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Biomedical subjects

K Inada

Publications and source records attributed to K Inada.

At least 91 records · Page 5Linked to original sources
PubMed1990

[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↗
PubMed1989

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↗
PubMed1989

[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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

Localization of prealbumin in human eye.

Although the aqueous humor contained several serum proteins and the concentration of each protein was very low in normal eyes, the aqueous/serum ratio of prealbumin was reported to be higher than the ratios of other human aqueous proteins in a previous paper. This study investigated the possibility of the intraocular synthesis of prealbumin, by examining postmortem human eyes using the peroxidase-antiperoxidase method. The immunohistochemical survey revealed the presence of prealbumin in the nonpigmented layer of the ciliary epithelium and in the ganglion cell layer of the retina. Some cells situated on the inner side of the internal nuclear layer of the retina also showed staining. We believe that this is the first study to demonstrate the possibility of synthesis of prealbumin in the human eye by immunohistochemistry.

Adult↗
PubMed1988

Increase of aqueous humor proteins with aging.

Quantitative analyses by crossed immunoelectrophoresis were carried out on 31 eyes of 26 cataract patients, age 4-80 years, to detect age changes in the human aqueous humor especially in the following aqueous humor proteins: prealbumin, albumin, alpha 1-acid glycoprotein and transferrin. There was a significant correlation between age and concentration of each of the 4 proteins. The results reported in this paper may be due to senile alteration of the pathway that serum proteins follow from the leaky vessels of the ciliary body to the anterior chamber and/or to a decrease of the aqueous flow rate with advancing age. The relationship between the ages and the aqueous humor protein levels established in this study can be utilized as controls in studying the aqueous humor proteins in uveitis and other ocular diseases.

Adult↗
PubMed1987

[Analysis of the chemosensitivity test by subrenal capsule assay].

The antitumor activity of several chemotherapeutic agents against a total of 30 clinical samples obtained from 30 human tumors from the esophagus (12), stomach (10), colorectum (6) and lung (2), were tested by subrenal capsule assay (SRCA) using normal immuno-competent BDF, mice. The antitumor activity was evaluated by changes in both tumor size (delta TS method) and tumor growth inhibition rate (TGIR method). Among the 30 tumors, 15 were also tested by human tumor clonogenic assay (HTCA) and the results obtained in the two assays were compared. In the SRCA, adequate growth of the tumor in the control group for evaluation of the response of the treated group was obtained from 27 out of 30 tumors (90%). With activity criteria set at delta TS less than or equal to -1.0 dmm and TGIR greater than or equal to 50%, 41% of the drugs tested were active in delta TS while 27% were active in TGIR. When relationships between antitumor activities evaluated by delta TS and TGIR was compared, both activities were well correlated (r = -0.64). Correlations between tumor responses in the HTCA and in the SRCA were tested in 6 tumors treated with 20 drugs. The overall accuracy was 60% by the TGIR method and 70% by the delta TS method, respectively.

Animals↗
PubMed1986

A sandwich immunoassay for human prolyl 4-hydroxylase using monoclonal antibody.

Monoclonal antibody was used in a sandwich enzyme immunoassay and in a radioimmunoassay for human serum immunoreactive prolyl 4-hydroxylase. The enzyme immunoassay utilized a monoclonal antibody as a solid phase and horseradish peroxidase-labeled rabbit antibody (Fab') to human prolyl 4-hydroxylase as a conjugate. Sensitivity was 0.1 ng (0.4 fmol) of enzyme per tube. With a conjugate purified by an enzyme-bound affinity column, sensitivity was increased to 0.01 ng (0.04 fmol) per tube, and linearity was obtained between 0.01 to 30 ng (0.04-125 fmol) per tube. The radioimmunoassay used a 125I-labeled rabbit antibody (IgG) as the conjugate. Sensitivity of this technique was 0.4 ng of enzyme per tube. The enzyme immunoassay gave reproducible quantitation and evidenced a higher enzyme concentration in the serum of patients with liver disorders. Protein immunoblotting showed that the serum immunoreactive prolyl 4-hydroxylase trapped in the sandwich immunoassay was mainly the beta-subunit.

Antibodies, Monoclonal↗