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Biomedical subjects

T Okamura

Publications and source records attributed to T Okamura.

At least 469 records · Page 26Linked to original sources

[Neurotransmission and nitric oxide (NO)].

The history of how we reached the goal of determining the mechanism of vasodilatation caused by non-adrenergic, non-cholinergic nerve stimulation in cerebral arteries was traced. We concluded from this project that electrical and chemical (by nicotine) stimulations evoke an increased influx of Ca2+ into nerve terminals and activate nitric oxide (NO) synthase, resulting in the synthesis and release of NO that stimulates the guanylate cyclase in smooth muscle, thereby causing the accumulation of cyclic GMP and eliciting muscle relaxation. Reviewed also are the neurally-induced inhibitory responses of extracranial arteries, intestines, etc. with respect to NO.

Animals↗

Involvement of nitric oxide in endothelium-dependent, phasic relaxation caused by histamine in monkey cerebral arteries.

Monkey cerebral artery strips partially contracted with prostaglandin F2 alpha responded to histamine with biphasic patterns of relaxation. The delayed and sustained relaxation was suppressed by cimetidine, whereas the phasic response was abolished by treatment with chlorpheniramine and NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor. The inhibition by L-NA was reversed by L-arginine. D-NA was without effect. Endothelium denudation abolished the phasic relaxation. We hypothesized that endothelium-dependent, phasic relaxations caused by histamine are mediated by NO that is released by H1-receptor stimulation, whereas the sustained relaxation is associated with the activation of H2-receptors in the smooth muscle of monkey cerebral arteries.

Animals↗

Localization of components of the renin-angiotensin system within the kidney and sustained release of angiotensins from isolated and perfused kidney.

We found colocalization of renin, angiotensin (Ang) I and Ang II in juxtaglomerular (JG) cells of the kidney. Coexistence of Ang II in renin granules was demonstrated by electron microscopic immunogold labeling of these components. Coexistence of both Ang I and Ang II in the high density renin storage granules were also demonstrated by gradient centrifugation of renal homogenate. These findings supported the synthesis of Ang I and Ang II in juxtaglomerular cells. Isolated and cultured JG cells showed the synthesis of Ang I, Ang II and renin. Ang I and Ang II were secreted from isolated and perfused rat kidneys at steady rates over 2 hr. Their secretion rates were proportional to that of renin. The rate of Ang II secretion from the kidney was higher than that from the vascular bed. Ang II was also found in renal lymph. These findings indicate that a large amount of Ang II is generated in JG cells by the intracellular action of renin and may play a significant role in the regulation of renal function.

Angiotensins↗

[A study of falls experienced by institutionalized elderly].

This study was conducted to determine what factors are related to falls, conditions contributing to falls and the associated injuries. Subjects who had lived in 3 institutions for the elderly in the western region of Shizuoka Prefecture were chosen. Subjects (n = 181) had an average age of 76.4 +/- 7.8 years, and all were interviewed regardless of their history of falls. For those who had experienced falls further interviews were conducted. The following results were obtained: 1) There were 64 subjects (35.4% of the subjects) who had experienced falls, some having experienced multiple falls (for a total count of 89 falls). 2) The frequency of falls of differed by sex or age was significantly. The frequency of females was significantly higher than that of males. The frequency for those in their 70's was lower than in other age groups. 3) At the time of experiencing falls the majority of subjects had hypertension, eye symptoms, insomnia, paralysis, functional restrictions, were going up or down stairs, working, and had difficulty reading characters in newspapers, had experiences of stumbling or need of medical attention within for the past 2 years. Results of this study showed that, while the use of tranquilizers or hypnotics were not statistically significant, they were closely connected to and increase in falls among the aged. 4) In the causes of falls, intrinsic factors figured in 34 (34.0%) cases, and the extrinsic factors in 66 (66.0%). 5) Both falls and fall-caused external injuries were higher among females than males. Furthermore, female subjects mainly suffered contusions and fractures while male subjects mainly suffered abrasions.

Accidental Falls↗

Mechanism of relaxation induced by K+ and nicotine in dog duodenal longitudinal muscle.

