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C Hirashima

Publications and source records attributed to C Hirashima.

7 recordsLinked to original sources

Isolated pericardial effusion and transient abnormal myelopoiesis in a fetus with Down's syndrome.

Isolated pericardial effusion was detected in a fetus at 34 weeks of gestation. A male infant weighing 2,044 g was born by cesarean section because of a non-assuring fetal heart rate pattern at 35 weeks of gestation. Transient leukocytosis (36,100/microl) with 49% blast cells was seen in this neonate. The infant's karyotype was 47, XY + 21. The pericardial effusion disappeared after treatment with prednisolone at a dose of 2 mg/kg/day. Hypothyroidism was subsequently found. Thus, the subject patient with Down's syndrome developed isolated pericardial effusion, transient abnormal myelopoiesis (TAM), and hypothyroidism. Because more than 20% of the infants with TAM and Down's syndrome develop acute nonlymphocytic leukemia in early childhood, he is being closely observed.

Adult↗

[IP3 receptor].

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Adenosine Triphosphate↗

Local injection of OK432 can augment the TH1-type T-cell response in tumor-draining lymph node cells and increase their immunotherapeutical potential.

The effect of local injections with streptococcal preparation OK432 on the therapeutical potential of tumor-draining lymph node (LN) cells was investigated in mice. Peritumoral injections with OK432 on days 2, 4, 6, 8 and 10 showed no effect on the in vivo growth of s.c. inoculated B16F10 melanoma. The B16F10-draining OK432-treated LN cells, however, showed a high level of anti-B16F10 cytolytic activity after an in vitro culture first with both anti-CD3 monoclonal antibody (MAb) and activated B cell blasts, and subsequently with interleukin (IL)-2 without in vitro restimulation. Such in vitro expanded LN cells showed a remarkable antitumor effect against pulmonary metastasis of B16F10 melanoma, even without the concurrent administration of IL-2. In addition, the therapeutical protocol was also found to be moderately effective against poorly immunogenic MCA fibrosarcoma, and the in vivo antitumor effect was specific to the tumor from which the LNs were harvested. Interestingly, 2 kinds of comparative analyses of the cytokines revealed that the B16F10-bearing state induced the draining LN cells to develop a Th2-type response. However, the OK432 treatment was able to effectively augment their Th1-type response. Collectively, our results suggest that peritumoral injections with OK432 significantly increased the therapeutical potential of the tumor-draining LN cells by augmenting their Th1-type response.

Animals↗

Effects of interleukin-12 on in vitro culture with interleukin-2 of regional lymph node lymphocytes from lung cancer patients.

In the present study, we carried out a functional analysis of regional lymph node lymphocytes (RLNL) from patients with lung cancer after in vitro activation by interleukin-2 (IL-2) and interleukin-12 (IL-12). IL-12 (100 U/ml) enhanced both the proliferation and cytotoxic activity of RLNL in a culture with low doses of IL-2 (5-10 JRU/ml). After comparing an RLNL culture with a low dose of IL-2 alone, a higher proportion of CD8+ cells and CD56+ cells and a lower proportion of CD4+ cells were found in the culture with both IL-12 and a low dose of IL-2. Such a combination of the cytokines effectively activated RLNL in terms of the expression of IL-2 receptors. In the culture condition of IL-12 and a low dose of IL-2, a synergistic effect was observed in the production of such cytokines as interferon gamma, tumor necrosis factor alpha (TNF alpha), and TNF beta, as well as in tumor cytotoxicity. However, the addition of IL-12 inhibited the cytotoxicity of RLNL in the culture with a high dose of IL-2 (100 JRU/ml). This inhibition is considered to be partially due to the endogenous production of TNF alpha by lymphocytes, because the neutralization of TNF alpa bioactivity partially restored the cytotoxic activities of RLNL. Furthermore, in the presence of hydrocortisone, IL-12 synergistically enhanced the cytotoxic activity of RLNL cultured with a high dose of IL-2. These results provide useful information about the improvement of adoptive immunotherapy against cancer using RLNL.

