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Biomedical subjects

H Kida

Publications and source records attributed to H Kida.

At least 127 records · Page 7Linked to original sources

Engraftment of human tumor-infiltrating lymphocytes and the production of anti-tumor antibodies in SCID mice.

We report here the placement of nondisrupted 1-mm3 pieces of fresh human lung tumor biopsy tissue into the subcutis of severe combined immunodeficient (SCID) mice results in the engraftment of tumor-infiltrating leukocytes (TIL) in all but 5 of 148 mice inoculated with 39 different biopsy tissue specimens. In mice coengrafted with tumor and TIL the normal histologic architecture of the tumor and TIL interface was maintained for up to 22 wk. The TIL in the xenograft were shown to divide and were maintained exclusively at the site of tumor inoculation. It is established here that plasma cells in the TIL population produce Abs that react in western blots with tumor cell lysates. These Abs were shown to react with high and low m.w. proteins derived from both the membrane and cytosolic fractions of tumor cell lysates. The production of human Ig was found to be T cell dependent, and immunohistochemistry and in situ hybridization of DNA, using a human-specific cDNA probe, established the human identity of the tumor and TIL. High levels of human Ig in the sera of mice inoculated with tumor biopsy tissue are associated with the growth arrest of adenocarcinoma xenografts. Our results establish the co-engraftment of human tumors and TIL into SCID mice as new animal model with which to evaluate TIL function and novel therapeutic strategies that are designed to augment TIL anti-tumor activity.

Animals↗

Interleukin-12 activates human gamma delta T cells: synergistic effect of tumor necrosis factor-alpha.

gammadelta T cell populations are known to expand in response to intracellular bacterial infectious agents regardless of previous priming. We have shown previously that soluble factor(s) produced by Mycobacterium-stimulated monocytes activate cord blood gammadelta T cells to proliferate. In this study, we investigated whether cytokines produced by monocytes are responsible for gammadelta T cell activation in vitro: interleukin (IL)-1beta, IL-6, IL-8, IL-12, tumor necrosis factor (TNF)-alpha and granulocyte/macrophage colony-stimulating factor were examined. Recombinant human IL-12 stimulated gammadelta T cells, but not alphabeta T cells in peripheral blood mononuclear cells, to express CD25 on their surfaces, and to expand in number in vitro. IL-12-primed gammadelta T cell numbers increased to a greater extent in the culture to which exogenous IL-2 (5 U/ml) was added. Anti-TNF-alpha monoclonal antibody inhibited IL-12-induced up-regulation of CD25 on gammadelta T cells, suggesting that endogenous TNF-alpha may play a role in IL-12-induced activation of gammadelta T cells. Recombinant TNF-alpha synergistically augmented IL-12-induced activation of gammadelta T cells. Furthermore, IL-12 up-regulated TNF receptors on gammadelta T cells in vitro: TNF-alpha binding to its receptor induced CD25 expression on the gammadelta T cells in an autocrine or paracrine fashion, or perhaps both. It also became evident that both IL-12 and TNF-alpha were produced by mycobacterial lysate-stimulated monocytes. Taken together, these results suggest that upon confrontation with mycobacterial organisms, gammadelta T cells can be quickly and antigen-nonspecifically activated by soluble factors including IL-12 and TNF-alpha, both of which are produced by mononuclear phagocytes in response to mycobacterial organisms.

Adult↗

Mapping of transregulatory domains of pseudorabies virus early protein 0 and identification of its dominant-negative mutant.

Pseudorabies virus (PRV) early protein 0 (EP0) is a transactivator containing the RING finger domain. Analysis of transactivating activity of truncated forms of the EP0 molecule consisting of 410 amino acids revealed that amino-terminal region containing the RING finger domain, amino acids 1 to 84, and the region between amino acids 114 to 242 containing acidic amino acid sequences were required for the transactivation. On the other hand, the mutant consisting of amino acids 1 to 113 exhibited a dominant-negative property.

Animals↗

Protective immune response of chickens against Newcastle disease, induced by the intranasal vaccination with inactivated virus.

Intranasal vaccination of chickens with inactivated Newcastle disease virus (NDV) induced both local and systemic antibody responses, resulting in protection against intranasal challenge with a lethal dose of a virulent NDV strain. The immune response was enhanced by the use of cholera toxin B subunit (CTB) as an adjuvant and only small amounts of the challenge virus were recovered from the birds vaccinated together with CTB. On the other hand, subcutaneous vaccination with the same antigen induced only a serum antibody response in chickens, allowing the challenge virus to replicate in the sinus. The present results indicate that secretory antibodies induced on the respiratory mucosal surface by intranasal vaccination with inactivated NDV protected chickens from lethal infection by inhibiting virus replication at the portal of entry for the virus.

