Biomedical subjects

T Akiyoshi

Publications and source records attributed to T Akiyoshi.

At least 163 records · Page 9Linked to original sources

PubMed1987

Natural killer cell activity in the perigastric lymph nodes from patients with gastric carcinoma or benign lesions.

Natural killer cell (NK) activity against K-562 myeloid cell line was evaluated in the perigastric lymph nodes from 60 patients with gastric carcinoma and from 35 patients with benign lesions. Lymph node cells (LNC) in either group of patients showed significantly lower level of NK activity when compared to that in peripheral blood mononuclear cells (PBM) from the same patient. In LNC, the proportions of Leu-7+ and Leu-11+ cells were significantly lower than those in PBM. In addition, LNC contained a cell population, presumably nonadherent and OKT3+ cells, which exhibit suppressor function toward NK activity of autologous PBM. These results indicate that the relative inactivity in the perigastric lymph nodes may be partially attributable to the low level of mature effector cell population mediating NK activity and, at least in part, to a coexistent population of suppressor cells.

Carcinoma↗

PubMed1987

Activated killer cell activity of spleen cells from patients with gastric carcinoma.

The activated killer cell activity of spleen cells (SPC) from patients with gastric carcinoma were assayed in comparison with those of peripheral blood mononuclear cells (PBM) from the same patient or patients with benign lesions. The cytotoxic activity induced by alloactivation in mixed lymphocyte culture (MLC) of SPC was significantly higher than that of PBM from the same patient as well as from patients with benign lesions. The cytotoxicity induced by phytohemagglutinin (PHA) activation of SPC was also significantly higher than that of PBM from the same patient. Therefore, the productibility of interleukin 2 (IL2) and the ability to generate cytotoxic cells after activation with IL 2 (LAK) were examined. Subsequently, it was found that the ability of SPC to produce IL 2 and to induce LAK cells was significantly greater than that of PBM. The results indicate that the spleen may be a potential reservoir of the precursors of these activated killer cells in patients with gastric carcinoma.

Carcinoma↗

PubMed1987

Activated killer cell activity in lymph nodes.

The activated killer cell activity of cells from the perigastric lymph nodes (LNC) in patients with gastric carcinoma or benign lesions was assayed in comparison with that of peripheral blood mononuclear cells (PBM). The cytotoxic activity induced by phytohemagglutinin (PHA) activation in LNC from patients with either carcinoma or benign lesions was significantly decreased as compared to that in PBM, although the ability to produce interleukin 2 (IL 2) in LNC was significantly increased. Therefore, the ability to generate cytotoxic cells after activation with IL 2 was examined, and decreased capacity in LNC was observed. In LNC, the proportion of OKT3+ cells was similar to that in PBM, with a prevalence of OKT4+ cells over OKT8+ cells. Also, the percentage of Leu-11+ cells was remarkably reduced. The results indicated that decreased levels of the activated killer cell activity, which might be partially attributable to the composition of lymphocyte subsets, existed in lymph nodes, and this might facilitate tumor metastasis to the regional lymph nodes.

Cytotoxicity Tests, Immunologic↗

PubMed1987

Depression of the generation of cell-mediated cytotoxicity in regional lymph nodes of patients with gastric carcinoma.

The capacity to generate cytotoxic cells in mixed cell culture was studied on the regional lymph node cells (LNC) from patients with gastric carcinoma, in comparison with that of the similar lymph node cells from patients with benign lesions. Generation of cytotoxic cells in LNC from cancer patients was significantly depressed, as compared to either that in peripheral blood mononuclear cells (PBM) from the same patient or that in LNC from patients with benign lesions, whereas no significant difference between those in PBM and LNC was observed in patients with benign lesions. The addition of LNC from cancer patients to autologous PBM did not result in suppression of the cytotoxic response. There was no significant difference between the ability to produce interleukin 2 (IL 2) in LNC from patients with carcinoma and benign lesions. However, OKT11+ and OKT3+ cells in LNC from cancer patients were significantly decreased without any alteration of the OKT4/OKT8 ratio, as compared to that from patients with benign lesions. In contrast, B-1+ cells were significantly increased. These results indicated that the relative inactivity of the generation of cytotoxic effector T cells in LNC from patients with gastric carcinoma might be partially related to the reduction of T cell population in the regional lymph nodes.

