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Biomedical subjects

N Ohsawa

Publications and source records attributed to N Ohsawa.

At least 109 records · Page 6Linked to original sources
PubMed1990

Quantitative in vivo assay of human granulocyte colony-stimulating factor using cyclophosphamide-induced neutropenic mice.

Administration of human granulocyte colony-stimulating factor (hG-CSF) to mice with cyclophosphamide (CPA)-induced neutropenia for 4 consecutive days from the day after the CPA dosing (100 mg/kg) resulted in a dose-dependent increase in the peripheral blood neutrophil count 6 hours after the final hG-CSF injection. Within the hG-CSF dose range of 0.1 to 10 micrograms per mouse per day, there was a strong linear relationship (r greater than .9) between the logarithm of the dose and the peripheral blood neutrophil count in the treated mice. Using the same hG-CSF preparation, 38 experiments indicated that the regression lines are highly reproducible. Such an association never occurred with intact mice, and 100 mg/kg of CPA induced the highest response to hG-CSF. This linear relationship between the two variables allows us to determine the biologic potency of a test hG-CSF preparation relative to a reference standard using a parallel line assay, with a coefficient of precision of around .2. When assayed by this bioassay procedure, which we have termed CPA-mouse assay, natural hG-CSF and recombinant hG-CSF (produced by Chinese hamster ovary cells) were nearly equipotent in specific biologic activity. These results confirm the CPA-mouse assay as an especially useful assay method for quantifying the in vivo activity of hG-CSF.

Agranulocytosis↗
PubMed1990

Changes in serum autoantibodies to thyroid peroxidase during antithyroid drug therapy for Graves' disease.

Thyroid microsomal antigen is considered to be identical with thyroid peroxidase (TPO). Although there have been many reports concerning changes in microsomal autoantibody during the course of antithyroid drug therapy for Graves' disease, little is known about this matter in relation to TPO autoantibody (TPOab). Therefore, in this paper, we studied serial changes in the latter autoantibody. Initial levels of serum TPOab (% immunoprecipitation) in 13 patients with hyperthyroid Graves' disease ranged from -11.3% to +84.5% (mean +/- SD, 38.9 +/- 31.8%). Of three patients with persistently increased serum TPOab throughout drug therapy, all had recurrence of hyperthyroidism after the drug was discontinued. Of seven patients whose TPOab levels were initially high but subsequently decreased, four had remission of the disease after drug therapy. Inhibition by TPOab of the TPO activity was also demonstrated by both guaiacol and iodide assays, and changes in this inhibitory activity during therapy varied among individuals. This inhibition was not correlated with disease remission. The decrease in serum TPOab observed in some antithyroid drug-treated patients may reflect a decline in disease activity or may be a direct effect of the drug.

Adolescent↗
PubMed1990

Can the type of variant albumin in familial dysalbuminemic hyperthyroxinemia be determined by measuring iodothyronines in serum?

A recent report documented the existence of three putative types of variant albumin in dysalbuminemic hyperthyroxinemia (DH) and suggested that measurement of the total concentration of three iodothyronines (T4, T3 and rT3) in serum of affected subjects could aid in their differentiation. In the present report, we describe three affected subjects from a single family which DH exhibited, in addition to increased serum total T4 levels, variable changes in the concentrations of total T3 and rT3. The concentrations of the following iodothyronines were above the normal limit: T4, T3 and rT3 in the propositus, T4 and T3 but not rT3 in her sister, and T4 but not T3 and rT3 in her mother. These differences cannot be caused by structurally different types of variant albumins, because the three subjects are members of the same family. They rather correlated with the relative abundance of the variant albumin in serum of the affected family members. Although previously reported subjects with DH always had serum T4 levels above the normal limit due to the predominantly higher affinity of the variant albumin for T4, significant increases in the concentration of serum T3 and rT3, reaching at times values above the upper normal range, have also been observed. Since a number of factors, including the relative abundance of the variant albumin, influence the concentration of iodothyronines in serum, their measurement alone cannot be used to determine the inherited type of DH.

Adult↗
PubMed1990

[Recent progress in polyamine research].

Polyamines are recognized as cell growth factors in relation to cell proliferation, differentiation, regeneration and malignant transformation. Polyamines play an important role in the growth of normal cells like vascular endothelial cells and also exert various effects on the proliferation and metastasis of malignant cells. The recent studies on the biosynthesis have clearly elucidated its mechanism at the gane levels, which reflects to the development of the inhibitors of the polyamine biosynthesis. One of the main purposes of the studies on the various polyamine synthesis inhibitors is for the development of new anti-cancer agents, based on the characteristics of the polyamine functions. The clinical effects of several inhibitors, however, have not been shown to be satisfactory and the reason is now the most important research subject in this field. The measurement of the polyamine contents in biological fluids including urine and blood has been shown to be useful as the tumor marker. The recent studies have indicated that the mechanism of increased secretion of urinary polyamines is due to the release from the degraded cancer cells. The results now stimulated the research which aims to elucidate the usefulness of the measurement of urinary polyamines as the parameters of the sensitivity to the anticancer drugs in patients with cancer.