Adjuvants, Immunologic↗

Negative regulation of immediate-early gene expression of pseudorabies virus by interferon-alpha.

Pseudorabies rabies (PrV) replication in Vero cells was suppressed by treatment with human natural interferon-alpha (IFN-alpha). Messenger RNA transcribed from the PrV immediate-early (IE) gene was reduced in the IFN-alpha-treated cells. Transient expression assays showed that transcription from the PrV IE promoter was selectively inhibited in the IFN-alpha-treated cells. Analysis of deletion mutants of the PrV IE promoter sequence suggested that at least one element between the transcription initiation site (+1) and -90 in the PrV IE promoter was concerned with the negative regulation.

Animals↗

Somatic alterations of the DPC4 gene in human colorectal cancers in vivo.

BACKGROUND & AIMS: The chromosome region 18q21 has been shown to be frequently deleted in colorectal cancers, and such frequent allelic loss is a hallmark of the presence of a tumor-suppressor gene. The DPC4 gene, which is located at 18q21, has been identified as a tumor-suppressor gene from examination of pancreatic cancers. The aim of the present study was to determine if it might also be altered in colorectal cancers. METHODS: Mutation analyses of the DPC4 gene were performed on complementary DNA samples from 31 primary colorectal cancer specimens using a combination of polymerase chain reaction, single-strand conformation polymorphism, and DNA sequencing. RESULTS: Four missense mutations producing amino acid substitutions and a somatic 12-base pair deletion in the coding region of the DPC4 gene were detected in the 31 cancers (16%; 5 of 31). CONCLUSIONS: The DPC4 gene may play a role as a tumor-suppressor gene in a fraction of colorectal cancers; however, while allelic loss at 18q21 is very often seen in colorectal cancers, only a minority show DPC4 mutations, suggesting that there might be another tumor-suppressor gene in this chromosome region.

Adult↗

Development of immuno-PCR for diagnosis of bovine herpesvirus 1 infection.

A highly sensitive immuno-PCR method specific for the detection of antigens of and antibodies to bovine herpesvirus 1 was established. This assay attained a high sensitivity of up to 10(7.0) times higher than that of enzyme-linked immunosorbent assay (ELISA) or PCR for antigen detection and 10(5.0) times higher than that of ELISA for antibody detection.

Animals↗

The first case of insulin-dependent diabetes mellitus with prominent spurious hyperglucagonemia due to interference of immunoglobulin G in glucagon radioimmunoassay (OAL-123) system.

A 51-year-old male was admitted to our hospital because of diabetic ketoacidosis. His symptoms were promptly improved with intensive insulin therapy, but his plasma glucagon immunoreactivity measured by the OAL-123 radioimmunoassay (RIA) system showed persistently high values (3,090-3,210 pg/ml). A computed tomographic scan, abdominal angiography and endoscopic examination of his gastrointestinal tract showed no evidence of glucagonoma. After removing the immunoglobulin fraction from the plasma, his immunoreactive plasma glucagon level returned to normal. Moreover, the immunoglobulin G fraction purified from the patient's plasma inhibited the binding of [125I]glucagon to rabbit antiglucagon antiserum, OAL-123. Dot-blot analysis demonstrated that the immunoglobulin G of this patient cross-reacted against OAL-123. Therefore, it was considered that the prominent hyperglucagonemia in this patient was due to the presence of IgG, which interfered with the measurement of plasma-immunoreactive glucagon.

Diabetes Mellitus, Type 1↗

VH and VL gene complexes encoding an anti-spectrin antibody are defined by nucleotide sequencing of cDNA from a hybridoma generated from Hu-PBL-SCID mouse.

Previously we reported that human imunocompetent cells engrafted into scid mice mount a sustained and vigorous humoral immune response to murine erythrocytes. One of the dominant and consistently observed reactivity pattern of these antibodies in immunoblot analysis is with the alpha and beta isoforms of spectrin. In order to define the human xenoreactive response more completely, a hybridoma was generated (from a hu-PBL-scid mouse) whose antibody reacted with two high molecular weight species 225 to 250 kDa. We report here that this conserved antibody species reacts with both the murine and human erythrocyte proteins and cDNA nucleotide sequence analysis of the light and heavy chain genes encoding this antibody reveals that the light chain variable region gene has been previously observed in association with an autoreactive antibody. In addition to characterizing a conserved human B cell clonotype this is the first report of a human monoclonal antibody being generated from the hu-PBL-scid model using the standard hybridoma technology.

Amino Acid Sequence↗

Viral diseases of livestock in Zambia.

