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Biomedical subjects

S Onodera

Publications and source records attributed to S Onodera.

At least 19 recordsLinked to original sources

Down-regulation of protein kinase C potentiates atrial natriuretic peptide-stimulated cGMP accumulation in vascular smooth-muscle cells.

It has been reported that atrial natriuretic peptide (ANP) produces inositol phosphates and diacylglycerol in vascular smooth muscle cells (VSMC). The purpose of this study is to investigate whether diacylglycerol produced by ANP affects ANP-induced cyclic GMP (cGMP) accumulation through the activation of protein kinase C. Short-term (15 min) treatment of rat aortic VSMC with protein kinase C activating phorbol 12-myristate 13-acetate (PMA, 100 nM) decreased ANP (100 nM)-induced cGMP accumulation by 34.7% in the presence of IBMX (0.5 mM). However, the long-term (24 h) treatment to decrease the activity of protein kinase C led to an enhancement of the cGMP accumulation by 69.6% compared with that of control VSMC. There were no significant differences in Bmax and Kd for ANP and ANP-dependent particular guanylyl cyclase activity between long-term PMA-treated and control VSMC. In the present study, we show that the activation of protein kinase C attenuates the cGMP accumulation induced by ANP and that down-regulation of protein kinase C results in an enhancement of the cGMP accumulation. These data are consistent with the role of protein kinase C as a negative regulator in ANP-receptor/guanylyl cyclase pathway.

Animals

A novel transthyretin mutation associated with familial amyloidotic polyneuropathy.

We characterized the mutation associated with familial amyloidotic polyneuropathy in a Japanese patient. Sequence analysis of polymerase chain reaction-amplified exons of the transthyretin gene revealed a novel point mutation resulting in a substitution of arginine for glycine at position 47. The mutation was confirmed using allele-specific olgonucleotide hybridization procedures. This most likely represents a de novo mutation since neither parent carries the mutant allele.

Adult

Hemoglobin Kansas found in a patient with polycythemia.

A 62-year-old woman, long suspected of having heart disease, was admitted to our hospital for thorough examination. Her hemoglobin level was 17.7 g/dl and her 2.3-DPG level was 8.90 microM/ml RBC. The patient proved to have polycythemia, hemoglobin Kansas, and diabetes mellitus. To our knowledge, this is the third case of hemoglobin Kansas in the world.

2,3-Diphosphoglycerate

[Significance of antimicrobial activities testing of antimicrobial agents in human urine].

In order to clarify the in vivo effect of the new quinolones in the urinary tract, we investigated the antimicrobial activities against Escherichia coli in the human urine. Human urine was prepared from a normal volunteer. After cations were removed by chelating resin, human urine was supplemented with 50, 100, or 500 micrograms of Mg2+ per ml using MgCl2 or 10, 50, or 150 micrograms of Ca2+ per ml using CaCl2. The pH of human urine was adjusted to 5.5, 7.0, or 8.0 with HCl or NaOH. Four clinical isolates of E. coli and E. coli NIHJ JC-2 were used. And antimicrobial activities of the new quinolones (norfloxacin, enoxacin, ofloxacin and ciprofloxacin) against these strains were measured using various urines as mediums. Antimicrobial activities of the new quinolones were reduced in the presence of high concentration of magnesium or low pH of urine. However, there was no influence of calcium concentration of urine on antimicrobial activities of the new quinolones. From these results, the component of the urine should be checked in the treatment of the patients with urinary tract infection.

4-Quinolones

[Single-dose treatment of tosufloxacin (TFLX) for acute uncomplicated cystitis].

The effectiveness of a single 300-mg dose of tosufloxacin and of 3-day treatment with tosufloxacin (300 mg daily) were compared in a prospective trial in order to clarify the cost-effectiveness of tosufloxacin for acute uncomplicated cystitis. Fifty female patients (25 patients of each group) with acute uncomplicated cystitis received one of these treatment regimens, and the clinical data and follow-up culture results were analyzed. The effectiveness rates of single-dose treatment and 3-day treatment after 3 days were 100% and 96%, respectively. The recurrence rates of single-dose treatment and 3-day treatment after 14 or 28 days were 0% (0/13 patients) and 15% (2/13 patients), respectively. There was no significant difference in the effectiveness rate and the recurrence rate between these two groups, statistically. All isolated strains were eliminated in both regimens. From these results, it is suggested that single-dose treatment of tosufloxacin is effective enough for acute uncomplicated cystitis.