Dog duodenal longitudinal muscle strips precontracted with bradykinin responded to K+ (10 mM) with a transient relaxation, which was abolished by tetrodotoxin and oxyhemoglobin, but not influenced by atropine, ouabain and apamin. The induced relaxation was suppressed by treatment with 10(-5) M NG-nitro-L-arginine (L-NNA) a nitric oxide synthesis inhibitor, but not by the D-enantiomer. The inhibitory effect was antagonized by L- but not D-arginine. High concentrations (20 mM or higher) of K+ produced a relaxation followed by a sustained contraction; nicardipine abolished the contraction, but did not alter the relaxation. Nicotine produced a contraction, which was converted to a relaxation by atropine. The relaxant response was abolished by tetrodotoxin, hexamethonium and oxyhemoglobin, but was unaffected by timolol and phentolamine. L-NNA suppressed the relaxation, and L-arginine reversed the inhibition. The addition of K+ (20 mM) increased the content of cyclic GMP in the strips, the effect being prevented by tetrodotoxin and L-NNA. These findings suggest that K+ selectively stimulates the nonadrenergic inhibitory nerve, whereas nicotine stimulates both the excitatory cholinergic and inhibitory nerves. Nitric oxide released from the inhibitory nerve appears to transmit information to duodenal smooth muscle by increasing the production of cyclic GMP.

Adenosine Triphosphate↗

[Investigation of two cases of adenoid cystic carcinoma of the esophagus].

A 59-year-old man and a 55-year-old man with adenoid cystic carcinoma of the esophagus are presented. They were also treated with esophagectomy but whose prognosis were significantly different. The former has been still alive for 3.5 years and the later died at 7 months after the operation. In the patient with good prognosis, the tumor was 1.6 x 1.2 cm in size and pathologically invaded muscularis propria (mp) with no metastases to lymph nodes (pathological stage I). It has been reported that the prognosis of adenoid cystic carcinoma of the esophagus is poorer than that of other histological type of carcinomas. However, it is suggested that if the tumor can been resected when it is small in size with no metastases, it will be able to expect for good prognosis as in this presentation.

Carcinoma, Adenoid Cystic↗

[A case of idiopathic hemochromatosis associated with gastric cancer].

A 76-year-old male was admitted to our hospital because of general fatigue in June 1987. He had received total gastrectomy against gastric carcinoma two years previously. The examinations revealed the elevation of GOT, GPT and gamma-GTP, and increased CT number of the liver. Specimen of the liver biopsy showed deposition of iron and slight fibrosis. He was diagnosed as idiopathic hemochromatosis. He was given deferoxamine, and his elevated GOT, GPT and gamma-GTP were normalized. Idiopathic hemochromatosis is frequently associated with various malignancies including hepatic carcinoma. However, only a few cases of idiopathic hemochromatosis associated with gastric carcinoma have been reported.

Adenocarcinoma↗

[Chemotherapy of biliary tract infections (XXXVII). Excretion into bile and gallbladder tissue levels of levofloxacin and its clinical effect in biliary tract infections].

Evaluations were made on biliary excretion and penetration into the gallbladder tissue of levofloxacin (LVFX, DR-3355), a new quinolone antibacterial agent, and its clinical efficacy in biliary tract infections. 1. Gallbladder tissue concentrations and biliary concentrations of LVFX at 2-6 hours at oral administration of 100 mg were 0.58-1.99 micrograms/g and 0.49-5.63 micrograms/ml, respectively. These tissue and biliary levels are almost equal or somewhat higher than the serum levels (0.55-1.63 micrograms/ml) of the compound. 2. The concentrations of LVFX and optical isomer DR-3354 in the serum, gallbladder tissue, and bile were determined after a single or a concomitant administration of LVFX 100 mg and/or ofloxacin (OFLX) 100 to 200 mg. The concentration ratio of LVFX to DR-3354 paralleled with the ratio of the 2 compounds administrated. 3. At a dose of 100 mg, the glucuronide of LVFX in the common duct bile was detected at proportions between 0.9 and 36.0%. 4. A total of 11 patients with biliary tract infections, including 6 cholecystitis 3 cholangitis, and 1 each of cholecystocholangitis and liver abscess was treated with LVFX at 100-200 mg t.i.d. for 3-14 days. Clinical results were excellent or good in 8 cases and fair in 3 cases, resulting in an efficacy rate of 72.7%. 5. A side effect and an abnormal change in laboratory findings were observed in both 1 case each and they were both mild. It was concluded that LVFX showed good penetration to the biliary tract as does OFLX, and that it would be a useful oral agent for the treatment of biliary tract infections.

