Biomedical subjects

S Kondo

Publications and source records attributed to S Kondo.

At least 595 records · Page 33Linked to original sources

PubMed1994

Kupffer cells cytotoxicity against hepatoma cells is related to nitric oxide.

We have previously demonstrated that rat resting macrophages have cytotoxicity against tumor cells. In the current study we have performed an in vitro experiment to explore the mechanism of Kupffer cells-mediated cytotoxicity against hepatomas. The coculture of tumor cells with Kupffer cells (derived from rat livers) stimulated syngeneic and allogeneic Kupffer cells to produce nitric oxide. Kupffer cell-mediated cytotoxicity was paralleled to the amount of nitric oxide and was abolished by the addition of NG-monomethyl-L-arginine. The ability to stimulate Kupffer cells to produce nitric oxide resided on the membranous fragment of tumor cells.

Animals↗

PubMed1994

Transfection with a bcl-2 expression vector protects transplanted bone marrow from chemotherapy-induced myelosuppression.

The use of cytokines such as granulocyte-colony-stimulating factor (G-CSF) to ameliorate chemotherapy-induced myelosuppression may not only stimulate the recovery of normal hematopoietic cells but may also enhance the proliferation of the tumor cells with functional receptors for these cytokines. In this study, we show that administration of recombinant human (rh) G-CSF decreased the in vitro and in vivo cytotoxic effects of Adriamycin or etoposide on L1210 murine leukemic cells with receptors for rhG-CSF. Transplantation of bone marrow cells expressing high levels of bcl-2 from a retroviral construct [MPZenNeo(bcl-2)] (bcl-2-BMT) did not decrease the in vivo cytotoxic effect of etoposide on L1210 cells, but enabled recovery of myelopoiesis following etoposide-induced myelosuppression to almost the same extent as did the administration of rhG-CSF. These findings suggest the possibility that bcl-2 transfection could be used to protect transplanted bone marrow from chemotherapy-induced myelosuppression on behalf of administration of rhG-CSF, in case of treatment of tumors with functional receptors for rhG-CSF.

Animals↗

PubMed1994

Vascular endothelial growth factor/vascular permeability factor is detectable in the sera of tumor-bearing mice and cancer patients.

We developed an enzyme-linked immunosorbent assay (ELISA) for vascular endothelial growth factor/vascular permeability factor (VEGF/VPF). The assay revealed that VEGF/VPF levels in the sera of mice were significantly increased from undetectable level by s.c. transplantation with a solid tumor. We also measured VEGF/VPF levels in serum specimens obtained from cancer patients with several types of cancers. VEGF/VPF levels in the sera from cancer patients were significantly higher than those in the sera from the individuals with no sign of cancer.

Animals↗

PubMed1994

Induction of apoptosis in murine ACTH-secreting pituitary adenoma cells by bromocriptine.

Bromocriptine, a dopamine agonist, is now an accepted primary therapeutic agent for patients with prolactinomas and other pituitary adenomas. In this study, we demonstrated that bromocriptine inhibited the proliferation of murine ACTH-secreting pituitary adenoma (AtT-20) cells. In addition, the antitumor activity of bromocriptine was inhibited both by actinomycin D and cycloheximide, suggesting that it was dependent on new RNA and protein synthesis. Interestingly, the results of DNA fragmentation assays and cell cycle analysis clearly demonstrated that bromocriptine induced apoptosis in AtT-20 cells.

Adenoma↗

PubMed1994

Angiographic changes in the hepatic artery after skeletonization resection for biliary tract cancer.

