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Biomedical subjects

S Iwai

Publications and source records attributed to S Iwai.

At least 109 records · Page 6Linked to original sources
PubMed1997

Oral vancomycin hydrochloride therapy for postoperative methicillin-cephem-resistant Staphylococcus aureus enteritis.

The postoperative development of methicillin-cephem-resistant Staphylococcus aureus (MRSA) enteritis can be fatal unless it is detected at an early stage and treated with effective antibacterial agents. We report herein a Japanese multicenter collaborative clinical study on the efficacy and safety of oral vancomycin hydrochloride (VCM) in the treatment of MRSA enteritis. A total of 49 patients who had been diagnosed as having, or were strongly suspected of having, MRSA enteritis during the early postoperative period, were given oral VCM as four standard doses of 0.5 g per day. The VCM concentrations in the blood, urine, and feces were then measured. No side effects were observed and the clinical efficacy of oral VCM in the 31 evaluable patients was excellent. There was a 100% clinical response rate and a 95.8% bacterial elimination rate in the feces. The clinical complete response (CR) rate to oral VCM differed significantly between patients in whom MRSA was detected only in the feces (100%) and those in whom MRSA was isolated from an additional source (57%) (P < 0.01). Although VCM concentrations in the stools were extremely high, the levels in the blood and urine were very low. These results demonstrate that oral VCM should be the treatment of choice for postoperative MRSA enteritis due to its safety and efficacy.

Adult↗
PubMed1997

Decoy approach using RNA-DNA chimera oligonucleotides to inhibit the regulatory function of human immunodeficiency virus type 1 Rev protein.

Human immunodeficiency virus type 1 (HIV-1) encodes two regulatory proteins, Tat and Rev, that bind to target RNA sequences. These are the trans-activation responsive (TAR) RNA and the Rev-responsive element (RRE), respectively. The Rev protein shifts RNA synthesis to viral transcripts by binding to the RRE within the env gene. In the present study we prepared a RNA-DNA chimera consisting of 29 or 31 nucleotides to inhibit the Rev regulatory function by means of the decoy approach. The chimera oligonucleotides (anti-Rev oligonucleotides [AROs]) contained an RNA "bubble" structure (13 oligonucleotides; the Rev-binding element in RRE) that bound Rev with a high affinity in an in vitro assay. The controls were RNA-DNA chimera oligonucleotides (negative control oligonucleotides [NCOs]) similar to ARO, but without the bubble structure, that bound with considerably less affinity to Rev. When the inhibitory effects of these decoys on HIV-1 replication were examined, we found that AROs, but no NCOs, reduced more than 90% of the HIV-1 production generated by productively infected human T-cell lines. The production of primary HIV-1 isolates in healthy donor-derived peripheral blood mononuclear cells was also similarly inhibited by AROs. In addition, the induction of viral mRNAs and antigens in latently HIV-1-infected ACH-2 cells by tumor necrosis factor alpha was specifically inhibited by AROs, but not by NCOs. No apparent cytotoxicity was caused by either decoy. Thus, the use of a Rev-binding element-based decoy, the RNA-DNA chimera oligonucleotide, may represent a safer approach to gene therapy for reducing the virus load in HIV-1-infected individuals.

Cell Line↗
PubMed1997

[Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents. Special references to bacteria isolated between July 1995 and June 1996].

Isolated bacteria from infections in general surgery during the period from July 1994 to June 1995 were investigated in a multicenter study in Japan, and the following results were obtained. One hundred and sixty-four strains were isolated from primary infections, and 202 strains were isolated from postoperative infections. From primary infections, anaerobic Gram-positive bacteria were predominant, while from post operative infections, aerobic Gram-positive bacteria were predominant. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus faecalis was the highest, followed by that of Staphylococcus aureus from postoperative infections. Among anaerobic Gram-positive bacteria, the isolation rate of Peptostreptococcus spp. was the highest from both types of infections. Among anaerobic Gram-negative, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa in this order, and from postoperative infections, P. aeruginosa was the most predominantly isolated, followed by Enterobacter spp. and Klebsiella spp. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroides fragilis group was the highest from both types of infections. We noticed that MICs of cefazolin against three out of 23 strains of E. coli were higher than 100 micrograms/ml. Among anaerobic bacteria, there were many resistant strains against penicillins and cephems with MICs higher than 100 micrograms/ml, and the same trend was observed among other Bacteroides spp. and Prevotella spp.

