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Biomedical subjects

H Fukazawa

Publications and source records attributed to H Fukazawa.

At least 37 records · Page 2Linked to original sources
PubMed1999

Myotonic dystrophy associated with QT prolongation and torsade de pointes.

A rare case of myotonic dystrophy (MD) with congestive heart failure, associated with QT prolongation and torsade de pointes (TdP) is reported. A 53-year-old woman was admitted to the hospital because of congestive heart failure. Electrocardiograph (ECG) showed first-degree atrioventricular block and QT prolongation. During hospitalization, TdP appeared but returned to sinus rhythm spontaneously. As the patient had quadriplegia, a myopathic face, cataracts, diabetes mellitus, and an increased number of cytosine-thymineguanine (CTG) repeats (760 repeats), she was diagnosed as having MD. Electrocardiographic analysis of her family also revealed abnormal QT(U) prolongation in her daughter and brother who both had MD, while ECG findings of other family members without MD were normal. Thus, the presence of QT(U) prolongation was associated with MD in this family.

Cardiotonic Agents↗
PubMed1999

Increased serum soluble Fas in patients with Graves' disease.

We addressed the role of soluble Fas (sFas), which suppresses Fas-mediated apoptosis, in the pathogenesis of Graves' disease (GD). The serum concentration of sFas was measured by enzyme-linked immunosorbent assay and the expression of sFas mRNA in thyroid tissues by reverse transcriptase-polymerase chain reaction. The serum concentration of sFas was significantly increased in untreated GD (mean+/-SD: 1.57+/-0.48 ng/mL) compared to age-matched control subjects (0.77+/-0.46 ng/mL). The serum sFas level tended to decrease after the medication of antithyroid drugs for 6 to 8 weeks and was significantly decreased in patients who were euthyroid for more than 3 years (0.98+/-0.23 ng/mL), compared to that in untreated GD. The concentration of serum sFas was significantly correlated with anti-thyrotropin (TSH) receptor antibody titers, but not with the other clinical parameters (free triiodothyronine [FT3], free thyroxine [FT4], TSH, antithyroglobulin antibody titer, antimicrosomal antibody titer, or 123I uptake). The sFas mRNA was detected in thyroid tissue, cultured thyrocytes, and intrathyroidal lymphocytes. sFas was detected in supernatant of cultured thyrocytes from patients with GD. Its production by thyrocytes was induced by culture with interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). The present study confirms serum sFas increases in GD and provides evidence of local production of sFas by thyrocytes and its regulation by cytokines. These data suggest that sFas may play a role in the pathogenesis of GD.

Adolescent↗
PubMed1999

Studies of the active substances in herbs used for hair treatment. III. Isolation of hair-regrowth substances from Polygara senega var. latifolia TORR. et GRAY.

Four active principles, 1, 2, 3 and 4, were isolated from Polygara senega var. latifolia TORR. et GRAY by a combination of partition and column chromatography on silica gel and octadecyl silica gel (ODS), monitored by a hair-regrowth activity assay. Compounds 1, 2, 3 and 4 were identified as senegose A, senegin II, senegin III, and senegasaponin b by comparison of their spectral data with those of authentic samples.

Animals↗
PubMed1999

Antagonistic effect of N-methyltyramine on alpha2-adrenoceptor in mice.

We examined the effect of N-methyltyramine (NMT) on alpha2-adrenoceptor. NMT (10(-8)-10(-3) M) inhibited the binding of [3H]p-aminoclonidine to alpha2-adrenoceptor dose-dependently. However, the IC50 value for NMT (5.53 x 10(-6) M) was higher than that for RX821002, an alpha2-adrenoceptor antagonist (1.07 x 10(-8) M). RX821002 (5 mg/kg, i.p.) inhibited hypermotility induced by scopolamine (8 mg/kg, s.c.) in male ddY mice. NMT (20 or 100 mg/kg, i.p.) was found to have a dose-dependent inhibitory effect similar to that of RX821002. These findings indicate that NMT has the properties of an alpha2-adrenoceptor antagonist. However, the affinity of NMT for alpha2-adrenoceptor is weaker than that of RX821002.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1998

1a-docosahexaenoyl mitomycin C: a novel inhibitor of protein tyrosine kinase.

