ultrastructure were noted.

Animals↗
PubMed2001

Glycosidase inhibitors of gem-diamine 1-N-iminosugars. structures in media of enzyme assays.

The relationships between structures and inhibitory activities of glycosidase inhibitors of gem-diamine 1-N-iminosugars in media of enzyme assays have been investigated. It has been proved that gem-diamine 1-N-iminosugar smoothly undergoes a structural change to a hydrated ketone or its derivative via a hemiaminal in the media (pH 5.0-6.3), and that the products generated in the media as well as the parent gem-diamine 1-N-iminosugars potently inhibit glycosidases.

Animals↗
PubMed2001

Solution structure of a telomeric DNA complex of human TRF1.

BACKGROUND: Mammalian telomeres consist of long tandem arrays of double-stranded TTAGGG sequence motif packaged by TRF1 and TRF2. In contrast to the DNA binding domain of c-Myb, which consists of three imperfect tandem repeats, DNA binding domains of both TRF1 and TRF2 contain only a single Myb repeat. In a DNA complex of c-Myb, both the second and third repeats are closely packed in the major groove of DNA and recognize a specific base sequence cooperatively. RESULTS: The structure of the DNA binding domain of human TRF1 bound to telomeric DNA has been determined by NMR. It consists of three helices, whose architecture is very close to that of three repeats of the c-Myb DNA binding domain. Only the single Myb domain of TRF1 is sufficient for the sequence-specific recognition. The third helix of TRF1 recognizes the TAGGG part in the major groove, and the N-terminal arm interacts with the TT part in the minor groove. CONCLUSIONS: The DNA binding domain of TRF1 can specifically and fully recognize the AGGGTT sequence. It is likely that, in the dimer of TRF1, two DNA binding domains can bind independently in tandem arrays to two binding sites of telomeric DNA that is composed of the repeated AGGGTT motif. Although TRF2 plays an important role in the t loop formation that protects the ends of telomeres, it is likely that the binding mode of TRF2 to double-stranded telomeric DNA is almost identical to that of TRF1.

Amino Acid Motifs↗
PubMed2001

Differences between T-cell reactivities to major myelin protein-derived peptides in opticospinal and conventional forms of multiple sclerosis and healthy controls.

In Japanese, susceptibility to the conventional form of multiple sclerosis (C-MS) is associated with the HLA-DRB1*1501-DRB5*0101 haplotype while susceptibility to the opticospinal form of MS (OS-MS) is associated with HLA-DPA1*0202-DPB1*0501. To clarify the characteristics of T cells autoreactive to myelin proteins in each MS subtype, we established T-cell lines reactive to such myelin antigens as myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG) from 5 of 10 OS-MS patients, 6 of 11 C-MS patients and 7 of 13 healthy controls (HCs), and T-cell epitopes and their restriction molecules were determined. We found that (a) intermolecular epitope spreading was found to be significantly more frequent in MS patients than in HCs (P=0.0128), (b) intramolecular epitope spreading also tended to occur more frequently in MS patients than in HCs (P=0.0584), (c) in OS-MS, HLA-DR-restricted and MOG-autoreactive T cells were more frequently established as compared with those reactive to MBP or PLP epitopes and (d) in C-MS, HLA-DQ-restricted and PLP-autoreactive T cells dominated those autoreactive to MBP or MOG epitopes. A DPB1*0501-restricted MBP-reactive T-cell clone from a patient with OS-MS provided evidence that the first HLA class II anchor amino acid of peptide bound to disease-susceptible DP5 molecule was distinct from that for the DR2 molecule. Taken together, these differences in specificities of myelin-autoreactive T cells between C-MS and OS-MS as well as the difference in the anchor motif of the binding peptides between each MS subtype-susceptible HLA class II molecule may contribute to the development of distinct clinical phenotypes.

Adult↗
PubMed2001

Combination of HLA-A and HLA class II alleles controls the susceptibility to rheumatoid arthritis.

Two hundred and four unrelated Japanese patients with rheumatoid arthritis (RA) were typed for HLA by serological typing and DNA typing. The serological typing revealed that frequencies of HLA-A11, DR4, DR53 and DQ4 were increased and those of DR8 and DQ1 were decreased in the patients. The DNA typing has precisely defined the disease-associated HLA class II alleles; DRBl*0405, DQAl*03 and DQBl*0401 showed positive associations, while negative associations were found with DRBl*0803, DQAl*0103 and DQBl*0601. The risk for RA was found to be closely associated with particular amino acid sequences of DR-beta chain, including glycine residue at the 86th position in addition to those between 70 and 74, which are known to confer binding specificity and affinity to antigenic peptides. The observation that the frequency of HLA-A11 was increased in the DRBl*0405-positive patients suggested the interaction of these two alleles in the susceptibility to RA. On the other hand, the frequency of DPB1*0201 was increased in the DRBl*0405-negative patients and the frequency of HLA-A2 was increased in the DPBl*0201-positive patients, especially in the younger onset group. These findings suggested that the combination of HLA-A2 and DPBl*0201 may confer the susceptibility in the DRBl*0405-negative patients. Our results suggested the possibility that the susceptibility to RA is controlled by the interaction of HLA-A and DRBl genes or by that of HLA-A and DPBl genes in different patient subgroups.

