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Biomedical subjects

K Inada

Publications and source records attributed to K Inada.

At least 37 records · Page 2Linked to original sources

Development of liver metastasis in colorectal carcinoma. With special reference to venous invasion and basement membrane laminin.

The development of hepatic metastases in 344 patients with colorectal carcinoma was examined for correlation with the presence of both venous invasion by the primary tumor and basement membranes in the tumor tissue. The former was detected by Victoria blue and hematoxylin-eosin staining and the latter by antilaminin antibody. A significant difference in the incidence of venous invasion was noted between patients with and those without liver metastasis at surgery. Basement membrane deposition was found in half of all cases of well differentiated adenocarcinoma, which was significantly high compared with other tumor types. This was more distinct in metastatic foci in the liver and lymph nodes than in the primary lesion, but less marked in intravascular tumor tissue. Basement membrane deposition was seen more frequently in Dukes' A tumors than in B tumors, although this was not statistically significant. No relationship was found between basement membrane laminin positivity and five-year survival, nor was there any correlation between the incidence of liver metastasis and tumor histologic type. Venous invasion was considered to be intimately related to the development of liver metastasis. Deposition of laminin-positive basement membrane was dependent on the grade of tumor differentiation, whereas it had no direct relation to the development of liver metastasis.

Basement Membrane

A large amount of endothelin-1 is present in human breast cancer tissues.

Endothelin (ET)-1 concentration was measured in tissue extracts from 157 human breast cancers, 26 benign breast tumors and 10 normal breast tissues. ET-1 was detectable in all tissue extracts by specific radioimmunoassay, the concentration ranging from 0.12 to 11.95 pg/mg protein. ET-1 concentration was significantly higher in tissue extracts from breast cancer than in those from benign breast tumor or normal control tissue, suggesting that this peptide is synthesized by breast cancer cells. When 157 breast cancer specimens were categorized into 4 groups in terms of clinical staging, no significant difference was found among these clinical staging groups. Furthermore, no significant associations were observed between ET-1 concentrations and the age of patients, tumor size, lymphnode involvement, histological type or steroid hormone receptor status.

Adult

[A report on 107 cases of obturator nerve block].

The obturator nerve passes in close proximity to the inferolateral bladder wall. Transurethral resection of bladder tumors close to these areas may stimulate the obturator nerve, causing violent adductor contraction and possible inadvertent bladder perforation. To avoid this reaction, local anesthetic blockade of the obturator nerve as it passes through the obturator canal is effective to stop adductor spasm during spinal anesthesia. We performed obturator nerve block in 107 cases by use of insulated needle and nerve stimulator, and measured the depth of the obturator nerve and that of the pubic tubercle. Obesity index was positively correlated with the depth of the obturator nerve as well as the pubic tubercle. However, no correlation was found between the obesity index and the difference of the depth of the obturator nerve and the depth of the pubic tubercle. It is suggested that if the needle is advanced in the direction of the obturator canal about 40mm further after reaching the pubic tubercle, the needle reaches the obturator nerve.

Adult

[Production of IL-6 and IL-1 alpha by human corneal epithelial cells].

By using enzyme-linked immunosorbent assay (ELISA), it was demonstrated that cultured human corneal epithelial cells produced interleukin-6 (IL-6) without any stimulation. As lipopolysaccharide (LPS)-stimulation did not induce further production of IL-6 and IL-1 alpha, it was suggested that IL-6 was produced naturally as in the case of IL-1 alpha production which has been previously reported by the author. Production of IL-1 alpha and IL-6 in the human corneal epithelial cells may play a role in amplifying immune responses on the ocular surface.

Adult

Lymphocytes in thymoma: association with myasthenia gravis is correlated with increased number of single-positive cells.

