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Biomedical subjects

S Iwata

Publications and source records attributed to S Iwata.

At least 145 records · Page 8Linked to original sources

Efficacy of short-term treatment of pertussis with clarithromycin and azithromycin.

The recommended treatment for pertussis is erythromycin, 40 to 50 mg/kg per day for 2 weeks. The newly developed macrolides, clarithromycin and azithromycin, have been demonstrated to be superior to erythromycin because of improved absorption and a longer half-life. As a result, we conducted two separate comparison studies to evaluate the efficacies of clarithromycin, 10 mg/kg per day, twice a day for 7 days, and azithromycin, 10 mg/kg per day, once a day for 5 days, compared with the standard erythromycin regimen. A total of 17 patients, including 10 infants 1 year of age or less, for whom pertussis had been confirmed by culture, were allocated to receive either clarithromycin or azithromycin treatment, and each patient was matched (age, sex, and immunization status) with historical control subjects who had been treated with erythromycin. Eradication rates examined at 1 week after treatment were as follows: 9 of 9 with clarithromycin versus 16 of 18 with erythromycin (psi M-H = 1.13), and 8 of 8 with azithromycin versus 13 of 16 with erythromycin (psi M-H = 1.23). No bacterial relapse after treatment was detected in either group. All isolated strains of Bordetella pertussis were susceptible to clarithromycin, azithromycin, and erythromycin, and no change in drug susceptibility has been confirmed for the past 20 years in Japan. Because of the very low incidence of pertussis resulting from widespread use of acellular pertussis vaccination, this study did not enroll a large number of patients; however we conclude that short-term treatment with clarithromycin or azithromycin is expected to be equal or superior to the standard long-term erythromycin regimen for pertussis.

Adolescent↗

Cytochrome c oxidase.

Within the past year, the structures of the cytochrome c oxidase from the soil bacterium Paracoccus denitrificans and of the metal centers of the cytochrome c oxidase from bovine heart mitochondria, both determined at 2.8 A resolution by X-ray crystallography, have been reported. The structures form a basis for understanding the mechanism of this redox-coupled transmembrane proton pump, which is the key component of the respiratory chain of most aerobic organisms.

Animals↗

Energy metabolism and regeneration in transgenic mouse liver expressing creatine kinase after major hepatectomy.

BACKGROUND & AIMS: The catalysis of a creatinine/phosphocreatine system by creatine kinase is not expressed in the liver. The aim of this study was to examine the energy energy metabolism and regeneration after hepatectomy using transgenic mouse liver expressing creatine kinase to clarify the effects of phosphocreatine on liver regeneration. METHODS: Transgenic mice were divided into two groups: group 1 was fed normal chow, and group 2 was fed 10% creatine chow for 5 days. Hepatic energy metabolism was evaluated before and after hepatectomies. Changes in remnant liver weight gain and bromodeoxyuridine labeling index were measured after 70% and 80% hepatectomies. RESULTS: Hepatic adenosine triphosphate level 24 hours after 70% hepatectomy was significantly higher in group 2 than group 1 (P<0.05). In group 2, mitochondrial adenosine triphosphate synthesis was enhanced because of elevated intramitochondrial adenine nucleotide content before hepatectomy, leading to sufficient adenosine triphosphate synthesis after a 70% hepatectomy. Bromodeoxyuridine DNA labeling index 24 hours after a 70% hepatectomy was significantly higher in group 2 than group 1. Rapid liver weight gain was observed in group 2 after a 70% hepatectomy. CONCLUSIONS: Abundant phosphocreatine promotes liver regeneration by reinforced hepatic energy metabolism. Gene transfer of creatine kinase to the liver may be a potential method in liver surgery.

Adenine Nucleotides↗

Induction of endotoxin tolerance in transgenic mouse liver expressing creatine kinase.

