[Molecular structure and immunological characteristics of insulin].
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Amino Acid Sequence↗
Biomedical subjects
K Noma
Publications and source records attributed to K Noma.
[Diagnostic significance of serum glutamate dehydrogenase in hepatobiliary diseases].
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Alanine Transaminase↗
Evaluation of left ventricular function in an experimental model of congestive heart failure due to combined pressure and volume overload.
During a 6 month observation period after operation, typical symptoms of congestive heart failure, such as cyanosis, systemic oedema, ascites and pleural effusion occur in the majority of rats which have a combined arteriovenous shunt (AV-shunt) and renal hypertension (Goldblatt II). In the present study, the left ventricle dilated to twice the size of that of age-matched Wistar controls. Developed wall stress increased significantly due to an augmented ratio of radius to wall thickness. Normalized stress-length (stress-midwall circumference) area and maximum rate of stress development (d sigma/dtmax) indicated decreased myocardial work and power capacity. Although the congestive symptoms can only partially be related to impaired cardiac function, this model may be useful for pathophysiological and pharmacological studies of chronic heart failure.
Animals↗
Delayed enhancement of hepatocellular carcinoma on dynamic CT: sign of extrahepatic collaterals after transcatheter arterial chemoembolization or transcatheter arterial chemoinfusion.
BACKGROUND: We examined the factors of delayed enhancement of hepatocellular carcinoma (HCC) on dynamic computed tomography (CT). METHODS: Dynamic CT and angiography were compared in 113 patients who had undergone transcatheter arterial chemoembolization or transcatheter arterial chemoinfusion and were suspected of developing new HCCs. RESULTS: Eight of 113 patients had HCC nodules that enhanced gradually from the arterial phase to the portal venous phase on dynamic CT and were fed by extrahepatic arteries on angiography. The feeding artery was an omental branch of the splenic artery in one lesion, an omental branch of the gastroduodenal artery in five, and the intercostal artery in two. CONCLUSION: We believe that the recurrence of HCCs delayed enhancement on dynamic CT because the hepatic artery was hidden and long narrow extrahepatic collaterals fed the tumor.
Aged↗
Down-regulation of IL-10 enhances the efficacy of locoregional immunotherapy using OK-432 against malignant effusion.
To determine the significance of interleukin (IL)-10 in antitumor immune response, the effect of the down-regulation of tumor-derived IL-10 on locoregional immunotherapy was investigated. C3H/HeN mice were intraperitoneally (i.p.) inoculated with IL-10-producing murine breast cancer cell line, FM3A, and treated with locoregional administration of OK-432 with or without anti-IL-10 monoclonal antibody (mAb). Anti-IL-10 mAb did not affect the in vitro growth of FM3A cells. Administration of OK-432 plus anti-IL-10 mAb remarkably delayed the retention of malignant ascites and prolonged the survival of mice compared with the administration of OK-432 alone. Spleen cells which were collected from mice treated with OK-432 plus anti-IL-10 mAb and further stimulated in vitro with inactivated FM3A cells exhibited significantly higher cytotoxicity against FM3A cells than those from mice treated with OK-432 alone or from the control mice. The expression of major histocompatibility complex (MHC) class II molecules on spleen cells was up-regulated in vitro by the addition of OK-432 and anti-IL-10 mAb. Using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), cytokine mRNA levels of peritoneal exudate cells (PEC) and spleen cells were assessed on day 7 (before treatment) and day 14 (after treatment). In PEC, increased expression of IL-2 was observed with the administration of OK-432 plus anti-IL-10 mAb. In spleen cells, the expression of IL-2, IL-12 and IFN-gamma were strongly induced, and IL-4 expression was reduced by the administration of OK-432 plus anti-IL-10 mAb. It is suggested that down-regulation of tumor-derived IL-10 induces the up-regulation of the T helper type (Th) 1 population, resulting in an enhancement of the efficacy of locoregional immunotherapy with OK-432.
Animals↗
T-cell receptor V beta gene usage of human cytotoxic T-cell clones obtained from gastric cancer patients.