Using preoperative and postoperative arteriography, angiographic changes in the hepatic artery were studied after skeletonization of the hepatoduodenal ligament and hepatic resection for biliary tract carcinoma. Of 52 patients evaluated (32 with carcinoma of the bile duct, 20 with gallbladder cancer), no angiographic changes were apparent after operation in 30 (58 per cent) and there were pathological findings in 22 (42 per cent; smooth stenosis in five patients, irregular stenosis in seven, a beaded appearance in four, dilatation in two, obstruction in four). Based on angiographic findings, patients were classified into three subgroups (no change, 30 patients; irregular form, 18; obstructed, four). Postoperative liver function was also evaluated. No definite correlation was evident between angiographic findings and the incidence of hepatic failure or liver dysfunction in the first month after operation. Given that connective tissue and lymph node dissection in the hepatoduodenal ligament is essential for curative resection of biliary tract carcinoma, these findings suggest that skeletonization is an acceptable operative procedure.

Adolescent↗

PubMed1994

A role for CD4+ T cells in the pathogenesis of skin fibrosis in tight skin mice.

The tight skin (Tsk/+) mouse represents a murine model of heritable fibrosis with some similarities to the skin fibrosis seen in human scleroderma. Tsk/+ animals display alterations in connective tissue in some internal organs. Skin fibrosis can be adoptively transferred to normal recipients with Tsk/+ bone marrow or spleen cells and older Tsk/+ animals develop autoantibodies against topoisomerase suggesting that some of the pathogenesis in the Tsk/+ mouse may be mediated by autoimmunity. To determine the role of T cell subsets in the pathogenesis of fibrotic disease, Tsk/+ mice were bred with CD4- and CD8-deficient (CD4-/- and CD8-/-) mice. Tsk/+ CD4-/- mice showed a marked reduction in skin fibrosis as well as decreased cellularity and only mild collagen disorganization as compared to Tsk/+ CD4+ CD8+ control mice yet did not differ from Tsk controls in the level of serum anti-topoisomerase activity. In contrast, Tsk/+ CD8-/- mice exhibited the same histology in the skin as Tsk/+ controls yet had significantly reduced levels of serum anti-topoisomerase activity. Lung pathology, i.e. emphysema, was unaffected by both the CD4 or CD8 mutations. These data show that only some of the pathological effects of the Tsk mutation are T cell dependent and that different T cell subsets affect different parameters in this multi-organ model of fibrotic disease.

Animals↗

PubMed1994

Developmental competence of bovine oocytes frozen at different cooling rates.

Experiments were conducted to determine the optimal cooling conditions for improving the developmental competence of in vitro-matured bovine oocytes when frozen in 1.6 M 1,2-propanediol. Bovine oocytes were cooled from 0 degree to -5.5 degrees C at 1 degree C/min, seeded, and then cooled to -30 degrees C at different cooling rates (0.3 degree, 0.6 degree or 0.9 degree C/min) and then plunged into LN2. When frozen-thawed oocytes were fertilized in vitro, the proportions of fertilization and developmental competence did not differ among the three groups frozen at different cooling rates. The findings indicated that a cooling rate of less than 1.0 degree C/min in the freezing procedure did not affect the developmental competence of postthaw in vitro-matured bovine oocytes.

Animals↗

PubMed1994

bcl-2 gene prevents apoptosis of basic fibroblast growth factor-deprived murine aortic endothelial cells.

Growth factors such as basic fibroblast growth factor (bFGF) have been found to promote the survival and proliferation of endothelial cells. However, the mechanism by which growth factors control the regeneration and degeneration of the endothelial cells remained poorly understood. In this study, we demonstrated that apoptosis of murine aortic endothelial (MAE) cells was induced by deprivation of bFGF but required new RNA and protein synthesis. Furthermore, enforced expression of bcl-2 gene in MAE cells using gene transfer techniques decreased apoptosis induced by deprivation of bFGF. These findings suggest that bcl-2 interferes with a pathway for endothelial cell death that is induced by deprivation of bFGF.

Animals↗

PubMed1994

Calcium regulating activity of 26,27-dimethyl analog of 24R,25-dihydroxyvitamin D3.