Adult↗

[A case of repetitive monomorphic ventricular tachycardia].

We present a case treated with aprindine and metoprolol combined with a DDD type pacemaker for repetitive monomorphic ventricular tachycardia. A 50-year-old man was admitted because of palpitation and near syncope attack. Electrocardiogram showed repetitive monomorphic ventricular tachycardias (RBBB LAD type) and R-R interval of about 440 msec and I degree A-V block in sinus rhythm. Electrophysiologic study disclosed that overdrive pacing in HRA suppressed ventricular tachycardias. Left ventriculography revealed a dilated left ventricular and decreased contractility. Antiarrhythmic agents such as quinidine sulfate, procainamide, disopyramide, mexiletine, lidocaine and propranolol were not effective. But, the combination of propranolol and aprindine decreased the rate of the ventricular tachycardia. With aprindine 60 mg/day and metoprolol 60 mg/day combined with the atrioventricular sequential pacing at 85/min, ventricular tachycardia completely disappeared.

Aprindine↗

Different susceptibility of vasodilator nerve, endothelium and smooth muscle functions to Ca++ antagonists in cerebral arteries.

Effects of selective (nicardipine) and nonselective (Cd++) Ca++ channel antagonists on the responses of isolated dog cerebral arteries to vasodilator nerve stimulation, substance P, serotonin and prostaglandin F2 alpha were investigated; the relaxation caused by the nerve stimulation and the peptide is mediated by NO, possibly from the nerve and endothelium, respectively. Relaxant responses to nerve stimulation by electrical pulses and nicotine in the endothelium-denuded arteries were attenuated by Cd++, but not influenced by nicardipine; the concentrations of these antagonists were sufficient to suppress contractions caused by prostaglandin F2 alpha and serotonin to a similar extent. Increase in cyclic GMP by nicotine was also suppressed solely by Cd++. In the endothelium-intact arteries treated with indomethacin, relaxations induced by substance P were not affected by nicardipine, but were significantly attenuated by Cd++. The peptide-induced increase in cyclic GMP was suppressed by Cd++, but not by nicardipine. It is concluded that functional properties of the Ca++ channel responsible for increasing cytosolic Ca++ in the nerve and endothelium for the synthesis and release of nitric oxide or endothelium-derived relaxing factor differ from those of the channel in smooth muscle. Because Ca++ is a prerequisite for the synthesis of NO, smooth muscle does not appear to be the site of production of NO that transmits vasodilator information from the nerve or endothelium to cerebroarterial smooth muscle.

Animals↗

Intracellular signals in IgG-mediated anaphylactic contraction of single smooth muscle cells.

Single smooth muscle cells from the taenia coli of guinea pigs passively sensitized with anti-egg albumin IgG fraction were used to evaluate the intracellular signal transduction system during anaphylactic contraction. 125I-IgG was bound to single smooth muscle cells, and sensitized smooth muscle cells contracted in response to antigen treatment. In response to neuraminidase treatment, 125I-IgG binding to the cells was decreased, along with an inhibition of anaphylactic contraction. Pretreatment with islet-activating protein (IAP), neomycin, quercetin and H-7 inhibited anaphylactic contraction, whereas pretreatment with phorbol 12,13-dibutylate augmented the contraction. The signal produced by the interaction between IgG bound to the smooth muscle cells and antigen appears to be transmitted to the intracellular contractile element via the signal transduction system involving G protein. Phospholipase-C and -A2 appear to be the effectors in the signal transduction system for anaphylactic contractions. Protein kinase C, activated with reference to phospholipase-C, also may be involved in anaphylactic contraction.

Anaphylaxis↗

[Therapeutic evaluation of imipenem/cilastatin sodium for bacterial infections in patients with hematological diseases].

