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Biomedical subjects

H Oshima

Publications and source records attributed to H Oshima.

At least 253 records · Page 14Linked to original sources
PubMed1987

Improvement of cytotoxicity of tumor necrosis factor (TNF) by increase in basicity of its N-terminal region.

Two new recombinant TNFs (named rTNF-Scw1 and -Scw2) with higher basicity than conventional recombinant human TNF-alpha (rTNF-alpha) in the N-terminal region were constructed. Their sequences were constructed based on those of partially purified cytotoxic factors from the culture supernatant of acute monocytic leukemia cells THP-1, which unlike rTNF-alpha are cytotoxic to T24 bladder carcinoma cells in vitro. These new rTNF-Ss showed a broader cytotoxicity to tumor cells than rTNF-alpha. This increase in the basicity of the N-terminal region over that of conventional TNF significantly increased the cytotoxicity on tumor cells in vivo as well as in vitro.

Amino Acid Sequence↗
PubMed1987

Identification of inhibin secreted by cynomolgus monkey Sertoli cell cultures.

An inhibin was identified in the media of primary Sertoli cell-enriched cultures from the cynomolgus monkey, Macaca fascicularis, and some of its biochemical properties were studied. Conditioned monkey Sertoli cell culture medium (m-SCCM), when added to pituitary cells from 6-week-old male rats, inhibited the basal secretion of FSH but not that of LH. This specificity was lost after the addition of GnRH; mSCCM inhibited not only FSH but also LH release, determined by both RIA and mouse interstitial cell bioassay, from pituitary cells exposed for 6 h to 10 nM GnRH. FSH-inhibiting activity persisted when m-SCCM was boiled for 30 min, but activity was lost after incubation for 1 h at 37 C with 0.1% trypsin. m-SCCM inhibin activity was completely retained by Concanavalin A-Sepharose and could be eluted with 0.2 M alpha-methyl-D-glucoside. Gel filtration high pressure liquid chromatography with a Superose-12 column revealed inhibin activity between 20-60K, with the greatest activity at 40K. Our results indicate that primate Sertoli cells produce an inhibin-like factor which could play a role in controlling gonadotropin secretion in males.

Animals↗
PubMed1987

Ketoconazole as a possible universal inhibitor of cytochrome P-450 dependent enzymes: its mode of inhibition.

Modes of inhibition and binding of ketoconazole, an orally antimycotic agent, to NADPH-cytochrome P-450 dependent enzymes were investigated using subcellular fractions of human and rat testes, human adrenocortical adenoma tissue and rat adrenals and livers. Ketoconazole competitively inhibited the activities of steroid 17 alpha-hydroxylase and C17-20 lyase in rat and human testes, 16 alpha-hydroxylase in human testes and 21-hydroxylase in rat adrenal glands. Ki values were in the order of 10(-8)M for human testicular enzymes, while the order was 10(-7)-10(-6) M for rat adrenal and testicular enzymes. Kinetic studies indicated that ketoconazole bound to cytochrome P-450 and not to other components of monooxygenase systems. Spectrophotometric studies also revealed direct binding of ketoconazole to cytochrome P-450 component by inducing type II difference spectra in all tissue preparations examined, indicating that ketoconazole is possibly a universal inhibitor of NADPH-cytochrome P-450 dependent monooxygenases which are involved in metabolism of many substances including steroids, toxins, carcinogens and others.

Adenoma↗
PubMed1987

Expression of alien H-2 and non-H-2 antigens on a murine mammary tumor cell line, MM46.

Tumor-associated surface antigens on MM46, a transplantable ascites tumor from a spontaneous mammary carcinoma in a C3H/He mouse, were investigated. A complement-dependent microcytotoxicity test showed the expression of MM antigen, whose specificity appeared to be identical or cross-reactive with that of Ly-6.2 antigen, as reported previously. Moreover, MM46 was also found to express alien H-2 antigenic specificities, H-2.31 and H-2.28. H-2.31 represents the private specificity of the H-2Kd molecule, while H-2.28 represents a public specificity among molecules encoded by H-2K, H-2D, and H-2L loci in the majority of original H-2 haplotypes, including H-2d, but not H-2k, of inbred laboratory mice. The expression of MM antigen was found to be closely associated with the appearance of hypotetraploid tumor cells. These results suggest that alien H-2 and non-H-2 antigens appeared during ascites tumor cell conversion.

