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Biomedical subjects

S Iwata

Publications and source records attributed to S Iwata.

At least 127 records · Page 7Linked to original sources
PubMed1997

[Trend of bacterial meningitis in children over a 14 year period (1981 through 1994) in Japan--an analysis based on studies in 27 institutions].

We observed 266 children with purulent meningitis in 27 institutions in Japan during the 14 years from 1981 on dividing these years into 3 periods, 1981-1985, 1986-1990 and 1991-1994, and studied the trend of causative organisms identified in 254 among the 266 patients. Their ages were less than 3 months after birth in 50 children and 3 months or older in 216: there were 141 boys and 125 girls. The causative organisms were H. influenzae in 134 patients and S. pneumoniae in 50, most of them being aged 3 months or older. Next to the above bacteria ranked S. agalactiae in 29 and E. coli in 12, many of the patients were aged less than 3 months. Staphylococcus spp. was found in 7 patients and about 70% of them were aged 3 months or older. L. monocytogenes was found in 4 patients and N. meningitidis in 3 and they were aged 3 months or older in both patient groups. S. pyogenes, Enterococcus spp., Peptostreptococcus spp., P. Mirabilis and Enterobacter spp. were detected each in 1 patient. The causative organism was unknown in 21 patients and there was no double infection. H. influenzae were detected in 18 patients in 1981-1985 period (36.7%), in 56 in 1986-1990 (54.9%) and in 60 in 1991-1994 (63.8%) showing an increasing tendency, but S. pneumoniae exhibited neither an increasing nor decreasing tendency. There was a decreasing tendency with S. agalactiae and E. coli, but the details were not clear because there were few patients aged less than 3 months. Although the period of coexistence of 4 main bacterial species was not made clear in this study. Listeria is considered to develop mainly in the early childhood, and we believe that the conventional way of using a cephem preparation and ampicillin combined for patients under 6 years need not be altered. However, panipenem (phonetic) is likely to be effective for insensible S. pneumoniae for the time being.

Escherichia coli↗
PubMed1997

Antitumorigenic activities of chalcones (II). Photo-isomerization of chalcones and the correlation with their biological activities.

Some chalcones are known to be phototransformed in a solution from trans into cis isomers. 3-Hydroxy-3'-methylchalcone (3'Me-3-C) has been found to be isomerized from trans into cis by irradiation of daylight in the methanolic solution. The presence of a hydroxyl in the 2'- or 4-position in the trans-chalcone structure prevents phototransformation into cis isomers. The feasibility of phototransformation of chalcones was discussed using UV-spectral analysis. The phototransformed cis-3'Me-3-C showed more potent antitumorigenic activity than the original trans form. The generally recognized parallelism between antitumorigenic and antiinflammatory activities was not observed in trans and cis 3'-Me- and 4'-Me-3C, which are antitumorigenic but inactive in 12-O-tetradecanoylphorbol 13-acetate (TPA)- and arachidonic acid (AA)-induced mouse ear edema. However, inhibitory activity against ornithine decarboxylase (ODC) was commonly observed in both naturally occurring and synthetic antitumorigenic chalcones.

Animals↗
PubMed1997

[Clinical evaluation of faropenem against infections in pediatric fields].

The recent increases in the prevalence of penicillin-resistant Streptococcus pneumoniae becomes a point at issue clinically. We carried out a clinical study in 40 cases in the pediatrics department, as faropenem (FRPM) was proved to have an excellent antimicrobial activity against penicillin-resistant Streptococcus pneumoniae. The study was planned to investigate in detail the movement of stools that had been a problem in a clinical development studies out before. In this study, an observation of the daily movement of stools was one of the principal evaluation items, hence the patients were divided into two groups. One group (S-group) were administered FRPM only, the other group (E-group) were administered FRPM in combination with a medicine for intestinal disorders (Enteronon-R). An observed frequencies of any loose bowel movements were 94.7% in S-group, and 63.2% in E-group, hence the study suggested that the combination drug was effective. The patients observed higher frequencies of development of the movement of stools, all of them were recovered from in the course of administration or within 4 days after administration, however whether or not being treated symptomatic therapy. Clinical efficacy rates of FRPM on mainly respiratory infections were 94.6%. In this study, 4 strains (patients) of penicillin-resistant Streptococcus pneumoniae were isolated. Against penicillin-resistant Streptococcus pneumoniae, FRPM demonstrated more potent antibacterial activity than the oral penicillins and cephems tested here except cefditoren. Clinical efficacies was deemed effective in all of the 4 cases, and bacteriologically, 3 organisms were eradicated. As for side effects including diarrhea and loose stool, no serious side effects were observed. Based on the above results, FRPM is effective against most infections in the pediatric field which Streptococcus pneumoniae are isolated at high frequencies highly, and is considered to cases in be useful an attention will have to be paid to stool movement, however.

