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Biomedical subjects

Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 451 records · Page 25Linked to original sources
PubMed1996

The F(ab')2 fragment of an anti-ICAM-1 monoclonal antibody attenuates liver injury after orthotopic liver transplantation.

Long-term storage of liver grafts results in increased adhesion of leukocytes onto the sinusoidal walls. This eventually leads to posttransplant graft damage through disturbances of hepatic microcirculation. Intracellular adhesion molecule-1 (ICAM-1) is known to be involved in attachment of leukocytes. This study was designed to examine whether ICAM-1 participated in the pathogenesis of posttransplant liver injury. Inbred Lewis rats were used as both donors and recipients to avoid immunoreactivity. Donor livers were stored for either 1 or 6 hr in ice-cold Euro-Collins solution and subsequently implanted. Expression of ICAM-1 was examined immunohistochemically. In some rats that received livers stored for 6 hr, the intact IgG (1.0 mg/kg) or the F(ab')2 fragment (0.5 mg/kg) of an anti-ICAM-1 mAb (1A29) was administered via the tail vein immediately after reperfusion of portal blood. In the group receiving livers stored for 6 hr, ICAM-1 began to be expressed on the sinusoidal endothelial cells as early as 15 min after reperfusion of the portal blood. Strong ICAM-1 expression was observed from 2 hr up to 24 hr after reperfusion. In contrast, expression of ICAM-1 was not evident at any time point after surgery in the 1-hr storage group as well as in untransplanted, normal livers. Serum alanine aminotransferase (ALT) levels were significantly higher in the 6-hr storage group compared with those of the 1-hr storage group (1-hr: 171 +/- 9 IU/L; 6-hr: 825 +/- 109 IU/L, P < 0.05; mean +/- SEM) 24 hr after transplantation. Serum ALT levels were markedly reduced by treatment with the F(ab')2 fragment of 1A29 (247 +/- 34 IU/L, P < 0.05 vs. 6-hr storage group). This was associated with reduced accumulation of leukocytes in the liver. In marked contrast, treatment with the intact IgG of 1A29 increased serum ALT levels dramatically (5297 +/- 634 IU/L, P < 0.05 vs. 6-hr storage group) and reduced serum complement. Histological examination revealed focal hepatocellular necrosis 24 hr after surgery in the 6-hr storage group. Treatment with the F(ab')2 fragment decreased the liver damage; in marked contrast, treatment with the intact IgG strikingly aggravated the injury, as characterized by massive necrosis throughout the liver. Liver damage caused by the intact IgG might be related to activation of the complement system by the Fc portion of the antibody. Taken together, these results indicate that ICAM-1 is involved in the mechanism of postoperative liver injury following liver transplantation.

Animals↗
PubMed1996

Donor-specific prolongation of rat skin graft survival induced by rat-donor cells and cyclophosphamide under coadministration of monoclonal antibodies against T cell receptor alpha beta and natural killer cells in mice.

Because of the recent interest in human xenotransplantation, we investigated the possibility of inducing tolerance in a xenogeneic combination using cyclophosphamide (CP). Donor-specific prolongation of xenogeneic Fisher 344 (F344) rat skin graft survival for up to 60 days was induced in C57BL/6 (B6) mice by giving F344 bone marrow cells and spleen cells on day 0, CP on day 2, and monoclonal antibodies against murine TCR-alpha beta and NK1.1 on days--1 and 3. The inoculation of the xenogeneic cells brought accelerated repopulation of TCR-alpha beta+ T cells, even under the administration of anti-TCR-alpha beta mAb. The quick increase of the host TCR-alpha beta+ T cells caused by the xenogeneic cell injection was deeply suppressed by CP. Mixed lymphocyte reaction, CTL activity, and antibody production against donor F344 were profoundly suppressed for 50 days. Mixed xenogeneic chimerism was observed for 1 month after the inoculation of donor cells in the spleen and peripheral blood of the recipient B6 mice, but was never observed in the thymus. Moreover, when irradiated F344 cells were used in place of viable cells, chimerism was never detected and graft survival was only slightly prolonged. Clonal deletion of V beta 5- or V beta 11-bearing murine T cells was not observed on day 50 in the thymus or spleen of the recipient B6 mice. These results suggest that treatment with viable xenogeneic donor cells, CP, and mAbs against T and NK cells can induce a temporary peripheral mixed chimerism and donor-specific prolongation of xenogeneic skin graft survival. The destruction with CP of T and B cells that are xenoreactive and thus proliferating after antigen stimulation, followed by mechanism other than intrathymic clonal deletion, may be the mechanism of the hyporesponsiveness in the present system.