Aneuploidy↗
PubMed1987

Endogenous production of tumor necrosis factor in normal mice and human cancer patients by interferons and other cytokines combined with biological response modifiers of bacterial origin.

The priming effect of endogenous biological response modifiers (BRMs), interferons (IFNs), and interleukin-2 (IL2), and the triggering effect of BRMs of bacterial origin, OK-432 and Corynebacterium parvum, on endogenous production of the tumor necrosis factor (TNF) were investigated in mice. TNF activity in serum was measured by in vitro cytotoxicity assay with L-929 cells as a target. The i.v. injection of OK-432 (3KE per mouse) triggered TNF maximally (mean value: 30 U/ml) after 2 h, with a similar time course to that of triggering by lipopolysaccharide. The priming activities of IFNs and IL2 were examined in the system of TNF-triggering by OK-432. The i.v. injection of recombinant IFN-gamma (rIFN-gamma, 10(4) U per mouse) increased TNF production to 790 U/ml; this priming effect was observed just after its injection, was maximal after 2 to 6 h, and disappeared after 24 h. Other types of interferon, rIFN-alpha A/D(Bgl) (2 X 10(5) U per mouse), rIFN-beta (10(6) U per mouse), and natural IFN-alpha/beta (10(6) U per mouse) showed maximal priming activity 6 h after their injection (200 to 800 U/ml) but no effect just after their injection. Recombinant IL2 (10(6) U per mouse) had priming activity that showed a similar time course to that of interferons other than IFN-gamma (a maximal TNF production: 100 U/ml). The i.v. injection of C. parvum, like OK-432, triggered TNF production at doses of 0.06 and 0.3 mg per mouse 2 h after its injection and the triggered TNF activity was enhanced by rIFN-gamma. These findings suggest that combinations of the above endogenous BRMs as priming agents and OK-432 or C. parvum as a triggering agent could induce endogenous production of TNF even in human cancer patients. In fact, combined administration of rIFN-gamma and OK-432 produced TNF in human cancer patients. The advantage of this method for treatment of human cancer patients is discussed.

Animals↗
PubMed1987

Monoclonal antibodies directed to different tumor-associated antigens on a murine mammary tumor cell line, MM46.

Seven monoclonal antibodies to a murine mammary carcinoma MM46 were produced by fusing a mouse hybridoma cell line Sp2/O-Ag14 or a myeloma cell line P3-X63-Ag8-U1 with spleen cells from C3H/He mice immunized with MM46. Their specificities were investigated by the complement-dependent cytotoxicity test and binding inhibition assay using 125I-labeled monoclonal antibodies. The complement-dependent cytotoxicity test showed that all of them reacted with MM antigen-positive tumor cells such as MM46 and FM3A/R. Three of them reacted with both C57BL/6 lymph node cells and EL4 tumor cells, suggesting that these 3 antibodies recognize Ly-6.2 antigen. One reacted with all tumor cells so far tested (MM46, FM3A/R, MM48, MH134, and Meth A) except EL4. One antibody that cross-reacted with MH134 was also obtained. Binding inhibition assay confirmed hat the 7 monoclonal antibodies detected at least 4 different epitopes on MM46. These results suggest that there are at least 4 different molecules on the cell surface of MM46: namely, molecules that are 1) restricted to MM antigen-positive tumor cells, 2) present on several tumor cells, 3) broadly distributed on tumor cells, and 4) cross-reactive with Ly antigen.

Animals↗
PubMed1987

Endogenous production of cytotoxic factor in mice induced by a combination of interferon-gamma and heterologous fibrinogen.