Bacterial Infections↗
PubMed1997

Inhibition of HIV-1 replication by targeting the Rev protein.

Human immunodeficiency virus type 1 (HIV-1) encodes two regulatory proteins, Tat and Rev. The Rev protein facilitates the transport of unspliced and singly-spliced RNA to the cytoplasm in infected host cells by binding to target RNA (Rev response element: RRE). A variety of approaches targeting Rev function, including gene therapy, have been developed that inhibit HIV-1 replication in cells cultured in vitro. This minireview summarizes the recent developments as well as our application of the Rev-binding element-based decoy approach using RNA-DNA chimera oligonucleotide modeling.

Anti-HIV Agents↗
PubMed1997

[Isolation rate of Enterococcus spp. from surgical infections and their susceptibilities].

Enterococcus spp. isolated from surgical infections during the period from July 1982 to June 1995 were investigated in a multicenter study involving 19 hospitals in Japan, and the following results were obtained. 1. Though the isolation rate of Enterococcus faecalis and other Enterococcus spp. were not high from primary infections, and from postoperative infections the isolation rate of other Enterococcus spp. was also low, the isolation rate of E. faecalis was highest from postoperative infections after 1993. 2. Vancomycin (VCM) showed strongest activity against E. faecalis, and followed by those of ampicillin (ABPC), imipenem. levofloxacin (LVFX) and meropenem in this order. Against other Enterococcus spp., VCM showed strongest activity, and followed by those of ABPC and LVFX. There were no resistant strains against VCM.

Ampicillin↗
PubMed1997

Detection, purification and characterization of a protein that binds the (6-4) photoproduct-containing DNA in HeLa cells.

HeLa cell proteins that bind DNA containing the pyrimidine(6-4)pyrimidone photoproduct were detected by the electrophoretic mobility shift assay using synthetic oligonucleotide duplexes as probes. The major species was purified to near homogeneity, and the amino acid sequences of the proteolytic peptides revealed that it was the human damage-specific DNA-binding protein, which was reported previously. The substrate specificity of this protein was determined using damaged or modified DNA duplexes.

Base Sequence↗
PubMed1996

Interaction of the basic protrusion of Escherichia coli ribonuclease HI with its substrate.

In order to determine the actual distance between the active site and the substrate binding site, termed the basic protrusion, of Escherichia coli ribonuclease HI, synthetic oligonucleotide duplexes with gradually extended overhangs were used, in which the enzymatic cleavage was restricted to a single site with 2'-O-methylnucleosides. The affinity of the enzyme for each substrate was determined by kinetic analysis. It was found that the affinity increased markedly when one nucleotide was attached to the 3' end of the DNA strand of the nine-base-pair hybrid duplex and then increased slightly as the DNA strand was extended further, whereas elongation of the strand in the other direction caused no change. When a mutant enzyme, in which three lysine residues in the basic protrusion were altered to alanine, was used, no increase in the kcat/K(m) value was observed. The results indicate that, for the productive binding, the axis from the 3' to the 5' end of the RNA strand of the substrate duplex must be oriented in agreement with the direction from the active site to the basic protrusion of the enzyme. The distance between the active site and the basic protrusion in the enzyme-substrate complex was shorter than that anticipated in modeling studies. A dynamic structure refinement, referred to as the normal mode analysis, was carried out in order to simulate the fluctuations of the basic protrusion.

Escherichia coli↗
PubMed1996

Solution Strucutres of DNA duplexes containing a DNA x RNA hybrid region, d(GG)r(AGAU)d(GAC) x d(GTCATCTCC) and d(GGAGA)r(UGAC) x d(GTCATCTCC).

