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Biomedical subjects

K Kuwano

Publications and source records attributed to K Kuwano.

At least 127 records · Page 7Linked to original sources
PubMed1986

Suppressive effect of human natural killer cells on Epstein-Barr virus-induced immunoglobulin synthesis.

The suppressive effect of human natural killer (NK) cells on Epstein-Barr virus (EBV)-induced immunoglobulin (Ig) synthesis by autologous B cells was investigated. By Percoll discontinuous density gradient centrifugation, low-density fractions enriched for NK cells were isolated from human peripheral blood lymphocytes. These NK-enriched fractions were added to purified autologous B cells in the presence of EBV, were cultivated for 8 days, and were examined for their suppressive effect on Ig synthesis by an enzyme-linked immunosorbent assay. The fractions markedly suppressed both IgM and IgG synthesis induced by EBV. It was possible to reduce the suppressive effect of NK-enriched cells by complement-dependent lysis of NK cells and Leu-11, but not by OKT3 monoclonal antibody, indicating that NK cells may be responsible for the suppression of Ig synthesis. Upon close examination of interferon (IFN) activity, it was revealed that the co-cultures of NK-enriched cells and EBV-infected B cells generated production of IFN-alpha, which might be produced by NK cells in response to EBV-stimulated B cells. Addition of anti-IFN-alpha but not anti-IFN-gamma serum almost completely abrogated the suppressive effect of NK-enriched cells on Ig synthesis, indicating that IFN-alpha produced are required for the NK cell-mediated suppression of Ig synthesis. However, addition of IFN-alpha into purified B cells showed no direct suppressive effect on EBV-induced Ig synthesis by B cells in the absence of NK cells. Nevertheless, NK cells when previously incubated with IFN-alpha and added to B cells showed a suppressor activity on Ig synthesis to a level higher than that of untreated NK controls. These results strongly suggest the possibility that NK cells display an interaction with EBV-infected B cells and produce IFN-alpha, which in turn activates NK cells. These activated NK cells suppress the Ig synthesis by B cells, which undergo transformation induced by EBV.

Antibodies, Monoclonal↗
PubMed1985

Induction of interferon-gamma production by human natural killer cells stimulated by hydrogen peroxide.

Interferon (IFN)-inducing activity of hydrogen peroxide in human peripheral mononuclear cells was investigated. Among the mononuclear cells, purified nonadherent cells produced IFN, but not B cells and monocytes. The maximal titer of IFN by purified nonadherent cells was observed after a 72-hr cultivation in the presence of 10(-2) mM H2O2 without affecting their viability. Furthermore, the purified nonadherent cells, but not the unpurified mononuclear cells, showed an augmented cytotoxicity to K562 when stimulated with hydrogen peroxide. By using Percoll discontinuous density gradient centrifugation, peripheral blood nonphagocytic and nonadherent mononuclear cells were divided into the low and high density fractions for which natural killer (NK) cells and T cells were enriched, respectively. The NK-enriched low density fractions, but not the T cell-enriched high density fractions, showed IFN production by the stimulation of hydrogen peroxide. IFN production as well as large granular lymphocytes and HNK-1+, Leu-11+ cells of the NK-enriched fractions were abrogated by treatment of the cells with monoclonal antibody against human NK cells (HNK-1+) but not against T cells (OKT3) in the presence of complement. Moreover, hydrogen peroxide-inducing IFN production seems to be regulated by monocytes. The antiserum neutralizing IFN-alpha and IFN-beta failed to neutralize substantially IFN-produced NK cells. The treatment with either pH 2 or antiserum-neutralizing human IFN-gamma resulted in marked reduction, indicating that a major part of IFN was IFN-gamma. The purified nonadherent cells showed IFN production and augmented cytotoxicity when cultured separately from activated macrophages by opsonized zymosan; furthermore, both IFN production and enhancement of cytotoxicity were abrogated by catalase. These results suggest that both exogenous and endogenous hydrogen peroxide might be responsible for a part of immunoregulation.

Adult↗
PubMed1978

Clinical study on gastric secretion with special reference to pepsin secretion.