To determine the possibility that methyl substitution in 26- and 27-positions of 24R,25-dihydroxyvitamin D3 [24,25(OH)2D3] alters activities of the original compound, the effects of 24,25(OH)2D3 on calcium (Ca) regulating activity were compared with those of its methyl analog [24,25(OH)2(CH3)2D3] in addition to 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3]. 24,25(OH)2D3 at 10(-6) M and 24,25(OH)2(CH3)2D3 at 10(-7) M and above significantly stimulated both bone resorption in neonatal mouse calvaria cultures and formation of osteoclast-like multinucleated cells (MNC) in mouse bone marrow cultures. A stimulative effect of 1,25(OH)2D3 on bone resorption and MNC formation was recognized in very low concentrations (10(-11) M and above). Although a potency of 24,25(OH)2(CH3)2D3 in stimulating bone calcium (Ca) mobilization and intestinal Ca transport was higher than that of 24,25(OH)2D3, the potencies of both compounds were similar to that of 1,25(OH)2D3 unlike in vitro experiments. As 1,24R,25-trihydroxy-26,27-dimethylvitamin D3 showed almost the same effect as 24,25(OH)2(CH3)2D3, the dihydroxy form is suggested to be hydroxylated at 1 alpha position and converted to trihydroxy form in vitamin D-deficient rats. From these results, methyl substitution in 26- and 27-position of 24,25(OH)2D3 was found to elevate Ca regulating activity of the original compound. In addition, it is suggested that the basis for a similarity in potency between 1,25(OH)2D3 and 24,25(OH)2D3 or its dimethyl analog in vitamin D-deficient rats is likely the result of 1 alpha-hydroxylation.

24,25-Dihydroxyvitamin D 3↗

PubMed1994

Reduced cerebellar blood flow and oxygen metabolism in spinocerebellar degeneration: a combined PET and MRI study.

Fourteen patients with spinocerebellar degeneration (SCD) were subjected to MRI and PET studies. The quantitative MRI data revealed significant cerebellar and pontine atrophy in the patients with olivopontocerebellar atrophy (OPCA), and cerebellar atrophy in the patients with late cerebellar cortical atrophy (LCCA). We failed to demonstrate significant differences in the pons between LCCA patients and normal controls. PET measurements revealed decreases in cerebral oxygen metabolic rate (CMRO2) in the cerebellar hemisphere and vermis in both groups of patients. The markedly decreased cerebral blood flow (CBF) and CMRO2 in the pons were found only in the patients with OPCA. PET data corrected for the tissue shrinkage on the basis of MRI morphometry indicated a net reduction in cerebellar CMRO2 and CBF. The present study has demonstrated that a combination of functional and anatomical data offers further evidence in favour of the current acceptable classification of SCD based on clinicopathological grounds. Our data further suggest that the amount of atrophy in the cerebellum could not fully account for the decreased metabolic rates observed in PET studies.

Adult↗

PubMed1994

Analysis of acute myeloid leukemia cells by flow cytometry, introducing a new light-scattering classification.

