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Biomedical subjects

K Fukao

Publications and source records attributed to K Fukao.

At least 163 records · Page 9Linked to original sources

[Measurement of microsomal function in hepatectomized rat].

Trimethadione (TMO) is exclusively metabolized to dimethadione (DMO) by cytochrome P-450 dependent mono-oxygenase in liver microsomes. We have chosen TMO as an indicator compound for estimating the microsomal function of the liver. TMO tolerance test was performed in the CCl4 intoxicated injury or 68% partial-hepatectomized rats. Serum DMO/TMO ratios in 2 hours following oral administration of TMO in these rats in vivo were well correlated with changes in content of hepatic cytochrome P-450 and activity of TMO N-demethylase in vitro. TMO tolerance test could also determine quantitatively the changes of the functional capacity of the liver in the 68% partial hepatectomy. These results suggest that TMO tolerance test is a useful tool for the surgical indication in the hepatectomy.

Animals↗

[Monoclonal antibody to human pancreatic carcinoma cells].

A monoclonal antibody (MoAb, SK-930) of the IgG2a subclass to human pancreatic carcinoma cells (MIA-PaCa 2) was obtained by hybridization of spleen cells from immunized Balb/c mice with murine myeloma cells. SK-930 was investigated for reacting in indirect immunofluorescence on FACS against a panel comprising 12 types of different origin. SK-930 reacted with seven out of 11 tumor cells and with one PBL. Immunoperoxidase techniques (ABC method) showed that SK-930 antigen was present on pancreatic adenocarcinoma cells, but could not be detected on normal pancreatic tissue. Immunoprecipitation experiments and SDS-PAGE analysis revealed that SK-930 recognized 134K dalton peptide on tumor cells. These results suggest that SK-930 reacts with a novel pancreatic cancer-associated antigen.

Antibodies, Monoclonal↗

Sheep red blood cell receptor and the epitope detected by Leu-5 monoclonal antibody in primates.

The expression of the epitope detected by the monoclonal antibody Leu-5 and the rosette formation with sheep red blood cells was examined for the mononuclear cells of 25 primate species including human subject. The plot of rosette-forming cells against Leu-5-positive cells enabled us to classify these species into three large groups: hominoids--Old World monkeys (Leu-5-positive cells greater than or equal to rosette-forming cells), New World monkeys (Leu-5-positive cells less than rosette-forming cells), and prosimians (Leu-5-positive cells less than 5%, some of them with both Leu-5-positive cells and rosette-forming cells less than 5%).

Animals↗

Epitope expression on primate lymphocyte surface antigens.

The cross-reactivity of peripheral blood mononuclear cells from 28 nonhuman primates was investigated with ten kinds of Leu series of monoclonal antibodies specific to human T-, natural killer/killer-, and B-cells. The chimpanzees possessed all ten epitopes examined but the orangutan lacked Leu4 and Leu7 epitopes and the gibbons lacked Leu4, Leu7, and Leu12 epitopes. In addition to the above epitopes, the Old World monkeys lacked Leu1 and Leu10 epitopes. The Leu3a/Leu2a cell ratios varied from 0 to 1.56 among the 12 macaque species and this enabled classification of these species into three groups. In the New World monkeys, Leu2a epitope was absent, whereas Leu11a epitope was detected in several species and Leu3a epitope was found only in the owl monkeys. The prosimians expressed only HLA-DR epitope.

Animals↗

Mutagenicity of cyclosporine. Induction of sister chromatid exchange in human cells.

To examine whether cyclosporine (CsA) has mutagenic potential against human cells, we analyzed sister chromatid exchange (SCE) induction by CsA using human lymphocytes in vitro. SCE frequencies increased significantly in the lymphocytes treated with 1 microgram/ml and 5 micrograms/ml CsA, though the frequencies seemed to be less than one hundredth of those induced by mitomycin C (MMC). The value of induced SCE depended on CsA concentration. This result indicates that CsA has SCE inducibility. The data also suggest that CsA has a mutagenic effect on human lymphocytes.

Adult↗

Hepatic coma and amino acids in the nerve endings of the central nervous system.