This review is to provide information on viral diseases of livestock in Zambia. The distribution of the diseases as well as the control measures and limited research that has been done, are described. Foot and mouth disease (FMD) causes serious economic losses in the cattle industry. So far five serotypes (SAT1, SAT2, SAT3, O and At of FMD virus have been isolated in Zambia. Other notifiable viral diseases are rabies, Rift Valley fever, Lumpy skin disease, African horse sickness, bluetongue, African swine fever, Newcastle disease, Marek's disease, fowlpox and infectious bursal disease. Based on the reports of clinical and/or serological diagnoses, these are widespread in the country, although their precise incidence rates are not known. With the establishment of a veterinary school equipped with modern diagnostic facilities and the increasing number of qualified veterinary personnel, this review would stimulate surveillance study on the viral diseases for the ultimate goal of achieving effective disease control measures.

Animals↗

Detection of viral genome in non-neural tissues of cattle experimentally infected with bovine herpesvirus 1.

To obtain further information on the latent infection with bovine herpesvirus 1 (BHV-1) in the natural host, we examined the nasal secretions and various tissues of experimentally infected calves using virus isolation, polymerase chain reaction (PCR), and immuno-PCR/antigen (Immuno-PCR/Ag) assays. In the nasal secretions, viral DNA was detected in samples with virus isolation titers of 10(4.3) TCID50 or more by PCR. On the same samples, Immuno-PCR/Ag remained positive up to day 19 p.i. the last day of test. BHV-1 DNA was detected from the following tissues in all the calves at day 22 p.i.: trigeminal ganglia, ovaries, lungs, nasal and tracheal mucosae, spleen, prescapular and precrural lymph nodes, and peripheral blood leukocytes (PBL), but not skeletal muscles. Virus was not recovered from any of these tissues. The present findings suggest a possible role of leukocytes in BHV-1 latent infection.

Animals↗

Bovine clostridial infections in Zambia (1985-1994).

Retrospective surveillance study of clostridial infections of cattle in Zambia, for the period 1985 to 1994, showed that out of the 318 cases observed, 62.8% and 24.2% were from Western and Southern provinces, respectively. Of the 6 clostridia species identified, Clostridium septicum (38.1%) followed by C. chauvoei (36.2%) and C. perfringens (13.2%) were dominant. Although the highest incidence for clostridial infections was in 1989 (75 cases) and 1990 (77 cases), the number of C. perfringens cases seemed to increase. More cases were found in the dry season until the onset of the rains, that is, the period August to December.

Animals↗

Inhibition of pseudorabies virus replication by a chimeric trans-gene product repressing transcription of the immediate-early gene.

A chimeric gene encoding a fusion protein consisting of the DNA-binding domain of the immediate-early (IE) protein of pseudorabies virus (PRV) and a tail-truncated Vmw65 of herpes simplex virus 1, lacking the transcription activation domain, was constructed. The chimeric gene product inhibited transcription from the PRV IE promoter in a transient expression assay. A HeLa cell line stably transformed with the chimeric gene showed remarkable resistance to PRV infection. In the transformed cells infected with PRV, transcription of the PRV IE gene was repressed, indicating that the resistance of the cells to PRV infection was due to interference with IE gene transcription by the fusion protein.

Base Sequence↗

Induction of protective antibody responses against pseudorabies virus by intranasal vaccination with glycoprotein B in mice.

Intranasal vaccination of mice with glycoprotein B (gB) of pseudorabies virus (PRV) induced specific IgA and IgG antibody responses in the secretion of the respiratory tract, resulting in protection of the animals against intranasal challenge with a lethal dose of virulent PRV. The immune response was enhanced by the use of cholera toxin B subunit as an adjuvant. The present results indicate that local vaccination with gB is a promising strategy to confer protective immunity on animals against PRV infection by inducing secretory antibodies on their mucosal surfaces where the primary replication of the virus occurs.

Administration, Intranasal↗

Perpetuation of influenza A viruses in Alaskan waterfowl reservoirs.

To provide information on the mechanism of perpetuation of influenza viruses among waterfowl reservoirs in nature, virological surveillance was carried out in Alaska during their breeding season in summer from 1991 to 1994. Influenza viruses were isolated mainly from fecal samples of dabbling ducks in their nesting places in central Alaska. The numbers of subtypes of 108 influenza virus isolates were 1 H2N3, 37 H3N8, 55 H4N6, 1 H7N3, 1 H8N2, 1 H10N2, 11 H10N7, and H10N9. Influenza viruses were also isolated from water samples of the lakes where they nest. Even in September of 1994 when the most ducks had left for migration to south, viruses were still isolated from the lake water. Phylogenetic analysis of the NP genes of the representative isolates showed that they belong to the North American lineage of avian influenza viruses, suggesting that the majority of the waterfowls breeding in central Alaska migrate to North America and not to Asia. The present results support the notion that influenza viruses have been maintained in waterfowl population by water-borne transmission and revealed the mechanism of year-by-year perpetuation of the viruses in the lakes where they breed.

Alaska↗