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Biomedical subjects

Y Hatano

Publications and source records attributed to Y Hatano.

At least 55 records · Page 3Linked to original sources
PubMed1999

Differential effects of lidocaine and mexiletine on relaxations to ATP-sensitive K+ channel openers in rat aortas.

BACKGROUND: In cardiac myocytes, lidocaine reduces but mexiletine increases adenosine triphosphate (ATP)-sensitive K+ currents, suggesting that these class Ib antiarrhythmic drugs may differentially modify the activity of ATP-sensitive K+ channels. The effects of lidocaine and mexiletine on arterial relaxations induced by K+ channel openers have not been studied. Therefore, the current study was designed to evaluate whether lidocaine and mexiletine may produce changes in relaxations to the ATP-sensitive K+ channel openers cromakalim and pinacidil in isolated rat thoracic aortas. METHODS: Rings of rat thoracic aortas without endothelia were suspended for isometric force recording. Concentration-response curves were obtained in a cumulative fashion. During submaximal contractions to phenylephrine (3 x 10(-7) M), relaxations to cromakalim (10(-7) to 3 x 10(-5) M), pinacidil (10(-7) to 3 x 10(-5) M), or diltiazem (10(-7) to 3 x 10(-4) M) were obtained. Lidocaine (10(-5) to 3 x 10(-4) M), mexiletine (10(-5) to 10(-4) M) or glibenclamide (5 x 10(-6) M) was applied 15 min before addition of phenylephrine. RESULTS: During contractions to phenylephrine, cromakalim and pinacidil induced concentration-dependent relaxations. A selective ATP-sensitive K+ channel antagonist, glibenclamide (5 x 10(-6) M), abolished these relaxations, whereas it did not alter relaxations to a voltage-dependent Ca2+ channel inhibitor, diltiazem (10(-7) to 3 x 10(-4) M). Lidocaine (more than 10(-5) M) significantly reduced relaxations to cromakalim or pinacidil in a concentration-dependent fashion, whereas lidocaine (3 x 10(-4) M) did not affect relaxations to diltiazem. In contrast, mexiletine (more than 10(-5) M) significantly augmented relaxations to cromakalim or pinacidil. Glibenclamide (5 x 10(-6) M) abolished relaxations to cromakalim or pinacidil in arteries treated with mexiletine (10(-4) M). CONCLUSIONS: These results suggest that lidocaine impairs but mexiletine augments vasodilation mediated by ATP-sensitive K+ channels in smooth muscle cells.

Adenosine Triphosphate↗
PubMed1999

Propofol has both enhancing and suppressing effects on human platelet aggregation in vitro.

BACKGROUND: Volatile anesthetics are known to suppress platelet aggregation. In contrast, there is conflicting information regarding the effect of propofol on platelet function. The present study was designed to clarify the effects of propofol on platelet function and the mechanisms underlying these effects. METHODS: Propofol or an equivalent volume of 10% Intralipos (as a control) was added to test tubes 5 min before the induction of each reaction. Platelet aggregation induced by epinephrine, arachidonic acid (AA), prostaglandin G2 (PGG2), or STA2 (a thromboxane A2 [TXA2] analog) was measured using an eight-channel aggregometer. To determine type 1 cyclooxygenase activity, AA (0.5 mM) was added to an assay mixture containing type 1 cyclooxygenase, and the concentration of the final product, malonaldehyde, was measured by spectrophotometry. Epinephrine-, adenosine diphosphate-, AA-, and PGG2-induced TXA2 formation was measured using a commercially available radioimmunoassay kit. To estimate TXA2 receptor-binding affinity, 3H-S145, a specific TXA2 receptor antagonist, was added, and the radioactivity of receptor-bound 3H-S145 was determined using a liquid scintillation analyzer. Inositol 1,4,5-triphosphate formation was measured in STA2-stimulated platelets using a commercially available inositol 1,4,5-triphosphate assay kit. RESULTS: Propofol (40 microM) enhanced, whereas 100 microM suppressed, adenosine diphosphate- and epinephrine-induced secondary aggregation without affecting primary aggregation. Propofol (40 microM) also enhanced, but 100 microM suppressed, AA-induced aggregation. Propofol (100 microM) enhanced PGG2- and STA2-induced aggregation. Propofol (100 microM) suppressed AA-induced TXA2 formation but did not alter that induced by PGG2. Propofol (30-100 microM) suppressed AA-induced malonaldehyde formation, indicating inhibition of type 1 cyclooxygenase activity. Propofol did not alter TXA2 receptor-binding affinity. Propofol (30 and 100 microM) augmented inositol 1,4,5-triphosphate formation in STA2-stimulated platelets. CONCLUSIONS: The present findings clearly indicate that high concentrations of propofol suppress the activity of type 1 cyclooxygenase, the enzyme that converts AA to PGG2. Furthermore, propofol also enhanced STA2-induced inositol 1,4,5-triphosphate formation. These results may explain the inconsistent findings of previous investigators.

