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E Miyahara

Publications and source records attributed to E Miyahara.

31 records · Page 2Linked to original sources

Profile of T-cell receptor V beta gene usage of cytotoxic T cells induced by intrapleural administration of a streptococcal preparation, OK432, in malignant effusions.

T-cell receptor (TCR) gene rearrangements were analyzed in tumor-infiltrating lymphocytes (TIL) using the reverse transcription-polymerase chain reaction (RT-PCR) to determine whether oligoclonal expression of TCRV beta occurs in TIL, and if so, whether it is involved in the clinical response and mechanisms of locoregional immunotherapy using a streptococcal preparation, OK432. Patients with malignant effusion of various origins were treated with intrapleural administration of OK432, and clinical responses were assessed by cytological and chest X-ray examinations. Pleural exudate cells (PEC), obtained before and after the administration of OK432 (designated as pre- and OK432-PEC, respectively), were subjected to TCR analysis. Both pre-PEC and OK432-PEC showed highly diverse expressions of TCRV beta gene usage in either type of PEC. The frequency of TCRV beta 20 gene expression in OK432-PEC was significantly higher than in pre-PEC. Moreover, the over-expression of the TCRV beta 20 gene usage was also induced in the peripheral blood lymphocytes and pre-PEC of patients by in vitro OK432 stimulation, but not in the PBL of one healthy volunteer. Single-strand conformational polymorphism (SSCP) analysis revealed the clonotypes of these TCRV beta 20 genes. Autologous tumor-specific killing activity could be detected in OK432-PEC and was significantly reduced by treatment with a TCRV beta 20-specific monoclonal antibody. These findings suggest that the rearrangement of TCRV beta 20 gene usage may be involved in the autologous tumor-specific action of malignant effusions in the treatment with OK432.

Aged↗

[T cell receptor V beta repertoire of locoregional lymphocytes in malignant effusions].

We analyzed the T cell receptor (TCR) V beta repertoire of lymphocytes obtained from patients with malignant effusion treated by locoregional immunotherapy. Polymerase chain reaction using a panel of V beta subfamily specific oligonucleotide primers(V beta 1-20) was employed after reverse transcription of mRNA isolated from the locoregional cells. No major oligoclonality of TCR repertoire was observed in effusion lymphocytes before the treatment. The expression level of V beta 13.1 repertoire was significantly higher in effusion lymphocytes than in peripheral blood lymphocytes before treatment. V beta 20 gene expression increased significantly after locoregional administration of OK-432. It is suggested that TCR V beta 13.1 may be responsible for effusion lymphocytes and TCR V beta 20 for OK-432-related antigenic stimulus.

Adult↗

[Skin reaction to OK-432 and its dosage for locoregional administration].

Establishment of optimal dosage of OK-432, a streptococcal preparation, was studied based on its skin test was studied. Locoregional immunotherapy using OK-432 was conducted for patients with malignant fluids. More OK-432 was administered to patients having a weaker skin reaction to OK-432 and less to those having a stronger one, corresponding to their redness diameter of skin reaction. There was a marked difference in OK-432-skin test among patients. Some patients with malignant fluids having small redness responded to the treatment after a large amount of OK-432, and others were well controlled by a smaller dosage of OK-432. It is suggested that OK-432-skin test may provide the optimal dosage for local treatment of malignant fluids.

Ascitic Fluid↗

How surrounds affect chromaticity discrimination.

Chromatic discrimination thresholds were measured with and without surrounds along two cardinal axes of chromaticity space. On one axis the level of short-wavelength-sensitive (SWS)-cone excitation was varied for constant long-wavelength-sensitive (LWS)-cone and medium-wavelength-sensitive (MWS)-cone excitations, and on the other axis there were equal and opposite changes in LWS-cone and MWS-cone excitations for constant levels of SWS-cone excitation. Results for two of three observers showed that with a dark surround, discrimination mediated by SWS cones was regulated by the level of SWS-cone excitation of the starting chromaticity, showing a function with the form of a threshold-versus-radiance function. For an equiluminant white or yellow surround, the discrimination for all three observers showed a minimum at the level of SWS-cone excitation of the surround, giving a V-shaped function for the white surround. An additional experiment with dimmer white surrounds indicated that while the minimum remained at the white point, the function gradually changed toward the shape with a dark surround. Discrimination thresholds mediated by LWS and MWS cones with a dark surround showed a minimum near the LWS-cone excitation of equal-energy white, giving a V-shaped function. The effect of yellow and white surrounds was to deepen the V. The data can be described by a model of chromatic discrimination incorporating a threshold term, a cone gain control, and an opponent gain control into two equations, one for SWS-cone discrimination and one for LWS-cone and MWS-cone discrimination.

Adult↗

[A case of advanced gastric cancer responding to an FAP (5-FU, ADM, platinum compounds) combined chemotherapy].

