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N Chiba

Publications and source records attributed to N Chiba.

At least 37 records · Page 2Linked to original sources
PubMed2001

[The trend of childhood bacterial meningitis in Japan (1997.7-2000.6)].

We surveyed the epidemiology of purulent meningitis in pediatrics for 3 years between July 1997 and June 2000 in Japan and obtained the following results. The number of cases of purulent meningitis was 428, which was equivalent of 1.1-1.7 children out of 1,000 hospitalized those in pediatrics per year. The age-distribution for the infections was the highest under 1 year of age and it decreased as the age increased. Under 1 year of age, the highest distribution was observed in one month of age and under 1 month of age, the highest distribution was observed in 7 days of or younger ages. Haemophilus influenzae was the most common pathogen causing the infections, followed by Streptococcus pneumoniae, group B streptococcus, and Escherichia coli. Relationship between causing pathogens and age-distribution was as follows: group B streptococcus and E. coli were major pathogens under 4 months of age and H. influenzae and S. pneumoniae were major pathogens over 3 months of age. Susceptibility tests performed at each facility demonstrated that 25.3% of H. influenzae isolates and 38.7% of S. pneumoniae isolates were drug-resistant. Analysis of resistant genes for H. influenzae and S. pneumoniae isolates, which were stored and sent, demonstrated higher rates of resistance than those observed in susceptibility tests. These results suggest that the increase in insufficient efficacy of usual treatment with combination of ampicillin and cefotaxime is predictable against the infections. Therefore, the treatment for the infections should be reconsidered.

Female↗
PubMed2001

Association of amino acid substitutions in penicillin-binding protein 3 with beta-lactam resistance in beta-lactamase-negative ampicillin-resistant Haemophilus influenzae.

The affinity of [(3)H]benzylpenicillin for penicillin-binding protein (PBP) 3A was reduced in 25 clinical isolates of beta-lactamase-negative ampicillin (AMP)-resistant (BLNAR) Haemophilus influenzae for which the AMP MIC was > or =1.0 microg/ml. The affinities of PBP 3B and PBP 4 were also reduced in some strains. The sequences of the ftsI gene encoding the transpeptidase domain of PBP 3A and/or PBP 3B and of the dacB gene encoding PBP 4 were determined for these strains and compared to those of AMP-susceptible Rd strains. The BLNAR strains were classified into three groups on the basis of deduced amino acid substitutions in the ftsI gene, which is thought to be involved in septal peptidoglycan synthesis. His-517, near the conserved Lys-Thr-Gly (KTG) motif, was substituted for Arg-517 in group I strains (n = 9), and Lys-526 was substituted for Asn-526 in group II strains (n = 12). In group III strains (n = 4), three residues (Met-377, Ser-385, and Leu-389), positioned near the conserved Ser-Ser-Asn (SSN) motif, were replaced with Ile, Thr, and Phe, respectively, in addition to the replacement with Lys-526. The MICs of cephem antibiotics with relatively high affinities for PBP 3A and PBP 3B were higher than those of AMP and meropenem for group III strains. The MICs of beta-lactams for H. influenzae transformants into which the ftsI gene from BLNAR strains was introduced were as high as those for the donors, and PBP 3A and PBP 3B showed decreased affinities for beta-lactams. There was no clear relationship between 7-bp deletions in the dacB gene and AMP susceptibility. Even though mutations in another gene(s) may be involved in beta-lactam resistance, these data indicate that mutations in the ftsI gene are the most important for development of resistance to beta-lactams in BLNAR strains.

Ampicillin↗
PubMed2001

Gastric acid secretory response in Helicobacter pylori-positive patients with duodenal ulcer disease.