A series of derivatives of mitomycin C conjugated with various fatty acids at position 1a was synthesized and the effect of these compounds on protein kinase activities was evaluated. 1a-Docosahexaenoyl mitomycin C (DMMC) selectively inhibited protein tyrosine kinase (PTK) activity in the postnuclear fraction of v-src-transformed NIH 3T3 cells although neither derivatives conjugated with other fatty acids or docosahexaenoic acid or mitomycin C did not. DMMC inhibited the activity of calmodulin-dependent kinase III and protein kinase A very weakly, and only barely affected protein kinase C activity. DMMC also attenuated autophosphorylation of immunoprecipitated p60v-src irreversibly. The addition of thiol compounds to the reaction mixture reversed the inhibition by DMMC, suggesting that some thiol moiety of PTK protein might be involved. DMMC also inhibited kinase activity of p210bcr-abl immunoprecipitated from the lysate of K562 cells. These results indicate that DMMC is a novel inhibitor of PTK.

3T3 Cells↗
PubMed1998

Left ventricular function and coagulation activity in healed myocardial infarction.

We investigated the plasma levels of molecular markers for the thrombotic and fibrinolytic status in patients with healed myocardial infarction to determine the relation between left ventricular (LV) function and coagulation activity. Our findings demonstrated that the coagulation activity was increased in patients with healed myocardial infarction along with LV dysfunction, suggesting that anticoagulant therapy is considered in patients with severe LV dysfunction to prevent systemic thromboembolism.

Blood Coagulation Factors↗
PubMed1998

Effect of mitral regurgitation on coagulation activity in atrial fibrillation.

We measured the plasma levels of molecular markers for thrombotic and fibrinolytic status in patients with nonrheumatic atrial fibrillation (AF) to investigate the relation between coagulation activity and mitral regurgitation (MR). Our findings demonstrated that a greater degree of MR was associated with less coagulation activity in patients with nonrheumatic AF, suggesting that MR protects against left atrial thrombus and systemic thromboembolism.

Aged↗
PubMed1998

Role of thyroid-stimulating blocking antibody in patients who developed hypothyroidism within one year after 131I treatment for Graves' disease.

OBJECTIVE: We recently reported that thyroid-stimulating blocking antibody (TSBAb) may not contribute to the development of hypothyroidism more than six years after 131I treatment. In the present study, we attempted to determine whether hypothyroidism that develops within a shorter period of time following 131I therapy is associated with TSBAb. DESIGN: Retrospective study. PATIENTS: Sera were obtained from 8 patients who developed hypothyroidism within 6 months after 131I therapy (Group 1), 8 patients who became euthyroid one year after 131I therapy (Group 2), and 7 patients who developed transient hypothyroidism (Group 3). MEASUREMENTS: Thyroid stimulating antibody (TSAb) activity was measured as the amount of cyclic adenosine monophosphate (cAMP) produced by cultured FRTL-5 cells, and TSBAb activity as the inhibition of cAMP produced in response to 100 mU/l bovine TSH. RESULTS: At about 3 months after 131I treatment, TSAb activity increased significantly in Groups 2 and 3, but did not change in Group 1. In contrast, TSBAb activity in Group 1 increased significantly and was positive in 6 patients at that time. At 12-18 months after 131I treatment, TSBAb activity tended to decrease and remained positive in 3 patients but became negative in 3 patients. It did not change in the patients in Groups 2 and 3. The patients in Group 1 were treated with levothyroxine, 75-125 micrograms/day. Levothyroxine was discontinued in the 3 patients whose TSBAb activity disappeared. Two of them remained euthyroid, and 1 became hypothyroid. CONCLUSION: Results indicate that the hypothyroidism that develops within a short time after 131I treatment may be caused by TSBAb activity. Thyroid function may be recovered when TSBAb activity disappears.

Analysis of Variance↗
PubMed1998

Effects of thyroid hormone on carbonic anhydrase I gene expression in human erythroid cells.