Biogenic Polyamines↗
PubMed1990

[Coronary circulation, myocardial metabolism and cardiac catecholamine flux in patients with syndrome X].

To clarify the pathogenesis of syndrome X (Sx), hemodynamics, coronary circulation, myocardial lactate metabolism and cardiac catecholamine flux were studied before and during bicycle ergometry in 25 patients (pts) and these data were compared with those in 15 with effort angina (EA) and in eight controls. The results were as follows: 1. The cardiac index during exercise decreased in EA pts probably due to their coronary lesions, while those in the controls and Sx were well preserved. 2. An increase of coronary blood flow during exercise, both in Sx and EA pts, was significantly impaired and the myocardial extraction ratio of lactic acid was significantly lower compared with those in the controls. The cardiac norepinephrine release during exercise was markedly higher in Sx, compared with that in controls and in EA. These results suggested that in Sx, excessive sympathoadrenergic stimulation may play an important role in restricting coronary reserve and in accelerating myocardial anaerobic metabolism.

Angina Pectoris↗
PubMed1990

Diagnosis of familial dysalbuminemic hyperthyroxinemia and investigation of the nature of the variant albumin.

A variant albumin with abnormally increased thyroxine-binding affinities has been identified, and termed as familial dysalbuminemic hyperthyroxinemia (FDH). The aims of this study are to seek for a method of diagnosis to distinguish FDH from other causes of hyperthyroxinemia and to investigate the nature of this abnormal albumin. Percent T4 bound to albumin was high in FDH, ranging 29-48% (normal range 3-8%), as measured in [125I] T4 loaded serum using a single immunoprecipitation by anti-human albumin antibody. A subject with T4 autoantibody in serum had a lower value. Only a single subject with TBG deficiency had an overlapped value (33%) with that of FDH, but the level of serum T4 could differentiate TBG deficiency from FDH. Isoelectric focusing (IEF) showed a distint albumin band with an isoelectric point of pH 5.05 in all FDH subjects, and this band was not compatible with any of 4 albumin bands seen in normals. These data suggest that only two simple measurements including the level of serum T4 and the single immunoprecipitation for [125I] T4-bound albumin can distinguish FDH from other causes of hyperthyroxinemia.

Adult↗
PubMed1990

Methodology of ECG interpretation in the Nagoya program.

The outline of the Nagoya Program, the most representative software package for computerized electrocardiography in Japan, is described. First, the history and current status of research and its transfer to commercial products for computerized interpretation of electrocardiograms is briefly reviewed. Second, development and testing of the Nagoya Program is depicted, referring to a gold standard for evaluation and the database being used for this purpose, and to its participation in the CSE study. Third, a description of signal acquisition and wave identification is given, followed by the detection of rhythm disturbances. Next, algorithms for contour classification, which consist of decision-tree logic established through trial and error and making use of the database of ECGs, are described. Finally, special features and future plans of the Nagoya Program are mentioned.

Algorithms↗
PubMed1990

[Rheological analysis of suppressed leukocytosis in patients with pregnancy induced hypertension (PIH)].

It is documented that the number of leukocytes in peripheral blood increases considerably during pregnancy. We observed that the range of leukocytosis differs in normal pregnancy differs from that in cases with severe pregnancy induced hypertension (PIH). The data obtained in our university hospital, for example, give the number of leukocytes after twenty-four weeks of gestation as 9,000 +/- 1,600/mm3 (mean +/- SD) for normal cases (93 measurements in 37 cases) and 6,600 +/- 1,100/mm3 for PIH (72 measurements in 18 cases; p less than 0.001). To elucidate the cause and relation to PIH, we studied changes in the activity of leukocytes during pregnancy by means of a modified Nuclepore filtration method (Kikuchi et al., 1983). The time required for leukocytes to squeeze through filter pores under constant suction varies greatly depending on their active states; more active cells show greater resistance to pore passage, which can be clearly shown by exposing cells to various stimuli. The filtration time for 0.5ml blood containing 5,000/mm3 leukocytes minus that of leukocyte poor blood with the same hematocrit was taken as an index of the activity, which we called the rheological activity of leukocytes (RAL). RAL values for blood taken at delivery were 3.4 +/- 1.5 sec for normal cases and 5.0 +/- 2.1 sec for PIH (N.S.). RAL values obtained after the addition of a chemotactic stimulant FMLP (formyl-methionyl-leucyl-phenylalanine) (10nM) to the same samples were 21 +/- 10 sec for normal cases and 405 +/- 265 sec for PIH (p less than 0.001). Leukocyte activity, particularly, response to chemotactic stimulation, was the before thought to be considerably increased in PIH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Correlations among chemical constituents, cytotoxicities and tissue responses: in the case of natural rubber latex materials.

