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Biomedical subjects

M Hara

Publications and source records attributed to M Hara.

At least 505 records · Page 28Linked to original sources
PubMed1996

[Prospective clinical study of the combination therapy of auranofin and methotrexate for rheumatoid arthritis--a multi-center study].

In a study to evaluate the usefulness of DMARDs combination therapy for RA, AF and MTX were concurrently given to RA patients who had responded poorly to over three months of monotherapy of either AF or MTX. The study was composed of two stages. In the first stage, patients were concurrently given AF and MTX for six months in order to evaluate the efficacy of combination therapy. In the second stage, patients who had responded to the earlier combination therapy were again put on monotherapy of the additive DMARD. Safety evaluation was conducted with 126 patients, and both efficacy and utility were evaluated in 100 patients. Lansbury index for RA significantly improved in both groups of patients starting with the AF and followed by the MTX combination (Group I) and those who started with MTX alone followed by the AF combination (Group II). The ratio of patients who achieved slight improvement or better in the overall improvement rating was significantly higher in Group I at 74.6%, vs. 51.1% in Group II patients. Ten patients (16.9%) and 2 patients (4.9%) were switched to their additive DMARD monotherapy of MTX and AF respectively, having responded to the combination therapy in stage I with slight improvement or a better rating. Adverse events were observed in 44 patients (34.9%), but the combination therapy neither increased the incidence of adverse events nor caused new adverse events. Combination therapy of AF and MTX appeared to be useful both in terms of efficacy and safety for patients who have experienced the dwindling effect of monotherapy.

Adult↗
PubMed1996

[A case of valve thrombosis of CarboMedics prosthesis four years after mitral valve replacement: relationship of anticoagulant therapy to coagulation and fibrinolysis activating factors].

A 50-year-old man experienced acute heart failure four years after initial mitral valve replacement (MVR) for left atrial thrombosis using a CarboMedics prosthesis, despite satisfactory coagulation control with warfarin. After initial MVR, late cardiac tamponade occurred twice and left circumflex branch stenosis was treated with percutaneous transluminal coronary angioplasty (PTCA). Re-MVR with an Edwards-TEKNA valve was performed after echocardiography and cineradiography showed mitral valve thrombosis, with thrombi on both mitral valve leaflets and covering most of the left atrial wall. Post-surgery progress was favorable with warfarin and dipyridamole therapy. After six weeks cardiac catheter revealed complete right external iliac artery occlusion. Cardiac dysfunction and atrial flutter apparently accelerated thrombosis after a common cold activated coagulation. Cardiac tamponade, circumflex branch stenosis, and right external iliac artery occlusion occurred despite satisfactory coagulation control by warfarin. Warfarin suppresses some coagulation factors but cannot always correct hypercoagulability. Two months after re-MVR, coagulation tests showed normal TT, F1 + 2, and D-Dimer but an increase in TAT, suggesting involvement of additional coagulation factors. After artificial valve replacement, therapy should achieve a PT-INR level of 3.0-4.5, with close follow-up using other indices of fibrinolysis and coagulation activity in addition to TT.

Acute Disease↗
PubMed1996

[Home oxygen therapy (HOT) in patients with pulmonary tuberculosis sequelae--comparison between patients medically treated and those surgically treated].

In Japan there are about 40,000 patients under home oxygen therapy (HOT), of whom about 30 to 40% are pulmonary tuberculosis sequelae (TBS). These patients can be divided into three groups depending on the treatments they had, Group 1: those who had medical treatments only, Group 2: those who had artificial pneumothorax, and Group 3: those who had thoracoplasties or other surgical treatments. The purpose of this study was to observe the distributions and possible differences in the survival rates among these groups. The study included 1537 patients with TBS under HOT followed at National Hospitals and Sanatoriums nationwide in Japan. In 819 patients the treatments were specified and of those 354 were in Group 1, 29 in Group 2, and 436 in Group 3, so that the proportion of surgically treated patients in PTS was estimated between 28.4% (436/ 1537) to 53.2% (436/819). The ages at the onset of tuberculosis, at the start of HOT and the intervals in between were 36.6, 66.2 and 29.8 in Group 1, and 26.8, 65.5, and 38.1 in Group 3 respectively. Though the ages at the start of HOT were the same, those at the onset of tuberculosis were about ten years younger in Group 3 than in Group 1. Comparing Group 1 and 3, the survival rates after the initiation of HOT (Kaplan-Meier method) was better in Group 2 (surgically treated) than in Group 1 (medically treated). It is speculated that the reason could be a better preservation of the function of the remaining lung in the surgically treated and a higher incidence of obstructive impairments in the medically treated patients.

