Biomedical subjects

H Udono

Publications and source records attributed to H Udono.

30 records · Page 2Linked to original sources

PubMed1993

Heat shock protein 70-associated peptides elicit specific cancer immunity.

Vaccination of mice with heat shock protein 70 (hsp70) preparations derived from the Meth A sarcoma, but not from normal tissues, renders the mice immune to a substantial challenge with Meth A sarcoma. The immunogenicity is dose dependent and tumor specific. Treatment of an antigenically active hsp70 preparation with ATP followed by removal of low-molecular weight material leaves hsp70 intact, as judged by SDS-PAGE but results in loss of antigenicity, as judged by tumor rejection assays. Separation of this low-molecular weight material on a C18 reverse-phase column shows a diverse array of peptides with molecular mass between 1,000 and 5,000 daltons. Our data indicate that antigenicity of hsp70 preparations derives, not from hsp70 per se, but from associated peptides. These observations may suggest a novel method of using the peptide-binding property of hsp70 for specific vaccination against cancer and infectious diseases.

Adenosine Triphosphate↗

PubMed1993

Heat shock protein vaccines against cancer.

Vaccination of mice with heat shock proteins (HSPs) derived from a tumor makes the mice resistant to the tumor from which the HSP was obtained. This phenomenon has been demonstrated with three HSPs--gp96, hsp90, and hsp70. Vaccination with HSPs also elicits antigen-specific cytotoxic T lymphocytes (CTLs). The specific immunogenicity of HSPs derives apparently, not from the HSPs per se, but from the peptides bound to them. These observations provide the basis for a new generation of vaccines against cancer. The HSP-based cancer vaccines circumvent two of the most intractable hurdles to cancer immunotherapy. One of them is the possibility that human cancers, like cancers of experimental animals, are antigenically distinct. The prospect of identification of immunogenic antigens of individual cancers from patients is daunting to the extent of being impractical. The observation that HSPs chaperone antigenic peptides of the cells from which they are derived circumvents this extraordinary hurdle. Second, most current approaches to cancer immunotherapy focus on determining the CTL-recognized epitopes of cancer cell lines. This approach requires the availability of cell lines and CTLs against cancers. These reagents are unavailable for an overwhelming proportion of human cancers. In contrast, the HSP-based vaccines do not depend on the availability of cell lines or CTLs nor do they require definition of the antigenic epitopes of cancer cells. These advantages, among others, make HSPs attractive and novel immunogens against cancer.

Animals↗

PubMed1993

Effect of accessory cells on stimulation of murine T-cell leukemia with antibodies to the CD3/T cell antigen receptor complex.

Stimulation of EL4 and RL male 1 leukemia cells in vitro with immobilized anti-CD3 epsilon monoclonal antibody (mAb) (145-2C11) or anti-TCR beta mAb (H57-597) in the absence of accessory cells induced interleukin-2 (IL-2) production, and caused growth inhibition. The growth inhibition was, however, transient and the tumors started to grow again within 5 days in immobilizing plates treated with antibodies at concentrations of 2.5-100 micrograms/ml. Addition of mitomycin C-treated accessory cells to the culture inhibited IL-2 production and resulted in augmented and persistent growth inhibition. No recovery of tumor growth was observed. Furthermore, DNA from EL4 and RL male 1 leukemia cells stimulated with anti-CD3/TCR mAbs was fragmented even in the absence of accessory cells, but fragmentation was much greater in the presence of accessory cells. Marginal and high expression of the bcl-2 gene were observed in EL4 and RL male 1, respectively, indicating that apoptosis of these leukemias mediated by signalling through the CD3/TCR complex has no direct relationship with expression of the bcl-2 gene.

Animals↗

PubMed1993

[Transcranial Doppler sonography in acute intracranial hypertension model--usefulness of pulsatility index].