Adult↗
PubMed1999

Macrophage inflammatory protein 1 alpha expression by synovial fluid neutrophils in rheumatoid arthritis.

OBJECTIVE: To determine the contribution made by synovial fluid (SF) neutrophils to the augmented expression of macrophage inflammatory protein 1 alpha (MIP-1alpha) in rheumatoid arthritis (RA). METHODS: Neutrophils were isolated from samples of SF from RA patients and peripheral blood (PB) samples from RA patients and healthy controls. Cell associated MIP-1alpha was visualised immunohistochemically, and cell associated MIP-1alpha as well as MIP-1alpha secreted into the SF was assayed by ELISA. Steady state expression of MIP-1alpha mRNA was assessed by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Freshly isolated SF neutrophils contained significantly higher concentrations of both MIP-1alpha protein and its transcript than PB neutrophils from either RA patients or healthy controls; incubation in the absence or presence of tumour necrosis factor alpha for 24 hours resulted in a significant increase in MIP-1alpha secretion by RA SF neutrophils compared with neutrophils obtained from either normal PB or RA PB; and expression of MIP-1alpha by SF neutrophils was well correlated with both RA disease activity and SF mononuclear cell (MNC) counts. CONCLUSION: Expression and secretion of MIP-1alpha by SF neutrophils may be indicative of local and systemic inflammation in RA. Moreover, this C-C chemokine may contribute to the recruitment of MNCs from the bloodstream into synovial joints and tissues.

Adult↗
PubMed1999

Heterogeneity in expression of cytokine mRNA in freshly isolated peripheral blood eosinophils of patients with cutaneous-disease-associated eosinophilia.

BACKGROUND: It is thought that there are subpopulations of eosinophils concerning cytokine production: some of them predominantly produce Th1 cytokines, while others produce Th2. METHODS: By semiquantitative RT-PCR, the in vivo levels of the cytokine mRNA were measured in freshly isolated eosinophils and peripheral blood mononuclear cells (PBMCs) of 19 patients with eosinophilia, including 6 with atopic dermatitis, 4 with drug eruption, 1 with chronic dermatitis, 2 with erythroderma, 3 with bullous pemphigoid, 1 each with urticaria, adult T cell lymphoma, and hypereosinophilic syndrome, and 7 healthy individuals. Eosinophils and PBMCs were isolated by centrifugation over Ficoll-Paque and magnetic cell separation using anti-CD16 antibody. RESULTS: The IL-4/IFN-gamma ratio in eosinophils as well as PBMCs was increased and correlated well with IgE levels in atopic dermatitis. In other cytokines, such as IL-8, TNF-alpha and TGF-beta1, the levels of mRNA expression were variable among each sample. CONCLUSION: Not only helper T lymphocytes but also eosinophils may take part in the pathogenesis of cutaneous diseases by virtue of heterogeneity of Th1 and Th2 cytokine production.

Adult↗
PubMed1999

The role of endothelium-derived nitric oxide in relaxations to levcromakalim in the rat aorta.

The present study was designed to examine the role of basally released nitric oxide in relaxations to an ATP-sensitive K+ channel opener. Whether relaxations to levcromakalim are modulated by endothelial removal or the inhibitors of vasodilator effects of endothelium-derived nitric oxide, were investigated in the rat aorta. During contractions to phenylephrine (3 x 10(-7) to 10(-6) M), levcromakalim (10(-8) to 10(-5) M) or a nitric oxide donor, 1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7, 10(-9) to 10(-5) M), was added in a cumulative fashion. Relaxations to levcromakalim (10(-8) to 10(-5) M) were significantly reduced by the endothelium-removal. In aortas with endothelium, relaxations in response to levcromakalim were decreased by selective inhibitors of nitric oxide synthase (N(G)-nitro-L-arginine methyl ester, 10(-4) M) and soluble guanylate cyclase (1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one; ODQ, 10(-5) M) and a scavenger of nitric oxide (carboxy-PTIO, 10(-3) M). Relaxations to levcromakalim in aortas treated with these inhibitors are comparable to those seen in aortas without endothelium. KCl (30 mM) and an ATP-sensitive K+ channel inhibitor, glibenclamide (10(-5) M), abolished relaxations to levcromakalim in aortas with or without endothelium, whereas glibenclamide did not alter relaxations to NOC-7 (10(-9) to 10(-5) M) in aortas without endothelium. These results suggest that in rat aortas, inhibition of vasodilator effects of basally released nitric oxide can reduce relaxations via ATP-sensitive K+ channels, although these channels do not mediate relaxations to exogenously applied nitric oxide.