An experience with an advanced gastric cancer patient with metastases to bilateral breasts, uterus, abdominal lymph nodes, bilateral axillary and supraclavicular lymph nodes, and bone marrow, responded extremely well to an FAP combined chemotherapy as reported here. The patients received four courses of 5-FU (370 mg/m2/day, for five days, continuous infusion), ADM (30 mg/m2 on day 1, i.v.) and CDDP (55 mg/m2 on day 1, i.v.) every 3 weeks in our hospital. This was followed by 7 months of outpatient therapy with 5-FU (550 mg/m2 on day 1, i.v.), ADM (30 mg/m2 on day 1, i.v.) and CBDCA (330 mg/m2 on day 1, i.v.) for every 4 weeks. The complete remission of the primary and metastatic lesions, that was confirmed by the histological examinations, was obtained after 10 months since the initial treatment started. The toxicity was generally moderate, however, the alopecia was severe. The patient has been living for 6 months without any signs of the recurrence after the complete remission obtained.

Adenocarcinoma↗

[The expression of NCC-ST-439, a tumor marker, in human breast cancer patients].

The expression and serum level of NCC-ST-439, a tumor marker, has been investigated in 20 primary and 28 recurrent breast cancer patients, and the positive rate was found to amount to 21.1% in primary cases and 42.9% in recurrent cases, respectively, thereby indicating a positive correlation between the expression of NCC-ST-439 and the progression of the diseases. The accordance rate between NCC-ST-439 and CEA was 64.6%; in contrast, the rate between NCC-ST-439 and CA 15-3 was 82.1%, suggesting a difference in specificity against tumor between NCC-ST-439 and CEA. The change in the serum level of NCC-ST-439 in recurrent cases clearly correlated with the effectiveness of the therapy. These findings suggest that measurement of the NCC-ST-439 level, especially in combination with the CEA level, may be useful for the early detection and the monitoring of relapses in breast cancer patients.

Antigens, Tumor-Associated, Carbohydrate↗

Computerized color-vision test based upon postreceptoral channel sensitivities.

An automated, computerized color-vision test was designed to diagnose congenital red-green color-vision defects. The observer viewed a yellow appearing CRT screen. The principle was to measure increment thresholds for three different chromaticities, the background yellow, a red, and a green chromaticity. Spatial and temporal parameters were chosen to favor parvocellular pathway mediation of thresholds. Thresholds for the three test stimuli were estimated by four-alternative forced-choice (4AFC), randomly interleaved staircases. Four 1.5-deg, 4.2 cd/m2 square pedestals were arranged as a 2 x 2 matrix around the center of the display with 15-minute separations. A trial incremented all four squares by 1.0 cd/m2 for 133 ms. One randomly chosen square included an extra increment of a test chromaticity. The observer identified the different appearing square using the cursor. Administration time was approximately 5 minutes. Normal trichromats showed clear Sloan notch as defined by log (deltaY/deltaR), whereas red-green color defectives generally showed little or no Sloan notch, indicating that their thresholds were mediated by their luminance system, not by the chromatic system. Data from 107 normal trichromats showed a mean Sloan notch of 0.654 (SD = 0.123). Among 16 color-vision defectives tested (2 protanopes, 1 protanomal, 6 deuteranopes, & 7 deuteranomals), the Sloan notch was between -0.062 and 0.353 for deutans and was < -0.10 for protans. A sufficient number of color-defective observers have not yet been tested to determine whether the test can reliably discriminate between protans and deutans. Nevertheless, the current data show that the test can work as a quick diagnostic procedure (functional trichromatism or dichromatism) of red-green color-vision defect.

Automation↗

Modulation of CD4 antigen expression on the lymphocyte surface by immunosuppressive acidic protein in cancer patients.

The immunomodulatory effect of human immunosuppressive acidic protein (IAP) on lymphocyte surface antigens was investigated. IAP inhibited lymphocyte responses to phytohemagglutinin in a dose-dependent manner. By flow cytometry, using fluorescein-isothiocyanate-labelled antibodies, the mean fluorescence intensity on peripheral blood lymphocytes (PBLs) decreased for CD4, slightly decreased for CD3 but showed no change for the CD8 and T cell receptor alpha-beta antigens in the presence of IAP. This CD4 antigen modulation by IAP was observed in PBLs freshly isolated from patients with unresectable cancer but not in those isolated from patients with resectable tumor or from healthy volunteers. The modulation of the CD4 antigen by IAP on the lymphocyte surface was correlated with an increment of serum IAP levels in cancer patients. The CD4 modulation could be induced in PBLs from healthy volunteers by culturing them with IAP in vitro. It is suggested that IAP may play a role in cancer-related immunosuppression through the down-modulation of the CD4 antigen on the lymphocyte surface.

CD3 Complex↗

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↗

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↗