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Biomedical subjects

T Akiyoshi

Publications and source records attributed to T Akiyoshi.

At least 91 records · Page 5Linked to original sources
PubMed1995

Lymphokine-activated killer cell function of lymphocytes from regional lymph nodes in patients with gastric carcinoma.

Lymphokine-activated killer (LAK) cells generated by culture of regional lymph node cells (LNC) with interleukin 2 (IL 2) for 4 and 11 days were examined for their functional capabilities in comparison with those of peripheral blood mononuclear cells (PBM) in 25 patients with gastric carcinoma. The cytotoxic activity of LAK cells induced from LNC for 4-day culture with IL 2 was significantly lower than that from PBM. However, the LNC-LAK cytotoxicity was markedly increased up to almost the same level as that of PBM after 11-day culture. The production of interferon-gamma (INF-gamma) and tumor necrosis factor-alpha (TNF-alpha) from nonadherent LAK cells in LNC was also significantly reduced as compared to that from PBM 4 days after culture, when stimulated with or without tumor target, Raji cells. After 11-day culture with IL 2, however, the levels of these cytokines produced by LNC-LAK cells either with or without stimulation by tumor target were comparable to those by PBM-LAK cells, although the release of these cytokines was markedly reduced when compared to that after 4-day culture. Phenotypic analysis revealed decreased proportion of cells mediating NK activity in LNC before and 4 days after culture. CD56+ and CD57+ cells in LNC were increased after 11-day culture, although the percentages of these cells were still low as compared to those in PBM. The proportions of OKIa1+ and CD25+ cells were uniformly increased after 4 and 11-day culture in both cell populations. Changes in subpopulations of CD4+ and CD8+ cells in LNC were not apparently different from PBM. These results indicated the differential LAK cell function of cells from regional lymph nodes from PBM in patients with gastric carcinoma.

Adult↗
PubMed1995

The expression of tumor-rejection antigen "MAGE" genes in human gastric carcinoma.

BACKGROUND & AIMS: The genes MAGE-1 and MAGE-3 both encode melanoma peptide antigens recognized by major histocompatibility complex-restricted cytotoxic T lymphocytes. The antigens may be a target for immunotherapy. There is, however, little information on the expression of these genes in gastric carcinomas. Therefore, the expression of MAGE genes in gastric carcinomas was evaluated. METHODS: The expression of MAGE-1, MAGE-2, and MAGE-3 genes in tumors and corresponding normal tissue specimens was studied using a reverse-transcription polymerase chain reaction. The results were analyzed according to clinicopathologic factors of the tumor. RESULTS: In the 68 gastric carcinomas studied, MAGE-1, MAGE-2, and MAGE-3 messenger RNA were detected in 41%, 31%, and 38%, respectively. Fifty percent of the gastric carcinomas expressed at least one of the MAGE genes. Messenger RNA for the three MAGE proteins was not detected in normal gastric tissue. MAGE gene expression in gastric carcinomas was not associated with a significant clincopathology of the tumor. However, gene expression was lower in mucinous carcinomas (3 of 10). CONCLUSIONS: MAGE-1, MAGE-2, and MAGE-3 are expressed in a high percentage of gastric carcinomas. These tumor rejection antigens may provide tumor-specific targets for immunotherapy.

Aged↗
PubMed1995

Surgical treatments for oesophageal cancer concomitant with gastric adenoma with severe epithelial atypia.

The various surgical treatments for oesophageal cancer concomitant with gastric adenoma with severe epithelial atypia (SEA) are discussed by presenting three such cases. As gastric adenoma with SEA had been considered to be a precancerous condition but not normally an indication for gastrectomy, we devised an operative strategy of laparotomy and thoracotomy. For Case 1, with early oesophageal cancer and gastric adenoma with SEA in the body of stomach, a laparotomy and local resection of the gastric lesion were carried out prior to thoracotomy in order to determine the safest reconstructive method after measuring the length of the well-nourished gastric tube. In Case 2, with advanced oesophageal cancer, a thoracotomy was first performed to assess the curability of surgery for the oesophageal cancer and a gastric adenoma was removed. In contrast, for Case 3 with advanced oesophageal cancer, and in whom post-operative survival was deemed to be short, a gastric adenoma was not resected. The most appropriate operative methods should thus be decided after careful consideration of the stage of the oesophageal cancer and characteristics of the gastric adenoma.