In the normal thymus the number of lymphocytes and the proportion of CD4+CD8+ double-positive cells decrease as a function of age. Six thymomas in elderly patients without myasthenia gravis had a large number of double-positive T cells, as seen in the normal thymic cortex. This suggests that the epithelial cells of thymoma have the function of cortical epithelium and can induce precursor T cells to differentiate to the double-positive stage but not further. In seven thymomas with associated myasthenia gravis, however, there was a conspicuous population of mature single-positive T lymphocytes. These mature T cells may include autoreactive T cells.

Adult

The clinical significance of venous invasion in cancer of the stomach.

Specimens from 235 surgically treated cases of gastric cancer were examined for venous invasion in order to investigate its clinical significance. A total of 87 (37.0 per cent) cases showed histologic evidence of venous invasion, with the incidence being 48.3 per cent of 180 cases, after the exclusion of 55 cases where cancerous invasion was limited to the mucosa. The frequency of venous invasion varied with the gross type of tumor, the depth of penetration and the degree of differentiation, being highest in tumors of type 2 and moderately differentiated adenocarcinoma. It increased proportionately depending upon the depth of penetration and the incidence increased in cases where there was evident lymphatic invasion or lymph node metastasis. The long term survival rate significantly decreased in patients with venous invasion when compared to those without it. In this report, we also discuss the marked difference in the incidence of liver metastasis between gastric and colorectal carcinomas in relation to venous invasion of the primary tumor. Double staining with Victoria blue and hematoxylin-eosin for elastic fibers proved useful for detecting venous invasion in the carcinomatous tissue, though endothelial markers have great specificity for differentiating small veins from lymphatics.

Adenocarcinoma

[Advances of immunohistochemistry and its application to histopathology--studies on liver metastasis of colorectal carcinoma--venous basement membrane laminin].

Recently developed immunohistochemical techniques are revolutionizing surgical pathology. Although much has been written describing sensitivity and specificity of reagents in the relationship to given diagnoses, little has been published regarding the evaluation in diagnostic histopathology. Of 4905 cases, immunohistochemical stains were done in our laboratory on 108 cases in 1988. Forty three markers of different kinds were used for 266 specimens. The mean number of markers used in one case was 2.5. Evaluation study of these cases revealed good to limited diagnostic value of immunohistochemical procedures in about 70% of those cases, but no diagnostic value in approximately 30% of the cases. Relationship between venous invasion and basement membrane was investigated to clarify the mechanism of liver metastasis of the colorectal carcinoma by histologically and immunohistochemically using the anti-laminin antibody. Ninety cases of colorectal carcinoma with liver metastasis were studied. Venous invasion was found in 60 of 66 cases of synchronous liver metastasis, and in 14 of 24 cases of metachronous liver metastasis. Venous invasion was considered highly significant to development of liver metastasis, though there was a definite difference in several aspects between the two groups. Well-defined laminin-containing basement membrane was found in the primary tumor in 35 of 90 cases and in metastatic foci in 15 of 28 cases in which examination was performed. It was most frequently seen in well differentiated adenocarcinoma, though statistically not significant compared to moderately differentiated adenocarcinoma. No definite correlation was found between development of liver metastasis and basement membrane associated tumor cells.

Adult

Endotoxic properties of chemically synthesized lipid A analogs. Studies on six inflammatory reactions in vivo, and one reaction in vitro.

Biological activities of two groups of synthesized lipid A analogs, the counterpart of biosynthetic precursor, Lehmann's Ia type, 406, and E. coli lipid A type, 506, as well as their non-phosphorylated, and mono-phosphorylated analogs were investigated. The activities employed included four bone marrow cell reactions in mice, mice skin reaction, leukocytes migration in rabbits' cornea, and hemagglutination. Compound 406 and 506 elicited bone marrow reactions in mice and hemagglutination of mouse RBC, although 406 failed to elicit hemorrhage and necrosis also in mice skin. Compound 406 did not elicit corneal reaction in rabbits. The results suggest that for elicitation of this reaction and mice skin reaction, acyloxyacyl structure is required. Cytotoxicity and thromboplastin production of four bone marrow reactions had been reported by us to be endotoxic reactions, since these had not been elicited by peptidoglycan of Lactobacillus and Staphylococcus (1981) and 300 series synthesized analogs (1984) which did not have endotoxic structures. From these results, it seems that these two marrow reactions and hemagglutination require, as does the limulus test, the lipid A part structure as is present in 406.