Animals↗
PubMed1996

High-dose intraoperative radiotherapy for unresectable pancreatic cancer.

PURPOSE: The results of high-dose intraoperative radiotherapy (IORT) and/or external beam radiotherapy (EBRT) for unresectable pancreatic cancer were analyzed to evaluate the possible advantages of IORT in combination with EBRT. METHODS AND MATERIALS: Between 1983 and 1993, 115 patients with unresectable adenocarcinoma of the pancreas (53 with non-Stage IV disease and 62 with Stage IV disease) were treated with EBRT + IORT (55 patients), EBRT alone (44 patients), or IORT alone (16 patients). In non-Stage IV patients, the use of EBRT alone was due to the unavailability of IORT and the use of IORT alone was due to refusal of EBRT. The IORT dose was 30-33 Gy and the EBRT dose was 40-60 Gy. A historical control group comprised of 101 patients undergoing palliative surgery alone was also analyzed. RESULTS: Both non-Stage IV and Stage IV patients receiving EBRT with or without IORT had a better prognosis than the nonirradiated historical controls. Among non-Stage IV patients, the median survival of the EBRT + IORT group (8.5 months) and the EBRT group (8 months) was similar, although survival from 12 to 18 months was higher in the former group (38% vs. 10% at 12 months, p = 0.018, and 19% vs. 0% at 18 months, p = 0.023). In Stage IV patients, the prognosis was not influenced by the type of radiotherapy. Multivariate analysis revealed that a pretreatment carbohydrate antigen (CA) 19-9 level < 1000 U/ml was associated with better survival. In non-Stage IV patients with a CA 19-9 level < 1000 U/ ml, EBRT + IORT appeared to produce a better survival than EBRT alone (p = 0.047). This was supported by multivariate analysis. CONCLUSION: High-dose IORT + EBRT may be more effective than EBRT alone in patients with unresectable but localized pancreatic cancer and a low CA 19-9 level.

Adenocarcinoma↗
PubMed1996

Western versus Asian types of multiple sclerosis: immunogenetically and clinically distinct disorders.

The polymorphism of HLA-DRB1, -DRB3, and -DRB5 genes as well as magnetic resonance images of the brain and spinal cord were studied in 57 Japanese patients with multiple sclerosis (MS). Twenty-three patients clinically displayed selective involvement of the optic nerve and spinal cord and were classified as having Asian-type MS. The other 34 patients had disseminated central nervous system involvement and were classified as having Western-type MS. Patients with Asian-type MS had fewer brain lesions shown by magnetic resonance imaging, but more gadolinium-enhanced spinal cord lesions than did patients with Western-type MS (47% vs 17%). Furthermore, the DR2-associated DRB1*1501 allele and DRB5*0101 allele were associated with Western-type MS (41.2%), but not with either Asian-type MS (0%) or healthy control subjects (14.2%). Heterogeneity in the immunogenetic background and in the magnetic resonance imaging features between the two subtypes of MS thus suggests the presence of two etiologically distinct diseases in Asians.

Alleles↗
PubMed1996

Phylogenetic relationships of entomopathogenic nematophilic bacteria: Xenorhabdus spp. and Photorhabdus sp.

Phylogenetic relationships of Xenorhabdus spp. and Photorhabdus sp. were investigated on the basis of 16S rRNA gene sequences. Xenorhabdus spp. and Photorhabdus sp. were grouped together with Proteus vulgaris and Arsenophonus nasoniae. This group was distant from other members of the family Enterobacteriaceae. Xenorhabdus japonicus, previously proposed as a new species, was nearly located to Xenorhabdus nematophilus. Signature nucleotides of X. japonicus were identified that distinguish it other members of the family Enterobacteriaceae.