The stimulating effect of AOC-tetragastrin, caerulein, Histalog and secretin on human gastric acid and pepsin secretion was studied in gastric ulcer patients. The pattern of gastric acid and pepsin secretion after the administration of caerulein was closely resembled to that of gastrin. Slight increase of pepsin secretion after gastrin or caerulein could be based on "wash-out" action caused by the increase of acid secretion after the stimulants. Stimulating effect on gastric pepsin secretion of histalog and secretin would be independent of gastric acid secretion.

Ceruletide↗
PubMed1976

[Continuous local application of cytostatics for bronchial carcinoma and mediastinal lymph node metastasisization (author's transl)].

A carcinostatic substance (5-fluorouracil) was instilled into the mediastinal lymph nodes, the pleural cavity or the internal thoracic artery by continuous perfusion before operation on patients with bronchial carcinoma. Degenerative changes could be demonstrated histologically in the cancer cells in the lymph node metastases. This method was also effective for the controlateral lymph node metastases. As a treatment additional to operation, it may improve the chances of survival.

Adenocarcinoma↗
PubMedDate not supplied

Recognition of disparate HA and NS1 peptides by an H-2Kd-restricted, influenza specific CTL clone.

CTLs (CD8+) are known to recognize exogenous peptide in the context of class I MHC molecules. We observed that an influenza subtype H1 and H2 cross-reactive CTL clone B7, which was stimulated by a fusion protein containing a portion of HA2 subunit of A/PR/8 virus HA, recognized a synthetic peptide (residues 515-526) of the HA2 subunit of A/PR/8 virus strain. This CTL clone also recognized a structurally disparate NS1 peptide 50-68 of the same A/PR/8 virus. We examined the recognition of the NS1 peptide 50-68 and the HA peptide 515-526 by the subcloned CTL clone, B7-B7. Cold target inhibition experiments showed that the recognition of the HA peptide by the CTL clone B7-B7 could be competed by NS1 peptide-treated target cells and vice versa. The recognition of both NS1 peptide and HA peptide by the CTL clone B7-B7 was restricted by the same allele, H2Kd. In addition, this NS1 peptide requires approximately a 600-fold higher concn for optimal CTL recognition than did the HA peptide. We conclude that the TCR on clone B7-B7 recognizes the HA peptide or the NS1 peptide as comparable complexes with the same class I MHC molecules, although there is no obvious homology in the primary sequences of HA 515-526 and NS1 50-68 peptides. CTLs elicited with certain antigens appear to recognize distinctively different antigens complexed to the same presenting MHC molecule.

Amino Acid Sequence↗
PubMedDate not supplied

Kinetics and specificity at the clonal level of the cytotoxic T lymphocyte response to influenza pneumonia.

We have studied the kinetics and specificity of the cytotoxic T lymphocyte (CTL) response to influenza A/PR/8 (H1N1) virus pulmonary infection in the mouse detected using spleen cells from infected mice which were stimulated in bulk and limiting dilution cultures. A hybrid protein designated D-peptide, which contains the terminal 157 amino acids of the HA2 subunit of A/PR/8 virus, was used to stimulate influenza virus subtype-specific secondary CTL in vitro. Infection induced two specificities of precursor CTL, cross-reactive and subtype-specific. The kinetics of the subtype-specific CTL response detected by the D-peptide were similar to the cross-reactive CTL response detected by stimulation with live virus. The majority of the precursor CTL (CTL-p) are able to lyse virus-infected target cells in a cross-reactive fashion. The number of memory subtype-specific and cross-reactive CTL increased by approximately 2.5 logs10 during the first 3 weeks after infection.

Administration, Intranasal↗
PubMedDate not supplied

Mycoplasma interaction with lymphocytes and phagocytes: role of hydrogen peroxide released from M. pneumoniae.

Interferon (IFN) production by human peripheral lymphocytes stimulated with M. pneumoniae was investigated. The hydrogen peroxide released from M. pneumoniae was responsible for the induction of IFN from lymphocytes, since horseradish peroxidase inhibited the IFN production and abrogated the activity of IFN production in the supernatant of M. pneumoniae. The antiserum neutralizing IFN alpha and IFN beta failed to neutralize partially interferon produced by lymphocytes. Treatment either with pH 2.0 or antiserum neutralizing human IFN gamma resulted in a partial reduction of interferon. These results indicate that interferon produced by human lymphocytes stimulated with M. pneumoniae includes both types of IFN gamma and IFN beta.

Adult↗