The liver plays an important role in maintaining homeostasis during endotoxin-triggered systemic inflammatory response. To study the effects of phosphocreatine on hepatic energy metabolism after endotoxin administration, we used transgenic mice whose livers express creatine kinase (CK). CK catalyzes a phosphocreatine/creatine reaction, that is, an adenosine triphosphate (ATP) reservoir system. Because dietary supplementation with creatine leads to an accumulation of creatine and phosphocreatine in transgenic livers, we compared the CK transgenic mice fed with creatine with the normally fed CK transgenic mice. In the creatine-fed mice, hepatic ATP, energy charge ([ATP + 0.5 adenosine diphosphate (ADP)]/[ATP + ADP + adenosine monophosphate (AMP)]), and mitochondrial oxidative phosphorylation activities remained at high levels after injection of 10 mg/kg of lipopolysaccharide (LPS) as compared with those in normally fed mice. Furthermore, there were beneficial effects on the functional reserve for ATP synthesis and work-cost performance, as calculated by free cytoplasmic ADP and the Michaelis constant (Km). Interestingly, a reduction of tissue necrosis factor alpha and interleukin-lalpha (IL-lalpha), and suppression of the decrease in glucose levels after LPS injection were observed in the creatine fed mice. Survival rates at 72 hours after injection of 10 mg/kg of LPS significantly increased in the creatine fed mice compared with the normally fed mice (80% vs. 24%, P < .001). Therefore, we concluded that the presence of phosphocreatine in the liver maintains energy metabolism and attenuates cytokine response, resulting in endotoxin tolerance.

Adenine Nucleotides↗

Characteristic upregulation of dopamine D1-receptor in rat striatum after 6-hydroxydopamine treatment.

We measured the number of D1-receptors (Bmax) in the striatum whose dopaminergic terminals were destroyed to various degrees by 6-hydroxydopamine (6-OHDA) to clarify the relationship between the degree of denervation and the change in Bmax for D1-receptor. Rats were sacrificed 28 days after 6-OHDA treatment, and [3H]SCH23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine) binding capacity and monoamine content were measured in striatal homogenate. Bmax was significantly upregulated when dopamine content was reduced to less than 5% of that in the vehicle-treated striatum. In contrast, it was significantly decreased when dopamine content was 5-25% of that in the vehicle-treated striatum. The D1-receptors showed either upregulation or downregulation depending on the degree of denervation.

Animals↗

Chicken extract stimulates haemoglobin restoration in iron deficient rats.

Chicken essence is widely used as a traditional remedy for several ailments including anaemia. To test this claim for objective evidence, a series of experiments was carried out in anaemic rats by supplementing iron deficient diets with either liquid or lyophilised essence, which contains mainly protein and peptides (83 mg/ml) and free amino acids (3.1 mg/ml), very little iron (1 microgram/ml), and no fat. Haemoglobin returned to normal significantly more rapidly in rats supplemented with ad libitum liquid BEC over a period of up to 27 days compared with controls fed only water in addition to the ad libitum iron deficient diet. Haemoglobin was also significantly increased after 1 week in animals fed ad libitum diets supplemented with lyophilised chicken essence than with controls fed the unsupplemented diet. The effect was greater with supplementation at the level of 0.2% than at 1% lyophilised essence. The results indicate that the effects were mediated by increased appetite and by enhanced availability of food iron. These studies provide objective evidence for the traditional belief that chicken essence remedies anaemia.

Anemia, Iron-Deficiency↗

[A case of dural AVM detected after STA-MCA anastomosis].