The solution structures of two DNA duplexes containing a DNA*RNA hybrid region at different sites, d(GG)r(AGAU)d(GAC) x d(GTCATCTCC) (DHD, where D and H represent the DNA and DNA x RNA hybrid segments, respectively) and d(GGAGA)r(UGAC) x d(GTCATCTCC) (DDH), were determined by nuclear magnetic resonance spectroscopy to clarify the structural features of the D-H and H-D junctions. All proton-proton distances were derived from the NOESY spectra, with mixing times of 45 ms, and the restrained molecular dynamics were carried out starting from the typical A- and B-form conformations. Both duplexes were converged from the respective initial structures into structures with RMSD values of less than 1.0 angstrom. These structures were subjected to full relaxation matrix refinement to produce the final structures. In the case of the D-H junction, where the ribonucleotide was linked to the 3'-end of the DNA, the H2' and H2" signals of the deoxynucleotide overlapped completely, and the ribonucleotide had a H1'-H2' coupling constant larger than that of the normal C3'-endo sugar pucker. The dihedral angles, the pseudorotation phase angles, and the helical parameters changed at the H-D junction, but not at the D-H junction. A detailed comparison of the two duplexes revealed the structural heterogeneity between the DNA segment and the DNA x RNA hybrid region and the transitions at the junctions.

Base Sequence↗
PubMed1996

[Isolation rate of E. coli from surgical infections and their susceptibilities].

Escherichia coli isolated from surgical infections during the period from July 1983 to June 1995 were investigated in a multicenter study involving 19 hospitals in Japan, and the following results were obtained. 1. Although the isolation rate of E. coli was not high from postoperative infections, it was most frequently isolated from primary infections throughout the study period. E. coli, Klebsiella spp. and anaerobic bacteria were predominant from fresh infections. From the cases that had previous antibiotics treatment, Enterococcus spp. were the most predominant isolates followed by MRSA and Pseudomonas spp. in this order. 2. Against E. coli, cefozopran, carumonam and aztreonam had the strongest activity, followed by cefmenoxime, imipenem, latamoxef, gentamicin and ofloxacin. Recently, we have noticed that antibiotic resistant E. coli strains particularly against cefazolin are increasing year by year.

Anti-Bacterial Agents↗
PubMed1996

[Isolation rate of Pseudomonas aeruginosa from surgical infections and their susceptibilities].

Pseudomonas aeruginosa isolated from surgical infections during the period from July 1982 to June 1995 were investigated in a multicenter study involving 19 hospitals in Japan, and the following results were obtained. 1. Though the isolation rate of P. aeruginosa was not high from primary infections, it was more frequently isolated from postoperative infections throughout the study period. Enterococcus spp., P. aeruginosa and Staphylococcus aureus including MRSA were predominant among postoperative infections. From the postoperative cases that had previous antibiotic treatment, Enterococcus spp., MRSA and P. aeruginosa were more predominantly isolated than from those without previous treatments with antibiotics. 2. Cefozopran, ceftazidime, cefsulodin, aztreonam, carumonam, gentamicin, amikacin and ofloxacin had strong activities against P. aeruginosa. We recognize recently that antibiotic-resistant strains of P. aeruginosa against imipenem and ofloxacin have been increasing year by year.

Anti-Bacterial Agents↗
PubMed1996

[Trials and analysis of umbilical cord blood collection, separation and cryopreservation methods for transplantation].

Placental and umbilical cord blood, as an alternative course of haematopoietic stem cells for bone marrow reconstitution, have recently been showed to yield successful sibling-donor cord blood grafts children. The advantages of using cord blood are related to the high number of haematopoietic progenitors in circulation at birth. In our study there was a remarkable heterogeneity of volume, number of nucleated cells and the number of progenitors from sample to sample. Seven out of 40 samples of more than 61 ml blood volume contained 1.8 (+/- 1.0) x 10(5) CFU-GM or 6.0 (+/- 4.8) x 10(8) nucleated cells. 10 ml of whole blood was necessary for laboratory tests including ABO blood type, screening of infectious markers, HLA typing, as well as frozen sera and cells for the possible future tests. Collected cord blood of more than 70ml in volume may have sufficient numbers of CFU-GM for engraftment to pediatric patients weighing about 20 kg. A cord blood bank project is now going on by collecting blood with informed consent of the mother in cooperation with obstetrics and gynecology staff.

ABO Blood-Group System↗
PubMed1996

[A case of lung metastasis from breast cancer successfully treated by FLEP (5-FU leucovorin, etoposide CDDP) combined arterial infusion chemotherapy].