Adolescent↗
PubMed1996

[Laser laparoscopic cholecystectomy].

Clinical use of the Polish Nd-YAG laser with "naked fibre"--type tip in the laparoscopic cholecystectomy is discussed. Eleven subsequent patients with the symptomatic cholelithiasis confirmed with ultrasonography have been operated with this technique. Laser served mainly to dissect gall bladder from the liver. Biliary duct and cystic artery have been clipped. No complications of the laparoscopic laser cholecystectomy have been noted. Gall bladder wall has been perforated in 3 patients operated with contact technique. However, there have been no technical problems, and further preparation of the gall bladder has been successfully completed with laser in all cases. A value of laser in laparoscopic cholecystectomy seems lower than that of electrocautery. However, a non-contact photocoagulation in the hemostasis of blood vessels in gall bladder removal site seems promising. Laser prolongs the duration of surgery and markedly increases its cost. Further investigations are required to evaluate laparoscopic laser cholecystectomies as the effects of laser beam in the abdominal cavity remains unknown.

Adult↗
PubMed1996

[Atrial standstill].

Explore the source record for details and available documents.

Arrhythmias, Cardiac↗
PubMed1995

A long-term receptor stimulation is requisite for angiotensin II-dependent DNA synthesis in vascular smooth muscle cells from spontaneously hypertensive rats.

Angiotensin II stimulates DNA synthesis in aortic smooth muscle cells prepared from spontaneously hypertensive rats, with maximal levels detected 20 h after stimulation. Angiotensin II receptor antagonists inhibited the angiotensin II-induced DNA synthesis. In particular, the noncompetitive antagonist 2-ethoxy-1-[[2'(1 H-tetrazol-5-yl) biphenyl-4-yl]methyl]-1 H-benzimidazole-7-carboxylic acid (CV11974) was more effective than expected from its affinity for the angiotensin II receptor and its potency for inhibiting angiotensin II-induced increase in cytosolic free Ca2+ concentration 2-n-Butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1 H-tetrazol-5-yl)biphenyl-4-yl) methyl]imidazole, potassium salt (losartan), one of the antagonists, inhibited angiotensin II-induced DNA synthesis by 92% and 79%, even when added 2 and 4 h after angiotensin II stimulation, respectively. Angiotensin II also increases the mRNA of platelet-derived growth factor-A chain and basic fibroblast growth factor. The increase was observed within 4 h after angiotensin II stimulation. In this case, the addition of losartan at 4 h after angiotensin II stimulation hardly influenced the time course of the mRNA level of growth factors. Also, conditioned media of cells stimulated with angiotensin II did not influence DNA synthesis in the presence of CV11974. These results suggest that sustained receptor stimulation with angiotensin II is required for DNA synthesis in addition to the early intracellular signaling following phospholipase C activation in a manner independent of the induction of growth factors such as platelet-derived growth factor-AA and basic fibroblast growth factor.

Angiotensin II↗
PubMed1995

Local anesthetics reduce the inhibitory neurotransmitter-induced current in dissociated hippocampal neurons of the rat.

The effects of local anesthetics on amino acid-induced currents were examined using the whole-cell configuration of the patch clamp technique in dissociated hippocampal pyramidal neurons of the rat. Lidocaine (3 mM) decreased the glycine-induced Cl- current (Gly-ICl) more potently (to 46% of the control value) than the gamma-aminobutyric acid-induced Cl- current (GABA-ICl; to 75%), whereas the agent had little effect on the excitatory glutamate response. The reduction in the Gly-ICl was dose-dependent, with a dissociation constant (KD) of 3 mM and a Hill coefficient of 0.96. A non-competitive inhibition was suggested by a double reciprocal plot of the effects of lidocaine on the concentration-response curve of the Gly-ICl. Benzocaine, a neutral local anesthetic at physiological pH, decreased the Gly-ICl more potently than lidocaine, while QX314, a permanently charged quaternary derivative of lidocaine, produced a much smaller inhibition, thereby indicating that the neutral form of local anesthetics is more effective in reducing the Gly-ICl. The depression of the Gly-ICl and GABA-ICl in central neurons may contribute to local anesthetic-induced convulsions.

