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Biomedical subjects

T Okabe

Publications and source records attributed to T Okabe.

At least 361 records · Page 20Linked to original sources
PubMed1987

Constitutive expression of the granulocyte-macrophage colony-stimulating factor gene in human solid tumors.

We detected constitutive expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene in 3 human solid tumors by Northern blot analysis. Two of them were also found to secrete the GM-CSF protein by colony forming unit-culture assay. Southern blot analysis of each tumor DNA showed no gross rearrangement of the GM-CSF gene. This is the first report that demonstrates expression of the GM-CSF gene in solid tumors at the mRNA level.

Colony-Forming Units Assay↗
PubMed1987

Histologic assessment of bronchial anastomotic healing in canine lung transplantation.

Postoperative wound healing of the bronchial anastomosis was studied in dogs with autotransplantation (20 dogs, 7 days to 6 years postoperatively) and allotransplantation (62 dogs, 5 to 174 days postoperatively) of the left lung. In the group undergoing lung allotransplantation, the relationship among three histologic parameters was studied: the grade of lung allograft rejection, the degree of changes in the epithelium, and submucous lymphocyte infiltration along the donor bronchus within approximately a 0.5 cm area distal to the anastomosis. In lung autotransplantation, mucosal continuity began to be observed 1 week postoperatively. Mucosal continuity and apparent collagen formation on any bronchial contiguous site were demonstrated in most animals studied more than 3 weeks postoperatively. Bronchial anastomotic healing tended to be slower in lung allotransplantation than in autotransplantation, although a mucosal continuity at the anastomosis was sporadically observed in immunosuppressed dogs surviving more than 3 weeks postoperatively with a lung allograft. There were significant rank correlations among the three histologic parameters, which showed that lung allograft rejection is closely connected with wound healing of the bronchial anastomosis in lung allotransplantation. Meticulous mucosal approximation is most necessary during bronchial anastomotic procedures. Establishment of an exact method for early monitoring of lung allograft rejection is absolutely necessary for lung allotransplantation.

Animals↗
PubMed1987

[Studies on nephrotoxicity of cyclosporin. 1. Nephrotoxicity in rats receiving cyclosporin].

Cyclosporin (CS) is a potent immunosuppressant that has been used in organ transplantation, but it has a serious nephrotoxic effect. To investigate its effects on renal function and structure, we carried out biochemical and morphological examinations in rats. Male Wistar rats each weighing 250 g were used. Rats were given various dose regimens (100, 50, 25 and 10 mg/kg/day) of CS orally over a 21-day period. All the rats were killed and examined on the 22nd day. Blood urea nitrogen (BUN), serum and urinary creatinine and urinary N-acetyl-s-D-glucosaminidase (NAG) were measured before administration and on the 7th, 14th and 21st day after administration. Kidneys were examined with light and electron microscopes. All rats that had received 100 mg/kg/day CS died within 12 days after a severe loss in body weight. Rats that had received 50 or 25 mg/kg/day CS had lost weight which never returned to the weight before administration. A high CS dose caused a significant elevation of BUN unaccompanied by a corresponding rise in serum creatinine. Reduction of creatinine clearance was not prominent during the experimental course. Although the urinary NAG activity was increased in high dose groups, the elevation was not related to dose. Morphological alterations were confined to the proximal tubuli and they consisted of tubular cell vacuolation and increased number of lysosomes. However, these alterations were mild and not related to the CS dose.

Acetylglucosaminidase↗
PubMed1987

Effect of human recombinant granulocyte colony-stimulating factor on hematopoietic injury in mice induced by 5-fluorouracil.

Intravenous (IV) administration of 5-fluorouracil (5-FU) caused severe hematopoietic injury in mice. Daily administration of purified human recombinant granulocyte colony-stimulating factor (rG-CSF) accelerated recovery from neutropenia in these injured mice. Granulocyte-macrophage progenitors (CFU-GM) in spleen were markedly increased by rG-CSF, while rG-CSF was less effective on the regeneration of CFU-GM in femoral marrow. The accelerated recovery from neutropenia in the mice might be mainly due to the stimulation of granulopoiesis in spleen by rG-CSF.

Animals↗
PubMed1987

[Usefulness of the bladder assist device (BLAD)].