Cholelithiasis↗

PubMed1986

Protection of antiproliferative effect of cis-diamminedichloroplatinum (II) by sodium thiosulfate.

Utilizing the phytohemagglutinin (PHA) stimulation assay of human peripheral blood mononuclear cells (PBM), the protective effect of sodium thiosulfate (STS) on the antiproliferative action of cis-diamminedichloroplatinum (II) (DDP) against human cells was investigated. DDP alone significantly inhibited the proliferation of PBM over the concentration range of 10(-7) to 5 X 10(-5) M. The antiproliferative effect of DDP was significantly blocked when STS was added to the stimulation culture at the time of exposure to DDP at molar STS/DDP ratios of more than 500. However, STS at molar ratios of less than 100 induced minimal protection. Then, STS was added at various times after DDP exposure with a molar STS/DDP ratio of 1000. The protection was effective within 10 min after exposure to DDP at a concentration of 5 X 10(-5) M, whereas it was not effective beyond 30 min after the exposure. The results indicate that effective protection against DDP cytotoxicity in human cells can be achieved by the concurrent presence of STS with molar STS/DDP ratios of more than 500, but not when a molar STS/DDP ratio of less than 100 is used.

Cell Division↗

PubMed1986

Enhanced chemosensitivity of cells from malignant effusions under condition of exposure to high temperature.

Utilizing a clonogenic assay, the effects of hyperthermia and selected chemotherapeutic drugs on growth of cells from malignant effusions were studied. Fourteen of 25 samples obtained from 25 patients with various carcinomas formed at least 30 colonies per plate. Exposure of the cells to heat at 42 degrees C for 1 hr before the plating slightly inhibited the colony growth. The drugs, adriamycin (AM) and mitomycin C (MMC), were tested at 3 different concentrations. When the cells were treated with these two drugs for 1 hr at 42 degrees C, the percent of surviving colonies was significantly decreased, as compared to findings at 37 degrees C, in both groups, at 3 different concentrations. The combination of drugs and hyperthermia appeared to function synergistically in one-third of such cases. These results suggest that cells from malignant effusions in patients with various carcinomas were more sensitive to AM or MMC, under condition of a higher temperature (42 degrees C).

Ascitic Fluid↗

PubMed1986

A simplified method for determination of tritiated thymidine incorporation into cells from tissue in soft agar culture.

We designed a simple method for in vitro chemosensitivity testing of tritiated thymidine incorporation by cells from tumor tissue plated in soft agar. Cells from tumor tissue were cultured in a plastic dish, of which a Millipore membrane had been sealed to the underside, containing two layers of agar. After labeling the cells with tritiated thymidine, the dishes were placed in a boiling water bath to solubilize the agar. The labeled cells could be readily collected on the membrane by evacuating the solubilized medium through membrane filters sealed underside of the dish. Using this system, 11 (55 per cent) of 20 tumor specimens from 20 patients with various carcinomas showed an incorporation of over 200 dpm above background and 80 per cent or greater inhibition of thymidine uptake by sodium azide treatment. This method offered several advantages over the thymidine incorporation assay, including technical simplicity and a shorter time course.

Agar↗

PubMed1986

Augmentation of the generation of cell-mediated cytotoxicity after a single dose of adriamycin in cancer patients.

The effect of Adriamycin on the generation of cell-mediated cytotoxicity in the mixed cell culture was studied in patients with various carcinomas. Peripheral blood mononuclear cells (PBM) from the patients were cultured with the B-lymphoblastoid cell line Raji in mixed culture, and the induced cytotoxicity was measured by 51Cr release assay. In patients with various carcinomas, the capacity of PBM to be converted to cytotoxic cells was significantly augmented 5, 7, and 10 days after a single dose of 25 mg/sq m i.v., when compared to that of PBM obtained before Adriamycin injection. The peak level of the cytotoxicity observed 7 days after injection was more than 2-fold higher than that before treatment. Although the depletion of adherent cells from PBM either before or after treatment resulted in a decreased cytotoxic response, nonadherent cell fractions as well as unfractionated cells from PBM after drug treatment equally showed an augmented response when compared to that before injection. The distribution of T-cell subsets exhibited a significant increase in the percentage of OKT8 positive cells after administration. Furthermore, PBM obtained after treatment produced significantly higher levels of interleukin 2. The results appear to indicate that the imbalance of T-cell subsets and the increase of interleukin 2 production may be related to the augmenting effect of Adriamycin administration on cytotoxic response in cancer patients.