Adult↗
PubMed2001

Glycine blocks opening of a death channel in cultured hepatic sinusoidal endothelial cells during chemical hypoxia.

Using confocal microscopy, we investigated mechanisms underlying loss of plasma membrane integrity during necrotic death of cultured hepatic sinusoidal endothelial cells exposed to 2.5 mM potassium cyanide (chemical hypoxia). After 2-3 h, the anionic fluorophore calcein abruptly began to enter the cytosol, and nuclei labeled with cationic propidium after another 2-5 min. As calcein permeated, growth of blebs on the plasma membrane accelerated. Lucifer yellow, another anionic fluorophore, entered identically to calcein, whereas high molecular weight dextrans (40-2000 kDa) entered like propidium. Glycine slowed, but did not prevent calcein entry, whereas permeation of propidium and high molecular weight dextrans was blocked completely by glycine. These findings suggest that opening of a glycine-sensitive organic anion channel, or death channel, precipitates a metastable state characterized by rapid cell swelling and bleb growth. This metastable state culminates in non-specific breakdown of the plasma membrane permeability barrier and irreversible cell death.

Cell Death↗
PubMed2001

Identification of beta-lactoglobulin-derived peptides and class II HLA molecules recognized by T cells from patients with milk allergy.

BACKGROUND: Cow's milk allergy impairs the health and development of many infants since it deprives them of adequate nutrition. Cow's milk fractions contain many allergens, and beta-lactoglobulin (BLG) is one of the major allergens. OBJECTIVE: The purpose of this study was to determine T cell epitopes, antigen-presenting molecules and cytokine production by T cells in relation to BLG. The results can provide new therapeutic possibilities of using analogue peptides of BLG for infants with cow's milk allergy. METHODS: Using a mixture of a panel of overlapping synthetic peptides that cover the entire BLG molecule, we established polyclonal BLG-specific short-term T cell lines and clones from peripheral blood mononuclear cells of four patients with allergy to cow's milk carrying most of the common human leucocyte antigen (HLA) haplotypes seen in the Japanese population. We then identified the T cell epitopes and antigen-presenting molecules, and measured the production of cytokines interleukin (IL)-4, IL-5 and interferon-gamma in the culture supernatants. RESULTS: The T cell lines established from the four patients responded to seven different peptides. Three of the peptides stimulated the T cells of two donors, regardless of the HLA types. The patterns of inhibition of the proliferative responses of the cell lines by anti-HLA class II antibodies were heterogeneous; three were mainly inhibited by anti-HLA-DR mAbs, and the other was inhibited by anti-HLA-DQ mAbs. High levels of IL-5 were produced by these T cell lines. CONCLUSIONS: Patients' T cells recognized BLG in association with a variety of HLA-DR or -DQ as antigen-presenting molecules. Although some peptides did have a more potent T cell stimulatory activity than others, the T cell receptor ligands formed with the BLG molecule are heterogeneous. Peptides for the desensitization of T cells of the patients with cow's milk allergy need to be designed keeping in mind the different requirements in different ethnic groups.

Amino Acid Sequence↗
PubMed2001

Yeast Saccharomyces cerevisiae has two cis-prenyltransferases with different properties and localizations. Implication for their distinct physiological roles in dolichol synthesis.

BACKGROUND: Dolichol is a family of long-chain polyprenols, which is utilized as a sugar carrier in protein glycosylation in the endoplasmic reticulum (ER). We have identified a key enzyme of the dolichol synthesis, cis-prenyltransferase, as Rer2p from Saccharomyces cerevisiae. We have also isolated a multicopy suppressor of an rer2 mutant and named it SRT1. It encodes a protein similar to Rer2p but its function has not been established. RESULTS: The cis-prenyltransferase activity of Srt1p has been proved biochemically in the lysate of yeast cells lacking Rer2p. The polyprenol product of Srt1p is longer in chain length than that of Rer2p and is not sufficiently converted to dolichol and dolichyl phosphate, unlike that of Rer2p. The subcellular localization of these two isozymes has been examined by immunofluorescence microscopy and by the use of GFP fusion proteins. Whereas GFP-Rer2p is localized to the continuous ER and some dots associated with the ER, GFP-Srt1p shows only punctate localization patterns. Immunofluorescence double staining with Erg6p, a marker of lipid particles in yeast, indicates that Srt1p is mainly localized to lipid particles (lipid bodies). RER2 is mainly expressed in the early logarithmic phase, while the expression of SRT1 is induced in the stationary phase. CONCLUSIONS: We have shown that yeast has two active cis-prenyltransferases with different properties. This result implies that the two isozymes have different physiological roles during the life cycle of the yeast.