4-Quinolones

[A comparative study of cefepime for bacterial pneumonia].

The efficacy, safety and usefulness of cefepime (CFPM), a new cephem antibiotic, in bacterial pneumonia, were evaluated in a comparative study against ceftazidime (CAZ). Each drug was administered by intravenous drip infusion at a dose of 1.0 g (nominal potency) twice daily for 14 days, and the following results were obtained. 1. A total of 183 cases were enrolled in this study. Efficacy rates ("good" or better responses) as evaluated by the subcommittee were 90.3% (65/72) in the CFPM group and 94.0% (63/67) in the CAZ group, with no significant difference between the 2 groups. 2. Efficacy rates ("good" or better responses), as evaluated by attending physicians, (in the same bacterial pneumonia cases which were subjected to evaluation by the subcommittee) were 87.5% (63/72) in the CFPM group and 89.6% (60/67) in the CAZ group, with no significant difference between the 2 groups. 3. Bacteriologically, eradication rates were 96.9% (31/32) in the CFPM group and 96.7% (29/30) in the CAZ group with no significant difference between the 2 groups. 4. The incidence of side effects was 5.9% (5/85) in the CFPM group and 4.8% (4/84) in the CAZ group, with no significant difference between the 2 groups. No significant difference was also found between the 2 groups in the incidence of abnormal laboratory findings; 28.4% (23/81) of the case in the CFPM group and 34.1% (28/82) in the CAZ group. 5. As for overall usefulness of the drug in bacterial pneumonia cases, utility rates ("useful" or better evaluations) as evaluated by the subcommittee were 88.9% (64/72) in the CFPM group and 92.5% (62/67) in the CAZ group. The rates as evaluated by investigators (in cases judged as evaluable by the subcommittee) were 87.5% (63/72) and 85.1% (57/67), respectively. There were no significant differences between the 2 groups. These results indicated that CFPM is very useful for the treatment of bacterial pneumonia.

Adolescent

[A comparative study of cefepime for chronic respiratory tract infections].

The clinical efficacy, safety and usefulness of Cefepime (CFPM), a new cephem antibiotics, in chronic respiratory infections were evaluated in a comparative study against Ceftazidime (CAZ). Each drug was administered by intravenous drip infusion at a dose of 1.0 g (nominal potency), twice daily for 14 days, and the following results were obtained: 1. A total of 170 cases were enrolled in this study. Efficacy rates ("good" or better responses) as evaluated by the subcommittee were 86.2% (56/65) in the CFPM group and 84.5% (60/71) in the CAZ group, with no significant difference between the two groups. 2. Efficacy rates ("good" or better responses) as evaluated by attending physicians were 83.3% (55/66) in the CFPM group and 84.5% (60/71) in the CAZ group with no significant difference between the two groups. 3. Bacteriologically, eradication rates were 83.3% (40/48) in the CFPM group and 88.2% (45/51) in the CAZ group, with no significant difference between the two groups. 4. Side effects occurred in none of the patients in the CAZ group and in 4 of the 66 patients in the CFPM group. There was a significant difference between the two groups (Fisher's test p = 0.0489). The incidence of abnormal laboratory findings were 17.6% (12/68) in the CFPM group and 21.1% (16/76) in the CAZ group. There was no significant difference between the two groups. 5. The utility rates evaluated by the subcommittee were 81.8% (54/66) in the CFPM group and 84.5% (60/71) in the CAZ group with no significant difference between the two groups. Only in the incidence of side effects, there was a significant difference between the two groups (Fisher's test p = 0.0489), but there was no significant difference in other items of efficacy, safety and usefulness between the two groups. These results indicate that CFPM is useful for the treatment of chronic respiratory tract infections.

Adolescent

Genetic relatedness of Bradyrhizobium japonicum field isolates as revealed by repeated sequences and various other characteristics.