ATP-Binding Cassette Transporters↗
PubMed1999

Further genetic studies on the Katsunuma population of Drosophila melanogaster.

Changes in the genetic structure of the Katsunuma natural population of Drosophila melanogaster have been examined during the past 35 years. The frequency of recessive lethal genes on the second chromosome once increased from 15% to 30% in the early 1970s, then decreased to about 24% in the late 1970s, and thereafter showed no significant changes. Sterility genes, the frequency of which is always less than the lethals, showed a similar tendency. The SD (segregation distorter) mutant gene disappeared but some others such as rbl (reduced bristle) and bw (brown) persisted in the population. The frequency of inversion-carrying chromosomes gradually decreased in the period, such that the standard chromosome frequency in the second and third chromosomes increased from about 40% to more than 80%. Coincident with these frequency changes is the invasion of a transposable element P into the Katsunuma population. The P element should have invaded into Katsunuma in the late 1960s. It spread over the population apparently inducing deleterious mutations, causing the decrease in the allelism rate, and hence increasing the effective population size. Soon, however, most flies became resistant to the P element-mediated transposition as they began to harbor defective P elements. During the course of spreading, the P element must also have induced deleterious mutations on the polymorphic inversions, breaking up the heterotic gene complexes along the chromosomes, which probably caused the reduction in the frequency of inversion chromosomes. Temporal invasion of D. simulans, a sibling species of D. melanogaster, into Katsunuma occurred several times after 1978, and the species seems to have been settled since 1990. This, however, did not have any effect on the genetic structure of D. melanogaster population.

Animals↗
PubMed1999

Non-proteolytic activation of human prorenin by anti-prorenin prosegment (pf#1: 1P-15P) antiserum.

Recombinant human prorenin was activated by incubation with anti-prorenin prosegment (L1PPTDTTTFKRIFLKR15P) antiserum at 4 degrees C. This activation was dependent on the concentration of the antiserum and incubation time. After the activation no molecular weight alteration of prorenin was observed by immunoblotting analysis. A peptide of L1PPTDTTTF8P as well as L1PPTDTTTFKRIFLKR15P potently interfered with the activation. Most of the activated prorenin bound to Protein A Sepharose CL 4B. The Km and Vmax values of the activated prorenin were 0.2 microM and 23.7 micrograms Ang I/ml/h, respectively, which were similar in level to those of mature renin obtained by trypsinization.

Amino Acid Sequence↗
PubMed1999

Downregulation of intercellular adhesion molecule-1 expression on human synovial fibroblasts by endothelin-1.

OBJECTIVE: To study the effect of endothelin-1 (ET-1) on the expression of intercellular adhesion molecule-1 (ICAM-1) by synovial fibroblasts derived from individuals with rheumatoid arthritis (RA) or osteoarthritis (OA). METHODS: The expression of ICAM-1 protein and the abundance of ICAM-1 mRNA in synovial fibroblasts derived from individuals with RA or OA, or healthy controls, was assessed by flow cytometry and Northern blot analysis, respectively. mRNA expression of ET type A (ETA) and ET type B (ETB) receptors was assessed by reverse transcription polymerase chain reaction. RESULTS: Tumor necrosis factor-alpha (TNF-alpha) increased the expression of ICAM-1 by RA and OA fibroblasts. While ET-1 alone had no significant effect on ICAM-1 expression by either cell type, it inhibited the TNF-alpha induced increase in ICAM-1 expression, and this effect was more marked in RA fibroblasts. TNF-alpha also increased the amount of ICAM-1 mRNA in both cell types, and ET-1 inhibited this increase to a greater extent in RA fibroblasts than in OA fibroblasts. This inhibitory effect of ET-1 was reversed by addition of specific antagonist of ETA receptor. mRNA expression of ETA and ETB receptors was significantly greater in RA fibroblasts stimulated with TNF-alpha or even medium alone than in OA fibroblasts. CONCLUSION: These results suggest that ICAM-1 expression by fibroblasts is regulated not only by proinflammatory cytokines such as TNF-alpha and interleukin-1beta, but also by the vasoactive peptide ET-1, and that ET-1 may play an important role in inflammatory responses, especially in rheumatoid synovitis.

