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Biomedical subjects

N Ohsawa

Publications and source records attributed to N Ohsawa.

At least 19 recordsLinked to original sources
PubMed1992

Growth-inhibitory action of an estrogen-chlorambucil conjugate (KM2210) in human breast cancer cell line MCF-7: its relation to reduction of estrogen receptor and transforming growth factor-alpha secretion.

We investigated the effects of a benzoate of an estradiol-chlorambucil conjugate (KM2210) and chlorambucil on growth, estrogen receptor, and secretion of transforming growth factor (TGF)-alpha in the hormone-dependent human breast cancer cell line MCF-7. In the presence of 10(-10)-10(-6) M KM2210, the estrogen-induced growth of MCF-7 was completely inhibited. Inhibited growth of MCF-7 treated with 10(-8) or 10(-6) M KM2210 for 4 days was not rescued by removal of the drug and the addition of estradiol. By treatment of MCF-7 with KM2210 for 4 days, estrogen receptor-binding sites were decreased at 10(-8) M and were not detected at 10(-6) M but were unaltered by 10(-8) M chlorambucil. Moreover, estrogen receptor immunoreactivity and the level of estrogen receptor mRNA were decreased through treatment with 10(-6) M KM2210 for 4 days. These suppressions occurred prior to the onset of inhibitory action on MCF-7 growth. Secretion of TGF-alpha from MCF-7 was decreased by 4 days of treatment with 10(-8) and 10(-6) M KM2210 but not with chlorambucil. The addition of exogenous TGF-alpha generally restored the growth of MCF-7 treated with 10(-8) M KM2210. We concluded that KM2210 has irreversible or at least long-standing inhibitory effect on estrogen-dependent growth of MCF-7. It is conceivable that the decrease of estrogen receptor renders the cell unable to respond to estrogen with increased TGF-alpha secretion and succeeding cell growth.

Antineoplastic Agents↗
PubMed1992

Comparative studies by cell culture and in vivo implantation test on the toxicity of natural rubber latex materials.

Colony assay using V79 cells, the agar diffusion assay with L929 cells, and the 7-day rabbit muscle implantation test were employed to evaluate the cytotoxicity and tissue toxicity of natural rubber latex (NRL) materials. The in vivo implantation test showed that, among 13 histological parameters, thickness of inflammatory layer was the most useful index to evaluate tissue responses quantitatively. A comparison of the in vivo and in vitro parameters revealed the following correlations between the thickness of the inflammatory layer and cytotoxicity indices: Colony assay of the extracts, IC50: r = 0.80; Agar diffusion assay, Zone index: r = 0.73; Lysis index: r = 0.61. From these results, it appears that the colony assay provides a more reliable prediction of the tissue response than the agar diffusion assay.

Animals↗
PubMed1992

Postprandial hypotension in patients with non-insulin-dependent diabetes mellitus.

This study attempted to determine whether postprandial hypotension (PPH) is associated with diabetes mellitus by 24-h ambulatory blood pressure monitoring (24-h ABPM) and by monitoring blood pressure during 75-g oral glucose tolerance test (75-g OGTT) in 15 normal subjects and 35 patients with non-insulin-dependent diabetes mellitus. When we defined PPH as a postprandial decrease in systolic blood pressure of greater than 20 mmHg, the incidence of PPH in diabetics was 37% by 24-h ABPM and 20% by 75-g OGTT. The incidence of proliferative retinopathy and proteinuria was greater in diabetics with PPH than in those without PPH. All of the patients with PPH had somatic and autonomic neuropathy. The C-peptide response was lower in diabetics with PPH than in those without PPH. We revealed the presence of PPH in diabetics, and found that PPH was closely related to disease severity, especially diabetic autonomic neuropathy.

Adult↗
PubMed1992

Peroxidase and coupling activities of thyroid peroxidase in benign and malignant thyroid tumor tissues.

The coupling activity of thyroid peroxidase (TPO) in thyroid glands from patients with benign adenoma, papillary carcinoma, and diffuse goiter (Graves' disease) was measured for the first time, in addition to the peroxidase activity of these tissues. The peroxidase activity of TPO in the mitochondria-microsomes fraction was measured with guaiacol or iodide as the second substrate. In the case of papillary carcinoma, the mean protein-based specific activity obtained by the guaiacol assay was about 1/7 of that of diffuse goiter. The iodide oxidation activity of carcinoma was very low, about 1/25 [corrected] of that in diffuse goiter and 1/70 of that in adenoma. The peroxidase activity in adenoma was almost similar in the guaiacol oxidation assay and approximately one half in the iodide oxidation assay as compared with that in diffuse goiter. There was a close correlation between the guaiacol and iodide oxidation assays in individual patients with adenoma and diffuse goiter, but not in patients with papillary carcinoma. The coupling activity of TPO was measured with thyroglobulin purified from pooled toxic diffuse goiters and chemically iodinated to contain little additional T3 and T4. The specific coupling activity of TPO in mitochondria-microsomes from carcinoma was significantly lower (about 1/5) than that of diffuse goiter, and the activity in adenoma was not significantly different (about 1/2) from that of diffuse goiter. The data of coupling activities has a close correlation with that of peroxidase activities in individual patients with adenoma but not in patients with carcinoma. Based on these findings, the qualitative abnormality of TPO and its relation to the cold 123I scintigram in thyroid tumors are discussed.