Adenoma↗
PubMed1995

Immunohistochemical features of HLA-DR antigen expression and lymphoid infiltrates in gastric carcinoma after low-dose interleukin-2 and mitomycin C.

We immunohistochemically evaluated lymphoid cell infiltration and HLA-DR antigen expression in gastric tumor tissue obtained from advanced gastric cancer patients 1 day after the completion of the treatment with mitomycin C (MMC) 12 mg/m2 i.v. on day 1 and recombinant interleukin-2 (IL-2) i.v. every 12 h from day 4 through day 8. Then the results were compared with those in 11 patients pretreated with MMC alone, 5 treated with IL-2 alone, and 24 untreated patients. Widespread lymphoid infiltration was observed in 17% of untreated tumors, 27% of MMC-pretreated tumors, and 40% of tumors treated with IL-2 alone. However, 71% of carcinomas pretreated with MMC plus IL-2 exhibited widespread infiltration. The frequency of cases with high-grade infiltration of CD4+ cells was significantly higher in either group of patients treated with MMC alone or MMC plus IL-2. Because the CD8+ cell infiltration was not significantly altered, the ratio of CD4+ to CD8+ cells estimated as being > 1 was more frequently noted in patients given MMC alone or MMC plus IL-2, as compared with untreated control. Furthermore, 86% of tumors pretreated with MMC plus IL-2 exhibited positive HLA-DR antigen expression, whereas 29% of untreated carcinomas did so. MMC or IL-2 alone did not significantly increase HLA-DR expression. These results indicate that the combination of low-dose of IL-2 with MMC enhances the intensity of lymphoid cell infiltration in tumors, with the predominance of CD4+ cells, and HLA-DR antigen expression on tumor cells in patients with advanced gastric carcinoma.

Aged↗
PubMed1995

Multivariate analysis of limb long bone growth during the human prenatal period.

Prenatal development of the human limb bones (humerus, ulna, radius, femur, tibia, fibula) was studied. Cross-sectional data, consisting of 21 anthropometric measures of these bones were collected from 122 Japanese fetuses between the gestational ages of 18 and 40 weeks. Principal component analysis was applied to the data to provide multivariate assessments of morphological patterning among the variables. Three orthogonal components that accounted for 94.2% of the overall sample variation were extracted. The first component accounted for 88.2% of the variation and represented an axis of overall body size that was dependent on gestational age. The second and third components both reflected a trend in shape involving the cartilaginous parts of the humerus and femur. The findings indicated that different growth factors existed between the ossified and cartilaginous parts of fetal long bones. Multivariate allometric coefficients were extracted from the first principal component. The variables that were related to the construction of the articulate showed positive allometry, and the central widths of the diaphysis showed negative allometry compared with total size. In prenatal skeleton, certain shape changes are functionally linked to and required by changes in body size. A comparison among the coefficients of long bone length revealed that lower limb bones grew faster than upper limb bones during the period under study here. Allometric coefficients were equivalent among bones within a limb, whereas homologous bones in the upper and lower limb grew at different rates.

Bone and Bones↗
PubMed1995

The heterogeneity of microsatellite instability in multiple gastric cancers.

To obtain a better understanding of the role of genetic instability in developing gastric cancer, it is of great interest to examine microsatellite alterations in synchronous multiple gastric cancers that are thought may have the same genetic background and the same microenvironment of the stomach. We report our experience with two patients with synchronous multiple gastric cancers; patient 1 showed two carcinomas in the stomach, whereas patient 2 showed two carcinomas and two adenomas in the stomach. We examined the DNAs from the two cases for microsatellite instability and expected that the status of microsatellite instability in each tumor from the same stomach would be the same. However, patient 2 revealed heterogeneity in the microsatellite instability, i.e., an early cancer that showed some apparent alterations, whereas the other advanced cancer and two adenomas did not. On the other hand, neither of the two carcinomas in patient 1 showed microsatellite instability. To our knowledge, there has been no previous report of microsatellite instability in multiple gastric cancers. In this report, we describe a case that revealed such a heterogeneity of the microsatellite instability, in which the carcinogenic process of each tumor may undergo different genetic alterations even under the same genetic conditions and background.

Aged↗
PubMed1994

Molecular genotyping for N-acetylation polymorphism in Japanese patients with colorectal cancer.