Aged↗
PubMed1998

A new variant translocation of t(15;17) in a patient with acute promyelocytic leukemia (M3): t(15;19;17)(q22;p13;q12).

The reciprocal translocation (15;17) is specifically associated with acute promyelocytic leukemia [APL; M3 subtype according to French-American-British (FAB) classification]. A few patients with this disease have complex variant translocations. We describe a patient with M3 carrying t(15;19;17)(q22;p13;q12), which is a new type of variant translocation. The karyotypic interpretation was confirmed by Southern blot analysis with the use of RAR alpha and by fluorescence in situ hybridization (FISH) with the use of painting probes of chromosomes 15, 17, and 19 and a (15;17) translocation DNA probe. The results support the idea that the key event in APL is the formation of fusion gene PML/RAR alpha on the der(15).

Adolescent↗
PubMed1998

[Resection and reconstruction of sternum].

In case of sternal resection, it is necessary to preserve bone material indispensable for the stability of the anterior chest wall and air tightness of the thoracic cavity, and the support of the chest wall integrity must be restored by some means. Various techniques have been applied to the reconstruction of the chest wall following resection. During the last 10 years, we have performed reconstructive operation for 6 cases of the chest wall following resection of the sternum in recurrent cases of breast cancer or invaded case of primary breast cancer. In these patients, the chest wall was reconstructed using a rib-latissimus dorsi osteomyocutaneolus flap or a latissimus dorsi myocutaneous flap. The sternum was totally resected in 3 cases, and in all 3 cases, reconstructed using a rib-latissimus dorsi osteomyocutaneous flap. Although postoperative pulmonary function decreased, all cases could be relieved from endotracheal intubation within 17 hours after operation, and had no problems in activities of daily living or occurrence of chest flailing or paradoxical movement of the chest. An artificial material (expanded polytetrafluoroethlene patch) was used in only one patient for the reconstruction of the osseous thorax, but this case developed infection during postoperative chemotherapy. After this experience, we used only biological materials for the reconstruction of the chest wall and postoperatively performed radiotherapy and/or chemotherapy on all cases. We have observed no flap infection or detachment since then. One characteristic of using the latissimus dorsi myocutaneous flap is that it is easily elevated and rarely causes serious postoperative esthetic or functional problems. The flap is also easily utilized to reinforce the osseous thorax because ribs immediately below the latissimus dorsi muscle are readily mobilized as a pedicle graft. Reconstruction of the chest wall following resection of the sternum, described in this report, allowed us to perform radiotherapy and/or chemotherapy without serious postoperative complications on the cases relapsing after treatment of breast cancer. The 2-year survival rate is 50% and one of these cases survived up to 10 years after resection of the sternum. Thus we prefer to perform resection of the sternum for sternal recurrence of breast cancer if there are no metastatic lesions in other organs.

Adult↗
PubMed1998

Interleukin-13 down-regulates the expression of neutrophil-derived macrophage inflammatory protein-1 alpha.

OBJECTIVE AND DESIGN: To determine whether interleukin-13 (IL-13) possesses anti-inflammatory properties with respect to polymorphonuclear neutrophils (PMNs). Effects of IL-13 on production of the chemokine, macrophage inflammatory protein-1 alpha (MIP-1alpha), by PMNs were analyzed. SUBJECTS: Human peripheral blood PMNs obtained from healthy volunteers. METHODS: PMNs were stimulated by lipopolysaccharide (LPS) and/or IL-13 for selected periods of time, and MIP-1alpha expression was assessed by ELISA and Northern blot analysis. RESULTS: IL-13 suppressed expression and production of PMN-derived MIP-1alpha mRNA and protein in a dose- and time-dependent manner. Inhibition of protein synthesis caused significant enhancement of MIP-1alpha mRNA expression. The inhibitory activity of IL-13 was abrogated, however, in the presence of cycloheximide, suggesting that IL-13's effect was via synthesis of de novo repressor protein(s). CONCLUSIONS: PMN-derived chemokines are regulated by both proinflammatory and immunomodulatory cytokines. The coordinated production of these substances is likely to be important in the orchestration of inflammatory and immune responses.

Blotting, Northern↗
PubMed1998

Halothane and isoflurane attenuate the relaxant response to nonadrenergic and noncholinergic nerve stimulation of isolated canine cerebral arteries.