Adolescent↗
PubMed1997

[Local eosinophilia of the nose, the larynx and the trachea in rats sensitized with Japanese cedar pollen].

Eight Brown Norway rats were immunized twice at days 0 and 13 by intraperitneal injections of 10 micrograms Cry j I, one of major allergen to Japanese cedar pollinosis, mixed with 4.5 mg aluminium hydroxide gel. Serum level of Anti-Cry j I IgE antibody was detected by the method of ELISA. Mean value of serum levels of specific IgE to Cry j I in the sensitized rats was significantly higher than that in the non-sensitized five rats (p < 0.01). The grades of eosinophil and lymphocyte accumulation in the nasal mucosa of the sensitized rats were higher than those in the non-sensitized rats respectively (p < 0.05, p < 0.01). In the laryngeal mucosa, the grade of eosinophilia in the sensitized rats was higher than that in the control (p < 0.01), but no significant differences of lymphocyte accumulation in the larynx between the two groups were found. Only a small number of eosinophil and lymphocyte accumulations in the trachea of the both groups were observed and no significant differences of the grade of inflammatory cells accumulation between the two groups were found. According to the results of this fundamental study, allergic laryngitis in Japanese cedar pollinosis might be originated from Japanese cedar pollen.

Animals↗
PubMed1997

[Fundamental and clinical evaluation of cefozopran in low birth weight infants and neonates].

We conducted fundamental and clinical evaluations of a cephem antibiotic, cefozopran (SCE-2787, CZOP), in infants with low birth weights and mature infants. (1) Blood concentrations CZOP was intravenously given in bolus dose of 20 mg/kg to the newborn. The blood antibiotic concentrations were 69.7 micrograms/ml at 30 minutes after administration and the elimination half life was 2.99 hours in mature infants aged 1 to 3 days. They were 38.7 micrograms/ml and 2.85 hours in those aged 4 to 7 days, and 40.8 micrograms/ml and 3.81 hours in those aged 8 days or elder, respectively. In infants with lower birth weights aged 4 to 7 days the blood antibiotic concentrations were 48.6 micrograms/ml at 30 minutes after i.v. administration and the elimination half life was 3.77 hours. The blood antibiotic concentrations at 30 minutes after intravenous doses of 10, 20 and 50 mg/kg in mature infants aged 8 days or elder were 21.1, 40.8 and 153.6 micrograms/ml (value at 60 minutes) and the elimination half lives were 2.24, 3.81 and 3.07 hours, respectively. Administration of CZOP at doses of 20 and 40 mg/kg by intravenous drip infusion over 30 minutes gave the blood drug concentrations of 48.0 and 103.2 micrograms/ml at the end of the infusion and the half lives were 2.60 and 3.33 hours, respectively. (2) Urinary excretion The urinary excretion rates after i.v. bolus doses of 10, 20 and 40 mg/kg were 28.4 to 58.6% of dose. The urinary excretion rate after i.v. drip infusion of 40 mg/kg over 30 minutes was 49.0% of dose. (3) Transfer into cereblospinal fluid The transfer of the antibiotic into cereblospinal fluid in patients with serous meningitis was 4.1 to 15.5 micrograms/ml at 1 hours after administration. (4) Clinical results The clinical efficacy was judged "good" or "excellent" in 2 of the 3 patients with septicemia and in all of the 10 patients with suspected septicemia. It was judged "excellent" in all of the 9 patients with pneumonia, 3 with urinary tract infections and 3 with intrauterine infections. Prophylactic use of the antibiotic was effective in all of the 12 patients. Of the patients in whom bacteriological evaluation was successful, 7 of the 10 causative organisms were confirmed to be eradicated. No adverse drug reactions of signs and symptoms were recognized. Fourteen abnormal alterations of the laboratory test values such as elevation of gamma-GTP and that of GPT were recognized in 8 patients (16.7%). None of them were particularly serious. These results indicate that CZOP is a drug useful for treatment and prevention of infections in infants with lower birth weights as well as in mature infants.