BACKGROUND: Patients with duodenal ulcer (DU) have an increased parietal cell mass and sensitivity to secretagogues, with increased acid output. AIM: To determine the effect of Helicobacter pylori eradication on parietal cell sensitivity and gastric acid secretion. SUBJECTS AND METHODS: Twenty-five H pylori-positive DU patients and 18 H pylori-negative healthy volunteers were studied. Serum H pylori immunoglobulin G, basal acid output and acid secretory response to graded doses of pentagastrin were determined before and after treatment, at six months and at one year. Subjects were randomly assigned to ranitidine or sucralfate treatment for six weeks, and all DU patients received bismuth subsalicylate, metronidazole and tetracycline for the first two weeks. RESULTS: H pylori was eradicated in 66% of patients receiving sucralfate and 92% receiving ranitidine. Compared with healthy volunteers, DU patients demonstrated a 2.7-fold greater basal acid output, a 1.3-fold greater peak acid output, significantly higher acid output for each dose of pentagastrin and a 1.38-fold increase in the area under the pentagastrin dose acid response curve. Cure of H pylori, irrespective of ulcer healing regimen, resulted in a gradual decrease in acid secretory capacity with basal acid output, peak acid output and area under the pentagastrin dose acid response curve returning to healthy volunteer levels by one year. No demonstrable differences were observed in parietal cell sensitivity in all subjects before or after treatment. These data suggest that disturbances in acid secretion in H pylori-positive DU patients are not due to an increased parietal cell sensitivity to pentagastrin but rather due to an increased parietal cell mass with increased capacity to secrete acid, which gradually resolves following cure.

Adult↗
PubMed2001

Ranitidine bismuth citrate.

Recognition of the relationship between Helicobacter pylori infection and the development of gastroduodenal disease has increased greatly in recent years. To avoid complications of H pylori infection, such as the development of recurrent duodenal and gastric ulcers, effective therapies are required for eradication of the infection. This article reviews ranitidine bismuth citrate (RBC), a novel complex of ranitidine, bismuth and citrate, which was developed specifically for the purpose of eradicating H pylori. Dual therapy with RBC in combination with clarithromycin for 14 days yields eradication rates of 76%. Triple therapy bid for one week with a proton pump inhibitor, clarithromycin and either amoxicillin or a nitroimidazole (tinidazole or metronidazole) is advocated as the treatment of choice for H pylori eradication. Analogous regimens with RBC in place of proton pump inhibitors show effective eradication rates in comparative studies and with pooled data. RBC, used alone or in combination with other antibiotics, appears to be a safe and effective drug for the treatment of H pylori infection. Bismuth levels do not appear to rise to toxic levels.

Amoxicillin↗
PubMed2001

Selective nonpeptidic inhibitors of herpes simplex virus type 1 and human cytomegalovirus proteases.

The proteases encoded by herpesviruses including herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV) are attractive targets for antiviral drug development because of their important roles in viral replication. We randomly screened a chemical compound library for inhibitory activity against HSV-1 protease. 1,4-Dihydroxynaphthalene and three naphthoquinones were found to be potent inhibitors of HSV-1 protease with IC50 values of 6.4 to 16.9 microM. Inhibitory mode analysis of the compounds against HSV-1 protease suggested that, in spite of structural similarities, only 1,4-dihydroxynaphthalene was a competitive inhibitor, whereas the three naphthoquinones were noncompetitive inhibitors. Among all assayed dihydroxynaphthalene derivatives in the chemical compound library, 1,4-dihydroxynaphthalene proved to be the most potent inhibitor of HSV-1 protease. Therefore, the two hydroxyl groups located at positions 1 and 4 on the naphthalene structure seemed essential for exertion of a potent inhibitory activity against HSV-1 protease. In addition, we have found that these compounds are also potent inhibitors of HCMV protease with extremely low micromolar IC50 values. This differed from the results of inhibitory mode analysis of HSV-1 protease, 1,4-dihydroxynaphthalene was a noncompetitive inhibitor of HCMV protease, and three naphthoquinones were competitive inhibitors. These compounds showed no effective inhibitory activity against several mammalian serine proteases (trypsin, chymotrypsin, kallikrein, plasmin, thrombin and Factor Xa) at 100 microM. These results suggest that 1,4-dihydroxynaphthalene and three naphthoquinones may be useful in the development of nonpeptidic antiherpesvirus agents.