UNLABELLED: Stimulation of nonadrenergic noncholinergic (NANC) nerves elicits relaxation of canine cerebral arteries via the nitric oxide (NO)-cGMP pathway. The purpose of this study was to investigate the effects of halothane and isoflurane on the relaxant response of isolated canine cerebral arteries to NANC nerve stimulation. The isometric tension of isolated canine cerebral arteries, which had been denuded of endothelium, was measured in a tissue bath. The application of transmural electrical stimulation (TES) at a frequency of 5 Hz elicited a transient relaxation of arteries partially contracted with prostaglandin F2alpha. This effect was abolished by treatment with N(G)-nitro-L-arginine (3 x 10[-5] M), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10[-5] M), or tetrodotoxin (10[-6] M). Treatment with halothane (2.3%) or isoflurane (2.3% and 3.5%) attenuated the relaxant response to TES (P < 0.05). Halothane (2.3%) but not isoflurane (2.3% and 3.5%) attenuated relaxation induced by s-nitro-N-acetylpenicillamine. We suggest that halothane and isoflurane inhibit cerebroarterial vasodilation mediated via NO-cGMP pathway activated by stimulation of the NANC nerves. The sites of action of halothane and isoflurane on the NO-cGMP pathway may differ. IMPLICATIONS: Nonadrenergic noncholinergic nerves play a role in the regulation of vascular tone in cerebral arteries via the nitric oxide-cGMP pathway. This study showed that, in isolated canine cerebral arteries, halothane and isoflurane inhibit the relaxation caused by nonadrenergic noncholinergic nerve stimulation, but their sites of action may differ.

Animals↗
PubMed1998

Topostatin, a novel inhibitor of Topoisomerases I and II produced by Thermomonospora alba strain No. 1520. II. Physico-chemical properties and structure elucidation.

Topostatin is a new topoisomerase inhibitor isolated from the culture filtrate of Thermononospora alba strain No. 1520. The inhibitor inhibits topoisomerases I and II, and it has neither ability to stabilize the cleavable complex nor ability to intercalate into DNA strands. The molecular formula of topostatin was determined as C36H58N4O11S based on the FAB-MS analyses, and the structure was elucidated to be a novel 14-membered ring containing peptide and terpenoid by various NMR spectroscopies.

Enzyme Inhibitors↗
PubMed1998

[Percutaneous drainage of a bulla with tuberculous infection in a patient].

A 63-year-old man complaining of low grade fever and dry cough was admitted to our hospital. Chest X-ray showed infiltrative shadows and a bulla with a fluid level in the left upper lung field. Bacteriological examination of sputum and bronchoalveolar lavage fluid did not yield any diagnostic results. Percutaneous aspiration of the bulla under fluoroscopy was performed. Bulla with tuberculous infection was considered because a high ADA level was detected in the fluid of the bulla. A culture of the bulla fluid was positive for mycobacterium tuberculosis (TB), which was sensitive to all anti-mycobacterial drugs. The fluid in the bulla gradually increased, and occupied the entire space of the bulla three months later. Percutaneous aspiration of the bulla was performed again and a fluid smear was positive for TB. It was thought that systemic administration of anti-mycobacterial drugs had been ineffective, so percutaneous drainage and subsequent injection of anti-mycobacterial drugs into the bulla was performed. The fluid in the bulla subsequently disappeared and the bulla shrank gradually. Percutaneous drainage of a bulla with tuberculous infection should be considered in those who do not respond to medical management.

Antitubercular Agents↗
PubMed1998

[A case report of selective IgA deficiency in rheumatoid arthritis and anti-IgA antibody induced anaphylactic transfusion].

We described a case of rheumatoid arthritis (RA) with selective IgA deficiency. A 69 year-old female with RA was admitted because of gall bladder cancer, and also had selective IgA deficiency which serum IgA level was less than 5.0 mg/dl, and IgA 1 and IgA 2 subclasses were not detected. Prior to the operation, she was given red cell compatible blood transfusion because of severe anemia. After 30 min of transfusion, she developed chill, nausea, vomiting and hypotension. These anaphylactic reactions might be induced by the presence of anti-IgA antibody, since the level of this antibody titers in her serum was elevated, assessed by the methods of ELISA and Western blotting. Although a case of RA associated with selective IgA deficiency, and also with elevated serum anti-IgA antibody level is extremely uncommon, attention should be paid to the presence of anti-IgA antibody in patients with selective IgA deficiency to avoid any unexpected anaphylactic reactions.

Aged↗