Bacterial Infections↗
PubMed1997

[Pharmacokinetic and clinical studies with cefluprenam in the pediatric field. Pediatric Study Group of Gefluprenam].

Evaluation of efficacy and safety of cefluprenam (code number: E1077, abbreviation: CFLP), a newly developed injectable cephem antibiotics was conducted on adult patients with various infections, and followed by the study group organized from 39 institutions in pediatric field, as the drug showed no toxicity problems in suckling animals. Informed consents from legal representatives were obtained prior to the study. 1. Clinical efficacy. Two-hundred eighty one cases were included for analysis of clinical efficacy after 40 cases of exclusion or drop-out were subtracted from a total of 321 cases. However, the cumulative number of cases evaluable for analysis was considered to be 289, because 8 cases that had 2 different diseases at the same time were counted in each category of disease. In the cases in which causative organisms were identified (group A), 148 of 154 cases were rated as good or excellent, with an efficacy rate of 96.1%. As for clinical efficacies by disease, efficacy rates were 6/6 for purulent meningitis, 4/5 for sepsis, 95.7% (62/65) for pneumonia, 100.0% (29/29) for urinary tract infections, and 94.1% (16/17) for skin and soft tissue infections. The rate of excellent responses among excellent and good responses was 73.6% (109/148), showing a higher value than any of recent injectable beta-lactams. On 32 cases with S. pneumoniae infection, the efficacy rate of CFLP was 100.0%. In the cases where causative organisms were not identified (group B), 128 of 135 cases were rated as good or excellent, with an efficacy rate of 94.8%. In the all cases including both the group A and the group B, the efficacy rate was 95.2% (276/289) and the rate of excellent responses among excellent and good response was 70.7% (195/276). Against severe infections, CFLP exhibited excellent clinical efficacy, showing an efficacy rate of 8/8 for meningitis, 3/5 for sepsis and 100.0% (22/22) for severe pneumonia. As for bacteriological responses, eradication rates were 95.2% (177/186) in total. Against Gram-positive cocci, the eradication rate was 92.7% (76/82), with eradication rates of 94.3% (33/35) for Staphylococcus aureus, and 93.3% (28/30) for Streptococcus pneumoniae. Against Gram-negative rods, the eradication rate was 97.1% (101/104), and eradication rates were 100.0% (22/22) for Escherichia coli, 97.5% (39/40) for Haemophilus influenzae and 100.0% (19/19) for Molaxella catarrhalis. In cases in which more than 3 days of treatment with previous chemotherapy resulted in no response, the efficacy rate of CFLP was 94.2% (98/104), rated excellent in 68 cases and good in 30 cases. In these cases, the eradication rate was 98.1% (52/53). 2. Pharmacokinetics. CFLP was intravenously administerrd to 12 subjects at doses of 20 to 40 mg (potency)/kg. In 9 subjects aged more than 12 months, maximum serum levels (Cmax), T 1/2 beta and AUC of CFLP were 155.3 +/- 9.8 micrograms/ml, 1.43 +/- 0.18 hours and 111.7 +/- 15.0 micrograms.hr/ml, respectively, when a dose of 20 mg (potency)/kg was used. In 2 subjects aged not more than 12 months, the mean Cmax, T 1/2 beta and AUC were 153 micrograms/ml, 1.6 hour and 81 micrograms.hr/ml, respectively, at a dose of 20 mg(potency)/kg. The mean Cmax, T 1/2 beta and AUC were 332 micrograms/ml, 0.93 hours and 157.3 micrograms.hr/ml, respectively, in 1 subject at a dose of 40 mg (potency)/kg. In 10 subjects dosed 20 mg (potency)/kg, urinary levels were 2413 +/- 512, 1471 +/- 524, and 470 +/- 115 micrograms/ml in 0-2, 2-4, and 4-6 hours after dosing, respectively, showing a cumulative urinary excretion rate of 61.4 +/- 6.3%. In 1 subject dosed 40 mg (potency)/kg, urinary levels were 5700 and 4770 micrograms/ml in 0-2 p3d 2-4 hours after dosing, respectively, showing a cumulative urinary excretion rate of 42.1%. Cerebrospinal fluid concentrations of CFLP, on 10 subjects with purulent meningitis dosed 40-103 mg (potency)/kg were 3.2-32.9 micrograms/ml at 0.5-2 hours after administration within 4 days after the onset of