We investigated the effectiveness of the Bladder Assist Device on urinary tract infection of patients with indwelling catheters. The patients, except for those with cord bladder and vesicoureteral reflux, could urinate intermittently under the BLAD system. Irrigation of the bladder using BLAD made urine clear and decreased urinary bacteria. Because of intermittent urination in patients who had been using the BLAD system for two weeks, the urine became somewhat clear and the number of bacteria decreased. Combination of bladder irrigation and intermittent urination using this system may inhibit urinary tract infection of an indwelling catheter. BLAD is considered to be a useful device for patients with continuous indwelling catheters.

Adult↗
PubMed1986

Metabolism of 25-hydroxycholecalciferol in human promyelocytic leukemia cells (HL-60). Isolation and identification of (5Z)- and (5E)-19-nor-10-oxo-25-hydroxycholecalciferol.

Human promyelocytic leukemia cells incubated with 25-hydroxy[26,27-methyl-3H] cholecalciferol (1 microCi) or non-radioactive 25-hydroxycholecalciferol (550 micrograms) produced significant quantities of two vitamin D3 metabolites. The two metabolites were isolated and purified by methanol chloroform extraction and a series of chromatographic procedures. The metabolite purification and elution positions on these columns were followed by radioactivity and their ultraviolet absorption at 310 nm. The two metabolites have been unequivocally identified as (5Z)- and (5E)-19-nor-10-oxo-25-hydroxycholecalciferol by ultraviolet absorption spectrophotometry, mass spectrometry, Fourier-transform infrared spectrophotometry and co-chromatography with synthetic compounds on a high-performance liquid chromatograph. (5E)- but not (5Z)-19-nor-10-oxo-25-hydroxycholecalciferol was able to induce HL-60 cell phenotypic and functional differentiation. However, these two metabolites of 25-hydroxycholecalciferol did not bind specifically to the chick intestinal 3.7 S. receptor protein for 1 alpha,25-dihydroxycholecalciferol. The precise biological role of these metabolites is as yet unclear.

Animals↗
PubMed1986

Induction by recombinant human granulocyte colony-stimulating factor of differentiation of mouse myeloid leukemic M1 cells.

The effect of recombinant human granulocyte colony-stimulating factor (G-CSF) on induction of differentiation of mouse myeloid leukemic M1 cells was examined. Purified G-CSF caused dose-dependent induction of phagocytic activity and lysozyme activity in M1 cells. Its half-maximally effective concentration was 10 ng/ml. On treatment of M1 cells with G-CSF (100 ng/ml) for 4 days, 30-50% of the cells differentiated morphologically into macrophage cells; 30-40% of the cells were blast cells and 20-30% of the cells were forms intermediate between blastic cells and mature macrophages.

Animals↗
PubMed1986

Corticosteroid receptor in type II pneumocytes of the rat.

Glucocorticoid receptor in rat type II pneumocytes has been characterized. The Scatchard plot analysis of 3H-dexamethasone binding to type II cells showed a single class of binding sites. The apparent Kd of 3H-dexamethasone binding by a whole cell assay was 9.1 nM and the maximal binding capacity was 78.0 f mol/10(6) cells (0.31 pmol/mg cytosol protein).

Animals↗
PubMed1986

A macrophage factor that stimulates the proliferation of vascular endothelial cells.

Sarcoid macrophage-epithelioid cells have been shown to release a growth factor that stimulates the proliferation of vascular endothelial cells in vitro. In the presence of this factor, cultured endothelial cells can proliferate in a serum-free medium. Gel-chromatography on Sephadex G-75 revealed a single peak of activity on endothelial cells. The molecular weight was estimated at 7,000-10,000. The activity was heat-labile and trypsin-sensitive, and did not adhere to heparin-Sepharose.

Cell Division↗
PubMed1986

In vitro formation of macrophage-epithelioid cells and multinucleated giant cells by 1 alpha,25-dihydroxyvitamin D3 from human circulating monocytes.