Anesthetics, Local↗
PubMed1995

Effects of pinealectomy and constant light exposure on day-night changes of melatonin binding sites in the goldfish brain.

Effects of pinealectomy and constant light exposure on day-night changes of melatonin binding sites in the goldfish brain were examined. The density and affinity of binding sites were higher at mid-day than at mid-night in sham-pinealectomized goldfish under light-dark cycles. The rhythms disappeared after pinealectomy, or constant light exposure both of which abolish plasma melatonin rhythms. The effects of pinealectomy and constant light exposure were not additive. These results indicate that diel changes of melatonin binding sites in the goldfish brain are regulated by endogenous melatonin of pineal origin.

Animals↗
PubMed1995

Non-peptide bombesin receptor antagonists, kuwanon G and H, isolated from mulberry.

Kuwanon G and H, isolated from the methanol extract of Morus bombycis, inhibited specific binding of [125I]gastrin-releasing peptide (GRP) to GRP-preferring receptors in murine Swiss 3T3 fibroblasts with Ki values of 470 and 290 nM, respectively. Kuwanon H was one order of magnitude less potent for inhibiting [125I]bombesin binding to neuromedin B (NMB)-preferring receptors in rat esophagus membranes. This compound antagonized bombesin-induced increases in the cytosolic free calcium concentration and GRP-induced DNA synthesis in Swiss 3T3 cells. Thus, kuwanon H, and possibly kuwanon G also, are specific antagonists for the GRP-preferring receptor and can be useful for studying the physiological and pathological role of GRP.

3T3 Cells↗
PubMed1995

Novel angiotensin II receptor antagonists. Design, synthesis, and in vitro evaluation of dibenzo[a,d]cycloheptene and dibenzo[b,f]oxepin derivatives. Searching for bioisosteres of biphenylyltetrazole using a three-dimensional search technique.

Three-dimensional substructure searching (3D search), using the program MACCS-3D, was utilized for designing novel angiotensin II receptor antagonists which contain a bioisostere of the biphenylyltetrazole moiety of DuP 753. A 3D query was prepared from an overlay model of substructures of several potent AII antagonists. The search system retrieved 139 compounds from the database MDDR-3D, which consisted of 29,400 medicinal patent compounds. A tricyclic compound was selected from the retrieved compounds and then evolved by considering steric fitness to the overlay model and synthetic feasibility. Finally, various novel AII antagonists having dibenzo[a,d]cycloheptene or dibenzo[b,f]oxepin were designed and synthesized. The receptor binding activity (Ki) for several members of this series was in the 10(-10) M range, demonstrating the ability of 3D search technique to explore new lead structures.

Angiotensin II↗
PubMed1995

Corticotropin-releasing factor inhibits antigen-induced plasma extravasation in airways.

We investigated the potential of corticotropin-releasing factor (CRF) to reduce neurogenic plasma extravasation in sensitised guinea pig airways evoked by antigen challenge. Inhalation of 5% ovalbumin for 2 min in the presence of phosphoramidon (2.5 mg/kg, i.v.) increased extravasation of Evans blue dye in the trachea and main bronchi. The increase in plasma extravasation induced by antigen challenge was significantly reduced by pretreatment with CRF (30 nmol/kg, i.v.) (73% in the trachea and 42% in the main bronchi). The inhibition of plasma extravasation by CRF (30 nmol/kg, i.v.) alone was not different from the inhibition induced by the combination of CRF and the tachykinin NK1 receptor antagonist, CP-99,994 (4 mg/kg, i.v.) (73% in the trachea and 38% in the main bronchi). CRF (30 nmol/kg, i.v.) inhibited by 32% in the trachea and by 43% in the main bronchi plasma extravasation induced by aerosolised bradykinin but did not reduce the plasma extravasation caused by aerosolised substance P in the presence of phosphoramidon. These findings suggest that CRF reduces ovalbumin-induced plasma extravasation in guinea pig airways by inhibiting the release of tachykinins from primary sensory nerves.