Amino Acid Sequence↗
PubMed2000

An evidence-based approach to the management of uninvestigated dyspepsia in the era of Helicobacter pylori. Canadian Dyspepsia Working Group.

OBJECTIVES: To provide Canadian primary care physicians with an evidence-based clinical management tool, including diagnostic and treatment recommendations, for patients who present with uninvestigated dyspepsia. RECOMMENDATIONS: The management tool has 5 key decision steps addressing the following: (1) evidence that symptoms originate in the upper gastrointestinal tract, (2) presence of alarm features, (3) use of nonsteroidal anti-inflammatory drugs (NSAIDs), (4) dominant reflux symptoms and (5) evidence of Helicobacter pylori infection. All patients over 50 years of age who present with new-onset dyspepsia and patients who present with alarm features should receive prompt investigation, preferably by endoscopy. The management options for patients with uninvestigated dyspepsia who use NSAIDs regularly are: (1) to stop NSAID therapy and assess symptomatic response, (2) to treat with NSAID prophylaxis if NSAID therapy cannot be stopped or (3) to refer for investigation. Gastroesophageal reflux disease can be diagnosed clinically if the patient's dominant symptoms are heartburn or acid regurgitation, or both; these patients should be treated with acid suppressive therapy. The remaining patients should be tested for H. pylori infection, and those with a positive result should be treated with H. pylori-eradication therapy. Those with a negative result should have their symptoms treated with optimal antisecretory therapy or a prokinetic agent. VALIDATION AND EVIDENCE: Evidence for resolution of the dyspepsia symptoms was the main outcome measure. Supporting evidence for the 5 steps in the management tool and the recommendations for treatment were graded according to the strength of the evidence and were endorsed by consensus of committee members. If no randomized controlled clinical trials were available, the recommendations were based on the best available evidence. LITERATURE REVIEW: Evidence was obtained from MEDLINE searches for pertinent articles published from 1966 to October 1999. The searches focused on dyspepsia, diagnosis and treatment. Additional articles were retrieved through a manual search of bibliographies and abstracts from international gastroenterology conferences.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Binding of liganded vitamin D receptor to the vitamin D receptor interacting protein coactivator complex induces interaction with RNA polymerase II holoenzyme.

Because the vitamin D receptor interacting protein (DRIP) coactivator complex shares components with the RNA polymerase II (Pol II) holoenzyme complex, we tested whether the two protein complexes associate in cellular extracts. On initial purification steps, the DRIP complex copurified with the Pol II holoenzyme. Pol II was found to bind to the vitamin D receptor in a ligand-dependent fashion when either nuclear extracts or partially purified preparations were used as sources of DRIP and Pol II holoenzyme. A subpopulation of holoenzyme complexes bound to the receptor because BRCA1, which associates with the Pol II holoenzyme, did not associate with the liganded receptor, and only in certain of the holoenzyme- and DRIP-containing fractions did Pol II bind to the liganded receptor. Immunoprecipitation experiments revealed that the DRIP complex was not pre-associated with the Pol II holoenzyme, but the interaction between these two complexes was induced only in the presence of receptor and ligand. These data support a model in which the activation of transcription by hormone-bound receptor requires binding to the DRIP coactivator, and this induced ternary complex can then bind to the Pol II holoenzyme to activate transcription.

HeLa Cells↗
PubMed2000

The AML1 transcription factor functions to develop and maintain hematogenic precursor cells in the embryonic aorta-gonad-mesonephros region.