Animals

[Estrogen dependent plasminogen activator in breast cancer cells; experimental and clinical studies].

Hormonal regulation of plasminogen activator (PA) in rat mammary tumor induced by 7,12-dimethylbenz (a) anthracene (DMBA) was studied both in vivo and in vitro. PA activity in DMBA-tumor was markedly decreased by ovariectomy, and recovered in a dose-dependent fashion upon estradiol administration. This estrogen-stimulated production of the enzyme was prevented by actinomycin D, cycloheximide and tamoxifen. Furthermore DMBA-tumor cells in primary culture displayed similar estrogen-dependency toward the production of the enzyme without any cell proliferation. This indicates that estrogen might regulate de novo synthesis of PA at a transcriptional level via an estrogen receptor system, and that this hormone might support the growth of DMBA-tumor into adjacent tissues by inducing PA in a direct manner via a route distinct from a prolactin pathway. To examine whether PA reflects the functional state of estrogen receptors in human breast cancer, the enzyme activities were determined in extracts prepared from 160 breast cancer specimens and compared on qualitative and quantitative bases with the levels of steroid receptors. The results strongly suggest that PA can be used as an effective functional marker for hormone dependence in human breast cancer.

9,10-Dimethyl-1,2-benzanthracene

Enhancement of in-vitro granulopoiesis and induction of differentiation of M1 cells by a glucocorticoid-dependent factor produced from P388D1 cells.

P388D1 cells, a macrophage (M luminal diameter) cell line, cultured after stimulation by lipopolysaccharide (LPS), produced a glucocorticoid (GC)-dependent hemopoietic activity. The activity, when coexistent with hydrocortisone (HCS), increased the number of granulocyte (Gr) colonies 2-3 times more than that formed by CSF alone. HCS scarcely increased the number of Gr colonies stimulated with CSF. We designated this activity as GC-dependent myelopotentiator (GDMP). GDMP activity was partially purified by FPLC using Superose 12 and Mono Q columns. The molecular weight of GDMP was calculated as about 55 kD. GDMP activity was distinct from CSF and interleukin 1 (IL 1) found in the culture supernatant. GDMP was associated with the activity inducing differentiation of myeloleukemic M1 cells in the presence of HCS. The activity inducing differentiation of M1 cells and GDMP activity were absorbed with M1 cells preincubated with HCS, but not by the cells preincubated with medium alone. Thus, HCS may have induced GDMP receptor on M1 cells and the M1 cells were differentiated by GDMP. These results suggest that both normal Gr precursor cells and myeloid leukemic cells are differentiated by GDMP and HCS by the same mechanism.

Biological Products

Effects of intermittent pneumatic leg compression for prevention of postoperative deep venous thrombosis with special reference to fibrinolytic activity.

The mechanism of intermittent pneumatic leg compression for prevention of postoperative deep venous thrombosis was investigated. The incidence of postoperative deep venous thrombosis was studied using iodine-125 fibrinogen in 64 patients with malignant disease who had intermittent pneumatic leg compression for 48 hours postoperatively. Changes in euglobulin lysis time and B beta 15-42 peptide were investigated before and after operation in 16 patients with benign disease, in 27 patients with malignant disease who did not have postoperative intermittent pneumatic leg compression, and in another 29 patients with malignant disease who had postoperative intermittent pneumatic leg compression. The overall incidence of deep venous thrombosis was 6.25 percent. A prolongation of euglobulin lysis time was found postoperatively in all three groups, which was significant in malignant disease groups, although less significant in the group with intermittent pneumatic leg compression when compared with the benign disease group. Preoperatively, a significant increase in B beta 15-42 peptide was found in patients with malignant disease when compared with patients with benign disease. Postoperatively, the B beta 15-42 level increased in the same pattern in all groups and no significant differences in the levels were found among them. A significant shortening of euglobulin lysis time by intermittent pneumatic leg compression, in addition to its hemodynamic effects, is considered an important factor in the prevention of postoperative deep venous thrombosis.