Adenoma↗
PubMed1992

Thyroid-stimulating antibodies and thyroid stimulation-blocking antibodies during the pregnancy and postpartum period: a case report.

This report describes a unique pattern of changes in thyroid function and thyroid antibodies in a woman during the course of two pregnancies and two postpartum periods. A 25-year-old woman developed hypothyroidism in the postpartum period after the delivery of her first child. She was found to have potent thyroid stimulation-blocking antibodies (TSBAb) in the serum. One year later, she became pregnant again, and during the pregnancy, TSBAb had decreased to an undetectable level. She gave birth to the second healthy child and developed postpartum thyrotoxicosis, probably due to destruction of the thyroid gland, which gradually resolved. In this postpartum period, serum TSBAb levels increased. Eight months postpartum, she developed what appeared to be Graves' disease with an elevated 123I-thyroid uptake. Serum thyroid-stimulating antibodies (TSAb) were found at that time, and the TSBAb had disappeared from her serum.

Adult↗
PubMed1992

Epithelial hyperplasia and decreased colloid content of the thyroid gland in triiodothyronine-predominant Graves' disease.

Patients with T3-predominant Graves' disease have an increased serum T3 level despite a normal or even lower level of serum T4 caused by antithyroid drug treatment. This study investigated the morphological characteristics of the thyroid gland in this type of hyperthyroidism. Ultrasound showed a similar thyroid echogenicity in both T3-predominant and ordinary Graves' disease, but thyroid weight was significantly greater in T3-predominant Graves' disease than in the controls [91 +/- 37 g vs. 48 +/- 17 g (mean +/- SD); P < 0.01]. The height of thyroid follicular epithelial cells were significantly greater in T3-predominant Graves' disease than in the controls (9.6 +/- 1.0 vs. 6.4 +/- 1.1 microns), but the epithelial height did not correlate significantly with the serum TSH receptor antibody titers. Epithelial cells occupied 26.4 +/- 10.9% of the total thyroid tissue in T3-predominant Graves' disease, while they occupied only 14.5 +/- 6.8% in the controls. Intracolloidal vacuoles also occupied a significantly greater area in the T3-predominant group (6.6 +/- 3.9% vs. 1.9 +/- 1.0% for controls). These findings suggest that the thyroid gland is more active in T3-predominant Graves' disease and has a more rapid turnover of intrathyroidal iodine than in the ordinary type of Graves' disease.

Adolescent↗
PubMed1992

Biochemical studies of the relationship between iodothyronine 5'-monodeiodinase and protein disulphide isomerase in rat liver.

The relationship between type I iodothyronine 5'-monodeiodinase (5'-MD) and protein disulphide isomerase (PDI) was investigated by using a synthetic 18-amino acid peptide (LAP475c), which corresponds to the sequence of amino acids at position 373-390 of PDI including its active site, and anti-LAP475c antibody. Western blot analysis revealed that our anti-LAP475c antibody was highly specific for 57K protein in solubilized rat liver microsomal protein (SRLMP) that corresponded to PDI. Anti-LAP475c IgG (1:100 dilution) precipitated 46% of 5'-MD. These data suggest that PDI may play a regulatory role in the 5'-monodeiodination reaction.

Amino Acid Sequence↗
PubMed1991

Insulin-dependent diabetes mellitus in which glycemic control was improved during pregnancy but deteriorated after delivery with the occurrence of postpartum thyrotoxicosis: a case report.

We report a patient, a twin, with diabetes mellitus whose hyperglycemic state fluctuated during the course of the pregnancy and the subsequent delivery. She was diagnosed as having slowly progressive IDDM because of her clinical course and the findings of serum positive ICA/CF, positive HLA-DR4 and disconcordance of diabetes mellitus with her identical twin. Insulin therapy was not initially needed in the first two years because the endogenous insulin secretion was not completely reduced. After two years of insulin therapy the patient became pregnant. Her glycemic control was remarkably improved without changes in dietary intake and insulin dosage. After delivery glycemic control deteriorated after delivery with the occurrence of postpartum thyroiditis. Urinary excretion of CPR was increased during pregnancy but decreased after delivery. ICA/CF in serum were persistently detected in the whole observation period. It seems that the improved glycemic control during pregnancy was caused by the reduction in the autoimmune reaction and the deterioration in glycemic control during the postpartum period was induced by the acceleration of the autoimmune reaction by the same mechanism of postpartum autoimmune thyroiditis.

Adult↗
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↗