A case of dural arteriovenous malformation (AVM) in the posterior cranial fossa detected after STA-MCA anastomosis surgery. A 52-year-old male consulted a neighbourhood hospital for sudden headache and vomiting. He was diagnosed as having intraventricular hemorrhage on CT scan. Though the obstruction of the right internal carotid artery was revealed angiographically, his symptoms improved after conservative therapy. Two weeks after onset, his consciousness deteriorated and he developed left hemiparesis. Thereafter, he was transferred to our hospital. After thorough examination, right STA-MCA anastomosis surgery was performed. Approximately 2 months after surgery, right tinnitus developed and gradually exacerbated. Since it was thought to be due to increased blood flow in the right superficial temporal artery, it was kept under observation. On angiogram, 8 months after surgery, good blood flow supplied from the right superficial temporal artery to the territory of the right middle cerebral artery was shown, and a dural AVM fed by the right occipital artery was found. Fourteen months after the surgery, an enlarged dural AVM with backflow to the superficial cerebral veins fed by the enlarged right occipital artery and right ascending pharyngeal artery was revealed. Embolization therapy to the right occipital and ascending pharyngeal artery was performed using coils and ivalon, and irradiation of 30 Gy was added. After this treatment, right tinnitus improved. On angiography 2 years later, transverse sinus was slightly visible via the right occipital artery and ascending pharyngeal artery, but the dural AVM was significantly reduced. The origin of dural AVMs remains controversial. In our case, dural AVM was not found before the STA-MCA anastomosis surgery, and sinus thrombosis was not found throughout the course of observation. It is thought that the occult dural AVM was disclosed and enlarged by the increased blood flow through the external carotid artery via the STA-MCA anastomosis. Therefore, the dural AVM seemed to be congenital in origin.

Arteriovenous Malformations↗

[Establishment of reference intervals and physiological parameters for 13 serum proteins in healthy Japanese adults].

Using a nephelometry with a new calibrator in which values were assigned from EU/CRM470, a new international reference preparation, we have established for the first time the reference intervals of 13 different serum proteins in Japanese adults. Based on the NCCLS guideline C28-P, a new statistical and concrete procedure was revised and used for this study. It is clearly shown here that standardisation of serum proteins can be possible under the qualified assay system, making it possible to share the reference intervals among laboratories under well-controlled quality assurance. New aspects of serum protein variations were discovered in relation to physiologic changes and life styles.

Adult↗

Increased in vivo phosphorylation state of neuromodulin and synapsin I in striatum from rats treated with repeated amphetamine.

Repeated, intermittent treatment of rats with amphetamine results in a sensitization of locomotor and stereotyped behaviors that is accompanied by an enhancement in stimulus-induced dopamine release. The effects of repeated treatment with amphetamine on the phosphorylation state of neuromodulin and synapsin I, proteins involved in neurotransmitter release, were investigated. Rats were injected with 2.5 mg/kg AMPH, twice a week for 5 weeks (intermittent treatment). One week after the last injection, a challenge dose of 2.5 mg/kg AMPH was given 30 min before sacrifice. We previously reported an increase in neuromodulin phosphorylation with this sensitization paradigm. Site 3-phospho-synapsin I, site 1-phospho-synapsin I and phosphoser41-neuromodulin were detected with phosphorylation state-specific antibodies. Acute treatment with amphetamine did not increase the state of synapsin phosphorylation at either site 1 or site 3, but both site 1-phospho-synapsin I and site 3-phospho-synapsin I were increased (38% and 34%, respectively) after repeated, intermittent amphetamine. Immunoreactivity for phosphoser41-neuromodulin was increased by acute amphetamine. Site 3-phospho-synapsin I, site 1-phospho-synapsin I and phosphoser41-neuromodulin were also measured in striatum from rats receiving a different regimen in which amphetamine is given in escalating doses for 4 weeks. With this regimen, behavioral sensitization and enhanced dopamine release are exhibited in rats withdrawn 4 weeks, but not 3 days, after pretreatment. Small but significant increases in site 3-phospho-synapsin I and phosphoser41-neuromodulin were found in rats withdrawn 4 weeks from the escalating dose regimen, but not in those withdrawn 3 days. The increase in the phosphorylation state of synapsin I and neuromodulin reflect changes in the presynaptic signal transduction pathways which could play a role in the behavioral sensitization and contribute to the enhanced dopamine release reported in amphetamine-sensitized rats.

Animals↗

An international comparison of characteristics of the sensation of nasal obstruction between Canadian and Japanese patients.