BACKGROUND: N-acetylation polymorphism has been documented as a representative pharmacogenetic trait, and also has been implicated ecogenetically in an individual's susceptibility to cancer. However, there still remains controversy concerning the association between colorectal cancer and N-acetylation polymorphism. METHODS: A newly established molecular genotyping method using polymerase chain reaction-based restriction fragment length polymorphism to analyze the distribution of polymorphism in a large group of Japanese patients with colorectal cancer was used. RESULTS: Based on an analysis of 234 Japanese patient with colorectal cancer and 329 healthy control subjects, no significant difference was observed in either the distribution of acetylator phenotypes or of allele frequencies between the two groups. In addition, no significant difference in their distribution was found based on the age at which cancer was first detected, the location of tumors, or the histopathologic features. CONCLUSIONS: N-acetylation polymorphism does not appear to be implicated crucially as a genetic trait affecting an individual's susceptibility to colorectal cancer.

Acetylation↗
PubMed1994

Lymphokine-activated killer cell activity of peripheral blood, spleen, regional lymph node, and tumor infiltrating lymphocytes in gastric cancer patients.

Lymphokine-activated killer (LAK) cell activity of peripheral blood mononuclear cells (PBM), spleen cells (SPC), regional lymph node cells (LNC), and tumor-infiltrating lymphocytes (TIL), induced by activation with interleukin 2 (IL 2) for 4 days, was evaluated in patients with gastric carcinoma. TIL exhibited the lowest LAK activity and the cytotoxicity of LNC was significantly lower than that of either PBM or SPC. There was no difference between PBM and SPC. Then, there were significant correlations of LAK activity among PBM, SPC, and LNC, whereas poor correlations were observed in the cytotoxicity between TIL and PBM, SPC, or LNC. Phenotypic analysis of each cell population was performed before and after activation with IL 2. Before culture, the cells mediating natural killer (NK) activity such as CD16+, CD56+, and CD57+ cells were few in LNC and TIL. However, CD56+ and CD57+ cells in TIL were increased after culture. Then, CD4+Leu8+ and CD8+CD11+ cells, which identify suppressor cell function, were not elevated in LNC or TIL, as compared to that in PBM or SPC. Further, the proportions of OKIa1+ and CD25+ cells expressing T-cell activation and IL 2 receptor were uniformly increased in all cell populations after culture. These results indicate the differential reactivity of each lymphocyte population to IL 2 and fundamental dysfunction of LNC and, especially TIL, suggesting the specific influence of the local tumor environment on the lymphocyte function in the area in patients with gastric carcinoma.

Adult↗
PubMed1994

Neuroleptic malignant syndrome occurring after an emergency operation for traumatic duodenal perforation: report of a case.

Neuroleptic malignant syndrome (NMS) is a potentially fatal complication which may develop in psychiatric patients taking neuroleptic drugs. We report herein the successful treatment of a 33-year-old schizophrenic man, prescribed neuroleptic drugs, who underwent an emergency operation for traumatic duodenal perforation with a retroperitoneal infection. Five days after the operation, he began to demonstrate clinical features consistent with NMS such as high fever, abnormalities in vital signs, leukocytosis, and an elevated serum level of creatine phosphokinase; however, these findings were first presumed to be secondary to either the preexisting tissue injuries or to postoperative complications. A definite diagnosis of NMS was thus delayed until muscle rigidity and autonomic instability became evident. After a tentative diagnosis of NMS had been made, sodium dantrolene, a drug used specifically for the treatment of NMS, was administered and the patient's condition remarkably improved. Since NMS can be induced by either interrupting the course of neuroleptic drugs or by the additional administration of sedative drugs, and since its mortality rate is high if prompt and appropriate treatment is not carried out, surgeons should bear in mind the possibility of NMS developing postoperatively in psychiatric patients.

Adult↗
PubMed1994

Enhanced induction of lymphokine-activated killer activity following a single dose of cisplatin in cancer patients.

The effects of intravenous cisplatin (CDDP) administration on the generation of lymphokine-activated killer (LAK) activity in peripheral blood mononuclear (PBM) cells were investigated in cancer patients. The ability of PBM to generate LAK activity was significantly augmented 3, 5 and 7 days after a single dose, 50 mg m-2, of CDDP injection when compared to that before injection. NK activity of PBM was not altered. The distribution of lymphocyte subsets exhibited no significant change following CDDP injection, except CD2+ cells. However, the ability of monocytes in PBM to produce TNF-alpha was significantly enhanced 5 days after the drug administration, although IL-1-alpha and IL-1-beta production was not augmented.