Forty-nine isolates of Bradyrhizobium japonicum indigenous to a field where soybeans were grown for 45 years without inoculation were characterized by using four DNA hybridization probes from B. japonicum. nifDK-specific hybridization clearly divided the isolates into two divergent groups. Diversity in repeated-sequence (RS)-specific hybridization was observed; 44 isolates derived from 41 nodules were divided into 33 different RS fingerprint groups. Cluster analysis showed that the RS fingerprints were correlated with the nif and hup genotypes. We found multiple bands of RS-specific hybridization for two isolates that differed from the patterns of the other isolates. These results suggest that RS fingerprinting is a valuable tool for evaluating the genetic structure of indigenous B. japonicum populations.

Bacterial Typing Techniques

Construction of a transducing virus from double-stranded RNA bacteriophage phi6: establishment of carrier states in host cells.

Bacteriophage phi 6 contains three double-stranded RNA (dsRNA) genomic segments. We have constructed a plasmid that contains a cDNA copy of the middle (M) segment, with a gene for kanamycin resistance (kan) inserted into the PstI site. A transcript of this cDNA was incorporated in vitro into procapsids along with natural transcripts of the S and L segments. The procapsids were coated with nucleocapsid surface protein P8 and transfected into Pseudomonas syringae pv. phaseolicola. The resulting infectious virus, phi 6 K1, was found to contain an M segment that was 1.2 kbp larger than the normal 4.1 kbp. K1 formed small, turbid plaques, and its genome was unstable. Preparations of K1 contained from about 0.1 to 10% large, clear-plaque forms of the virus which were usually missing the kan gene, and in some cases, the resulting segment M was smaller than its normal size. Cells picked from lawns of host cells infected with K1 yielded colonies that were resistant to kanamycin (Kan). These colonies could be passaged on kanamycin-containing medium. The cells were found to contain large amounts of dsRNA corresponding to the viral genomic segments. Some strains continued to produce viable phage, while others lost this ability. One strain completely lost the small genomic segment S. Approximately 1 in 10,000 infected cells acquired the carrier state with the original phage isolate K1. However, we isolated a viral mutant that was able to induce the carrier state in 10 to 20% of the infected cells. The ability to use drug resistance as a test for the carrier state makes this system very useful for the study of the mechanisms of induction of persistent infections.

Bacteriophages

Heterologous recombination in the double-stranded RNA bacteriophage phi 6.

Bacteriophage phi 6 contains three double-stranded RNA genomic segments. We have constructed a virus with an insertion of a kanamycin resistance gene in genomic RNA segment M. The virus forms small, turbid plaques, and its genome is unstable. Virus from a single plaque contained from about 0.1 to 10% large clear-plaque forms of the virus; these were usually missing the kanamycin resistance gene, and in many cases, the resulting segment M was larger or smaller than its normal size. Sequence analysis of the genomic RNA of the apparent deletions showed that they were formed by recombination events between segment M and either segment S or L. These heterologous recombination events resulted in the loss of the kanamycin resistance gene from segment M and the replacement of the 3' end of segment M with the 3' end of segment S or L. Although the 3' ends of the single-stranded RNA transcripts of the genomic segments appear to have extensive secondary structure, the sequences at the 3' ends are not involved in the specificity of genomic packaging.

Base Sequence

Inhibitory effect of pindolol on hypoxic pulmonary vasoconstriction.

The effects of a beta-agonist (isoproterenol) and beta-antagonists (propranolol and pindolol) on hypoxic pulmonary vasoconstriction (HPV) and on changes in some chemical mediators were examined in 28 isolated blood-perfused dog lung lobes. Hypoxic challenge (4 min) was repeated twice, and each drug was administered at a bolus dose of 0.2 mg between the hypoxic periods. The first hypoxia increased pulmonary vascular resistance (PVR) by 33% or more in all groups. Both isoproterenol and pindolol inhibited the second HPV completely, but propranolol did not influence HPV. During normoxia, isoproterenol and pindolol significantly decreased PVR by 17.5 and 6.7% (P less than 0.01), respectively, but propranolol had no effect on PVR. In the control and propranolol groups, plasma levels of adenosine 3',5'-cyclic monophosphate (cAMP) significantly decreased during hypoxia, but those of prostaglandin E2, 6-ketoprostaglandin F1 alpha, and thromboxane B2 did not change. cAMP increased from 17.0 +/- 4.0 to 76.7 +/- 15.6 pmol/ml in the isoproterenol group (P less than 0.01), and prostaglandin E2 increased from 87.0 +/- 13.6 to 1,015.4 +/- 309.7 pg/ml in the pindolol group (P less than 0.05). The results suggest that the mechanism of HPV inhibition is different between isoproterenol and pindolol.