Nine T-cell clones have been established from tumor-infiltrating lymphocytes (TIL) isolated from ascitic fluid of a gastric cancer patient. Five of them retained cytotoxicity against autologous tumor cells (AuTu), and were all CD4+. Each clone had different usage of T-cell receptor (TCR) V beta gene as assessed by Southern blot analysis. Using AuTu and two allogeneic gastric cancer cell lines as targets, we selected three clones with unique cytotoxic properties. Two of these clones (Clone 1 and 2) preferentially lysed AuTu, but showed no or marginal cytotoxicity against allogeneic gastric cancer cells, and one clone (Clone 7) showed appreciable cytotoxicity against AuTu and allogeneic gastric cancer cells. In the detailed analysis of TCRV beta gene usage, Clone 1, 2, and 7 expressed V beta 13.1/D beta 1/J beta 1.5/C beta 1, V beta 3/D beta 2/J beta 2.4/C beta 2, and V beta 9/D beta 1/J beta 1.4/C beta 1, respectively, and the primary structures of the three TCRVb genes did not share any common features, neither in the sizes of their complementarity determining region 3 (CDR3) nor in their amino acid compositions. Interestingly, PBL of the same patient expressed CDR3 identical to that of Clone 2 and 7, but not that of Clone 1. CDR3 identical to that of Clone 2 and 7 were also detected in TIL of other gastric cancer patients. These results show that some AuTu-specific CTL included in TIL are circulating in peripheral blood, and that the CDR3 identical to that of the CTL is expressed extensively in TIL among different gastric cancer patients. Screening of the expression of the CDR3 in other gastric cancer patients is recommended to develop an immuno-therapy of gastric cancer based on antigenic peptide.
Adenocarcinoma↗
Generation of cytotoxic effector lymphocytes by MLTC using tumor cells genetically modified to secrete interleukin-2.
The in vitro generation of effector lymphocytes cytotoxic to cancer cells, was investigated with a mixed lymphocyte-tumor culture (MLTC) system using genetically modified human cancer cells, followed by stimulation with the interleukin (IL)-2 plus immobilized anti-CD3 antibody (IL-2/CD3) system. A gastric cancer cell line, GC022588 (HLA-A2, 24, B35, 55, C1,3), was retrovirally transduced with the human interleukin (IL)-2 gene (GC/IL-2) or the neomycin-resistance gene (GC/Neo). The secretion of biologically active IL-2 was detectable in GC/IL-2 cells but not in GC/Neo or parental GC022588 cells. The cytotoxic activity against the parental GC022588 cells of peripheral blood mononuclear cells (PBMC) was greater among PBMC activated with MLTC using GC/IL-2 than among those activated with MLTC using GC/Neo or without MLTC. The IL-2/CD3 stimulation could efficiently expand the effector lymphocytes without any reduction of the cytotoxic activity generated. The cytotoxic activity generated by this system was reproducible in several HLA-A2- or A24-positive donors. The effector lymphocytes could kill the other adenocarcinoma cells expressing HLA-A2 or A24. The phenotypes of the effector lymphocytes generated with the system were 40% CD4+ and 70% CD8+. Both phenotypes may have been responsible for the cytotoxicity. The removal of adherent cells from PBMC before the MLTC did not affect the generation of cytotoxicity, whereas neutralization of tumor-derived IL-2 with a specific antibody during the MLTC significantly inhibited the generation of cytotoxicity. These results suggest that IL-2 gene-transduction augments the immunogenicity of the tumor cells that efficiently stimulate lymphocytes to be cytotoxic, and that the IL-2/CD3 system may be practical for the expansion of effector lymphocytes for use in adoptive immunotherapy for cancer. The mechanism by which IL-2 gene-modified tumor cells stimulate immune reactivity was discussed.
Adenocarcinoma↗
Locoregional immunotherapy of malignant ascites by intraperitoneal administration of OK-432 plus IL-2 in gastric cancer patients.
The clinical efficacy of intraperitoneal administration of OK-432 plus interleukin-2 (IL-2) for treating malignant ascites was evaluated in gastric cancer patients. Ten KE of OK-432 and 200,000 Jurkat units of IL-2 were intraperitoneally administered in tandem in the order given on alternate days at paracentesis. Of the 22 evaluable patients, 18 (81%) developed complete or partial responses, showing a cytologic disappearance of cancer cells and decrease of ascites. More than 50% of the patients obtained positive responses within 2 weeks after the initial administration of the drugs. Improvements of performance status and clinical symptoms such as abdominal fullness, followed by restoration of oral food intake and prolongation of survival time were observed in responders treated with OK-432 plus IL-2. Flow cytometric analysis demonstrated a predominant increase of the CD3+CD4+ cells, especially of the CD4+CD45RA- subset in the peritoneal cavity of the responders. Cytotoxicity assay after negative selection of the CD4+ cells with the antibody and complement revealed that the CD4+ subset possessed cytotoxic activity against autologous tumor cells. The results suggest that intraperitoneal administration of OK-432 plus IL-2 may not be only a practical but also an effective protocol for treating malignant ascites in gastric cancer patients.
Adult↗