The authors studied intracranial hemodynamics in experimental animals (Macaca Fuscatus) with acute intracranial hypertension by use of transcranial Doppler (TCD) ultrasound. The blood mean flow velocity in the middle cerebral artery (MCA-FV) and pulsatility index (PI) was recorded using TCD ultrasound (TC2-64, EME) as in the clinical study. Acute intracranial hypertension was produced to determine the correlation of MCA-FV with intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in 11 monkeys, and the correlation of PI with ICP and CPP in 7 monkeys. ICP was elevated by infusing 0.1-0.2 ml/min of saline into the balloon using infusion pump. ICP was raised until maximum level. Changes of MCA-FV, PI, ICP and CPP were evaluated until the CPP of 0mmHg. There was a significant correlation between MCA-FV and ICP (p < 0.01) as well as between MCA-FV and CPP (p < 0.01) in all 11 monkeys. There was also a significant correlation between PI and ICP (p < 0.01) and between PI and CPP (p < 0.01) in 7 monkeys. PI increased markedly when ICP was 80mmHg or greater or when CPP was 60mmHg or less. ICP was always above 80mmHg when PI was above 1.2. All PI values were above 1.0 when CPP was 40mmHg or less. Thus, we could not estimate the absolute values of ICP or CPP from MCA-FV and PI. It seems possible, however, to follow changes in intracranial hemodynamics at the time of increased ICP if MCA-FV and PI are measured continuously while paying attention to factors influencing MCA-FV.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Iatrogenic acute spinal epidural abscess with septic meningitis: MR findings.

A contaminated catheter used in epidural anesthesia in a 71-year-old female produced acute epidural abscess and septic meningitis. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in a culture of the epidural pus. Both T1- and T2-weighted MR images showed low intensity mass lesion compressing the thecal sac behind the vertebral body L3. The low intensity lesion was probably pus with gas component. In these low intensity lesions in MR findings with gas component, MR was superior to myelography because it visualized both the degree of compression to the thecal sac and extension of the lesion in all directions.

Abscess↗

PubMed1991

CD4-CD8- T cell receptor alpha beta T cells: generation of an in vitro major histocompatibility complex class I specific cytotoxic T lymphocyte response and allogeneic tumor rejection.

The generation of an in vitro major histocompatibility complex class I specific response of CD4-CD8- T cell receptor (TCR) alpha beta cytotoxic T lymphocytes (CTL) and their allogeneic tumor rejection were investigated. Inocula of BALBRL male 1 were rejected in C57BL/6 (B6) mice treated with minimum essential medium (MEM) (control), anti-L3T4 (CD4) monoclonal antibody (mAb) or anti-Lyt-2.2 (CD8) mAb and CTL against the tumor were generated in vitro. No rejection and no induction of CTL were observed in B6 mice treated with anti-L3T4 (CD4) plus anti-Lyt-2.2 (CD8) mAb. CTL with the classical Thy-1+ CD3+CD4-CD8+ TCR alpha beta phenotype were generated in mixed lymphocyte tumor cell culture (MLTC) spleen cells from B6 mice treated with MEM (control) or anti-L3T4 (CD4) mAb, whereas CTL with an unusual Thy-1+CD3+CD4-CD8- TCR alpha beta phenotype were generated in MLTC spleen cells from anti-Lyt-2.2 (CD8) mAb-treated B6 mice. Both types of CTL were reactive with both H-2Kd and Dd (Ld) class I antigen. These findings suggest that when CD4+ cells were blocked by anti-L3T4 (CD4) mAb, CD8+ CTL mediated rejection, and when CD8+ cells were blocked by anti-Lyt-2.2 (CD8) mAb, CD4+ cells were capable of mediating rejection, although less efficiently than CD8+ cells, by inducing CD4-CD8- TCR alpha beta CTL. The finding that adoptive transfer of CD4 and CD8-depleted MLTC spleen cells, obtained from anti-Lyt-2.2 (CD8) mAb-treated B6 mice that had rejected BALBRL male 1, resulted in rejection of BALBRL male 1 inoculated into B6 nu/nu mice confirmed the above notion. CTL clones with the CD4-CD8- TCR alpha beta phenotype specific for Ld were established.

Animals↗

PubMed1990

Roles of CD4+ and CD8+ cells, and the effect of administration of recombinant murine interferon gamma in listerial infection.