Animals

Measurement of biventricular septal-to-free wall diameters using sonomicrocrystals.

An ultrasonic system for the measurement of biventricular septal-to-free wall internal diameters in the dog was described. The ventricular endocardial ultrasonic microcrystals were implanted via the left and right atrial appendages and arranged in a straight line, with minimal invasion of the myocardium and pericardium. Reliable signals were obtained during right ventricular pressure overload and septal myocardial ischemia.

Animals

Effect of xamoterol in Shy-Drager syndrome.

BACKGROUND: Xamoterol, a cardioselective beta 1-adrenoceptor partial agonist, has been reported to be effective on postural hypotension. We investigated the effect of xamoterol in five patients with Shy-Drager syndrome (SDS) in relation to their prevailing sympathetic nerve activity and sensitivity of beta-adrenoceptors and the change in circadian variation of blood pressure. METHODS AND RESULTS: Ambulatory blood pressure over 24 hours was monitored by noninvasive sphygmomanometer (model 5200, Spacelab). Plasma norepinephrine levels of SDS patients were significantly lower than that of normal subjects (n = 5) both at rest (54 +/- 15 versus 178 +/- 83 pg/ml) and after 10-minute standing (74 +/- 24 versus 318 +/- 143 pg/ml). Infusion of isoproterenol (0.02 micrograms/kg/min) produced a mild rise of systolic blood pressure and tachycardia in normal subjects but resulted in marked hypotension and tachycardia in SDS subjects. After xamoterol administration (200 mg b.i.d.), systolic blood pressure and heart rate were significantly increased in the averages during the day; however, increases were more pronounced at night. In two of the five patients, the improvement in dizziness was large enough to enable them to increase their daily activities. CONCLUSIONS: Our observations suggest that 1) beta 1-selective, high intrinsic sympathomimetic activity of xamoterol increases blood pressure and heart rate in patients with SDS as a consequence of their prevailing beta 1-adrenoceptor hypersensitive state, and 2) blood pressure monitoring over 24 hours appears to have important advantages in evaluating the therapeutic effects on postural hypotension.

Adrenergic beta-Agonists

Time course of pulmonary vascular response to an acutely repetitive pulmonary microembolism in dogs--an analysis using pulmonary vascular impedance.

To understand the mechanism leading to progressive pulmonary hypertension, we investigated the time course of vascular response to an acutely repetitive pulmonary microembolism in dogs by using pulmonary vascular impedance. In a normal state, the mean pulmonary arterial pressure (mPAP) was transiently increased by emboli, and the impedance moduli of 0 Hz (= Rin), 1.5 Hz and 3 Hz were slightly increased. A four-element electrical vascular model showed the transient increase in peripheral pulmonary vascular resistance (R2) and inertia, and reduction in compliance (C). In contrast, in a state of a slight pulmonary hypertension, mPAP was continuously increased by the same amount of emboli, and the impedance moduli of both 0 Hz and 3 Hz were significantly increased. By a four-element model, a severe increase in R2 and reduction in C were observed, and these changes continued. Therefore, although the vascular response to pulmonary microembolism basically depends on the degree of mechanical obstruction, this response is thought to be modulated by the responsiveness of pulmonary vessels at that time, which is involved in the alteration in the local characteristics of pulmonary vessels, and/or the recruitment of a new blood flow.

Acute Disease

Site of hypoxic pulmonary vasoconstriction in pulsatile perfused canine lung lobes.

