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Biomedical subjects

N Ohsawa

Publications and source records attributed to N Ohsawa.

At least 163 records · Page 9Linked to original sources
PubMed1982

Production of human alpha 1-antichymotrypsin-like protein by a human malignant melanoma transplanted into nude mice.

A tissue culture line of a human malignant melanoma, SEKI, induced cachexia in nude mice (BALB/c-nu/nu) (Kondo et al., Cancer Res., 41: 2912-2916, 1981). During the investigation of the cause of the cachexia, the melanoma was found to produce a protein immunologically identical to human alpha 1-antichymotrypsin (alpha 1-Ach). Tissues of the SEKI melanoma contained the protein immunologically equivalent to 0.29 +/- 0.11 (S.D.) mg of human alpha 1-Ach per g of wet tissue, while the other six human malignant tumors transplanted into nude mice did not contain a detectable amount of it. In the serum of nude mice bearing the melanoma, this protein appeared soon after the tumor growth occurred and gradually increased up to the level equivalent to 5 mg of human alpha 1-Ach per dl. Removal of the tumor resulted in a rapid decrease of the protein in the serum to an undetectable level within 1 day. This problem was never detected in the serum of nude mice bearing the other 27 human malignant tumors or controls. Purification of this protein was carried out by the column chromatography using DE-52, Blue-Sepharose, and SP-Sephadex. The elution patterns were the same as those of alpha 1-Ach in human serum, and the molecular weight of the protein was estimated as 69,000 by Sephadex G-100 column chromatography and 65,000 by polyacrylamide gel electrophoresis with sodium dodecyl sulfate. This purified protein, however, did not exhibit inhibitory activity against chymotrypsin. These results show that this melanoma produced a protein immunologically identical and physicochemically very similar to human alpha 1-Ach. This melanoma-nude mouse system may provide a useful model for investigating the synthesis of human alpha 1-Ach and analysis of its physiological roles.

Animals↗
PubMed1982

Factor(s) responsible for the increase in alkaline phosphatase activity of postmitotic granulocytes from normal individuals and patients with chronic myeloid leukemia.

Using postmitotic granulocytes (PMGs) with low neutrophil alkaline phosphatase activity (NAP activity), factor(s) having the capacity to increase their NAP activity were examined in vitro. A high activity of the factor was demonstrated in the cystic fluid of a human squamous cell carcinoma, which is known to produce a large amount of granulocyte-macrophage colony-stimulating factor (GM-CSF). The NAP-stimulating factor increased NAP values both in PMGs from normal bone marrow and PMGs from patients with chronic myeloid leukemia (CML), and NAP values in cells treated with the factor approached or rose above those of normal peripheral granulocytes after 48 hr of culture. The effect of the factor was specific in that the factor caused stimulation only in granulocytic series. These findings may indicate that increases in NAP activity reflect maturation or granulocytes and that low NAP activity of neutrophils derived from patients with CML is due to the immaturity of these cells. The relationship between the factor responsible for the increase in NAP activity and GM-CSF is also discussed.

Alkaline Phosphatase↗
PubMed1981

Cells originating from sarcoid granulomas in vitro.

In an attempt to obtain in vitro experimental models for sarcoidosis, the primary cultures of granuloma cells were initiated with lymph nodes from 10 sarcoidosis patients. The cells migrating from tissue explants became confluent at 2 wk of culture. These cells exhibited overall morphologic features and enzymatic activities resembling those of in vivo granuloma epithelioid cells. By light and electron microscopy, the epithelioid cell in vitro contained a clear, large nucleus with 1 or 2 prominent nucleoli. The cytoplasm was characterized by the occurrence of lysosomal dense bodies and electron-lucent vacuoles, besides many mitochondria and well-developed Golgi complexes. The cell surface exhibited many processes, mainly lamellipodia. Large amounts of angiotensin converting enzyme activity (3.9 to 50.1 nmol/min/ml) lysozyme activity (3.9 to 23.0 micrograms/ml) were demonstrated in the medium used for culture. The results indicated that the major cell population grown in these cultures is derived from the epithelioid cells in sarcoid granulomas.