To determine differences in perception of nasal obstruction in Canadians and Japanese, we assessed subjective and objective nasal patency of 48 patients in Canada and 43 patients in Japan. Mean severity of the sensation of nasal obstruction in Canadian patients was significantly higher than in Japanese patients, while no significant differences in nasal resistances were found. Complaints of nasal obstruction in Canadian patients were directly concerned with nasal breathing, while Japanese patients complained of indirect matters, such as "unable to concentrate on job or study" or "nasal obstruction or nasal speech pointed out by other persons." The differences might be due to national characteristics.

Adult↗

[An immunohistochemical study of proliferating cell nuclear antigen (PCNA) and MIB-1 in epithelial hyperplasia and dysplasia of the vocal cords].

We investigated the proliferative activities in epithelial hyperplasia and dysplasia of the human vocal cords as precancerous lesions, using immunohistochemical staining with anti-PCNA and MIB-1 (anti-Ki-67) monoclonal antibody. The series for this study consisted of nine patients with hyperplasia, 12 with mild dysplasia, ten with moderate dysplasia, eight with severe dysplasia, eight with vocal cord polyps, and 14 with invasive squamous cell carcinoma. The following results were obtained: 1) The mean PCNA labeling index was 1.12 +/- 1.05 (MEAN +/- STD%) in polyp, 4.88 +/- 2.02 in hyperplasia, 2.76 +/- 1.76 in mild dysplasia, 3.80 +/- 2.03 in moderate dysplasia, 6.12 +/- 3.01 in severe dysplasia, and 19.07 +/- 10.37 in invasive cancer. 2) The mean MIB-1 positive rates were 5.50 +/- 2.47 (MEAN +/- STD%) in polyp, 13.08 +/- 6.86 in hyperplasia, 16.55 +/- 7.34 in mild dysplasia, 15.94 +/- 6.73 in moderate dysplasia, 21.43 +/- 8.16 in severe dysplasia, and 41.48 +/- 14.05 in invasive cancer. In cases of hyperplasia, dysplasia and invasive cancer, PCNA labeling index values and MIB-1 positive rates increased in proportion to the histological atypical grade increasing. Some lesions which recurred or progressed to cancer were found show high expression of PCNA and MIB-1. In cancer cases, there was no significant correlation between the PCNA labeling index, MIB-1 positive rates and either the degree of tumor cell differentiation or the T-classification. There was a positive correlation between the PCNA labeling index and MIB-1 positive rates among all cases. In this study, those cases showing a high PCNA labeling index and/or MIB-1 positive rates may indicate the possibility of recurrence or progression to malignancy in precancerous lesions of the vocal cords.

Aged↗

Effect of nipradilol, a beta-adrenergic blocker with vasodilating activity, on oxotremorine-induced tremor in mice.

The effect of nipradilol, a nonselective beta-adrenergic receptor blocker with nitroglycerin-like vasodilating activity, on oxotremorine-induced tremor was studied in mice. General tremor in mice was elicited by 0.5 mg/kg oxotremorine. The tremor was quantified using a capacitance transducer, then analyzed by a signal processor. The strength of the tremor was expressed in "points". The point values of the tremor (mean +/- SE) in control mice for 5 mg/kg (+/-)-propranolol, 2.5 mg/kg arotinolol, 0.5 mg/kg nipradilol, 1.0 mg/kg nipradilol and 2.5 mg/kg nipradilol were 87 +/- 16, 42 +/- 6, 38 +/- 6, 99 +/- 28, 28 +/- 6 and 31 +/- 7, respectively. The strength of the tremor was reduced by all beta-blockers. Although 1.0 mg/kg nipradilol significantly reduced the tremor, further inhibition of the tremor was not obtained with dosages up to 2.5 mg/kg of the drug. In conclusion, nipradilol was effective for suppressing oxotremorine-induced tremor, as were other beta-blockers.

Adrenergic beta-Agonists↗

[Bacteriological, pharmacokinetic and clinical evaluation of azithromycin in the pediatric field].