Individuals with hyperthyroidism exhibit concentrations of carbonic anhydrase I (CAI) in red blood cells that reflect the integrated serum thyroid hormone concentration over the preceding few months. Furthermore, triiodothyronine T3, at a physiological free concentration, decreases the CAI concentration in both human erythroleukemic YN-1 cells and burst-forming unit-erythroid (BFU-E)-derived cells. In the present study, the effect of T3 on CAI mRNA levels in various human erythroleukemic cell lines (YN-1, HEL and KU-812) and BFU-E-derived cells was studied. Northern analysis of RNA extracted from erythroid cells revealed a CAI mRNA of 1.5 kilobases. T3 significantly decreased the levels of CAI mRNA in YN-1 and BFU-E-derived cells in a dose-dependent manner. Incubation of T3-stimulated cells with actinomycin D prevented the decrease in CAI mRNA levels. By contrast, T3 had no effect on either the concentrations of CAI or the levels of CAI mRNA in HEL and KU-812 cells. These results suggest that YN-1 and BFU-E-derived cells may be useful models for investigating T3 actions on CAI mRNA in human cells.

Carbonic Anhydrases↗
PubMed1998

Effect of herbimycin A on tyrosine kinase receptors and platelet derived growth factor (PDGF)-induced signal transduction.

Herbimycin A is widely used as an inhibitor of Src family protein tyrosine kinases but is also reported to induce the downregulation of epidermal growth factor (EGF) receptor number in A431 cells without inhibiting its tyrosine kinase activity. To determine the specificity of the receptor downregulation, we examined its effect on a variety of cell lines which express different levels of EGF receptor and on other tyrosine kinase receptors. Long-term herbimycin A treatment decreased the amounts of all the tyrosine kinase receptors examined in a dose-dependent manner. It also reduced ligand-stimulated receptor autophosphorylation in accordance with the reduction in the receptor level. Herbimycin A inhibited platelet derived growth factor (PDGF)-induced tyrosine phosphorylation of cellular proteins and DNA synthesis in NIH3T3 cells but did not affect the serum-stimulated DNA synthesis. PDGF-induced tyrosine phosphorylation and activation of c-Src was inhibited but the protein level of c-Src was not reduced by herbimycin A. The reduced level of c-Src kinase activity correlated with the levels of both PDGF receptor and DNA synthesis. These results indicate that the herbimycin A treatment selectively downregulates receptor tyrosine kinases, independent of the number of receptors, and suggest that c-Src is to some degree involved in the selective inhibition of PDGF-induced mitogenesis by herbimycin A.

3T3 Cells↗
PubMed1998

Inhibitory effects of 5-S-GAD on phosphorylation of V-SRC and BCR-ABL tyrosine kinase.

We examined the inhibitory effects of N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine (5-S-GAD), a novel antibacterial substance from the immunized adult Sarcophaga peregrina (flesh fly), on protein phosphorylation using immune complexes of protein tyrosine kinases (PTKs) with anti-PTKs monoclonal antibody. We found that 5-S-GAD directly inhibited not only tyrosine phosphorylation of PTK p60(v-src), but also tyrosine phosphorylation of PTK p210(BCR-ABL). The inhibitory potency of 5-S-GAD was comparable to that of radicicol and herbimycin A of PTK inhibitor.

3T3 Cells↗
PubMed1998

Hyperthyroid Graves' disease and primary hypothyroidism caused by TSH receptor antibodies in monozygotic twins: case reports.

A 33-year-old woman with signs and symptoms of hypothyroidism, including increased thyroid stimulating blocking antibody (TSBAb) activity, was referred for treatment by her local physician. Her monozygote twin was treated for hyperthyroid Graves' disease 10 years earlier. This case of hyperthyroidism and hypothyroidism in identical twins suggests the involvement of environmental factors in the pathogenesis of autoimmune thyroid diseases.

Adult↗
PubMed1998

Measurement of red blood cell zinc concentration with Zn-test kit: discrimination between hyperthyroid Graves' disease and transient thyrotoxicosis.