A combined flow-cytometric evaluation of light scattering and the immunophenotype of acute myeloid leukemia (AML) cells from 71 newly diagnosed consecutive patients was conducted. Light-scattering characteristic of AML cells examined by flow cytometry and multiple surface markers were also analyzed using the same samples, to enable a comparison with the French-American-British (FAB) classification. Our AML cases could be classified into three light-scattering classification (LSC) types according to their physical properties on flow cytometry. These were type A, where forward light scattering (FSC) of the leukemic cell population was larger than that of lymphocytes, while side light scattering (SSC) was the same or larger than that of lymphocytes but smaller than that of monocytes; type B, where FSC of the leukemic cell population was larger than that of lymphocytes and SSC spread toward that of monocytes; and type C, where both FSC and SSC of the leukemic cell population spread beyond those of monocytes. Although a clear relationship between the FAB classification and LSC classification by the light-scattering profile of AML was not established, we observed the following findings. The majority of cases were classified as type A (58%), while type B comprised 25% and type C comprised 17%. While CD7 expression on AML cells is considered to be an immature characteristic, CD7 was expressed more frequently among LSC type A cases. Furthermore, all but one of the FAB M1 cases were classified as type A. On the other hand, CD7 was not expressed on type C leukemic cells. The percentage of cases in which more than 60% of leukemic cells possessed another immature surface antigen, CD 34ö, was 13/18 (72%) among FAB M1 cases, much higher than among FAB M2 (35%) or FAB M4 (27%) cases. A negative correlation was observed between mature antigen CD33 and CD34 among the FAB M2 cases. The frequency of CD7 expression was 25% among the total cases, and CD7-positive cases were frequent among FAB M1 and M2, but not among FAB M3 cases. These findings concerning LSC and immunophenotyping indicate that the scattergram pattern analysis may contribute towards more precise immunophenotyping, in that it reflects the maturation stage of each AML case.

Acute Disease↗

PubMed1994

Scintigraphic detection of neural-cell-derived small-cell lung cancer using glioma-specific antibody.

Radiolabeled GA-17, a murine monoclonal antibody that reacts specifically with glioma cells, bound to a small-cell lung cancer (SCLC) cell line NCI-H69 derived from neural cells, both in vitro and in vivo. The affinity constant of GA-17 F (ab')2 fragment binding to NCI-H69 was 1.02 x 10(8)/M while that to the glioma cell line U87MG was 1.22 x 10(8)/M. Iodine-125-labeled GA-17 F(ab')2 fragments injected i.v. localized well in NCI-H69 cells xenografted in nude mice. The percentage of the injected dose per gram accumulated in the xenografted tumor was 6.87 +/- 1.34% g-1 (mean +/- SD, n = 5) 24 h after injection. On the other hand, control monoclonal F(ab')2 fragments accumulated in the xenografted tumor at 0.75 +/- 0.30% g-1. The tumor-to-blood ratio was 1.8 for NCI-H69, while that of control F(ab')2 was 0.60. In conclusion, the radiolabeled GA-17 F(ab')2 fragment is expected to be useful clinically to visualize the small-cell lung cancer and in radioimmunotherapy.

Animals↗

PubMed1994

Genomic structure and chromosomal localization of processed pseudogenes for human RBP-Jk.

The functional gene for human recombination signal sequence-binding protein (RBP-Jk) and corresponding processed psudogenes have been isolated from various species, such as Drosophila, Xenopus, mouse, and human. Here we report the isolation of another two genomic pseudogenes of human RBP-Jk, named K2 and K7, from a cosmid library of Hela cells. The nucleotide sequences of both genes exhibited more than 95% homology to the functional human gene for RBP-Jk. Moreover, they did not contain any intron sequences and were interrupted by several stop codons in all frames. In situ hybridization demonstrated that the pseudogenes, K2 and K7, were localized at chromosomes 9p13 and 9q13, respectively. Their physical maps differed from those of the true functional gene and of the pseudogenes reported previously by Amakawa et al. (1993).

Base Sequence↗

PubMed1994

Susceptibility of ebiratide to proteolysis in rat intestinal fluid and homogenates and its protection by various protease inhibitors.

In order to estimate the intestinal stability of ebiratide [H-Met(O2)-Glu-His-Phe-D-Lys-Phe-NH(CH2)8-NH2], a novel adrenocorticotropic hormone (ACTH) analogue, after oral administration, the hydrolytic properties of ebiratide were determined in the rat small intestinal fluid and mucosal homogenates. Ebiratide was extremely stable in the rat small intestinal fluid, while it was degraded in various intestinal mucosal homogenates. Regional differences were observed in its proteolytic properties; e.g., the hydrolytic rates of ebiratide in jejunal and ileal mucosal homogenates were 2-3 times faster than that in duodenal and colonic homogenates. Degradation of ebiratide was markedly inhibited by aminoprotease inhibitors such as sodium glycocholate, puromycin, bestatin and bacitracin. These results suggest that co-administration of certain protease inhibitors are useful to improve the stability of ebiratide in the intestine.