Cytotoxicity, Immunologic↗

PubMed1986

Cholesterol gallstones in alloxan-diabetic mice.

Normal and alloxan-diabetic male mice (Crj-ICR) were fed a diet containing 0.5% cholesterol for 5 and 10 weeks, and gallbladder bile was analyzed for cholesterol, phospholipids and bile acids, feces for sterols and bile acids, and plasma and liver for cholesterol, phospholipids, and triglycerides. Normal mice developed no gallstones but the diabetic mice developed cholesterol gallstones with an incidence of 70% by 5 weeks and 80% by 10 weeks after feeding of the cholesterol diet. Diabetic mice fed the ordinary diet also developed stones (23%) by 10 weeks. In the diabetic mice, the gallbladder was enlarged about threefold, and biliary lipid concentration, diet intake, and fecal excretion of sterols and bile acids increased but body weight decreased. Cholic acid and beta-muricholic acid comprised over 40% each of the total biliary bile acids in normal mice, but cholic acid increased to about 80% and beta-muricholic acid decreased to a few percent in the diabetic mice. Fecal excretion of bile acids increased after cholesterol feeding in both normal and diabetic mice, but the increased bile acid in the normal animals was beta-muricholic acid and that in the diabetic mice was deoxycholic acid. The mice that developed gallstones showed a marked increase in biliary cholesterol value and decreases in gallbladder bile and bile acid concentration, but no difference in biliary and fecal bile acid composition, bile acid synthesis, fecal sterols, or plasma and liver lipid levels. Cholesterol absorption was increased in the diabetic mice when examined by plasma 14C/3H ratio and fecal 14C-labeled sterol excretion after a single oral administration of [14C]cholesterol and a simultaneous intravenous injection of [3H]cholesterol. These data led to the conclusion that cholesterol gallstones developed in alloxan-diabetic mice fed excess cholesterol, due to the hyperphagia and the enhancement of cholesterol absorption caused by increases in the synthesis and secretion of cholic acid.

Administration, Oral↗

PubMed1985

In vitro effect of interleukin 2 on depression of cell-mediated immune response after surgery.

Effect of exogenous interleukin 2 (IL 2) on the postoperative depression of cell-mediated immune response in vitro was studied in 8 patients with benign lesion and 11 patients with various carcinoma, undergoing major surgical procedures. When peripheral blood mononuclear cells (PBM) were obtained from patients 3 days after surgery, the proliferative response of PBM in mixed lymphocyte culture (MLC) was significantly decreased, as compared to that before operation. The depressed proliferative response was significantly increased and improved to the preoperative level, when exogenous IL 2 was added at a concentration of 50 per cent in culture. The defective generation of cytotoxic cells in MLC 3 days after operation was also significantly augmented and improved to the preoperative range by addition of 25 per cent IL 2 in culture. IL 2 produced minimal increase in these responses when PBM were obtained preoperatively. There was no significant difference between each value in these responses obtained from patients with benign lesion and carcinoma. These results show that PBM from patients who had undergone major surgery were responsive to exogenous IL 2. The postoperative depression of cell-mediated immune response may be reversible with exogenous IL 2.

Carcinoma↗

PubMed1985

Biliary excretion of latamoxef and N-methyltetrazolethiol in humans and rats.

The biliary excretions of latamoxef and N-methyltetrazolethiol (NMTT) were studied in patients with T-tubes inserted in their common bile ducts, and in bile fistulated male rats. The highest concentrations of latamoxef and NMTT in 6 patients with cholelithiasis were obtained 1-2 h after intravenous injection of a single 1-g dose, and the mean peak values were 66.2 and 0.85 microgram/ml, respectively. The values in patients with gallbladder carcinoma or pancreas head carcinoma were much lower than those with cholelithiasis. The biliary excretions of latamoxef and NMTT in rats were much higher and faster than in humans, with the highest levels being obtained within 30 min after injection. About 20% of the injected dose was recovered as latamoxef and 4% as decomposed materials in 2.5 h after injection. Latamoxef was not decomposed in human or rat bile when kept at -20 degrees C for 4 weeks if the pH was adjusted to 6; some decomposition occurred (10-20%) if the pH was not adjusted.