Azithromycin (AZM), a new macrolide antibiotic, in fine granules and in capsules was studied for pharmacokinetic and clinical evaluation in the pediatric patients. Antibacterial activity of AZM against 43 clinical isolates: AZM exhibited slightly lower activity against Gram-positive bacteria and 2-8-fold higher activity against Gram-negative bacteria than erythromycin or clarithromycin. Plasma or urine samples were collected from eight patients receiving the drug in fine granular form, and two patients receiving it in capsules for the determination of drug levels. The elimination half-lives of AZM after administration at dose of 10 mg/kg/day for 3 days were 50.0 and 51.2 hours for fine granules, and 41.5 hours for capsules. AUC0-infinity was 11.7 and 24.3 micrograms.hr/ml for fine granules, and 8.3 micrograms.hr/ml for capsules. The cumulative excretion rates up to 120 hours after the start of treatment were 8.24 and 13.84% for fine granules, and 3.83% for capsules. AZM was administered to 123 patients once daily at 3.7-20.0 mg/kg body weight over 3 to 5 days with reference to the standard dose of 10 mg/kg. The drug was used to treat patients with pharyngitis, tonsillitis, scarlet fever, pneumonia, mycoplasmal pneumonia, chlamydial pneumonia, otitis media, pertussis, intestinal infection, and SSTI. The effectiveness of AZM was evaluated in 109 cases. The drug was rated "excellent" in 65.1% of the patients and "good" in 29.4%, resulting in an efficacy rate of 94.5%. Furthermore, AZM eradicated 43 of 46 (93.5%) bacteria that had been identified before the treatment. Three patients complained of side effects of urticaria (1 case) and diarrhea (2 cases). Abnormal laboratory changes were reported as follows: decreased leukocyte (3 cases), increased eosinophil (5), increased platelet (2), increased eosinophil and platelet, elevated GPT (1), and elevated GOT and GPT (1). The abnormalities, however, were mild enough to raise no clinically significant problems. In conclusion, AZM in once daily regimen was effective and safe in treatment of pediatric infections.

Administration, Oral↗

Electron transfer from the tetraheme cytochrome to the special pair in the Rhodopseudomonas viridis reaction center: effect of mutations of tyrosine L162.

The structure of the photosynthetic reaction center (RC) from Rhodopseudomonas viridis is known to high resolution. It contains a firmly bound tetraheme cytochrome from which electrons are donated to a special pair (P) of bacteriochlorophylls, which is photooxidized upon absorption of light. Tyrosine at position 162 of the L-subunit of the reaction center (L 162 Y) is a highly conserved residue positioned halfway between P and the proximal heme group (c-559) of the cytochrome. By specific mutagenesis this residue was exchanged against the amino acids phenylalanine (F), glycine (G), methionine (M), leucine (L), tryptophan (W), threonine (T), and histidine (H). All mutants were expressed in Rps. viridis using a recently established transformation system [Laussermair & Oesterhelt (1992) EMBO J. 11, 777-783]. They were shown biochemically to synthesize all four subunits of the RC (cytochrome, subunits L, M, and H) and to assemble them correctly into the membrane. The structures of two mutants (L 162 F and L 162 T) were determined and found not to differ significantly from the wild-type structure. All mutants grew photosynthetically. The absorption spectrum of all the mutants is the same as in WT, but the redox potential of P and of c-559 was changed by the mutations. The kinetics of electron transfer from the heme group to the special pair were measured in chromatophores by flash absorption. As found earlier in the wild type (Y) several exponential components were needed to fit the data.(ABSTRACT TRUNCATED AT 250 WORDS)

Circular Dichroism↗

Structure at 2.8 A resolution of cytochrome c oxidase from Paracoccus denitrificans.

The crystal structure at 2.8 A resolution of the four protein subunits containing cytochrome c oxidase from the soil bacterium Paracoccus denitrificans, complexed with antibody Fv fragment, is described. Subunit I contains 12 membrane-spanning, primarily helical segments and binds haem a and the haem a3-copper B binuclear centre where molecular oxygen is reduced to water. Two proton transfer pathways, one for protons consumed in water formation and one for 'proton pumping', could be identified. Mechanisms for proton pumping are discussed.

Computer Graphics↗