Adult↗
PubMed1981

Neurophysin biosynthesis in vitro in oat cell carcinoma of the lung with ectopic vasopressin production.

The incorporation of labeled compounds into neurophysins of a transplantable human oat cell carcinoma of the lung with ectopic vasopressin production was studied in vitro. Neurophysins in cell extracts and in incubation media were isolated by immunoprecipitation and analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. When cells were incubated with L-[35S]cysteine for 12 h, SDS-polyacrylamide gel electrophoresis of the immunoprecipitates from cell extract and medium resolved two forms of neurophysins with apparent molecular mass of 10,000 (10K) and 20,000 (20K). Both forms of [35S]-neurophysins were completely displaced from the immunoprecipitates by excess human neurophysin. Incubation of cells with L-[35S]cysteine and D-[3H]-glucosamine hydrochloride revealed that glucosamine was incorporated into the 20K neurophysin region, but not into 10K species. To observe the kinetics of labeling of the two forms of neurophysins, cells were incubated with L[35S]cysteine for varying periods of time. After short labeling periods, most of the radioactivity resided in 20K species, which plateaued after 1 h, whereas 10K neurophysin progressively increased in its height. When cells were chased with unlabeled cysteine after the exposure to a short pulse of labeling, 20K neurophysin peak gradually decreased with an apparent initial half-life of 1 h. In contrast, the label in 10K neurophysin steadily increased, which exceeded the former by 3 h of chase. Analysis of 20K neurophysin in cell extract by isoelectric focusing on polyacrylamide gel demonstrated that it was principally composed of a protein with an apparent isoelectric point (pI) of 5.7. These results suggest that neurophysin is synthesized in ectopic vasopressin-producing tumors by post-translational processing from a glycosylated proneurophysin with an apparent molecular mass of 20,000 daltons and a pI of 5.7.

Animals↗
PubMed1981

TSH and prolactin secretions in Hashimoto's thyroiditis following withdrawal of thyroid hormone therapy.

Changes in the pituitary-thyroid axis in patients with Hashimoto's thyroiditis following withdrawal of thyroid suppressive therapy were analyzed. The group of patients with thyroid adenoma served as control (group I). Patients with Hashimoto's thyroiditis were divided into 2 groups on the basis of serum TSH levels 8 weeks after discontinuing the exogenous thyroid hormone (group II, less than 10 microunits/ml; group III, more than 10 microunits/ml). During treatment with L-T4(200 micrograms/day) or L-T3(50 micrograms/day), there was no significant difference in serum T4-I and T3 levels among the three groups. Following L-T4 withdrawal, basal serum TSH levels were higher at 2 to 8 weeks in groups II and III than in group I. Serum TSH response to TRH was greater at 4 to 8 weeks in groups II and III than in group I. Following L-T3 withdrawal, basal serum TSH levels were higher at 1 and 2 weeks in group II than in group I, while those of group III were consistently higher during the study. Higher TSH responses to TRH were observed at 1 to 8 weeks in groups II and III. Neither basal nor TRH-induced prolactin (PRL) secretion differed significantly among the three groups. We have demonstrated that pituitary TSH secretion in patients with Hashimoto's thyroiditis is affected more by withdrawal of thyroid hormone therapy than in patients with thyroid adenoma. In addition, the present findings suggest a difference between the sensitivity of thyrotrophs and lactotrophs in Hashimoto's thyroiditis after prolonged thyroid therapy is discontinued.

Adenoma↗
PubMed1981

Inappropriate secretion of antidiuretic hormone in nude mice bearing a human bronchogenic oat cell carcinoma.