Female

Identification of Re lipopolysaccharide-binding protein on murine erythrocyte membrane.

Our recent studies have suggested that bacterial lipopolysaccharide (LPS) attaches to Pronase-sensitive proteins on the murine erythrocyte membrane. In the present study, in order to identify the LPS-binding protein on the murine erythrocyte membrane, a unique method to detect LPS-binding protein on a nitrocellulose membrane was developed. Murine erythrocyte membrane proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, then transferred electrophoretically onto a nitrocellulose membrane. The membrane was incubated with LPS of Salmonella minnesota R595 (Re LPS) in phosphate-buffered saline (PBS), after the remaining sites were blocked with gelatin in PBS. We were able to obtain a non-background stain by adding the nonionic detergent octylglucoside at the low concentration of 0.1% to the Re LPS solution. The Re LPS bound to the protein on the nitrocellulose membrane was exposed to affinity purified anti-Re LPS antibodies (IgG) and then to alkaline phosphatase-conjugated anti-IgG. The alkaline phosphatase was detected on the membrane by an enzymatic reaction. This method demonstrated that Re LPS was bound to an erythrocyte protein of 96 kDa. Treatment of erythrocytes with Pronase led to disappearance of the Re LPS-binding protein on the erythrocyte membrane. There was no difference between LPS-responder and LPS-nonresponder murine erythrocyte membranes in amount and molecular weight of the Re LPS-binding protein.

Animals

Importance of fatty acid substituents of chemically synthesized lipid A-subunit analogs in the expression of immunopharmacological activity.

The immunopharmacological activities of chemically synthesized lipid A-subunit analogs, 4-O-phosphono-D-glucosamine derivatives carrying different N- and 3-O-linked acyl groups, were investigated. None of the synthetic compounds tested exhibited any detectable pyrogenicity at a dose of 10 micrograms/kg. Weaker lethal toxicity in galactosamine-sensitized mice was detected at 1 microgram per mouse for all the synthetic compounds except GLA-58. Among (RS) stereoisomers of 4-O-phosphono-D-glucosamine derivatives carrying a 3-O-tetradecanoyl (C14) group with different N-linked acyloxyacyl groups, i.e., 3-dodecanoyloxytetradecanoyl [C14-O-(C12)], 3-tetradecanoyloxytetradecanoyl [C14-O-(C14)], and 3-hexadecanoyloxytetradecanoyl [C14-O-(C16)] groups (termed GLA-57, GLA-27, and GLA-58, respectively), GLA-27 exhibited significant colony-stimulating factor-inducing and tumor necrosis factor-inducing activities, mitogenicity, polyclonal B-cell activation activity, macrophage activation, and adjuvanticity. The activities of GLA-57, which had an N-linked C14-O-(C12) group, were equivalent to or somewhat weaker than those of GLA-27 with a C14-O-(C14) group. Significant immunopharmacological activities were not observed for GLA-58, carrying a C14-O-(C16) group bound to the amino group. GLA-59, carrying 3-O-linked 3-hydroxytetradecanoyl (C14OH) and N-linked C14-O-(C14) groups, showed much higher activities than GLA-27, GLA-60, a compound which possesses the same fatty acid substituents as GLA-59 but with reversed binding sites, showed the strongest B-cell activation and adjuvant activities among the synthetic compounds. Among stereoisomers of GLA-59 and GLA-60 composed of fatty acid substituents with the (RR) and (SS) configuration, compounds with the (RR) configuration elicited stronger activities than the (SS) stereoisomers. The importance of fatty acid substituents, including stereospecificity for the expression of immunopharmacological activities of 4-O-phosphono-D-glucosamine derivatives, was demonstrated.

Adjuvants, Immunologic