Dimethylallyltranstransferase↗
PubMed2001

Differentiation of Herpes simplex virus types 1 and 2 in sera of patients with HSV central nervous system infections by type-specific enzyme-linked immunosorbent assay.

OBJECTIVE: To differentiate by enzyme-linked immunosorbent assay (ELISA) using type-specific glycoprotein G herpes simplex virus (HSV) type 1 and type 2 in serum collected from patients with HSV central nervous system (CNS)infections. METHODS: HSV 1 and 2 typing in convalescent sera of 17 patients with HSV acute encephalitis, myelitis, or meningitis was determined by the type-specific IgG ELISA kit (Gull Laboratory, Inc.). HSV CNS infections were diagnosed by polymerase chain reaction (PCR) or conventional serologic tests from acute to convalescent stages. RESULTS: In 13 of 17 patients, HSV type 1 and HSV type 2 antibodies were positive; 11 patients with HSV type 1 and 2 patients with HSV type 2 were found. All 10 patients with encephalitis showed equivocal or positive results for HSVtype 1. In two of three cases of myelitis, HSV type 1 was demonstrated. Each case of myelitis and meningitis reacted to both types 1 and 2. CONCLUSION: These data suggest that the kit is useful for type differentiation of HSV CNS infections from convalescent sera, and can play a supplementary role in HSV typing by PCR or previous serologic tests.

Adult↗
PubMed2001

Sciatic nerve regeneration through alginate with tubulation or nontubulation repair in cat.

A novel material for nerve regeneration, alginate, was employed in both tubulation and nontubulation repair of a long peripheral nerve defect injury. Twelve cats underwent severing of the right sciatic nerve to generate a 50-mm gap, which was treated by tubulation repair (n = 6) or nontubulation repair (n = 6). In the tubulation group, a nerve conduit consisting of polyglycolic acid mesh tube filled with alginate sponge was implanted into the gap and the tube was sutured to both nerve stumps. In the nontubulation group, the nerve defect was repaired by a simple interpolation of two pieces of alginate sponge without any suture. The animals in both groups exhibited similar recovery of locomotor function. Three months postoperatively, successful axonal elongation and reinnervation in both the afferent and efferent systems were detected by electrophysiological examinations. Intracellular electrical activity was also recorded, which is directly indicative of continuity of the regenerated nerve and restoration of the spinal reflex circuit. Eight months after operation, many regenerated myelinated axons with fascicular organization by perineurial cells were observed within the gap, peroneal and tibial branches were found in both groups, while no alginate residue was found within the regenerated nerves. In morphometric analysis of the axon density and diameter, there were no significant differences between the two groups. These results suggest that alginate is a potent material for promoting peripheral nerve regeneration. It can also be concluded that the nontubulation method is a possible repair approach for peripheral nerve defect injury.

Alginates↗
PubMed2001

The chloroplast clpP gene, encoding a proteolytic subunit of ATP-dependent protease, is indispensable for chloroplast development in tobacco.

ClpP is a proteolytic subunit of the ATP-dependent Clp protease, which is found in chloroplasts in higher plants. Proteolytic subunits are encoded both by the chloroplast gene, clpP, and a nuclear multi gene family. We insertionally disrupted clpP by chloroplast transformation in tobacco. However, complete segregation was impossible, indicating that the chloroplast-encoded clpP gene has an indispensable function for cell survival. In the heteroplasmic clpP disruptant, the leaf surface was rough by clumping, and the lateral leaf expansion was irregularly arrested, which led to an asymmetric, slender leaf shape. Chloroplasts consisted of two populations: chloroplasts that were similar to the wild type, and small chloroplasts that emitted high chl fluorescence. Ultrastructural analysis of chloroplast development suggested that clpP disruption also induced swelling of the thylakoid lumen in the meristem plastids and inhibition of etioplast development in the dark. In mature leaves, thylakoid membranes of the smaller chloroplast population consisted exclusively of large stacks of tightly appressed membranes. These results indicate that chloroplast-encoded ClpP is involved in multiple processes of chloroplast development, including a housekeeping function that is indispensable for cell survival.