Bacteria↗
PubMed1996

Allosteric activation of L-lactate dehydrogenase analyzed by hybrid enzymes with effector-sensitive and -insensitive subunits.

Subunit-hybrid enzymes of mutant tetrameric L-lactate dehydrogenases from Bifidobacterium longum were studied in an examination of the mechanism of allosteric activation by fructose 1,6-bisphosphate. We earlier developed an in vivo method for subunit hybridization in Escherichia coli and the hybrids formed were a mixture with different subunit compositions. The B. longum hybrids were separated by anion-exchange chromatography with a mutational tag. Hybrids formed between fructose 1,6-bisphosphate-desensitized subunits and wild-type subunits and also between fructose 1, 6-bisphosphate-desensitized subunits and catalytically inactive subunits. Kinetic analyses of the hybrid enzymes showed that (i) those residues from two symmetrically related subunits that constituted the fructose 1,6-bisphosphate-binding site could bind fructose 1,6-bisphosphate and activate the enzyme only if intact, (ii) hybrids with only one functional fructose 1, 6-bisphosphate-binding site were fully sensitive to fructose 1, 6-bisphosphate, but the allosteric equilibrium had shifted partially, and (iii) activation by fructose 1,6-bisphosphate at the fructose 1, 6-bisphosphate-binding site was transmitted to the active sites through a quaternary structural change, not through direct conformational change within a subunit. These results are evidence of the validity of the concerted allosteric model of this enzyme based on T- and R-state structures in the same crystal lattice proposed earlier.

Allosteric Regulation↗
PubMed1996

Structure and function of Cas-L, a 105-kD Crk-associated substrate-related protein that is involved in beta 1 integrin-mediated signaling in lymphocytes.

Integrin/ligand binding evokes tyrosine phosphorylation of various proteins. We reported previously that a 105 kD protein (pp105) was tyrosine phosphorylated by the engagement of beta 1 integrins in T lymphocytes. We show here that pp105 is a novel p130Cas (Crk-associated substrate)-related protein. Deduced amino acid sequence revealed that pp105 contains conserved motifs with p130Cas, and both pp105 and p130Cas bind to focal adhesion kinase (pp125FAK) and Crk. However, pp105 has a clearly distinct structure from p130Cas, and pp105 is preferentially expressed in lymphocytes, whereas p130Cas is expressed in adherent cells. With these findings, we designate pp105 as Cas-L, lymphocyte-type Cas. Furthermore, we demonstrate that integrin/ligand binding results in the recruitment of Crk, Nck, and SHPTP2 to pp105. These findings further define the roles of pp105/Cas-L and pp125FAK in the integrin-mediated signaling pathways.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Functional implications of the structure of the 'Rieske' iron-sulfur protein of bovine heart mitochondrial cytochrome bc1 complex.

Recently, we have determined the structure of the catalytic domain of the 'Rieske' iron-sulfur protein of bovine heart mitochondrial bc1 complex at 1.5 A resolution (Iwata, S., Saynovits, M., Link, T.A. and Michel, H. (1996) Structure, 4, 567-579). This is the first structure of a bis-histidine coordinated [2Fe-2S] cluster. The spectroscopic, electrochemical, and functional implications of the structure will be discussed.

