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Biomedical subjects

N Ohsawa

Publications and source records attributed to N Ohsawa.

At least 145 records · Page 8Linked to original sources
PubMed1984

[Bestrabacil: a possible target-oriented anticancer agent].

Bestrabucil, the benzoate of an estradiol-chlorambucil conjugate, was initially developed as a target-oriented anticancer agent for breast cancers with positive estrogen receptors, by conjugating a tumoricidal agent, chlorambucil, to a vehicle, estradiol. Further studies, however, revealed that regardless of the presence of estrogen receptors, bestrabucil selectively accumulates in malignant tumor cells. The unique feature of bestrabucil, selective affinity to tumor cells, was demonstrated in in vitro and in vivo studies. Significantly larger amounts of 3H-bestrabucil accumulated in malignant cells (3T3-SV40 transformed) than in normal cells (3T3). In vitro inhibition effects of bestrabucil on cell growth was observed only in malignant cells. Selective accumulation of bestrabucil in malignant tumor tissues was also demonstrated in in vivo experiments. After a single oral administration of 100 mg/kg of bestrabucil to female Wistar rats bearing Walker 256 carcinoma, bestrabucil accumulated significantly occurred in tumor tissues with little or no accumulation in normal tissues and blood. Anti-tumor effects and toxicities of bestrabucil and chlorambucil, were compared using Walker 256 carcinoma. Bestrabucil exerted its antitumor effects with little change in leucocyte counts in the peripheral blood, whereas chlorambucil showed significant side effects. Finally, selective accumulation of bestrabucil in malignant tumor tissues, was demonstrated clinically. Tumor specimens obtained during the operation of patients with various types of cancer, 24 hours after oral administration of 100 mg of bestrabucil, contained significantly larger amounts of bestrabucil compared with adjacent normal tissues. Clinical trials of bestrabucil are being carried out at present. Bestrabucil seems to be a promising target-oriented anticancer agent and deserves further investigation.

Administration, Oral↗
PubMed1983

Glucocorticoid receptor in chick erythrocytes.

Glucocorticoid receptor in chick erythrocytes has been characterized. The Scatchard plot analysis of (3H)-dexamethasone binding to red cells showed a single class of binding sites. The apparent Kd of (3H)-dexamethasone binding by whole cell assay was 0.33 nM and the maximum binding capacity was 5.1 fmole/10(7) cells. The apparent Kd of (3H)-dexamethasone binding to cytosol receptor was 0.48 nM. Steroid binding specificity was similar to that reported for leukocytes.

Animals↗
PubMed1983

Establishment and characterization of a carcinoembryonic antigen (CEA)-producing cell line from a human carcinoma of the exocrine pancreas.

A human carcinoembryonic antigen (CEA)-producing cell line, T3M-4, has been established from explant cultures of a primary human pancreatic exocrine adenocarcinoma transplanted into nude mice. The tumor had metastasized in the patient. The tumor obtained from metastatic lymph nodes was the initial source for implantation in athymic nude mice. In the primary culture, host fibroblasts were eliminated by the use of the antiserum raised against nude mouse cells. T3M-4 cells have been continuously propagated in vitro during the past 26 months. The cells grew in a monolayered sheet with about 31 hours of population doubling time. The cells exhibited epithelial morphologic features resembling the structure of the original tumor, and they showed tumor takes when inoculated into athymic nude mice. Xenografts established from the cell line have retained a similar histology to the original tumor on serial transplantation. Chromosomal analysis revealed the cell line to be a human aneuploid one with a hyperdiploid mode. T3M-4 cells possess the characteristic function of CEA secretion in vitro in culture and in vivo in nude mice bearing the tumors produced by inoculation with the cultured cells. In view of these characteristics, T3M-4 cell line represents a new human pancreatic exocrine adenocarcinoma cell line that produces CEA.

Adenocarcinoma↗
PubMed1983

Long-term survival and aldosterone secretion pattern of aldosteronoma in culture.

In an attempt to obtain an in vitro experimental model for aldosteronoma, primary culture was initiated with adenomas from 3 patients with primary aldosteronism. The cells grown in culture retained the morphology and functional properties characteristic of aldosteronoma cells well for periods of up to 200 days. The cells formed monolayer cell colonies and showed an epithelioid morphology with small nuclei containing prominent nucleoli. The cells possessed a clear, eosinophilic cytoplasm resembling that of aldosteronoma cells in vivo. The cultured cells continued to secrete large amounts of aldosterone throughout the culture period. The cells responded to angiotensin II and III by increased release of aldosterone into the culture medium. They also responded to Db-cAMP and ACTH by increased secretion of the hormone.

Adenoma↗
PubMed1983

Association of hypercalcemia with tumors producing colony-stimulating factor(s).

Two human malignant tumors, which we previously reported to produce colony-stimulating factors (CSFs), were found to be accompanied by remarkable hypercalcemia. A patient with a CSF-producing lower jaw cancer (squamous cell carcinoma) developed a marked granulocytosis (150,000/microliters) and hypercalcemia (more than 215 mg/dl). The tumor was successfully transplanted into nude mice, which developed marked granulocytosis (300,000/microliters) and hypercalcemia (20 mg/dl). White blood cell and serum calcium concentrations of these mice decreased promptly to normal levels when the tumor was excised. Treatment with prednisolone (1.5 mg/kg) or indomethacin (5 mg/kg) had no effect on the serum calcium level of these mice. Parathyroid hormone or prostaglandin E was not increased in the serum of the mice or in the tumor tissue. However, the mice bearing the tumor excreted extremely large amounts of calcium in their urine, and their bony tissues contained less calcium and phosphorus than controls. Moreover, histology of bony tissues of these nude mice clearly demonstrated the decrease in trabecular tissues and cortical thickness as well as remarkable activation of osteoclasts. Another patient with a CSF-producing bronchogenic squamous cell carcinoma showed mild granulocytosis and hypercalcemia. The biopsied tumor tissue was transplanted into nude mice, which developed marked granulocytosis (300,000/microliters) and also severe hypercalcemia (18 mg/dl). These results suggest the presence of a new syndrome of granulocytosis and hypercalcemia associated with CSF-producing tumors. The causal mechanism of the hypercalcemia was shown to be some humoral factor which activates osteoclasts other than parathyroid hormone. Neither prostaglandins nor osteoclast-activating factor seemed to be the cause of the hypercalcemia.