The ability of heterologous fibrinogen in combination with interferon (IFN)-gamma to induce endogenous production of cytotoxic factor was examined. Heterologous but not homologous fibrinogen induced high production of cytotoxic factor in IFN-gamma-primed mice. The cytotoxic activity was maximal 1 h after this triggering. The LD50 value of heterologous fibrinogen in mice was greater than 250 mg/kg i.v. But heterologous fibrinogen induced antibody, causing anaphylaxis. Therefore, the effect of successive injections of fibrinogens from a different species was tested. Cytotoxic factor could be produced repeatedly by successive treatments with a combination of IFN-gamma and heterologous fibrinogen from one species for 1 week, although the cytotoxic activity induced by successive injections gradually decreased. After the decrease of the triggering effect of heterologous fibrinogen of one species, heterologous fibrinogen from a different species could induce cytotoxic activity at the same level as that after the first triggering. Thus, a combination of IFN-gamma and heterologous fibrinogen is effective for cytotoxic factor production, provided different heterologous fibrinogens are used successively. This combination should be useful for endogenous cytotoxic factor production in clinical trials.

Animals↗
PubMed1987

Damaging effect of peripheral mononuclear cells of dermatomyositis on cultured human skin fibroblasts.

When human skin fibroblasts were incubated with mononuclear cells (MNC) from 6 patients with dermatomyositis (DM), striking attachment of MNC around fibroblasts was observed. Simultaneously, cell number and 3H-thymidine incorporation of fibroblasts after 4 days of incubation were significantly decreased. MNC of normal subjects, of patients with systemic lupus erythematosus, myasthenia gravis, rheumatoid arthritis, and other miscellaneous diseases with skin manifestations did not show this effect. MNC of patients with DM did not adhere to KYM-1 cells (human rhabdomyosarcoma cell-line) and did not inhibit cell proliferation of these cells. Our study strongly suggests that cell mediated injury of fibroblasts might play an important role in the pathogenesis of DM.

Adult↗
PubMed1987

[A case of right triplicate and left duplicate ureters].

Ureteral triplication is a rare anomaly of the urinary tract. A 42-year-old male was found to have right triplicated and left duplicated ureters. The chief complaint was gross hematuria, but it disappeared after admission. Computerized tomographic scan, renal angiography and urine cytology revealed no pathological findings but 3 small aneurysms at the upper pole of the right kidney. Cystoscopic examination showed 3 ureteral orifices on the right side with bleeding from the lowest ureteral orifice. Right retrograde pyelography revealed 3 pelvic systems with calyceal communication of lower and middle pelvic system. Our case is consistent with altered type-D of Smith's classification.

Adult↗
PubMed1987

[Morphological changes in the contralateral testis in patients with testicular tumor].

Biopsy of contralateral testis of 20 patients with an unilateral testicular tumor was carried out to evaluate the morphological changes of the contralateral testis caused by the tumor. Serum beta-chorionic gonadotropin (beta-hCG), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and alpha-fetoprotein (AFP) levels before orchiectomy were examined as a function influencing morphological changes of the contralateral testis. Typical carcinoma in situ was found in a case of ipsilateral testis. The presence of a few atypical germ cells, however, was the only finding of the contralateral testis of three patients. Five of 20 patients revealed hypospermatogenesis in the contralateral intact testis. Most of the other patients also showed sloughing of germinal epithelium suggesting disorder of spermatogenesis. Johnsen's mean score count and tubular wall thickening were related to neither clinical stages, ESR, serum beta-hCG, AFP, LH nor FSH levels. Tubular wall thickening was observed in 8 of 10 patients with a tumor weighting over 150 g, but was found in only 1 of 10 patients with a lighter tumor (p less than 0.01).

Adult↗
PubMed1987

[Cytology of percutaneous aspiration biopsy of renal angiomyolipoma: a study of 4 cases].

Percutaneous aspiration biopsy of renal angiomyolipoma (AML) was carried out on four patients to investigate the cytological features of AML. The diagnosis was confirmed histologically after the removal of the tumor. The specimen was fixed in 95% alcohol and stained by the Papanicolaou's method. Cells obtained formed clusters in three of four cases. Cells originating from leiomyomatous element of AML varied in their size, but are usually small with small oval nuclei and rich cytoplasm of lacy appearance. The cytoplasm was fragile and the cell border was not clear. Nuclear chromatin was not increased and was distributed diffusely. Fat cells originating from fatty element of the tumor were mature type and obtained from all of three patients who had much typical lipomatous element in the tumor. In conclusion, cytology of aspiration biopsy is useful to establish preoperative diagnosis of AML in such occasions when there are difficulties in differential diagnoses between AML and renal cell carcinoma even by either computed tomography, angiography or ultrasonography.