To elucidate the site of hypoxic pulmonary vasoconstriction (HPV) in the dynamic lung, we studied the effect of alveolar hypoxia (0 approximately 4% O2) on excised canine lung lobes with pulsatile perfusion from artery to vein (antegrade perfusion: AP) or vein to artery (retrograde perfusion: RP), and compared responses to hypoxia with those to serotonin and histamine. In our preparation, increases in the pulmonary vascular resistance (R) resulted in a wide range of decreases in the flow wave amplitude at the lobar inflow site (FA). These decreases in FA reflected reductions in the compliance of the vasculature proximal to the main site of resistance. The FA/R ratios of serotonin were 2.29 in AP and 0.24 in RP indicating the predominant arterial constriction, those of histamine were 0.07 in AP and 1.24 in RP indicating the selective venous constriction. In contrast, the responses to hypoxia were 0.38 in AP and 0.42 in RP. These results suggest that HPV occurs not only on the arterial side but on the venous side in the dynamic lung, and the main site of HPV is located in the peripheral pulmonary vasculature, between muscular arteries and veins which are constricted by serotonin and histamine.

Animals

Spontaneous coronary artery dissection after a natural course for 10 years--a case report.

We encountered a patient with spontaneous coronary artery dissection complicated by acute inferior myocardial infarction. A 58-year-old male was admitted to our hospital due to acute inferior myocardial infarction in 1979. Coronary angiography performed 4 weeks after the onset showed a double lumen divided by a linear intimal flap in the right coronary artery, suggesting coronary artery dissection, but no apparent occlusion. Subsequently, he had been medicated with nitrates without any recurrent infarction. In February, 1989, 10 years after the first examination, coronary angiography was again performed and showed that the dissection had remained unchanged. Acetylcholine infusion into the right coronary artery induced coronary spasm. The prognosis of this condition seems to be better than has been generally considered, particularly in patients such as ours in whom the involvement of coronary spasm in the development of coronary artery dissection and myocardial infarction is suggested. When coronary spasm in controlled by treatment with nitrates or calcium antagonists, an uneventful course may be expected.

Acetylcholine

[Effects of FRG-8813, a new type histamine H2-receptor antagonist, on various experimental gastric and duodenal lesions in rats].

We examined the anti-ulcer effects of FRG-8813, a new type histamine H2-receptor antagonist, on various experimental gastric and duodenal lesions in rats. FRG-8813, administered orally, inhibited the formation of lesions dose-dependently in experimental models with the exception of the Shay ulcer model. The anti-ulcer potency of FRG-8813 was 4 approximately 10 times greater than that of cimetidine when the ED50 values of both compounds were compared. Famotidine and cimetidine inhibited lesion formation at higher doses than the anti-secretory doses. The anti-ulcer action of FRG-8813, however, appeared at even lower doses than those of anti-secretory action. These results suggest that FRG-8813 is able to prevent lesion formation with anti-secretory action plus other mechanisms unlike typical histamine H2-receptor antagonists.

Acetamides

[Effects of FRG-8813, a new-type histamine H2-receptor antagonist, on the healing of gastric and duodenal ulcer in rats and spontaneously ulcerative mice].

We examined the anti-ulcer effects of FRG-8813, a new-type histamine H2-receptor antagonist, in chronic ulcer models of rats and mice (W/WV). FRG-8813, given orally twice a day for 7 days, accelerated the healing of gastric or duodenal ulcer induced by acetic acid injection or application at the non-antisecretory doses (0.3 approximately 3 mg/kg). Administration of FRG-8813 to rats with ulcers increased the amounts of mucus in the gastric mucosa. These actions of FRG-8813 were more potent than those of famotidine or cimetidine. In W/WV mice, several ulcers spontaneously developed on gastric mucosa during the 8 weeks after the birth. The ulcers were aggravated by several unknown factors after the ulcer generation in W/WV mice. The aggravation of ulcers was inhibited by the 4-week administration of FRG-8813 with diet at the dose of 1 or 10 mg/kg/day, but was not inhibited by cimetidine at the dose of 100 mg/kg/day. From these results, we suggest that FRG-8813 is able to accelerate the healing of ulcers by antisecretory plus increasing actions on the integrity of the gastric mucosal defense mechanisms; therefore FRG-8813 is expected to be a useful drug for the treatment of gastric or duodenal ulcers in humans.

Acetamides