Animals↗
PubMed1995

Cloning of rat and mouse P2Y purinoceptors.

The cellular responses to ATP are mediated by specific high-affinity receptors designated as P2 purinoceptors, five subclasses of which have been defined pharmacologically-P2X, P2Y, P2U, P2T, and P2Z. A cDNA clone encoding a rat P2Y purinoceptor was isolated from an insulinoma cDNA library. The 373-amino acid rat P2Y purinoceptor sequence has 85.7% and 37.8% identity with chicken P2Y and rat P2U purinoceptors, respectively. The sequence of the mouse P2Y purinoceptor was also determined and there was 97.1% amino acid identity with the corresponding rat sequence. RNA blotting studies showed that rat P2Y purinoceptor mRNA was expressed at variable levels in many tissues including heart, brain, spleen, lung, liver, skeletal muscle and kidney, although it was not detected in testis. The cloned rat P2Y purinoceptor was expressed in Xenopus laevis oocytes and possessed the properties expected for this receptor subtype.

Adenosine Triphosphate↗
PubMed1995

Kinetic studies on the interaction of nonlabeled antagonists with the angiotensin II receptor.

Angiotensin AT1 receptor antagonists are divided into two types, surmountable and insurmountable, based on the way they inhibit angiotensin II-induced vasoconstriction. To elucidate what causes the difference, we studied how antagonists associate with and dissociate from AT1 receptor sites in rat liver membranes. Three antagonists, 6-propyl-7-oxo-4[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-4,7- dihydropyrazolo[1,5-a]pyrimidine-3-carboxylic acid (SRL1080227), 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H- benzimidazole-7-carboxylic acid (CV-11974) and 2-butyl-3-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-3H-imidazo- [4,5-b]pyridine (FK739), showed competitive antagonism when they were added simultaneously with [125I]angiotensin II, but CV11974 and SRL1080227 showed apparently noncompetitive antagonism when membranes were preincubated with each antagonist. The longer the preincubation time with CV11974 or SRL1080227 was, the more effectively the antagonist inhibited [125I]angiotensin II binding, while the inhibition by FK739 did not change with the preincubation time. To estimate their dissociation rate from the receptor binding site, we studied [125I]angiotensin II binding to membranes which had been preincubated with each antagonist and washed twice. Membranes pretreated with FK739 completely recovered the ability to bind [125I]angiotensin II with a period of 60 min, while membranes preincubated with CV11974 did not read this level of recovery. [125I]angiotensin II binding to membranes preincubated with SRL1080227 increased gradually, but did not reach the control level during the experiment. The kinetic properties of SRL1080227, CV11974 and FK739 were consistent with their characteristic modes in inhibiting angiotensin II-induced contraction of isolated rabbit aorta and decreasing blood pressure of spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin Receptor Antagonists↗
PubMed1995

Ras farnesyltransferase inhibitors suppress the phenotype resulting from an activated ras mutation in Caenorhabditis elegans.

Attachment of Ras protein to the membrane, which requires farnesylation at its C terminus, is essential for its biological activity. A promising pharmacological approach of antagonizing oncogenic Ras activity is to develop inhibitors of farnesyltransferase. We use Caenorhabditis elegans vulval differentiation, which is controlled by a Ras-mediated signal transduction pathway, as a model system to test previously identified farnesyltransferase inhibitors. We show here that two farnesyltransferase inhibitors, manumycin and gliotoxin, suppress the Multivulva phenotype resulting from an activated let-60 ras mutation, but not the Multivulva phenotype resulting from mutations in the lin-1 gene or the lin-15 gene, which act downstream and upstream of let-60 ras, respectively, in the signaling pathway. These results are consistent with the idea that the suppression of the Multivulva phenotype of let-60 ras by the two inhibitors is specific for Ras protein and that the mutant Ras protein might be more sensitive than wild-type Ras to the farnesyltransferase inhibitors. This work suggests that C. elegans vulval development could be a simple and effective in vivo system for evaluation of farnesyltransferase inhibitors against Ras-activated tumors.

Alkyl and Aryl Transferases↗