Adult↗
PubMed1983

A new simple enzymatic assay method for urinary polyamines in humans.

We developed a new simple enzymatic assay method for measuring urinary polyamines (total amount of putrescine, spermidine, and cadaverine), using an acylpolyamine amidohydrolase and a putrescine oxidase. First conjugated polyamines (putrescine, spermidine, and cadaverine) in urine were hydrolyzed by incubation with an acylpolyamine amidohydrolase at 30 degrees for 1 hr. then, free polyamines were separated by cation-exchange chromatography and incubated with a putrescine oxidase at 30 degrees for 30 min. Hydrogen peroxide formed in this reaction was measured spectrophotometrically (at 514 nm). Polyamine levels in urine were determined in 70 normal subjects, 124 patients with cancer, and 52 patients with diseases other than cancer. Elevation above 3 S.D.s of the normal mean was found in 90 (72.6%) of the 124 patients with cancer and in 6 (11.5%) of the 52 patients with diseases other than cancer. Serial studies in 19 patients with cancer indicated that polyamines in urine were reduced after successful surgery. Our new method is simple and rapid and therefore very useful for routine clinical application. Moreover, our data indicate that the determination of polyamine levels is useful as a marker of disease activity in patients with cancer.

Amidohydrolases↗
PubMed1982

Triacylglycerol lipases in adrenals and testes of rats.

Triacylglycerol lipase activities in adrenals and testes of rats were measured and the properties of the enzymes were characterized. The enzymes were extracted from acetone-ether dried powder of the tissues and the crude extracts were applied to a heparin-Sepharose affinity column. The enzymes bound to the column were then eluted at different ionic strengths. Two lipases could be detected in rat adrenals: one was inactivated by the antiserum raised against hepatic triacylglycerol lipase and the other had the properties of lipoprotein lipase. In testes, only lipoprotein lipase could be detected. The results are discussed in connection with the possible functions of these two lipases in organs utilizing lipoprotein-cholesterol for steroid hormone synthesis.

Adrenal Glands↗
PubMed1982

Lipoprotein lipase activity in adipose tissue of streptozotocin-induced diabetic rats.

Lipoprotein lipase activity of epididymal adipose tissue was measured in streptozotocin-induced diabetic rats. Diabetic rats of 3, 10 and 34 days duration were examined. The enzyme activity in adipose tissue of diabetic rats was similar to that of control rats of the same ages, compared on the tissue weight basis. However, since adipose tissue weight was markedly reduced in rats with both acute and chronic diabetes, total enzyme activity in the whole tissue was very low in such animals regardless of the duration of diabetes. We wish to point out that contradictory results on the adipose tissue lipoprotein lipase activity in diabetic rats in the previous reports have arisen depending on differences in the methods chosen to express enzyme activity.

Adipose Tissue↗
PubMed1982

HLA-D typing using Epstein-Barr virus-induced lymphoblastoid cell lines.

We examined whether Epstein-Barr virus-induced lymphoblastoid cell lines, established from homozygous typing cells (HTC-EBV-LCL), could be substituted for normal homozygous typing cells (HTC) in HLA-D typing. When using EBV-LCL as stimulators in one-way MLR, the stimulator: responder ratio was found to be most important. At a ratio of 1:10, the autologous MLR between EBV-LCL and PBL from the same donors exhibited low double normalized values (DNV) which could be distinguished from those of homologous combinations. The panel cells typed with HTC always exhibited low DNV in repeat one-way MLR in which EBV-LCL established from the same HTC were used. On the other hand, by employing our previously described method, we were able to establish the necessary HTC-EBV-LCL from unselected seropositive adult donors and utilize these cells for HLA-D typing. We suggest that our method makes it possible to circumvent the problem presented by the shortage of HTC, since our HTC-EBV-LCL can be substituted for normal HTC in HLA-D typing.

Cell Line↗
PubMed1982

Immune response to alien histocompatibility antigens on Epstein-Barr virus transformed cells.

Expression of alien histocompatibility antigens on Epstein-Barr virus transformed, cultured lymphoblastoid cell lines (LCL), which were established from normal peripheral blood lymphocytes (PBL), was studied by means of mixed lymphocyte reaction (MLR), cell mediated lysis (CML) and primed lymphocyte typing (PLT). Stimulation of PBL by autologous LCL resulted in some MLR responses and generation of cytotoxic effector cells against autologous LCL. Restimulation of PBL by 16 individual allogeneic PBL failed to prime an individual lymphocytes against autologous LCL in PLT tests. However, stimulation of PBL by a pooled normal PBL resulted in generation of cytotoxic cells against autologous LCL. Culturing of stimulated PBL in the presence of T cell growth factor (TCGF) for 30 days was shown to maintain cytotoxic effector cells in the cell population.

Cell Line↗