A 58-year-old man with bronchogenic oat cell carcinoma developed a typical syndrome of inappropriate secretion of antidiuretic hormone. The tumor tissue obtained at autopsy had been serially transplanted in nude mice for more than four years with 20 passages. The levels of vasopressin were remarkably increased in the plasma of nude mice bearing this tumor [24.4 +/- 18.3 (S.D.) pg/ml, n = 3] as well as in the tumor tissues ]134.3 +/- 72.2 ng/g, n = 3]. Furthermore, human nicotine-stimulated neurophysin was detected in both plasma and tumor tissues (7.4 +/- 3.7 ng/ml, n = 3, and 2.28 +/- 0.90 micrograms/g, n = 3, respectively). On ad libitum intake of water, nude mice bearing this tumor excreted significantly less urine with higher sodium concentration than did controls, but serum sodium concentrations did not differ from those of controls. When tumor-bearing mice were hydrated with 2 ml of water twice a day i.p., their diuretic response was found to be suppressed in parallel with the tumor size. However, these mice did not become hyponatremic because they drank less water. When a larger amount of water was loaded which could not be compensated by restriction of water drinking, serum sodium concentrations were markedly decreased. On the basis of these results, the lung cancer, when transplanted into nude mice, produced and secreted its own antidiuretic hormone, which induced inappropriate secretion of antidiuretic hormone in the mice. These mice may provide a useful experimental model for the study of excessive secretion of antidiuretic hormone and associated pathophysiological disorders.

Animals↗
PubMed1981

Epstein-Barr virus-induced lymphoblastoid cell lines from seropositive adult donors and their HLA-antigens.

Epstein-Barr virus (EBV)-induced lymphoblastoid cell lines (LCL) were established from seropositive adult Japanese donors. HLA-A, -B, -C and -DR antigens expressed on these EBV-LCL cells were identical to those of peripheral blood lymphocytes. There were no extra reactions upon DR typing; the extra reactivity in A, B and C typing was due to contaminating DR antibodies in the typing sera. In one-way mixed lymphocyte reactions with a stimulator : responder ratio between 1 : 10 and 1 : 20, autologous EBV-LCL exhibited low stimulation which could be distinguished from that of unrelated combinations. EBV-LCL may be useful for the screening of anti-DR antisera and as targets in cell-mediated lympholysis. Furthermore, EBV-LCL established from homozygous typing cells may be useful in HLA-D typing.

Cell Line↗
PubMed1981

Effect of HLA-DR matching between living kidney donors and recipients and of pretransplant blood transfusions on graft survival.

The effect of HLA-DR matching between living kidney donors and related recipients on 1-year graft survival was examined in 35 transplant recipients excluding 2-haplotype identical siblings. All 11 DR-compatible grafts survived 1 year; 7 of 24 DR-incompatible grafts ceased to function within 1 year (p less than 0.05). Among 24 DR-incompatible recipients, 6 of 11 who had preoperatively been transfused with less than 1000 ml blood lost their graft function. On the other hand, 12 of 13 who had received at least 1200 ml blood maintained their graft function beyond 1 year (p less than 0.05). All DR-compatible recipients received pretransplant blood transfusions and all produced anti-DR antibodies against random panel B cells after transplantation, but not against the graft donor's B lymphocytes. The anti-DR antibodies disappeared within 3 months. In recipients whose sera broadly reacted to random panel B cells at 1 years after transplantation, only 4 of 10 grafts survived. In recipients whose sera had lost their anti-DR reactivity within 1 year, all 20 grafts survived (p less than 0.05).

Antibody Formation↗
PubMed1981

Serum sialyltransferase and liver catalase activity in cachectic nude mice bearing a human malignant melanoma.

Cachexia is rare in nude mice bearing human malignant tumors even when the transplanted tumors become as large as the body size of the host. In our series on heterotransplantation of a variety of human malignant tumors into nude mice, a malignant melanoma (SEKI) was found to induce severe body weight loss in the host at the early stage of transplantation. There was no electrolyte disturbance, hyper- or hypoadrenocorticism, hyperthyroidism, or destruction of cells of vital organs to account for the weight loss. Moreover, no evidence was obtained for concomitant infection with bacteria, Mycoplasma or fungi. These cachectic mice revealed remarkably increased levels of serum sialyltransferase and decreased liver catalase activity. The removal of tumor tissues from these mice resulted in prompt recovery of body weight, serum sialyltransferase, and liver catalase activity within 1 to 2 weeks. On the basis of the results obtained, the SEKI melanoma was thought to have produced a pathophysiological state in host nude mice which was very similar to that of cachexia in cancer patients. Nude mice bearing transplants of SEKI melanoma may provide a useful system for the study of cancer cachexia in humans.