Adult↗
PubMed1987

Endogenous production of TNF-like cytotoxic factor in BCG-primed mice by heterologous fibrinogen.

The triggering activities of heterologous fibrinogen and fibrin on endogenous production of tumor necrosis factor (TNF)-like cytotoxic factor in vivo were examined. The triggering activities of fibrinogen or fibrin from four species injected into the peritoneal cavity of C3H/He mice infected i.p. with bacillus Calmette-Guérin (BCG) were tested. Heterologous, but not homologous, fibrinogen and fibrin showed triggering activity. The route of triggering by heterologous fibrinogen to elicit TNF-like activity systemically was studied. Injection of heterologous fibrinogen i.v. into mice infected i.v. with BCG resulted in a 40-fold higher serum TNF-like activity level than after its i.p. injection. The serum TNF-like activity level was maximal 1 h after i.v. injection of heterologous fibrinogen. When heterologous fibrinogen was injected several times i.v. into mice bearing solid-tumors, TNF-like activity was also released into the serum after every injection, although the activity decreased progressively on second and third injections to 10 and 1%, respectively, of that after the first injection. We used heterologous fibrinogens derived from different species for triggering every week to avoid this gradual decrease of TNF-like activity. In this way TNF-like activity was induced as highly as the primary induction. These results showed that TNF-like cytotoxic factor could be produced in vivo locally or systemically by heterologous fibrinogen or fibrin. Thus both agents should be useful as nontoxic triggering agents.

Animals↗
PubMed1987

Role of in vivo scavenger function of macrophages in priming for endogenous production of tumor necrosis factor.

The effects of systemic administrations of immune complex, complement activators, and insoluble particles on endogenous production of tumor necrosis factor (TNF) were investigated in mice. Production of serum TNF was triggered by i.v. injection of OK-432, a streptococcal preparation, and measured by in vitro L-929 cytotoxicity assay. Intravenous injection of IgG-opsonized sheep red blood cells (10(8)/mouse) enhanced OK-432-triggered TNF production significantly. This effect was maximal (about 30-fold enhancement) 1.5 to 3 h after the injection and disappeared within 10 h. Complement activators other than immune complex also possessed this activity. Zymosan (0.1 mg/mouse) enhanced OK-432-triggered TNF production maximally (about 25-fold) 3 to 6 h after its i.v. injection, its effect lasting for 10 h, and disappearing within 24 h. Heat-aggregated IgG and cobra venom factor also had similar enhancing effects. In addition, systemic pretreatment with insoluble particles enhanced OK-432-triggered TNF production. The enhancement by latex beads (2 microliters volume of solid/mouse) was maximal (about 60-fold) 3 to 6 h after their i.v. injection, was sustained for at least 20 h, and disappeared within 48 h. Glass beads, dextran beads, alum, silica, and carbon particles all had similar enhancing effects. Based on these results, the in vivo scavenger function of macrophages, as well as direct activation with cytokines, may participate in priming for endogenous production of TNF; alternatively, particles or macromolecules which can be scavenged by macrophages may activate macrophages and prime for TNF production.

Animals↗
PubMed1986

[Studies on the glucocorticoid receptor in human peripheral lymphocytes. I. Fundamental investigation on the method of measurement of the glucocorticoid receptor in whole cell and nucleus].