The levels of amino acids in the cerebral cortex and synaptosomes of 6 autopsied patients who had died of chronic liver diseases with portasystemic shunt were examined and compared with those of controls. The level of threonine in the cerebral cortex and synaptosomes of the 6 patients, who had developed hepatic coma before death, was significantly higher than that of 9 patients without hepatic coma. However, the levels of the neurotransmitters, aspartate, glutamate, and glycine, showed no significant difference between the two groups. In animal experiments, threonine uptake into the synaptosomes was enhanced by an increase of threonine concentration in the cerebral cortex, and at the same time ammonia further promoted threonine uptake. The high level of threonine in the synaptosomes was released just like a neurotransmitter on potassium stimulation in the patients with hepatic coma. Since threonine has no post-synaptic action, it is thought that threonine released in this way somehow interferes with brain action. This phenomenon may play an important role in the development of hepatic coma.

Amino Acids↗

The generation of interleukin-2-dependent suppressor T-cells from patients with systemic metastasis of gastric carcinoma and the phenotypic characterization of the cells defined by monoclonal antibodies.

Suppressor cells, which might be activated in patients with gastric carcinoma, were successfully enriched by the use of interleukin-2 (IL-2) prepared from human tonsils and spleens. That is, peripheral blood lymphocytes cultured for 3 or 4 weeks with IL-2 strongly inhibited the patient's own lymphocyte-proliferative responses to alloantigen or phytohemagglutinin (PHA). Quantitative fluorescence measurement for immunologic analysis of phenotypic characterization of the cells was made on FACS-IV with monoclonal antibodies anti-Leu-1 anti-Leu-2a, anti-Leu-3a, anti-Leu-4, anti Leu-5, anti-Leu-7, and anti-HLA-DR and goat anti-human immunoglobulin (Ig). Functional suppressor T-cells expanded with IL-2 showed the following phenotype: Leu-1+ Leu-2a+, Leu-3a-, Leu-4+, Leu-5+, Leu-7-, HLA-DR+, human Ig-. The IL-2-dependent suppressor T-cells could be obtained only when the cells were derived from patients with systemic metastasis of gastric carcinoma. These findings suggest that generation of IL-2-dependent suppressor T-cells is the result of large tumor burdens; this may exert negative cellular control in the immune responses, thus inducing the status of the lower cell-mediated antitumor immunity, and may promote cancer progression in gastric cancer patients.

Adult↗

[Study of cellular autofluorescence of cultured human cancer cell lines using a fluorescence-activated cell sorter (FACS-IV)].

Quantitative cellular autofluorescence measurement of viable cultured human cancer cells and freshly prepared peripheral blood lymphocytes (PBL) obtained from gastric cancer patients and their cultured PBL with T-cell growth factor (CTC) was undertaken on a FACS-IV. The number of cells with fluorescence and its intensity were significantly higher in CTC than in PBL (p less than 0.001). It can be seen that cancer cell lines have different amounts of autofluorescence in values of individual cells. Although the autofluorescence intensity in cancer cells was generally low, one cell line (SC-1) displayed a higher autofluorescence (7.2%) than the others. Our preliminary results suggest that autofluorescence measurement of cells excited by laser beam for early detection of cancer may be limited, and further induction of highly advanced biological techniques will be needed.

Cell Line↗

[Culture of TCGF-dependent immunosuppressor T cells in gastric cancer patients and phenotypic characterization of the cell surface, using monoclonal antibodies and a fluorescence-activated cell sorter (FACS)].

We cultured immunosuppressor T cells from gastric cancer patients using T-cell growth factor (TCGF) prepared from human tonsil or spleen. Peripheral blood lymphocytes cultured for 3-4 weeks with TCGF strongly inhibited the lymphocyte-proliferative response to alloantigen or PHA. Quantitative fluorescence measurement for immunological analysis of phenotypic characterization of the cells was made on a FACS-IV, using monoclonal antibodies (anti Leu-I, anti Leu-2a, anti Leu-3a, anti Leu-4, anti Leu-5, anti Leu-7, anti HLA-DR) and goat anti-human immunoglobulin. Immunosuppressor T cells grown in the presence of TCGF showed phenotype Leu-1+, 2a+, 3a-, 4+, 5+, 7-, HLA-DR+, human Ig-. Culture of immunosuppressor T cells activated by tumor cell antigen in vitro was successful only when the cells derived from patients with disseminated, nonresectable type of gastric carcinoma. Our findings suggest that TCGF-dependent immunosuppressor T cells are the result of a large tumor burden; this may explain the depression of in vitro or in vivo cell-mediated immune responses frequently found in such cancer patients.