Animals↗

PubMed1985

Altered bile acid metabolism in nonobese, spontaneously diabetic (NOD) mice.

Cholesterol and bile acid metabolism was examined in nonobese, spontaneously diabetic (NOD) female mice before and after the development of diabetes. After the development of glucosuria, the plasma and liver cholesterol levels, gallbladder bile weight after 5-h fasting, biliary cholesterol, phospholipid and bile acid concentrations, the lithogenic index, the pool size of bile acids, and fecal sterol excretion markedly increased, but fecal bile acid excretion and fractional turnover rates for the cholic acid and chenodeoxycholic acid groups decreased. The distribution percentage of bile acids in the small intestine did not change, but it increased in the gallbladder and decreased in the large intestine. One striking finding was a change in the bile acid composition: increases were recorded in cholic and deoxycholic acids while decreases occurred in bile acids derived from chenodeoxycholic acid, such as beta-muricholic and ursodeoxycholic acids in the bile and alpha-muricholic, beta-muricholic, omega-muricholic, and hyodeoxycholic acids in the feces. Therefore, the cholic acid group/chenodeoxycholic acid group (CA/CDCA) ratio increased in the bile, feces, and small and large intestines after the development of diabetes. These changes were very similar to those observed in alloxan-treated mice, suggesting that the changes found in NOD mice are caused by insulin deficiency.

Animals↗

PubMed1985

Augmentation of the cell-mediated cytotoxic response induced in mixed cell culture by adriamycin.

The effects of adriamycin (AM) on the generation of cell-mediated cytotoxicity in primary stimulation cultures of human peripheral blood mononuclear cells (PBM) with B-lymphoblastoid cell line Raji were assessed. When AM was added to the culture on day 1 for 24 hr at a concentration of 10(-8)M, the cell-mediated cytotoxic response was significantly augmented as compared to that in untreated culture. The augmented cytotoxic response was significantly depressed when unfractionated cells harvested from untreated culture were added to the effector cells from AM-treated culture. The response was slightly more reduced by addition of cells from untreated culture after treatment with OKT3. However, the addition of cells from untreated culture after removal of adherent cells resulted rather in an increase of the cytotoxic response. When adherent cell fraction was removed from the effector cells, the cytotoxic response in nonadherent fraction from AM-treated culture was similar to that observed in unfractionated cells from the same culture. On the other hand, nonadherent fraction from untreated culture gave an increased cytotoxic response, which was of almost the same magnitude as that of cells from the augmented, AM-treated culture. These results suggested that the augmentation of cytotoxic response observed in AM-treated culture might be due to inhibition by AM of the generation of suppressive activity in the adherent cell population during PBM-Raji cell culture.

Antibodies, Monoclonal↗

PubMed1985

Impaired production of interleukin-2 after surgery.

The capacity of peripheral blood mononuclear cells (PBM) to produce interleukin-2 (IL-2) was studied serially before and following operation in patients undergoing various surgical procedures. In patients who had major surgery, significant decrease in IL-2 activity was observed 1, 3 and 6 days after operation as compared to that before surgery, although there was no significant change throughout the post-operative course in patients undergoing minor surgery. IL-2 activity returned to the pre-operative level by the 8th post-operative day. However, it remained significantly depressed 8 days after surgery in patients who had undergone major surgical procedures of more increasing severity. Distribution of T cell subsets, especially OKT4 positive cells, did not differ significantly from the pre-operative value throughout the post-operative course. However, the depressed production of IL-2 3 days after surgery could be abolished when adherent cells were removed from PBM by plastic adherence procedures. These results indicated that adherent cells, but not quantitative change in T cell subsets, might be responsible for the depression of IL-2 production after surgery.

Cell Adhesion↗

PubMed1984

Scanning electron microscopic structure of the finger print as related to the dermal surface.