There have been several reports about the glucocorticoid receptor (GC-R) in human peripheral lymphocytes (HPL). However, little has been investigated about the validity of the assay method of GC-R in HPL. such as the effect of receptor occupancy by intrinsic cortisol or administered GC. In the present study, it was clarified that receptor-bound prednisolone or cortisol was almost completely dissociated from the receptor by washing lymphocytes three times with 30 min equilibration at 37 degrees C between each centrifugation. The GC receptor was measured by whole cell binding assay using [3H] dexamethasone as a ligand. The receptor number and dissociation constant (Kd) of lymphocytes, which were preincubated with prednisolone (10(-7) M) or cortisol (10(-6) M) at 37 degrees C for 1 h, were equal to those lymphocytes preincubated without GC. These data indicated that the receptor number and Kd of HPL can be determined without the effects of receptor occupancy by this assay procedure. The GC and GC-R complex in the nucleus are quite important for the action of GC. However, there have been few reports about the assay of nuclear GC-R in HPL. In this study, it was elucidated that nuclear receptor-bound [3H] dexamethasone could be measured by centrifugation (2000 g, 10 min) of the nuclei of lymphocytes after being lysed in 1.5 mM MgCl2 (0 degree C). By these assay procedures, the receptor number in whole lymphocytes of normal HPL (n = 22) was determined to be 10.48 +/- 2.40 (M +/- SD) fmoles/10(6) cells, and Kd was 5.8 +/- 1.24 nM, while the receptor number and Kd in the nuclei were 5.68 +/- 1.53 and 6.29 +/- 1.49, respectively.

Adolescent↗
PubMed1986

[Studies on the glucocorticoid receptor in human peripheral lymphocytes. II. Regulation by glucocorticoid].

The effect of glucocorticoid (GC) on the GC receptor in human peripheral lymphocytes was studies in vivo and in vitro. Excluding the effect of receptor occupancy, the GC receptor was measured by whole cell binding assay using [3H] dexamethasone as a ligand. The numbers of GC receptor in lymphocytes (whole cell, 8.42 +/- 1.88; nucleus, 3.56 +/- 1.38 fmoles/10(6) cells (M +/- SD) of patients treated with prednisolone (n = 26, mean: 33.7 mg/day) were significantly reduced when compared with those of normal subjects (n = 21; 10.48 +/- 2.40, 5.68 +/- 1.53) and those of patients without GC therapy (n = 9: 10.56 +/- 2.10, 5.26 +/- 1.07), respectively. The dissociation constants among these subjects were almost similar (5-7 nM). There were negative correlations between the receptor numbers (both whole cell and nucleus) of patients and daily dosage of prednisolone. The GC receptor numbers in both the whole cell and the nucleus were significantly decreased after 48 h in vitro preincubation with active GC. When new protein synthesis was blocked by cycloheximide (1 microgram/ml), GC did not reduce its own receptor number in vitro. Thus, the new protein synthesis may be required for this reduction in receptor number by GC. These results strongly suggest that GC down-regulates its own receptor in human peripheral lymphocytes.

Adult↗
PubMed1986

[Studies on the glucocorticoid receptor in human peripheral lymphocytes. III. Correlation between receptor number and clinical response to glucocorticoid].

Although the clinical response to glucocorticoid (GC) therapy varied considerably from patient to patient, it is not known how to predict the responsiveness of each patient. In the present study, it was evaluated whether the responsiveness to GC in an individual patient was predictable by the GC receptor number. GC receptor number in human peripheral lymphocytes was measured by whole cell binding assay using tritiated dexamethasone as a ligand. There was a significant negative correlation between receptor number and dose of GC being given to the patient (down-regulation). The relative receptor number was expressed as a percentage of the receptor number to the mean of the receptor number in the group of patients stratified by every 10mg/day of the dosage of prednisolone. This relative receptor number was constant in an individual subject regardless of GC dosage. In 12 patients with lupus nephritis who had a high receptor number (more than 100%), 9 patients (83%) showed improvement in their urinary findings after GC treatment. On the other hand, only 3 of 11 lupus nephritis patients with a low receptor number (less than 100%) showed improvement after GC therapy. In patients with various collagen diseases treated with 40-60 mg/day of prednisolone, there were significant correlations between receptor number and each of % creatinuria, total cholesterol in serum, and fasting urinary calcium excretion, which were known to be affected by GC administration. Thus, the relative receptor number in lymphocytes was well correlated with both therapeutic and metabolic effects of GC in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