Adrenocorticotropic Hormone↗

PubMed1994

Expression of functional Fas antigen on adult T-cell leukemia.

The expression of Fas antigen was analyzed in the peripheral blood mononuclear cells of 12 patients with adult T-cell leukemia (ATL) by flow cytometry. The induction of apoptosis in these cells by adding an anti-Fas antibody and the expression of activated T-cell surface antigens, CD25 and CD26, were also studied. It appears that the cells in ATL expressed a significantly larger number of Fas antigens than those in normal subjects (p < 0.01) and their fluorescent intensity was also shown to be much stronger in ATL (p < 0.01). The large number of ATL cells showed apoptosis in a short-term culture in the presence of the anti-Fas antibody. There was no difference in the expression of Fas antigen among ATL cells with different phenotypes of CD4+/CD8-, CD4-/CD8- and CD4+/CD8+ as well as with clinical subtypes of ATL. Interestingly, the expression of Fas and CD26 antigens showed a negative correlation (p < 0.01, r = 0.78). The strong expression of functional Fas antigen in ATL leads to the impression that anti-Fas antibody could be one of the treatment modalities for ATL which is known to be a very difficult disease to cope with.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1994

High-level expression of the photorepair gene in Drosophila ovary and its evolutionary implications.

DNA photolyase catalyzes light-dependent repair of cis, syn-cyclobutane dipyrimidines (pyrimidine dimers); its apoenzyme is encoded by the photorepair (phr) gene. The phr cDNA was cloned from D. melanogaster; it has an open reading frame to encode a 61,483-Da protein. The phr cDNA hybridized to band 44C-D of Drosophila polytene chromosome, equivalent to the locus of the phr- gene. Drosophila photolyase is made of an apoenzyme with a molecular weight of 62 kDa. Drosophila photolyase is extraordinarily abundant in the embryo and adult ovary, whereas mRNA of the phr gene is abundant only in the ovary. The action spectrum of Drosophila photolyase for photoreactivation has a maximum at 440 nm. The phr gene of Drosophila has about 60% identical amino acid sites with that of goldfish but only 13-18% with those of microorganisms. Implications of the unique characteristics of the Drosophila phr gene are discussed overviewing the diversified characteristics of phr genes in various organisms that have presumably evolved from a common ancestral gene.

Amino Acid Sequence↗

PubMed1994

Effect of cyclosporin on hair-existing area of nude mice.

We investigated the effect of cyclosporin, as well as minoxidil, testosterone, estradiol and corticosteroid on the hair growth on the hairy part of nude mice. Aliquots of solutions of cyclosporin and other agents were applied once per every day topically on the tails and the lower backs of 5 week-old BALB/c nude mice, for as long as 6 weeks. Cyclosporin prolonged the hair-existing phase of the hair cycle, but did not change the term of the hair cycle, i.e., the resting phase was not affected. Minoxidil, testosterone and estradiol did not influence the hair growth cycle. Combination of cyclosporin and other agents demonstrated that there was neither additive nor synergistic effect, but a high dose of corticosteroid inhibit the cyclosporin effect, as well as suppressing completely the reappearance of the growing phase.

Administration, Topical↗

PubMed1994

Effect of cyclodextrin on improvement of enantioselectivity in the reduction of ketopantolactone with baker's yeast.

Addition of beta-cyclodextrin improves enantioselectivity dramatically in the reduction of ketopantolactone mediated by baker's yeast. It has been found that the selectivity increases with the decrease in concentration of ketopantolactone in bulk solvent, and beta-cyclodextrin controls its effective concentration. The role of beta-cyclodextrin is discussed.

4-Butyrolactone↗