A 33-year-old woman had undergone left mastectomy after diagnosis of breast cancer. One year after operation, multiple lung metastasis was confirmed by chest X-ray and CT scan. The patient received 6 courses of cyclophosphamide, epirubicin, and 5-FU (CAF) combined chemotherapy. However, the lesions were increased and the result of this chemotherapy was judged to be "progressive disease" (PD). A catheter was placed in the thoracic aorta, and FLEP combined intraaortic infusion chemotherapy was performed. The patient received 4 courses of 5-FU (325/mg/m2/day, civ, on day 1-5), leucovorin (30 mg/body/day, iv, on day 1-5), etoposide (60/mg/m2/day, ia, on day 7 and day 21), cisplatin (60/mg/m2/day, ia on day 7 and 21) every 4 weeks. The multiple lung metastasis almost disappeared on chest examination, and found to be less than 1 cm in diameter on CT scan. This result suggests FLEP combined chemotherapy is effective as a second-line treatment of recurrent breast cancer.

Adult↗
PubMed1996

[Bacteria isolated from surgical infections and its susceptibilities to antimicrobial agents. Special references to bacteria isolated between July 1994 and June 1995].

Isolated bacteria from infections in general surgery during the period from July 1994 to June 1995 were investigated by a multicenter study in Japan, and the following results were obtained. One hundred and fifty-three strains were isolated from primary infections, and 143 strains were isolated from postoperative infections. From primary infections, both anaerobic Gram-positive and-negative bacteria were predominant, and from postoperative infections, aerobic Gram-positive bacteria were predominant. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus faecalis was highest, followed by that of Staphylococcus aureus from both types of infections. Among anaerobic Gram-positive bacteria, the isolation rate of Streptococcus intermedius was highest from primary infections, but from postoperative infections anaerobic Gram-positive bacteria was uncommon. Among aerobic Gram-negative bacteria, Escherichia coli was most predominantly isolated from primary infections, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa in this order. From postoperative infections, P. aeruginosa was most predominantly isolated, followed by Serratia marcescens and E. coli. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroides fragilis group was the highest from both types of infections. We have noticed that resistant strains against imipenem and ofloxacin were increasing among P. aeruginosa and resistant strains against cefazolin were increasing among E. coli. MICs of cefazolin against four out of 30 strains of E. coli were higher than 100 micrograms/ml, and MICs of imipenem was higher than 50 micrograms/ml against 5 out of 22 strains of P. aeruginosa.

Anti-Bacterial Agents↗
PubMed1996

[Clinically isolated bacterii seen in complicated infections].

The spectrum of causative bacterial agents responsible for post-operative infections in the surgical field have dramatically changed with time. This could be due to recent technical progress in bacterial extraction or the result of more effective antibiotics used post-operatively. Nevertheless nosocomial infections including those caused by MRSA still demand our close attention. Commonly extracted bacterii include Staphylococcus spp., E. faecalis, E. coli, Klebsiella spp., E. cloacae, P. aeruginosa and Bacteroides spp., but with regards to pathogenicity, extraction frequency and drug resistance, agents requiring the highest note of caution may be MRSA, P. aeruginosa and Bacteroides spp. MRSA is still the bacterium which makes the most frequent appearance in the clinical field, and the only effective antibiotic to MRSA is vancomycin. In addition, P. aeruginosa is the most common bacterial agent seen in post-operative infections and also the agent to which many of the cephem drugs do not express a high degree of antibacterial effect. Furthermore, about half of the Bacteroides spp. are beta-lactamase-producing strains which deactive the effect of penicillin and cephem drugs within the infection site. A drug which proves effective against E. coli may nevertheless become somewhat ineffective against this agent when found in a mixed infection and if the drug lacks stability against beta-lactamase. Clinically, mixed infections including some or even all the above agents are known to occur, continuously drawing our close attention.

Bacteroides↗
PubMed1995

Atomic model of a pyrimidine dimer excision repair enzyme complexed with a DNA substrate: structural basis for damaged DNA recognition.

T4 endonuclease V is a DNA repair enzyme from bacteriophage T4 that catalyzes the first reaction step of the pyrimidine dimer-specific base excision repair pathway. The crystal structure of this enzyme complexed with a duplex DNA substrate, containing a thymine dimer, has been determined at 2.75 A resolution. The atomic structure of the complex reveals the unique conformation of the DNA duplex, which exhibits a sharp kink with a 60 degree inclination at the central thymine dimer. The adenine base complementary to the 5' side of the thymine dimer is completely flipped out of the DNA duplex and trapped in a cavity on the protein surface. These structural features allow an understanding of the catalytic mechanism and implicate a general mechanism of how other repair enzymes recognize damaged DNA duplexes.

Adenine↗