Animals↗
PubMed1996

Preservation of skin free-flap using trehalose.

In this study, we looked for a solution able to preserve traumatically amputated tissues such as nose tip, ear, and scalp for at least 48 hr that was easy to handle and low in price. Trehalose is a nonreducing disaccharide that can protect many prokaryotes, fungi, and yeasts against adverse conditions by stabilizing cell membranes. In order to study its protective effect, 60 skin free-flaps of the ears of rabbits were preserved in Euro-Collins (EC) solution or in modified Euro-Collins solution in which 7% trehalose replaced glucose (EC + 7%T) for 24, 48, and 72 hr at 4 degrees C. After completion of preservation, these flaps were transferred to the other ear with microvascular anastomosis. After 7 days, we obtained a survival rate of 100% of flaps after preservation for 24 hr in both solutions. But, after preservation for 48 hr or longer, this decreased to 60% (6 of 10 preserved flaps survived) in EC solution and 90% (9 of 10 flaps) in EC + 7%T solution. This difference became clearer after 72 hr of preservation, when the survival rate was higher and light microscopic observation showed less damage for flaps preserved in EC + 7%T solution (20% in EC and 70% in EC + 7%T) (P < 0.05). Thus, EC + 7%T solution was superior to EC solution in the preservation of skin free-flaps of the ear of rabbits. Trehalose shows great promise in the preservation of many organs, including storage of traumatically amputated tissues such as nose tip, ear, and scalp.

Adipose Tissue↗
PubMed1996

Effect of RS61443 in combination with leflunomide or FK506 on rat heart allograft survival.

Mycophenolate Mofetil (RS61443) is a potent inhibitor of de novo purine synthesis and lymphocyte proliferation. It is known to prevent ongoing rejection and even reverse established rejection, alone and in combination with, cyclosporin. We investigated whether RS61443 in combination with leflunomide (Lef) or FK506 (FK) could prolong allograft survival in a rat heart model, since combination therapy might help to overcome drug toxicity. Abdominal heart grafting was performed from DA to LEW rats (250 g) and RS61443, 10 mg/kg or 30 mg/kg monotherapy or combination treatment (RS 10 mg/kg with Lef 5 mg/kg or FK 0.5 mg/kg) was begun orally at transplantation and continued daily until the ninth posttransplant (post-Tx) day. Ventricular motion was graded daily and rejection was defined as lack of contractions, confirmed by histology. Results were analysed using non-parametric tests. A two-tail P value < 0.05 was considered significant. RS at 10 mg/kg was ineffective and all grafts were rejected under immunosuppression between 5 and 6 post-Tx day, whereas RS at 30 mg/kg was immunosuppressive for as long as it was given. The combinations of RS at 10 mg/kg with either Lef at 5 mg/kg or FK at 0.5 mg/kg were immunosuppressive in the majority of cases, for as long as they were given. However, the combination of RS at 10 mg/kg with FK at 0.5 mg/kg was attendant with graft vein anastomosis rupture (3/5). The combination of RS with Lef was clinically therapeutic for as long as it was given; grafts were rejected 3-4 days after withdrawing immunosuppression. The combination of RS with FK resulted in over-immunosuppression, leading to graft vein anastomosis non-healing and rupture within 5 days of grafting; histology demonstrated evidence of bacterial infection with complete destruction of the vein wall. These data suggest that the combination of RS with Lef or FK in subtherapeutic doses might be a potentially promising strategy for combination therapy in solid organ transplantation.

Animals↗
PubMed1996

An unusual variation of left ventricular-right atrial communication.

We herein present a 5-month-old boy with an infravalvular-type left ventricular-right atrial communication without an abnormal tricuspid valve leaflet. The thick chorda of the anterior tricuspid leaflet was inserted into the upper edge of the ventricular septal defect which was placed just under the commissure. The jet from the septal defect pushed this thick chorda and opened the commissure, which thus caused the abnormal pathway from the left ventricle to the right atrium. This mechanism of left ventricular-right atrial communication has not yet been reported elsewhere.