Antigens, CD↗

Specific immunotherapy with tumour-draining lymph node cells cultured with both anti-CD3 and anti-CD28 monoclonal antibodies.

For providing costimulatory signals, we utilized anti-CD28 monoclonal antibody (mAb) for the in vitro culture of tumour-draining lymph node (LN) cells. The proliferation of B16 melanoma-draining LN cells in the culture with anti-CD3 mAb was remarkably enhanced by the addition of anti-CD28 mAb. In culture with both anti-CD3 and anti-CD28 mAb, the B16-draining LN cells produced a higher level of interferon-gamma, but not interleukin-4, than with anti-CD3 mAb alone. The B16-draining LN cells efficiently expanded in the culture with both anti-CD3 and anti-CD28 mAb and subsequently with a low dose of IL-2 (anti-CD3 plus anti-CD28/IL-2). The expanded cells consisted predominantly of CD8+ T cells and showed a specific cytolytic activity, in a major histocompatibility complex (MHC) class I-restricted manner, even without in vitro restimulation. In addition, the adoptive transfer of the B16-draining LN cells, expanded in the culture protocol of anti-CD3 plus anti-CD28/IL-2, showed a significant anti-tumour effect against metastatic B16 melanoma in combination with IL-2. The cured mice thus acquired a specific protective immunity. Moreover, this protocol was also moderately effective against poorly immunogenic 3LL carcinoma. Overall, our results suggest the potential for another immunotherapeutic strategy based on 'the costimulatory theory' other than vaccination with B7-transfected tumour cells.

Animals↗

Conditioning-specific modification of the rabbit's unconditioned nictitating membrane response.

Robust classical conditioning modifies responding to the unconditioned stimulus (US) in the absence of the conditioned stimulus (CS), a phenomenon the researchers called conditioning-specific reflex modification. Unconditioned responses (URs) to periorbital stimulation varying in intensity and duration were assessed before and after 1, 3, or 6 days of paired, explicitly unpaired, or no presentations of tone and electrical stimulation. After 3 days of pairings, conditioned responding (CRs) reached 94%, and there was an increase in latency to the peak of URs. The peak latency increase was replicated in a second experiment where rabbits reached asymptotic conditioning during 6 days of pairings. There was also a conditioning-specific increase in the amplitude of URs. There were no UR changes as a function of low level of CRs following 1 day of pairings. Data suggest that there are learning-specific changes in pathways mediating the US/UR, as well as in those mediating the CS/CR.

Animals↗

The augmenting effect of OK432-stimulated B cells on the in vitro generation of anti-tumor cytotoxic T lymphocytes from tumor-draining lymph node cells: the possible role of interleukin-12.

Effect of a local injection with a streptococcal preparation OK432 on the in vitro generation of anti-tumor cytotoxic T lymphocytes (CTLs) from tumor-draining lymph nodes (LN) was investigated. A peritumoral injection with OK432 on days 2, 4, 6 and 8 significantly increased both the total cell number and the proportion of B cells in the draining LN cells on day 10 after a subcutaneous inoculation with B16 melanoma. In an in vitro proliferative assay, OK432 showed a stimulatory effect on both normal splenic T and B cells. In a cytolytic assay, the OK432-injected B16-draining LN cells showed a higher level of anti-B16 CTL activity than the B16-draining LN cells after in vitro restimulation. This augmenting effect of OK432 was dependent on the B cells. Moreover, nonadherent cells from the OK432-injected B16-draining LN cells showed a low but significantly higher level of anti-B16 CTL activity than those from the B 16-draining LN cells after in vitro restimulation, whereas this augmenting effect of OK432 was abolished by the in vitro addition of anti-interleukin (IL)-12 monoclonal antibody. Collectively, these findings suggest that the augmenting effect of a local injection with OK432 on the potential of tumor-draining LN cells to turn into anti-tumor CTLs after in vitro restimulation was at least in part due to IL-12 derived from the OK432-stimulated B cells.

Animals↗