Cisplatin↗
PubMed1994

Minimal increase in serum interleukin-6 levels during laparoscopic cholecystectomy.

The chronologic changes in the serum levels of interleukin-6 (IL-6), a mediator for acute-phase inflammation, were compared between laparoscopic cholecystectomy (LC) and open cholecystectomy (OC), since these two types of operations were considered to be a unique model for examining the role of local tissue injury in postoperative inflammatory reactions. The increase in the serum IL-6 level during LC was found to be significantly smaller than that during OC and resulted in a smaller extent of postoperative elevations for C-reactive protein. These results suggest that laparoscopic surgery associated with minimal tissue injury can help limit an increase in the serum IL-6 level during surgery, thus contributing to a reduction in surgical stress.

Biomarkers↗
PubMed1994

Lymphokine-activated killer cell function of peripheral blood mononuclear cells, spleen cells and regional lymph node cells in gastric cancer patients.

Lymphokine-activated killer (LAK) cells generated by culture of peripheral blood mononuclear cells (PBMC), spleen cells (SPC) and regional lymph node cells (LNC) with IL-2 for 4 days were examined for their functional capabilities in 29 patients with gastric carcinoma. The cytotoxic activity of LAK cells induced from LNC was significantly lower than that from either PBMC or SPC, although there was no difference between PBMC or SPC. The induction of mRNA of interferon-gamma (IFN-gamma) or tumour necrosis factor-alpha (TNF-alpha) and the production of these cytokines in the non-adherent LAK cells from LNC were also significantly reduced compared with those from PBMC or SPC. Further, the LAK cells from LNC secreted significantly lower levels of these cytokines when stimulated with tumour target, Raji cells, although the production of these cytokines was markedly increased by stimulation with the targets in all three cell populations. Phenotypic analysis of each cell population revealed a decreased proportion of the cells mediating natural killer (NK) activity, including CD16+, CD56+, and CD57+ cells in LNC either before or after culture, although OKIa1+ and CD25+ cells were uniformly increased in all cell populations after culture. Changes in subpopulations of CD4+ and CD8+ cells in LNC were not apparently different from PBMC or SPC. These results indicated the differential reactivity of each lymphocyte population to IL-2 and the reduced LAK cell function of LNC compared with PBMC or SPC in patients with gastric carcinoma.

Adult↗
PubMed1994

Morphological changes of human mandibular bone during fetal periods.

Standardized photographs (lateral and basal view) of fetal mandibles (n = 80) were taken. Outline segments (from gnathion to condylion, on the coronoid process and from infradentale to gnathion in lateral view; and on the inferior margin in basal view) were analyzed into sine curves, according to Fourier series. Using the calculated Fourier coefficients, we statistically examined how mandibular shape changed with fetal growth. Materials were classified into four groups on the basis of the body length (BL): 100 < or = BL < 200 mm (BL1, n = 20); 200 < or = BL < 300 mm (BL2, n = 20); 300 < or = BL < 400 mm (BL3, n = 20); and 400 < or = BL < or = 500 mm (BL, 4 = 20). Statistical analyses were all done on these stature groups. On the outline from gnathion to condylion, the constant and the first term phase showed statistically greater values in BL4 than in the other groups, as assessed by t-test. The first term phase for the coronoid process significantly decreased with increments in stature in the canonical disciminant analysis. On the outline from infradentale to gnathion, although the cumulative contributions of the first two terms were constant (about 85%) in all four groups, the relative contributions with growing stature decreased in the first term and increased in the second term. The mean of the phase in the first term indicated slightly more than -90 degrees in BL1, and was less than -90 degrees in BL2 to BL4. The averages of the second term phases presented little change from BL1 to BL3, and were close to -100 degrees. From the canonical discriminant analysis, the constant was great and the first term amplitude was small in BL1 and BL4, and the constant was small and the first term amplitude was great in BL2 and BL3. Also, the second term amplitude in BL4 indicated a significantly bigger volume than in BL3. The constant for the inferior margin manifested statistically significant increments in BL2 to BL4, as assessed by t-test. We interpret the results as follows: 1. On the outline from gnathion to condylion, anteroinferior shift occurs in BL4, resulting in an acute gonial angle. The change of angle during the prenatal period precedes the postnatal findings that bring about a progressive decrease in the gonial angle. 2. The tip of the coronoid process indicates a forward shift with increasing fetal body stature.(ABSTRACT TRUNCATED AT 400 WORDS)

Fourier Analysis↗
PubMed1994

Laboratory correlates of chemoimmunotherapy with low-dose recombinant interleukin-2 and mitomycin C in patients with advanced carcinoma.