Studies were made on the effects of in vivo administration of anti-CD4 mAb, anti-CD8 mAb, or a combination of both mAbs on multiplication of bacteria, the levels of serum transaminases, and mortality in mice infected with Listeria monocytogenes. Results showed that in sublethal infection, CD8+ cells enhanced the peak of bacterial multiplication and liver cell necrosis, and CD4+ cells suppressed CD8+ cell-mediated enhancement. Results also showed that either CD4+ or CD8+ cells were necessary for, and capable of, mediating clearance of the bacteria. CD8+ cells were more efficient than CD4+ cells, but for optimal clearance both were necessary. In lethal listeriosis, treatment of mice with anti-CD8 mAb or a combination of both anti-CD4 and anti-CD8 mAbs, but not anti-CD4 mAb only, protected mice from death by decreasing multiplication of bacteria in the liver and spleen after a peak of approximately 10(8) CFU, and lowering the elevated serum levels of transaminases. These findings indicated that CD8+ cells were responsible for causing irreversible systemic Listeria infection and severe liver necrosis. In lethal listeriosis, administration of rMuIFN-gamma markedly prolonged survival by decreasing multiplication of bacteria and promoting recovery from liver necrosis.

Alanine Transaminase↗

PubMed1990

Participation of a dominant cytotoxic T cell population defined by a monoclonal antibody in syngeneic anti-tumor responses.

Cytotoxic T lymphocyte (CTL) clones against a syngeneic Friend virus-induced erythroleukemia (FBL-3) were generated in C57BL/6 (B6) mice. A monoclonal antibody (mAb, N9-127) was then raised from spleen cells of a B6 mouse immunized syngenically against one of these CTL clones. This mAb detected the epitope (127Ep) of the T cell antigen receptor (TcR) on the immunizing CTL clone in tests of immunoprecipitation, specific blocking and proliferation, and induction of TcR-mediated nonspecific lysis of the clone. In addition, more than 10% of the FBL-3-specific CTL clones isolated independently from B6 mice were 127Ep+. Further investigations revealed that up to 30% of B6 anti-FBL-3 T cell blasts from mixed lymphocyte tumor cell cultures were positive for this epitope, and that its expression was confined to CD8+ T cells. This epitope was not detected in naive lymphoid cells from the spleen, lymph nodes or thymus or in T cell clones specific for tumors other than FBL-3. The FBL-3-specific CTL clones were next grouped into 127Ep+ and 127Ep- clones. Sequence analyses of the CTL clone used for immunization showed the rearrangements of V alpha 1J alpha 112-2 and V beta 10D beta 2.1J beta 2.7. Southern blot analysis of all the 127Ep+ CTL clones examined showed the same DNA rearrangement bands of both the TcR alpha and beta genes. These findings suggested that mAb N9-127 recognized the shared determinant of the TcR molecule which was expressed by the dominant CTL population in the response to FBL-3.

Animals↗

PubMed1989

Proliferative response of cloned CTL line 10B-5 upon stimulation with soluble clonotypic monoclonal antibody and its blocking by anti-Lyt-2 antibody.

Proliferation of the cloned cytotoxic T lymphocyte (CTL) line 10B-5 induced by anticlonotypic antibody and its blocking by anti-Lyt-2 mAb were studied. Clone 10B-5 was derived from spleen cells of a (BALB/c x C57BL/6)F1, (CB6F1)-nu/+ mouse immunized with UV female 1 sarcoma. 10B-5 cells lysed UV female 1 specifically and proliferated upon stimulation with UV female 1 and feeder cells in the presence of IL 2. Anti-clonotypic monoclonal antibody (mAb) N1-56 was produced by a hybridoma established by fusion of spleen cells from a CB6F1-nu/+ mouse that had been immunized by five injections of 10B-5 cells prefixed with 0.1% formaldehyde. N1-56 mAb immunoprecipitated 90 kd molecules cleavable to 45 kd molecules under reducing conditions, indicating its reaction with T cell antigen receptor (TCR). N1-56 mAb in its soluble form induced a proliferative response of 10B-5 cells. Thus, the antigen binding site of N1-56 mAb appeared to substitute for the specific antigen determinant on UV female 1 sarcoma. The F(ab')2, but not the Fab fragment of purified N1-56 mAb, stimulated proliferation, indicating that cross-linking of TCR molecules was necessary for stimulation. The proliferative response of 10B-5 cells induced by soluble N1-56 mAb was blocked by addition of anti-Lyt-2.2 mAb to the cultures. The specificity of Lyt-2 blocking was confirmed by an absorption test. The proliferative response of 10B-5 cells induced by Con A, but not that induced by IL 2, was blocked by anti-Lyt-2.2 mAb. These results indicated that blocking by anti-Lyt-2.2 mAb was at an early stage and that it could be bypassed by stimulation with IL2.