Animals↗
PubMed1996

Glucose and energy metabolism in rat liver after ischemic damage assessed by 13 C and 31 P NMR spectroscopy.

Glucose and energy metabolism in rat liver after ischemic damage was investigated by in vivo 31P NMR spectroscopy, 1H-detected 13C NMR spectroscopy, and in vitro 13C NMR spectroscopy using [1-13C]glucose as a tracer. Arterial ketone body ratio (AKBR; acetoacetate/beta-hydroxybutylate) and oxygen consumption of isolated mitochondria were also examined to evaluate hepatic function. The rats were divided into three groups: (A) without ischemia, (B) 10-min ischemia, and (C) 30-min ischemia. ATP was almost depleted at 10 min of ischemia and recovered after reperfusion, but the recovery was not complete. The recovery after 30-min ischemia was smaller than that after 10-min ischemia. [13C]Glucose was infused immediately after the reperfusion, and in vivo 1H-detected 13C NMR demonstrated sequential glucose incorporation into the liver. However, the incorporation depended on the blood sugar levels and did not reflect hepatic function. In vitro 13C NMR disclosed the glycogen C-1 signal in the nonischemic group and alanine C-3 and lactate C-3 signals in the ischemic groups. The intensity of glycogen was correlated positively (r = 0.648, P = 0.002) and those of alanine and lactate were correlated negatively (r = -0.831, P < 0.005 and r = -0.710, P = 0.005, respectively) to the ATP levels as measured by in vivo 31P NMR. These results suggested that ATP level participates in glycogenesis and gluconeogenesis in the liver. The AKBR and oxygen consumption of isolated mitochondria were the highest in the 10-min ischemia group, which might reflect mitochondrial compensatory response to the decreased ATP level.

Animals↗
PubMed1996

Structure of a water soluble fragment of the 'Rieske' iron-sulfur protein of the bovine heart mitochondrial cytochrome bc1 complex determined by MAD phasing at 1.5 A resolution.

BACKGROUND: The 'Rieske' iron-sulfur protein is the primary electron acceptor during hydroquinone oxidation in cytochrome bc complexes. The spectroscopic and electrochemical properties of the 'Rieske' [2Fe-2S] cluster differ significantly from those of other iron-sulfur clusters. A 129-residue water soluble fragment containing the intact [2Fe-2S] cluster was isolated following proteolytic digestion of the bc1 complex and used for structural studies. RESULTS: The structure of the Rieske iron-sulfur fragment containing the reduced [2Fe-2S] cluster has been determined using the multiwavelength anomalous diffraction (MAD) technique and refined at 1.5 A resolution. The fragment has a novel overall fold that includes three sheets of beta strands. The iron atoms of the [2Fe-2S] cluster are coordinated by two cysteine (Fe-1) and two histidine (Fe-2) residues, respectively, with the histidine ligands completely exposed to the solvent. This is in contrast to the four cysteine coordination pattern observed in previously characterised [2Fe-2S] ferredoxins. The cluster-binding fold is formed by two loops connected by a disulfide bridge; these loops superpose with the metal-binding loops of rubredoxins. The environment of the cluster is stabilised by an extensive hydrogen-bond network. CONCLUSIONS: The high-resolution structure supports the proposed coordination pattern involving histidine ligands and provides a basis for a detailed analysis of the spectroscopic and electrochemical properties. As the cluster is located at the tip of the protein, it might come into close contact with cytochrome b. The exposed N epsilon atoms of the histidine ligands of the cluster are readily accessible to quinones and inhibitors within the hydroquinone oxidation (QP) pocket of the bc1 complex and may undergo redox-dependent protonation/deprotonation.

Amino Acid Sequence↗
PubMed1996

Redox control of resistance to cis-diamminedichloroplatinum (II) (CDDP): protective effect of human thioredoxin against CDDP-induced cytotoxicity.