Heart Atria↗
PubMed1996

Molecular characterization of feline immunodeficiency virus genome obtained directly from organs of a naturally infected cat with marked neurological symptoms and encephalitis.

Feline immunodeficiency virus (FIV) was first isolated from cats with immunodeficiency syndrome. Recently, neurological abnormalities and brain lesions were shown in cats infected with FIV. To investigate the FIV genome associated with central nervous system (CNS) lesions, proviral DNA sequences from the V3-V6 region of the FIV env gene were directly amplified from uncultured necropsy tissues of a 2-year-old naturally FIV-infected cat with marked neurological symptoms and encephalitis. By in situ hybridization, FIV RNA was detected mainly in the astrocytes. Fifteen clones isolated from cerebrum, bone marrow and lymph node samples showed only a small number of mutations or deletions in this region. A representative clone, JN-BR1, was distantly related to the previous Japanese strain (TM2) belonging to the subtype B. However, it was relatively close to the Petaluma strain which is known to infect feline brain-derived culture cells and induce brain lesions in inoculated cats. By phylogenetic analysis, the JN-BR1 strain was placed in subtype A that included Petaluma strain and several other American and European strains. The JN-BR1 strain derived from brain with encephalitis in this study and the Petaluma strain may share a common genetic structure that is related to their neuropathogenicity.

Amino Acid Sequence↗
PubMed1996

Detection of apoptosis induced in peripheral blood lymphocytes from cats infected with feline immunodeficiency virus.

Peripheral blood lymphocytes (PBL) from cats infected with feline immunodeficiency virus (FIV) were examined for the occurrence of apoptosis after short-term culture. In the PBL from FIV-infected cats, changes in flow-cytometry scattergram, morphological characteristics of apoptosis and nucleosomal DNA fragmentation were observed. Percentages of apoptotic cells by flowcytometry analysis in PBL from FIV-infected cats (22.4% +/- 9.4%) were significantly higher than those in PBL from uninfected control cats (9.2% +/- 3.5%). The lymphocytes which underwent apoptosis included CD5+, CD4+ and sIgM+ cells, indicating that induction of apoptosis was not restricted to a special subset of lymphocytes. These findings provide evidence of the apoptotic state of PBL in cats with FIV infection.

Animals↗
PubMed1996

A case of choledocholithiasis with an endoclip nidus, 6 months after laparoscopic cholecystectomy.

A 69-year-old man developed obstructive jaundice 6 months after laparoscopic cholecystectomy. Endoscopic retrograde cholangiography suggested a common bile duct (CD) stone. A second operation was performed, and this revealed a CBD stone with an endoclip as a nidus. Since laparoscopic surgery has become a very common procedure, endoclips are used more frequently. Therefore, careful surveillance and strict follow-up are stressed to avoid CBD stone and various other complications caused by endoclips.

Aged↗
PubMed1996

Binding of mutated Ras- and p53-derived peptides to HLA-DR molecules.

We investigated binding of p53- and Ras-derived peptides with frequently observed missense mutations, to various L cell transfectants expressing a single species of HLA-DR complex, and found that: (i) all the synthetic peptides bound to various DR complexes with a variable affinity; (ii) some DR allelic products had a high affinity for both p53- and Ras-derived peptides (e.g., DRB1*1502), whereas others almost no affinity (e.g., DRB1*1101); and (iii) DR-binding motifs described in the literature can explain some of the allele-specific interactions between mutated peptides and DR complexes. Therefore, some mutated Ras- and p53-derived peptides could be tumor-specific antigens recognized by CD4+ T cells in an HLA-DR allele-specific manner.

Amino Acid Sequence↗
PubMed1996

Radiation therapy for T1,2 glottic carcinoma: impact of overall treatment time on local control.