Animals↗

PubMed1989

The roles of CD8+ and CD4+ cells in tumor rejection.

In vivo administrations of anti-Lyt-2.2 (CD8) mAb and anti-L3T4 (CD4) mAb selectively eliminated CD8+ cells and CD4+ cells, respectively. The relative potencies of CD8+ cells and CD4+ cells and their roles in primary tumor rejections were studied by investigating the effects of these mAbs on tumor growth. CD8+ cells were themselves fully capable of mediating rejection in 5 different tumor rejection systems: two radiation leukemia virus (RadLV)-induced leukemias, B6RV2 and BALBRVD, a radiation-induced leukemia BALBRL male 1, and a plasmacytoma BALBMOPC-70A in CB6F1 mice, and a Friend virus-induced leukemia B6FBL-3 in B6 mice. On the other hand, CD4+ cells were capable of resisting tumor growth of B6FBL-3, but not of the other four tumors. Furthermore, for efficient rejection of CB6F1UV female 1 sarcoma by CB6F1 mice, synergy of CD8+ and CD4+ cells was necessary. Blocking of UV female 1 rejection was abrogated by delayed administration of anti-L3T4 (CD4) mAb but not anti-Lyt-2.2 (CD8) mAb, indicating the involvement of CD4+ cells in only the initial phase of rejection.

Animals↗

PubMed1989

Blocking of cytotoxic T-cell function of MOLF/Ei mice by anti-Ly 35.1 monoclonal antibody.

Ly 35.1 antigen is an alloantigen expressed only on T cells of Mus musculus molossinus-derived inbred strains. Previous findings indicated that the genetic locus coding for Ly 35 antigen was closely linked to Ly 2/3 on chromosome 6 and that epitopes detected by Ly 2.1 and Ly 35.1 monoclonal antibodies (mAb) were closely associated, as shown by binding inhibition assay. In this study, we examined the blocking effects of anti-Ly 2.1 and anti-Ly 35.1 mAb on cytotoxic T-cell function of MOLF/Ei mice generated against BALB/c. MOLF/Ei cytotoxicity was blocked by Ly 35.1 mAb, but not by anti-Ly 2.1 mAb. Additional tests showed that cytotoxicity was blocked by Ly 3.1 mAb, but not Ly 3.2 or Ly 2.2 mAb. These results suggested that MOLF/Ei mice express Ly 3.1, but not Ly 2.1 antigen at a functional level, and that Ly 35.1 may be a functional epitope of Ly 2 antigen in the MOLF/Ei strain.

Animals↗

PubMed1988

Anti-idiotypic antibodies against UV-induced tumor-specific CTL clones. Preparation in syngeneic combination.

In this study, we first established several CTL clones of (BALB/c x C57BL/6)F1 origin that were specific for either syngeneic UV female 1 or UV male 1 fibrosarcoma cell lines. All the CTL clones had Thy-1+ Lyt-2+ L3T4- phenotypes and showed Kd restriction when lysing the corresponding target cells. Sera obtained from syngeneic animals immunized with three CTL clones, 10B-5 for UV female 1, and CTL9 and CTL10 for UV male 1, showed specific inhibition of target cell lysis with the corresponding CTL clones. The inhibitory activities were found in sera of the majority of immunized animals. Because the inhibitory activity resides in protein A-binding fraction, mAb were produced by hybridizing spleen cells of hyperimmune animals. N1-56 was thus obtained from a mouse immunized with 10B-5 CTL clone reactive with UV female 1. N1-56 was clonotype specific, reacting with 10B-5 but not with other CTL lines or leukemia cell lines. No N1-56+ cells were detectable in thymocytes, lymph node cells, or spleen cells of either naive or UV female 1-immune CB6F1 mice. Immunoprecipitation showed that N1-56 reacts with 90,000 Mr molecules on 10B-5 CTL clone under nonreducing conditions and 45,000 Mr molecules under reducing conditions, indicating its reactivities with idiotypic determinants of TCR on the CTL clone. N1-56 inhibited lytic activity of 10B-5, but neither N1-56 nor alpha-10B-5 hyperimmune serum inhibited that of alpha-UV female 1 mixed lymphocyte tumor cell culture cells. N1-56 induced proliferation of 10B-5 without addition of Ag.

Animals↗