1. To evaluate the efficacy and tolerance of imipenem/cilastatin sodium (IPM/CS) in severe infections associated with hematopoietic disorders, IPM/CS was administered to a total of 105 patients. 2. Out of 96 patients evaluable for efficacy, clinical responses were excellent in 23 patients, good in 30, fair in 15, poor in 19 and unknown in 9, and the overall response rate was 60.9%. 3. The most common underlying hematopoietic disease was acute non-lymphocytic leukemia and the most common infections were sepsis and suspected sepsis. 4. Daily dose, severity of infection and neutrophil count had effects on the clinical response. 5. The overall eradication rate of bacteria was 83.7%. 6. Side effects were observed in 10 patients (9.5%) and abnormal laboratory test results in 12 (11.4%). From the above findings, we have concluded that IPM/CS is very useful for the treatment of severe infections in compromised patients with hematopoietic diseases.

Adult↗

Determination of rates and yields of interchromophore (folate----flavin) energy transfer and intermolecular (flavin----DNA) electron transfer in Escherichia coli photolyase by time-resolved fluorescence and absorption spectroscopy.

Escherichia coli DNA photolyase, which photorepairs cyclobutane pyrimidine dimers, contains two chromophore cofactors, 1,5-dihydroflavin adenine dinucleotide (FADH2) and 5,10-methenyltetrahydrofolate (MTHF). Previous work has shown that MTHF is the primary photoreceptor which transfers energy to the FADH2 cofactor; the FADH2 singlet excited state then repairs the photodimer by electron transfer. In this study, we have determined the rate constants for these photophysical processes by time-resolved fluorescence and absorption spectroscopy. From time-resolved fluorescence, we find that energy transfer from MTHF to FADH2 and FADH degrees occurs at rates of 4.6 x 10(9) and 3.0 x 10(10) s-1, respectively, and electron transfer from FADH2 to a pyrimidine dimer occurs at a rate of 5.5 x 10(9) s-1. Using Förster theory for long-range energy transfer and assuming K2 = 2/3, the interchromophore distances were estimated to be 22 A in the case of the MTHF-FADH2 pair and 21 A for the MTHF-FADH degrees pair. Picosecond absorption spectroscopy identified an MTHF single state which decays to yield the first excited singlet state of FADH2. The lifetimes of MTHF and FADH2 singlets and the rates of interchromophore energy transfer, as well as the rate of electron transfer from FADH2 to DNA measured by time-resolved fluorescence, were in excellent agreement with the values obtained by picosecond laser flash photolysis. Similarly, fluorescence or absorption lifetime studies of the folate-depleted enzyme with and without photodimer suggest that FADH2, in its singlet excited state, transfers an electron to the dimer with 89% efficiency. The distance between FADH2 and the photodimer was calculated to be ca. 14 A.

Apoenzymes↗

Responses to dopamine of isolated human and monkey veins compared with those of the arteries.

Isolated human gastroepiploic vein tributaries responded to dopamine only with contractions, whereas the gastroepiploic artery branches in the same region of the omentum responded with relaxations. Treatment with phentolamine converted the vein contraction to a relaxation, which was not influenced by propranolol but was abolished by droperidol. The relaxation was converted to a contraction by SCH23390 but unaffected by domperidone. Endothelium denudation abolished the relaxation caused by substance P but did not significantly alter the dopamine-induced relaxation. Dopamine increased the cyclic AMP content in the human veins. Monkey mesenteric, renal and portal veins and vena cava contracted in response to dopamine. Treatment with phentolamine converted the contraction to a slight relaxation in the mesenteric and renal veins; however, even in the presence of high concentrations of the alpha adrenoceptor antagonist, no relaxation was induced in the portal vein and vena cava partially contracted with prostaglandin F2 alpha. It is concluded that gastroepiploic veins and arteries in the human omentum respond quite differently to dopamine; the alpha adrenoceptor-mediated contraction predominates over the relaxation mediated via dopamine D1 receptor subtype in the veins, and vice versa in the arteries. Dopamine relaxes the human vein, possibly as a result of increased production of intracellular cyclic AMP by stimulation of D1 receptors. The predominant action of dopamine on alpha adrenoceptors may contribute to increasing venous return and cardiac output.

Adult↗