Thioredoxin is a small ubiquitous protein with multiple biological functions, including cellular defense mechanisms against oxidative stress. In the present study, we investigated the role of human thioredoxin (hTRX) in the acquisition of cellular resistance to cis-diamminedichloroplatinum (II) (CDDP). The expression and activity of hTRX in Jurkat T cells was dose-dependently enhanced by exposure to CDDP, as determined by immunoblot analysis and insulin reducing assay. Furthermore, chloramphenicol acetyltransferase analysis using the hTRX promoter-reporter gene construct revealed that treatment of Jurkat cells with CDDP caused transcriptional activation of the hTRX gene, which might be mediated through increased generation of intracellular reactive oxygen intermediates. To examine the biological significance of hTRX induction, we established hTRX-overexpressing derivatives of L929 fibrosarcoma cells by stable transfection with the hTRX cDNA. The clones, which constitutively expressed the exogenous hTRX, displayed increased resistance to CDDP-induced cytotoxicity, compared with the control clones. After exposure to CDDP, the control cells showed a significant increase in the intracellular accumulation of peroxides, whereas the hTRX-transfected cells did not. Taken together, these results suggest that overexpressed hTRX is responsible for the development of cellular resistance to CDDP, possibly by scavenging intracellular toxic oxidants generated by this anticancer agent.

Animals↗
PubMed1996

Isolation, characterisation and crystallisation of a water-soluble fragment of the Rieske iron-sulfur protein of bovine heart mitochondrial bc1 complex.

A water-soluble fragment of the bc1 complex from bovine heart mitochondria was isolated containing the intact Rieske [2Fe-2S] cluster. The fragment consists of the last 129 amino acid residues of the Rieske iron-sulfur protein and has a molecular mass of 14592 Da including two iron atoms. The absorption, visible CD, and EPR spectra of the fragment are indistinguishable from those of the membrane-bound iron-sulfur protein. The redox potential as determined by EPR-monitored redox titration was + 306 mV. The far-ultraviolet CD spectrum is indicative of a protein with little regular secondary structure, while significant alpha-helix content was detected in the membrane anchor of the complete iron-sulfur protein. The fragment could be crystallized using poly(ethylene glycol) 6000 as precipitant. Needle-shaped single crystals have been grown by the hanging-drop vapor diffusion technique. These crystals belong to the space group P21 and diffract well beyond 0.2 nm resolution. Phase determination using the multiple-wavelength anomalous-scattering technique is underway.

Amino Acid Sequence↗
PubMed1996

Restricted redox oscillation in oxidative phosphorylation in jaundiced rat liver mitochondria and its relation to calcium ion.

High morbidity and mortality in surgical management for patients with obstructive jaundice was greatly attributed to the metabolic derangements in jaundiced liver mitochondria. Isolated liver mitochondria from jaundiced rat, produced by common bile duct ligation, were used to study the relationship among NADH level, oxygen consumption, and extramitochondrial calcium concentration. Alterations in NADH percentage and oxygen consumption were accomplished by incubating mitochondria with different substrates and monitoring oxygen consumption and NAD(P)H fluorescence simultaneously. In jaundiced liver mitochondria with glutamate + malate as substrate, respiration increased after the addition of exogenous Ca2+ at concentrations of 1 x 10(-7), 5 x 10(-7), and 1 x 10(-6) M. The maximal effect occurred at 5 x 10(-7) M. With different NADH-related substrates, the NAD(P)H fluorescence measurements (X axis) correlated linearly with state 3 respiration (Y axis), the slopes of the correlation curves being 2.27 and 0.79 in control and jaundiced mitochondria, respectively. After the addition of 5 x 10(-7) M Ca2+, the respirations of both control and jaundiced mitochondria increased and the slope for jaundiced mitochondria rose to 1.67. The matrix free Ca2+ concentration in jaundiced mitochondria, measured by fluo-3 loading, was higher than that in controls (162.1 +/- 16.7 nM, vs 129.7 +/- 12.6 nM, P < 0.01), while the matrix free/total Ca2+ ratio decreased from 34.9 +/- 6.0 (x10(-6)) to 27.2 +/- 4.4 (x10(-6), 9- < 0.05. The amplitude of the change in NAD(P)H fluorescence was reduced in jaundiced rat liver mitochondria and this correlated with the depression of respiration. A decrease in free/total Ca2+ ratio may be closely related to mitochondrial respiratory impairment in jaundice.

Animals↗