Adenosine Triphosphatases↗
PubMed2001

Concurrent chemoradiotherapy for oropharyngeal carcinoma.

The clinical results of definitive chemoradiotherapy for oropharyngeal carcinoma were retrospectively analyzed. Thirty-one patients with oropharyngeal carcinoma who received definitive radiation therapy between January 1986 and June 1998 were analyzed. The median age was 61 years. All patients had squamous cell carcinoma. According to the Union International Contre le Cancer 1997 classification system, stage I, II, III, IVA, and IVB were 1,0, 9, 14, and 7, respectively. Regarding the primary site, 23 tumors were in the lateral wall, whereas 2 were in the superior wall, and 3 each were in the anterior and posterior walls. The median total dose was 66 Gy, with a range of 60 Gy to 74.4 Gy. The overall treatment time ranged from 39 days to 113 days, with a median of 50 days. Seven patients underwent hemilateral radical neck dissection. Fourteen patients received concurrent chemotherapy using weekly cisplatin (50 mg/d) at least three times. The 5-year overall and cause-specific survival (CSS) rates were 55% and 62%, respectively. All local recurrences occurred within 2 years. The CSS rate in patients with lateral or superior wall origin was significantly superior to that of patients with anterior or posterior wall origin (p < 0.05). The 3-year CSS rate was 83% for patients treated with concurrent chemoradiotherapy using weekly cisplatin at least 3 times, whereas that was 53% for the remaining patients (p < 0.05). No serious adverse effects were observed. It is concluded that definitive concurrent chemoradiotherapy using weekly cisplatin for oropharyngeal carcinoma appear promising.

Adult↗
PubMed2001

In vivo cultured skin composed of two-layer collagen sponges with preconfluent cells.

Although various kinds of cultured skin substitutes have been developed, it takes several weeks to produce them before grafting. In their previous study, the authors succeeded in producing cultured skin easily in a short period of time by layering two collagen sponges. In the current study, to shorten this period even further, they grafted the cell-preconfluent artificial skin immediately after seeding the cells. They used two collagen sponges with different pore sizes and crosslink densities. They seeded 1,000,000 cells per square centimeter of fibroblasts and 1,000,000 cells per square centimeter of keratinocytes on the respective collagen sponges and grafted them on a full-thickness, excised wound on the back of severe combined immunodeficient mice. Two weeks after grafting, epithelium and dermislike tissue were formed. They then decreased the number of keratinocytes and grafted them. Four weeks after grafting, at seeding densities of 50,000 to 1,000,000 cells per square centimeter of keratinocytes, the preconfluent artificial skin took histologically, and human type IV and type VII collagen were stained immunohistochemically. This cell-preconfluent artificial skin composed of two-layer collagen sponges seems promising for widespread clinical use.

Animals↗
PubMed2001

Spinal injuries in snowboarders: risk of jumping as an integral part of snowboarding.

BACKGROUND: The purpose of this study was to clarify the occurrence rate and characteristics of spinal injuries caused by snowboarding that were sustained at the Okumino skiing area in Gifu Prefecture, Japan, from 1988 to 2000. METHODS: This study was a retrospective review of 13,490 cases of snowboard- or ski-related injury treated at Sumi Memorial Hospital over this period. RESULTS: A total of 7,188 patients sustained snowboard-related injuries, and 238 of these had spinal injuries caused by snowboarding (3.3%), whereas 6,302 patients sustained ski-related injuries, and 86 of these had spinal injuries caused by skiing (1.4%). Although there were no significant differences in the difficulty of slope, location of vertebral fracture, or spinal cord injury between snowboarders and skiers, the incidence of transverse process fractures was significantly higher in snowboard-related than in skiing-related injury (p < 0.05). In addition, there was a significantly higher incidence of spinal injury among beginner snowboarders than among beginner skiers (p = 0.04). Furthermore, intermediate or expert snowboarders were more likely to be injured because of jumping than beginners (p < 0.001), whereas about 70% of spinal injuries caused by skiing resulted from a simple fall. CONCLUSION: Spinal injuries sustained while snowboarding are increasing considerably in incidence and are characterized as complex injuries. We must educate young snowboarders of the risk of this sport, to prevent these serious injuries.

Adolescent↗
PubMed2001

Induction of MMP-9 in normal human bronchial epithelial cells by TNF-alpha via NF-kappa B-mediated pathway.