Natural rubber latex films obtained from 40 different brands of rubber gloves were tested by quantitative chemical analyses, two cytotoxicity tests (agar-diffusion assay using L929 cells and colony assay using V79 cells) and 7-day implantation test in the rabbit muscle. Multiple regression analysis of these data showed that dithiocarbamate accelerators caused the toxicities whereas antioxidants did not. Thickness of inflammatory layer was the most useful parameter to evaluate tissue response among 13 histological parameters investigated. There were good correlations between the cytotoxicity indices and the thickness of inflammatory layer.

Animals↗
PubMed1989

Impaired regulation of skin temperature in patients with diabetes mellitus evaluated by the cold exposure test.

This study aimed at evaluating vasomotor response of the hand in patients with diabetes mellitus. A skin temperature of the hand was measured before and after exposure to ice water, and the recovery rates of the skin temperature were determined at 3, 5, and 10 min after the cold exposure. Ninety-two diabetics ranging in age from 25 to 59 years and 43 normal subjects ranging from 23 to 69 years old participated in this study. Since the recovery rate was delayed in normal subjects over the age of 60, comparison was made between the diabetics and the normals under 60 years old. The skin temperature was significantly lower in 26 diabetics with severe peripheral neuropathy (PN) than 40 diabetics without PN. The recovery rate were markedly delayed in the patients with PN, and also delayed in diabetics with severe retinopathy. The recovery rate was not different between the patients with and without ischemic changes in electrocardiogram. The delayed recovery rate was most prominent in the diabetics who had both abnormal heart rate variation (HRV) and orthostatic hypotension, followed by those with abnormal HRV but without orthostatic hypotension. Recovery rates in the diabetics with abnormal HRV alone were within the normal range. Our data suggest that the dysfunction of the regulation of skin temperature in the patients with diabetes mellitus was due to peripheral sympathetic nerve abnormality. The cold exposure test would be useful in the estimation of the sympathetic nerve activity of the diabetics.

Adult↗
PubMed1988

CSE (common standards for quantitative electrocardiography) data testing in Japan.

The authors comment on the present status of computerized electro-cardiogram (ECG) works in Japan and demonstrate the preliminary tentative results of CSE (common standards for quantitative electrocardiography) data analysis using the Nagoya program. The more detailed results of the performance of several programs in CSE data analysis are discussed by Dr. Willems.

Diagnosis, Computer-Assisted↗
PubMed1988

[Urinary total polyamines levels in estrous cycle and during pregnancy in female rats].

Urinary total polyamines; putrescine, spermidine and cadaverine, levels were determined in the estrous cycle and during the pregnancy in female Wistar rats. Urinary total polyamines level in 12 estrous cycles in 4 female rats revealed the definite cyclic changes, showing high levels at estrous and low levels at diestrous stage. After the ovariectomy those cyclic changes disappeared. Urinary total polyamines levels were constantly low during the first half of the pregnancy of 8 female rats, whereas the levels increase abruptly from 10 days before parturition. After fetusectomy at 15th and 17th days of the pregnancy, those levels decreased gradually. These data suggested that the urinary total polyamines levels were closely related with the pituitary-ovarian function and the growth of fetus of rats.

Animals↗
PubMed1988

[Tumor-oriented anti-cancer agent with estrogen as a carrier].

Tumor oriented anticancer agents with estrogen as a carrier have been extensively studied since 1950's. Only Estracyt and bestrabucil have been evaluated to be useful in clinical trials. Although the use of estrogen as a carrier for anticancer agents aimed at the development of the anticancer drug for the receptor mediated chemotherapy, these two drugs did not show any affinity to estrogen receptor. The history tells us that the development of anticancer agents for the estrogen receptor mediated chemotherapy is extremely difficult. Estracyt is reported to exert its anticancer effect on prostate cancer through the specific binding to the estramustine binding protein (EMBP) which is present only in the prostate gland and cancer. Bestrabucil shows the selective uptake by the various malignant cells and is indicated that bestrabucil exerts its anti-cancer effects on various malignant tumors including breast cancer and hematopoietic malignancy, through the affinity to malignant cells. The mechanism is unknown and to be elucidated.

Animals↗
PubMed1987

Effects of DL-alpha-difluoromethylornithine on the growth and metastasis of B16 melanoma in vivo.

The effects of DL-alpha-difluoromethylornithine (DFMO), a specific irreversible inhibitor of ornithine decarboxylase, on the growth of experimental mouse B16-F10 melanoma cells were investigated. DFMO (3%) in drinking water was administered to B16-F10 melanoma-bearing mice. At 24 days, B16-F10 melanomas in DFMO-fed mice weighed 75% less than those in control mice (p less than 0.001). DFMO reduced putrescine and spermidine levels in B16-F10 melanoma by 98% and 84%, respectively, and prolonged the mean survival time from 25.9 +/- 1.2 to 35.7 +/- 2.2 days (p less than 0.001). The effects of DFMO on experimental metastasis were also investigated. DFMO treatment resulted in a significant decrease in pulmonary metastasis induced by i.v. injection of B16-F10 melanoma cells.

Animals↗