1 alpha,25-Dihydroxyvitamin D3, the active form of vitamin D3, induced maturation of circulating monocytes to form macrophage-epithelioid cells and multinucleated giant cells in vitro. Calcitriol not only promoted the differentiation of monocytes, as shown by the marked morphological changes and enhanced secretion of lysozyme, but also induced their prominent proliferation, as exhibited by enhanced DNA synthesis and the increased number of monocyte cell nuclei. The proliferation of monocytes was observed after the addition of physiological concentrations of calcitriol. Multinucleated giant cells were frequently observed among the monocytes. These marked morphological changes and the proliferation of monocytes were not observed in control cultures, which did not include calcitriol. These results indicate that calcitriol plays a critical role in the formation of the sarcoid granuloma and give an explanation of some of the clinical findings on sarcoidosis. In view of the evidence that sarcoid macrophages convert 25(OH)D3 to calcitriol, our results raise the possibility that the active metabolite of vitamin D3, which may be produced by macrophage-epithelioid cells, induces the differentiation and proliferation of circulating monocytes into macrophage-epithelioid cells, which in turn form sarcoidosis granulomas. This autostimulation mechanism of sarcoid granuloma formation may provide a model for future studies.

Adult↗
PubMed1986

Chromosomal aneuploidy in sarcoid granuloma cells.

Chromosomal examination and measurement of DNA content were performed in cultured sarcoid granuloma cells obtained from lymph node specimens of 11 patients with sarcoidosis. Chromosomal studies revealed that most of the cells were aneuploid; the chromosome number ranged from the near-haploid number to the near-diploid number, and the distribution of chromosome number was fairly wide. The DNA content of individual cells was measured by Feulgen microfluorospectrophotometry. The distribution of DNA content of the granuloma cells was fairly wide and did not show any recognizable peak. Flow cytofluorometry of DNA content of the cells also revealed wide frequency distribution of the DNA content in sarcoid granuloma cells. The majority of the sarcoid granuloma cells were aneuploid or hypodiploid in the short-term primary culture, suggesting that hypodiploidy may exist in granuloma cells of patients with sarcoidosis.

Adult↗
PubMed1986

Production of bone-resorbing activity and colony-stimulating activity in vivo and in vitro by a human squamous cell carcinoma associated with hypercalcemia and leukocytosis.

A squamous cell carcinoma of 33-yr-old patient who developed marked leukocytosis and hypercalcemia was transplanted into nude mice in which more marked leukocytosis and hypercalcemia also developed. This tumor (LJC-1-JCK) produced a colony-stimulating factor (CSF) and formed a cyst in the tumor from which a CSF-producing cell line (T3M-1) was established. The CSF causes predominantly formation of granulocytic colonies in addition to macrophage colonies. Bone-resorbing activity (BRA) was detected in the cystic fluid and was eluted as two separate peaks with proteins of an apparent molecular weight of 30,000-50,000 and 10,000-20,000. Colony-stimulating activity (CSA) was eluted at an apparent 30,000 mol wt. The conditioned medium of the T3M-1 cells also contained a BRA with an apparent 14,000 mol wt, whereas CSA eluted at an apparent 30,000 mol wt. PTH, epidermal growth factor, transforming growth factor-alpha, prostaglandin Es, and vitamin D could not account for the powerful BRA. In contrast to CSA, BRA was not inactivated by trypsin and more stable at 70 degrees C. When T3M-1 cells were transplanted into nude mice, marked hypercalcemia developed in addition to granulocytosis. Our findings suggest that the tumor produces and secretes a powerful BRA in vivo and in vitro, which is different from CSA in terms of molecular weight, heat stability, and trypsin treatment. We speculate that the synergistic action of CSF that stimulates macrophage colony formation and recruits osteoclast precursors, and BRA, which stimulates mononuclear phagocytes and/or osteoclasts were responsible for a marked increase in osteoclastic bone resorption and humoral hypercalcemia in the patient.

Animals↗
PubMed1986

A rat model for monitoring homograft rejection of the lung.

A new surgical procedure was devised for the experimental homograft of the lung. The pulmonary artery and vein and bronchus were anastomosed under the operation microscope using interrupted sutures in group W (30 outbred Wistar rats) and continuous sutures in group F (7 inbred F344/Ducrj Rats). Mean ischemia time during the operation was 95.3 +/- 10.3 min in the group W and 55.6 +/- 5.8 in group F. Eight out of 30 rats (27%) of group W and all rats of group F survived more than 24 hr after the surgery. Pulmonary functions of grafted lungs were evaluated by serial x-rays and the perfusion ratio was 27.4 +/- 11.6% (mean +/- S.D.) in group W and 25.4 +/- 7.7% in group F. A patent opening of the hilar anastomosis in these rats was confirmed at autopsy. This model with continuous suture would be useful for the rat lung transplantation.

Animals↗