In this study, we determined whether the proinflammatory cytokines tumor necrosis factor (TNF)-alpha and interleukin-1 beta contribute to the regulation of matrix metalloproteinase (MMP)-9 in human bronchial epithelial cells and whether the induction of MMP-9 is regulated by the transcription factor nuclear factor (NF)-kappa B. We demonstrated that TNF-alpha induced MMP-9 at both the protein and mRNA levels in human bronchial epithelial cells and that interleukin-1 beta did not. In contrast, induction of the tissue inhibitor of metalloproteinase-1 by TNF-alpha was less than that of interleukin-1 beta. Increased expression of MMP-9 and NF-kappa B activation induced by TNF-alpha were inhibited by pyrrolidine dithiocarbamate and N-acetyl-L-cysteine but were not inhibited by curcumin. These results suggest that TNF-alpha induces the expression of MMP-9 in human bronchial epithelial cells and that this induction is mediated via the NF-kappa B-mediated pathway.

Acetylcysteine↗
PubMed2001

Ionic mechanisms underlying burst firing of layer III sensorimotor cortical neurons of the cat: an in vitro slice study.

We examined the ionic mechanisms underlying burst firing in layer III neurons from cat sensorimotor cortex by intracellular recording in a brain slice. Regular spiking was observed in 77.4% of 137 neurons in response to constant intracellular current pulses of 0.5- to 1-s duration. The rest of the neurons showed burst firing. An initial burst followed by regular-spike firing was seen in 71.0% of 31 bursting neurons. The rest of the bursting neurons (n = 9) exhibited repetitive bursting. In the bursting neurons, spikes comprising the burst were triggered from the afterdepolarization (ADP) of the first spike of the burst. We examined the ionic mechanisms underlying the ADP by applying channel-blocking agents. The ADP was enhanced (rather than blocked) by Ca2+ channel blockade. This enhancement of the ADP by Ca2+ channel blockade was apparent even after blockade of the afterhyperpolarization by apamin or intracellular Ca2+ chelation by EGTA. The firing rate of the regular-spiking cells was increased by apamin, intracellular EGTA or Ca2+ channel blockers. In 17.9% of the neurons examined (n = 56), these agents switched the regular-spiking pattern into a bursting one. Burst firing could not be changed to regular spiking by these agents. Four neurons that responded with a single initial burst in control solution responded with repetitive bursting after application of these agents. We conclude that the main function of Ca2+ influx in layer III neurons is to activate Ca2+-dependent K+ conductance, which prevents or limits burst firing. At a time when spike amplitude was unchanged, the ADP was blocked and the burst firing changed to regular spiking by extracellularly applied tetrodotoxin (TTX) or intracellularly applied N-(2,6-dimethylphenylcarbamoylmethyl) triethyl ammonium bromide (QX314). We concluded that a TTX- and QX314-sensitive Na+ current underlies the ADP and therefore contributes to the burst firing of layer III neurons from the cat cortex.

Action Potentials↗
PubMed2001

Bronchial hyperresponsiveness and exhaled nitric oxide in patients with cardiac disease.

BACKGROUND: Increased concentrations of exhaled nitric oxide (NO) correlate with increased airway inflammation and measurement of exhaled NO is a noninvasive method for the management of bronchial asthma. In various cardiac diseases, bronchial hyperresponsiveness is observed, as is bronchial asthma. However, there have been few studies on the relationship between exhaled NO and bronchial responsiveness in cardiac diseases. OBJECTIVE: The aim of this study was to clarify the association between exhaled NO and bronchial hyperresponsiveness in patients with cardiac disease. METHODS: We measured expired NO and bronchial responsiveness to inhaled methacholine in 19 patients with cardiac diseases and 17 with bronchial asthma. We divided the cardiac disease patients into two groups according to their bronchial responsiveness to inhaled methacholine: BHR(+) group consisted of 12 patients with bronchial hyperresponsiveness and BHR(-) group consisted of 7 patients without bronchial hyperresponsiveness. RESULTS: The concentration of exhaled NO in the asthmatic patients was significantly higher than that in the BHR(+) and BHR(-) groups (142.0 +/- 17.0, 33.6 +/- 6.4 and 42.3 +/- 10.3 ppb, respectively, p < 0.01). There was no significant difference in exhaled NO between BHR(+) and BHR(-) groups. There were also no significant differences in the parameters of bronchial hyperresponsiveness between the cardiac BHR(+) and bronchial asthma groups. These results indicate that bronchial hyperresponsiveness in patients with cardiac diseases is not a consequence of eosinophilic inflammation or of exhaled NO. CONCLUSION: We conclude that bronchial hyperresponsiveness in patients with cardiac diseases can occur independently of NO production.

Adult↗