PURPOSE: Local control probabilities of T1,2 glottic laryngeal cancer were evaluated in relation to dose and fractionation of radiation therapy (RT). MATERIALS AND METHODS: Between 1975 and 1993, 96 T1N0M0 glottic cancers and 32 T2N0M0 glottic cancers were treated with definitive RT. Total RT dose was 60-66 Gy/2 Gy for most of the T1 and T2 tumors, although 10 T2 tumors were treated with hyperfractionation (72-74.4 Gy/1.2 Gy bid). Of the 128 patients, 90 T1 glottic tumors and 30 T2 glottic tumors were followed for > 2 years after treatment. Multivariate analyses using the Cox proportional hazards model and a logistic regression analysis were performed to evaluate the significance of prognostic variables on local control. RESULTS: The 5-year local control probability for T1 tumors was 85%, whereas that for T2 tumors was 71%. Multivariate analyses demonstrated that only overall treatment time (OTT) was a significant variable for local control. Total RT dose, normalized total doses at a fraction size of 2 Gy, and fraction size were not significant. Local control probability of T1 tumors with an OTT of 42-49 days was significantly higher than that of tumors with an OTT of > 49 days (P < 0.02). Only a 1-week interruption of RT, due to holidays, significantly reduced the 5-year local control probability of T1 glottic tumors from 89 to 74% (P < 0.05). CONCLUSIONS: These results indicate that OTT is a significant prognostic factor for local control of T1 glottic tumors.

Adult↗
PubMed1996

Identification of HLA-DR9 (DRB1*0901)-binding peptide motifs using a phage fUSE5 random peptide library.

We identified HLA-DRB1*0901-binding peptides by affinity-based selection of a phage random peptide library using the biotinylated DR9 complex. Analogue peptides with single amino acid residue substitutions of a DR9 binder revealed that two major anchors (WxxS, where x is any amino acid) play an essential role in binding to DR9. Determination of the binding affinity of synthetic wild-type-based analogue peptides showed that substituting W to F or L, and S to A, V, or F allow high affinity binding with DR9. Collectively, DR9-binding peptide motifs identified in this study are characteristic in that (a) only two anchors of the NH2-terminal half of binding peptides play important roles in binding, and (b) small neutral hydrophilic Ser is allowed as the second anchor for high-affinity binding, unlike the other DR-binding motifs heretofore reported. The implications of our results are discussed in light of the HLA-DR9-associated susceptibility to juvenile-onset myasthenia gravis and systemic lupus erythematosus with antiphospholipid syndrome, in particular, T-cell responses to autoantigens.

Amino Acid Sequence↗
PubMed1996

Single amino acid substitutions on a Japanese cedar pollen allergen (Cry j 1)-derived peptide induced alterations in human T cell responses and T cell receptor antagonism.

We generated T cell clones specific to a Japanese cedar pollen allergen (Cry j 1) and investigated effects of altered T cell receptor (TCR) ligand on changes of T cell responses. One of these Cry j 1-specific T cell clones established from patients with Japanese cedar pollinosis, ST1.9, recognized an antigenic peptide Cry j 1 p335-346 in the context of HLA-DRA+DRB3*0301 molecules and secreted interleukin-4 dominantly, with a smaller amount of interferon-gamma. ST1.9 represented one of the major T cell clones specific to Cry j 1 in the donor, because a short-term cultured polyclonal T cell line specific to Cry j 1 exhibited the same character as the ST1.9. We synthesized various analog peptides derived from Cry j 1 p335-346 with single amino acid substitutions and determined key residues for interactions between TCR of ST1.9 and HLA-DR molecules. We also analyzed changes in the responses of ST1.9 to Cry j 1 p335-346-derived analog peptides. Of interest was that the substitution of 339threonine to valine resulted in a significant increase in interferon-gamma production, with no remarkable changes either in proliferative response or interleukin-4 production. Analog peptides carrying the substitutions of 339threonine to glycine or glutamine revealed TCR antagonism, without changes in their binding affinities to the DR molecule. Therefore single amino acid substitutions on an allergen peptide carrying the T cell epitope may suppress helper-T-dependent class switch pressure to IgE in B cells either by inducing increased interferon-gamma production or by inhibiting proliferative responses in helper-T cells.

Allergens↗