Animals↗
PubMed1980

Decline of postheparin plasma lipoprotein lipase in acromegalic patients.

Lipoprotein lipase and hepatic triglyceride lipase in postheparin plasma were measured in seven patients with active acromegaly by an immunochemical method utilizing antiserum prepared against hepatic triglyceride lipase. A mild or moderate hypertriglyceridemia was shown, with plasma triglyceride concentrations between 156 and 544 mg/dl. Lipoprotein lipase was found to be decreased in all patients (p less than 0.001). Hepatic triglyceride lipase was also low in these patients (p less than 0.001). We speculate that acromegalic hypertriglyceridemia is mediated, at least in part, by the decline in lipoprotein lipase and possibly by the decline in hepatic triglyceride lipase activities.

Acromegaly↗
PubMed1980

Detection and assessment of human tumours producing granulocyte-macrophage colony-stimulating factor (GM-CSF) by heterotransplantation into nude mice.

Production of granulocyte-macrophage colony-stimulating factor(s) (GM-CSF) by human tumours was investigated using heterotransplantation of a number of different tumours in nude mice. An increase in granulocyte numbers (> 20,000/mm3) in the peripheral blood of nude mice accompanied the growth of 9 of the 25 transplanted tumours. GM-CSF activity tested against normal human marrow cells was relatively high in 6 of these 9 tumours. Moreover there was either weak activity or none at all in 14 of the 16 tumours that failed to cause a definite granulocytosis. The correlation between granulocytosis and GM-CSF activity was 0.36, which was statistically significant (P < 0.01). These findings indicate that the transplantation of human tumours into nude mice can provide a useful tool for detection and characterization of granulopoietic factors derived from the tumours.

Animals↗
PubMed1979

Granulocytosis and colony-stimulating activity (CSA) produced by a human squamous cell carcinoma.

A patient with a squamous cell carcinoma accompanied by a marked granulocytosis (100,000/mm3) of unknown origin was examined for Colony-Stimulating Activity (CSA). The pleural fluid and the tumor extract revealed high CSA. The floating cells in the pleural fluid were successfully transplanted into nude mice as a localized tumor with cyst formation. The tumor invariably caused a marked granulocytosis (100,000--300,000/mm3) with induction of a conspicuous splenic granulopoiesis in the transplanted mice. High CSA were demonstrated in their cystic fluid as well. Media conditioned by the primary cultures of these tumor cells revealed the same CSA, demonstrating the direct production of CSA by the tumor itself. These results indicate the presence of human CSA producing tumor and that such a tumor may in part account for a marked granulocytosis of unknown origin observed in some patients with cancer.

Adult↗
PubMed1979

Prolonged stimulation of adenylate cyclase activity and testosterone production by cholera enterotoxin with suppression of gonadotropin release in rats.

Endocrine effects of cholera enterotoxin (CET) on male gonads were investigated in normal and hypophysectomized rats. After intratesticular injection of 5 micrograms of CET in the bilateral testes of normal rats, serum testosterone concentration remarkably increased after 24 hr, remained significantly elevated for at least 3 days and returned to the control level in 7 days. Serum LH level decreased in the undetectable range after 1--3 days; serum FSH level also significantly decreased after 3 days. Both gonadotropin levels increased 28 days after the injection, when the CET-injected testis decreased in weight and was accompanied by marked loss of germinal cells. When 5 micrograms of CET was injected intratesticularly in the bilateral testes of hypophysectomized rats, adenylate cyclase activity of a CET-injected testis was remarkably stimulated after 6 hr, remained four times elevated for at least 3 days and returned to the control level in 7 days. In relatively good accordance with the increase in adenylate cyclase activity, testosterone content remarkably enhanced in the CET-injected testis. These in vivo data indicate that the intratesticular injection of CET prolongedly stimulates the adenylate cyclase activity of testicular cells including Leydig cells and increases testosterone production, and suggest that the prolonged enzyme stimulation results in the sustained elevation of serum testosterone concentration for at least 3 days, causing the stimulation of the negative feedback mechanism of hypophysealtesticular axis to decrease serum LH levels in the undetectable range.

Adenylyl Cyclases↗