Adult↗

[Tissue concentration of 5-FU following pre-operative administration of FT-207].

Forty patients with gastric cancer and 30 patients with colon cancer were administered FT-207 prior to the operation. The relation between a total dose (4-88g) and tissue concentration of 5-FU was investigated and the following results were obtained. (5-FU concentration was measured with the method of Gas chromatography mas fragmentography) 1) The relation between total doses of FT-207 (x) and concentration of 5-FU in the tissue (y) was demonstrated by the formula: y = 0.00317x + 0.025 (gastric cancer) r = 0.519, p = 0.0001 y = 0.0019x + 0.043 (colon cancer) r = 0.641, p = 0.0001 2) In most of the patients with rectal cancer who received radiation therapy prior to the operation, 5-FU concentration in the tissue was extremely low. 3) 5-FU concentration showed no difference between the normal and metastatic lymph nodes, or among the lymph node groups. Administration methods (oral intake or suppository) had no influence on the concentration of 5-FU. 4) Among the organs, 5-FU concentration was higher in the following orders: liver, normal mucosa, lymph node, tumor, normal serosa. 5) In five autopsy cases, 5-FU concentration of the tissue show a great difference among them, and some cases showed 10 times as high concentration as others in the tissue of every organ.

Female↗

Severe aplastic anaemia treated with anti-lymphocyte globulin. The relationship between clinical course and erythroid colony suppression by T cells.

A 6-year-old girl with severe aplastic anaemia improved promptly after treatment with anti-human lymphocyte globulin (ALG). Blood T lymphocytes were proved to have a suppressive effect on erythroid colony formation. ALG was administered intravenously at a dose of 15 mg/kg/d for 5 d. By the 14th d she showed a prompt increase in the reticulocyte count. Within the next 2 weeks slight increase of the platelet count was observed while the neutrophil count remained unchanged. The suppressive effect of T cells on erythroid colony formation weakened when the reticulocyte count exceeded 100 X 10(9)/l. About 4 months after administration of ALG, a decreased reticulocyte count was observed along with frequent nasal bleeding. Again the T cells exhibited a suppressive effect on erythroid colony formation. The results of serial co-culture studies revealed a close correlation between the T-cell suppressive effect on erythroid colony formation and reticulocyte response. The findings suggest an immune-mediated mechanism for the haematopoietic disorder in this patient.

Anemia, Aplastic↗

Gross appearance of carcinoma of the main hepatic duct and its prognosis.

Twenty-three patients with carcinoma of the hepatic hilus, including the upper one-third of the extrahepatic bile duct, were treated by surgical resections. Gross appearances of this lesion are classified into polypoid, nodular, schirrhous constricting and diffusely infiltrating types. Each type has a different resectability and prognosis from the macroscopic point of view. The cell type in all patients was adenocarcinoma. Operation was curative in 100 per cent of four patients with the polypoid type. The chance for survival was definitively better for patients with this type than with the other three. Preoperative percutaneous transhepatic cholangiography as well as endoscopic retrograde cholangiography and celiac angiography can provide an excellent index to the resectability of the tumor and prognosis. Our experience suggests that gross appearance of the tumor may be valid as a prognostic factor in the treatment of the lesion.

Adenocarcinoma↗

A new device for barium-enema examination following colostomy.

The authors developed a colostomy appliance for use during barium-enema examinations. It is 8 cm in diameter and 4 cm in height, and is made of acrylic resins. With the use of this device, 21 patients were fluoroscopically examined through the stoma; good contrast views of the lower intestinal tract were obtained in all cases without leakage of barium or air.

Barium Sulfate↗