We have previously reported in patients with hyperthyroidism that the red blood cell (RBC) zinc (Zn) concentration reflects the mean thyroid hormone concentration over the preceding months. In the present study, the concentration of RBC Zn was measured by a simple and easy method with a Zn-test Wako kit. Within-run and between-run precision were 1.4% and 1.3%, respectively. The relationship between RBC concentration and dilution was linear. The average recovery was 103%. A good correlation (r=0.97) was obtained between this method and atomic absorption spectrophotometry. The mean concentration of RBC Zn in 39 euthyroid controls was 12.6 +/- 1.3 mg/l, ranging from 10.4 to 15.1 mg/l. The RBC Zn concentrations in 38 patients with Graves' disease, in 10 patients with silent thyroiditis and in 3 patients with gestational thyrotoxicosis were 7.3 +/- 1.6 (3.2-9.8), 12.0 +/- 1.6 (9.5-14.2) and 11.8 +/- 1.7 (10.5-13.7) mg/l, respectively. The concentration of RBC Zn was able to differentiate hyperthyroid Graves' disease from transient thyrotoxicosis except in 1 case and was a better index than TSH-binding inhibitory immunoglobulin. These results indicate that measuring RBC Zn with the Zinc-test Wako kit is very useful in differentiating hyperthyroid Graves' disease from transient thyrotoxicosis.

Adult↗
PubMed1997

Interaction of the DNA topoisomerase II catalytic inhibitor meso-2,3-bis(3,5-dioxopiperazine-1-yl)butane (ICRF-193), a bisdioxopiperazine derivative, with the conserved region(s) of eukaryotic but not prokaryotic enzyme.

ICRF-193 [meso-2,3-bis(3,5-dioxopiperazine-1-yl)butane], a bisdioxopiperazine compound, has been shown to be a catalytic inhibitor of DNA topoisomerase II by stabilizing the enzyme in the form of a closed "protein clamp," an intermediate form in the catalytic cycle (Roca et al., Proc Natl Acad Sci USA 91: 1781-1785, 1994). In view of its usefulness as a probe in the functional analysis of the enzyme, we tried further to define the domain(s) of the enzyme interacting with the drug by examining its inhibitory activity on type II topoisomerases from various species of eukaryotes and prokaryotes. ICRF-193 inhibited the enzyme from yeast, fly, frog, plant, and mammals at IC50 values in the range of 1-13 microM. Experiments using fission yeast truncated mutant type II enzyme lacking both amino-terminal 74 amino acids and carboxy-terminal 265 amino acids revealed that ICRF-193 interacts with the 125 kDa "core" polypeptide of the enzyme. In contrast, prokaryotic type II enzymes, Escherichia coli DNA gyrase, topo IV, and phage T4 topo, were not affected by the drug. From these results, the domain(s) common to eukaryotic but not to prokaryotic type II enzymes interacting with ICRF-193 was speculated.

Amino Acid Sequence↗
PubMed1997

Effect of mitral valvuloplasty in mitral stenosis on coagulation activity.

We investigated the plasma levels of molecular markers for the status of thrombin generation and fibrinolysis in patients with mitral stenosis before and after percutaneous mitral valvuloplasty. Our results show that percutaneous mitral valvuloplasty results in decreased coagulation activity, suggesting that percutaneous mitral valvuloplasty is also useful for prevention of systemic embolism in patients with mitral stenosis.

Blood Coagulation↗
PubMed1997

Inhibition of anchorage-independent growth of ras-transformed cells on polyHEMA surface by antisense oligodeoxynucleotides directed against K-ras.

We examined the effect of antisense oligodeoxynucleotides (AS ODNs) directed against v-Ki-ras on the anchorage-independent growth of v-Ki-ras-transformed rat fibroblasts using plates coated with an antiadhesive polymer, poly(2-hydroxyethyl methacrylate) (polyHEMA). Among AS ODNs tested, 17mer AS ODN centered around codon 12 of v-Ki-ras inhibited the v-Ki-Ras expression and v-Ki-Ras-induced anchorage-independent growth, while its sense sequence did not affect it. Using polyHEMA plates, the direct addition of AS ODNs to the cells growing anchorage-independently and various treatment schedules of AS ODNs are now available to identify the most desirable conditions for AS ODNs treatment.

Animals↗