This paper aims to clarify the relationship of the dermis to epidermal ridge configuration. After fixation, human fingertip epidermis was peeled off from the dermis by alkaline treatment, and the dermal surface was observed with the scanning electron microscope (SEM). The SEM pattern of furrows, grooves, and papillae showed an exact negative fingerprint image. Papillae had various sizes and complicated shapes and were arranged continuously but irregularly on each side of the furrow. Size and shape variabilities were not dependent on the site of the fingerprint region. The papilla number tended to increase with age due to derivation of secondary papillae from the primary papilla as well as new formation of small papillae. The dermal surface exhibited some site-specific fibrous appearance at the furrow and papilla, whereas the surface was smooth at the groove. The characteristics of the dermal surface structure as related to the epidermis can be explained by a stronger dermis-epidermis adhesion at the furrow than at the papilla or at the groove.

Dermatoglyphics↗

PubMed1984

A trial of adjuvant combination chemoimmunotherapy for stage III carcinoma of stomach.

A chemoimmunotherapy program designed on the basis of experimental results was administered to 27 patients with stage III carcinoma of stomach following curative resection. The treatment regimen consisted of active immunotherapy with Vibrio cholerae neuraminidase (VCN)-treated autologous tumor cells admixed with bacillus Calmette-Guérin (BCG) and chemotherapy with drugs such as cyclophosphamide (CY), mitomycin C (MMC), and 5-fluorouracil (FU) which proved to enhance the immune response when administered at optimal dose and timing. Then, it was followed by long-term administration of tegafur (FT) and immunomodulators. This treatment significantly improved survival when compared to that of 41 historical control patients treated with surgery alone (P less than 0.001). As compared to 31 control patients concurrently treated with a bolus dose of MMC followed by long-term FT and immunomodulators, survival had a tendency, but not significantly, to be improved in patients treated with this therapy (P less than 0.1). However, the survival rate at 4.5 years was significantly higher than that of control patients (P less than 0.01). These results appeared to show that this type of adjuvant combination chemoimmunotherapy may be of benefit for this group of patients with gastric carcinoma.

Adult↗

PubMed1984

Immunodepression after surgery: impaired production of interleukin 2.

The capacity of peripheral blood mononuclear cells to produce interleukin 2 (IL 2) was studied serially before and after various surgical procedures in 34 patients. In the group of 6 patients who had minor surgery and were categorized into class 1, IL 2 activity did not differ significantly from the preoperative value, throughout the postoperative course. In the group of 14 class 2 patients who underwent major surgery, however, significant decreases in IL 2 activity were observed 1, 3 and 6 days after operation as compared to findings before surgery. Preoperative levels were reverted to by the 8th postoperative day. The remaining 14 patients underwent major and extensive surgical procedures, and were put into class 3. Here too, were also significant decreases in the activity 1, 3 and 6 days after operation. The activity remained significantly depressed 8 days after surgery, in this group of patients. These results show that depression in the production of IL 2 in postoperative surgical patients correlates relatively well with the extent of the surgical procedures.

Animals↗

PubMed1984

Combination chemoimmunotherapy for advanced gastric carcinoma.

Eighty-nine patients with advanced gastric carcinoma were treated with a combination chemo-immunotherapy regimen that consisted of active immunotherapy with Vibrio cholerae neuraminidase (VCN) treated autologous tumor cells admixed with BCG and drugs including cyclophosphamide, mitomycin C (MMC) and 5-fluorouracil, followed by long term tegafur (FT) and immunomodulators. This treatment significantly improved survival rate of patients in Stages III, IV and unresectable or recurrent carcinoma, compared to that of historical controls. As compared to controls treated with MMC followed by long term FT and immunomodulators concurrently, survival rate of those in Stage III tended to improve (P less than 0.1) and survival rate at 4.5 years in Stage III was significantly higher (p less than 0.01), although it was not improved in Stage IV. In patients with unresectable or recurrent tumor, survival time was not significantly lengthened with this therapy when compared with that in patients given BCG alone in the same treatment schedule (CCI-BCG group). However, none of 19 patients in CCI-BCG group survived more than 15 months, although 4 of 28 patients receiving this therapy survived. These results suggest that this combination chemo-immunotherapy is effective for a selected group of patients with advanced gastric carcinoma.

Adjuvants, Immunologic↗