Based on our clinical findings that the ability of cancer patients to generate lymphokine-activated killer (LAK) cells was remarkably augmented after mitomycin C (MMC) administration, we designed a treatment regimen that consisted of MMC 12 mg/m2, i.v. on day 1 and recombinant interleukin-2 (IL-2) 700 U/m2, i.v. every 12 hr from day 4 through day 8. Of 29 patients with advanced carcinoma treated with this regimen, 10 had a partial response (PR) and 4 had a minor response. The correlation of hematological and immunological changes associated with this treatment with the antitumor response to this therapy was investigated. Pretreatment values of total white blood cell and lymphocyte counts, and the level of increase of eosinophil counts in responder patients who showed a PR, were significantly greater than those in nonresponder patients. However, there was no correlation between clinical response and cytotoxic activities of peripheral blood mononuclear (PBM) cells, including NK and LAK activity, and the ability to generate LAK cells after the treatment. The capacity of adherent cells in PBM to produce IL-1-beta was increased after the treatment in both responders and nonresponders, whereas IL-1-alpha production was not increased. In addition, a significant increase in the ability to produce TNF-alpha was observed only in responders, indicating the correlation of TNF-alpha production with clinical response to this therapy. Since these correlations had been reported in the previous studies using IL-2, the present results suggested that the therapeutic effectiveness of this therapy against advanced carcinoma, is due to IL-2 probably augmented by its combination with MMC. In addition, these parameters might be predictive of therapeutic efficacy of this treatment.

Adult↗
PubMed1994

Production of interleukin-6 at operative wound sites in surgical patients.

BACKGROUND: Interleukin-6 (IL-6) plays a central role in the acute phase of inflammation after surgical injury. The serum concentration of IL-6 increases during an operation. The mechanisms of this increase in the serum IL-6 level, however, has not yet been fully clarified. STUDY DESIGN: To determine the possibility of production of IL-6 at the operative wound site and its regulation by humoral factors in surgical patients, the IL-6 secretion of biopsied skin obtained from an operative wound both before and after the operation were quantitated by using organ culture techniques. RESULTS: When skin explants obtained from the uninjured skin were cultivated and the amounts of IL-6 secreted into the culture medium were measured, IL-6 secretion increased exponentially during culture, which indicated that the stress of the skin incision induced IL-6 production. The skin specimens obtained from the operative wounds postoperatively secreted a significantly larger amount of IL-6 than those obtained from uninjured skin either preoperatively or postoperatively, implying that skin at the site of the operative wound had been more sensitized to produce IL-6 because of the surgical injury. The IL-6 secretion by skin explants was significantly enhanced either by tumor necrosis factor or interleukin-1, while it was inhibited by corticosteroids. CONCLUSIONS: Interleukin-6 production at the site of the operative wound is partly responsible for the elevation of the serum IL-6 level during the operation. Organ cultures of the skin explants may provide a feasible system for research on the cytokine networks in surgical patients.

Adrenal Cortex Hormones↗
PubMed1993

Chemopreventive effects of tamoxifen in ethyl methanesulphonate-induced rat mammary carcinogenesis.

Ethyl methanesulphonate (EMS), an alkylating agent and a potent mutagen, has been shown to be an effective carcinogen for the induction of mammary carcinoma in female Wistar King A rats. We therefore utilized this new system to assess the effects of tamoxifen (TAM) on mammary carcinogenesis. In Group A rats, given EMS orally for a period of 12 weeks, mammary carcinomas were first detected at the 13th week and were found in all surviving rats at the 20th week. The concomitant administration of TAM for 4 weeks, in Group B rats, retarded the development of the tumors significantly. There was a significant reduction in the incidence of estrogen receptor (ER)-positive tumors in the rats previously exposed to TAM; 100% in Group A versus 50% in Group B. Neither the progesterone receptor (PgR) nor androgen receptor (AR) status of the tumors were significantly different between these two groups. The inhibitory effects of TAM on tumor induction was also observed when TAM treatment started after EMS administration, though the intensity was smaller than that in Group B. These findings suggest the preventive action of TAM on EMS-induced mammary carcinogenesis, and indicate that this tumor system may provide a feasible model for research on chemoprevention and hormone therapy using an antiestrogen for human mammary carcinoma.

Animals↗