We examined the role of the AML1 transcription factor in the development of hematopoiesis in the paraaortic splanchnopleural (P-Sp) and the aorta-gonad-mesonephros (AGM) regions of mouse embryos. The activity of colony-forming units of colonies from the P-Sp/AGM region was reduced severalfold by heterozygous disruption of the AML1 gene, indicating that AML1 functioned in a dosage-dependent manner to generate hematopoietic progenitors. In addition, no hematopoietic progenitor activity was detected in the P-Sp/AGM region of embryos with an AML1 null mutation. Similar results were obtained when a dispersed culture was first prepared from the P-Sp/AGM region before assay of the activity of the colony-forming units. In a culture of cells with the AML1(+/+) genotype, both hematopoietic and endothelial-like cell types emerged, but in a culture of cells with the AML1(-/-) genotype, only endothelial-like cells emerged. Interestingly, introduction of AML1 cDNA into the P-Sp/AGM culture with the AML1(-/-) genotype partially restored the production of hematopoietic cells. This restoration was observed for cultures prepared from 9.5-day postcoitum (dpc) embryos but not for cultures prepared from 11.5-dpc embryos. Therefore, the population of endothelial-like cells capable of growing in the AML1(-/-) culture would appear to contain inert but nonetheless competent hematogenic precursor cells up until at least the 9.5-dpc period. All these results support the notion that the AML1 transcription factor functions to develop and maintain hematogenic precursor cells in the embryonic P-Sp/AGM region.

Animals↗
PubMed2000

Interleukin 18 and interleukin 1beta production is decreased in HIV type 1-seropositive hemophiliacs but not in HIV type 1-seropositive nonhemophiliacs.

In Japan, the proportion of hemophiliacs infected with human immunodeficiency virus type 1 (HIV-1) is 40%, whereas more than 90% are infected with hepatitis C virus (HCV). To evaluate the immunological status of hemophiliacs infected with HIV-1, we investigated the pattern of cytokine production in peripheral blood mononuclear cells (PBMCs) of HIV-1-seropositive and -seronegative hemophiliacs, HIV-1-seropositive non-hemophiliacs, and healthy individuals. The production of IL-18 and IL-1beta from PBMCs stimulated with Staphylococcus aureus Cowan strain 1 (SAC) in the HIV-1-seropositive hemophiliacs was significantly decreased in comparison with the other groups. On the other hand, IL-12 production in both HIV-1-seropositive groups was significantly lower than in HIV-1-seronegative groups. TNF-alpha and IL-6 production was similar among the four groups. In contrast, plasma levels of TGF-beta1 were increased in HIV-1-seropositive hemophiliacs, HIV-1-seropositive nonhemophiliacs, and HIV-1-seronegative hemophiliacs, with the highest levels being in HIV-1-seropositive hemophiliacs, suggesting that coinfection with HIV-1 and HCV increases the level of plasma TGF-beta in HIV-1-seropositive hemophiliacs. Treatment of PBMCs from healthy individuals with TGF-beta1 inhibited IL-18 and IL-1beta production without affecting IL-6, IL-10, or TNF-alpha production. Suppression of the expression of caspase 1 mRNA, which is known to be an IL-1beta-converting enzyme and which also cleaves the precursor of IL-18, was observed in the SAC-stimulated PBMCs from healthy individuals after treatment with TGF-beta1 and in the SAC-stimulated PBMCs from HIV-1-seropositive hemophiliacs, suggesting that the decreased production of IL-18 and IL-1beta in HIV-1-seropositive hemophiliacs may be related to the downregulation of caspase 1 mRNA induced by high levels of TGF-beta1 in plasma.

Adolescent↗
PubMed2000

The PEBP2beta/CBF beta-SMMHC chimeric protein is localized both in the cell membrane and nuclear subfractions of leukemic cells carrying chromosomal inversion 16.

The chromosomal inversion (16)(p13q22), which is associated with the M4-eosinophilia subtype of human acute myeloid leukemia, causes the fusion of two distinct genes. The polypeptide encoded by the chimeric gene, PEBP2p/CBFp-SMMHC, retains the ability to interact with, and dominantly interfere with the function of proteins possessing the Runt homology domain. The Runt protein homologs constitute the DNA binding subunit of the PEBP2/CBF transcription factor. We examined the subcellular localization of PEBP2beta/CBFbeta-SMMHC, as well as that of Runt protein homologs in leukemic cells carrying inversion 16 by immunoblot analysis. A significant amount of the PEBPbeta/CBFbeta-SMMHC protein was recovered from the nuclear fraction along with the Runt protein homologs. Furthermore, some of both polypeptides was retained in the DNA pellet that represents the material remaining after extraction of nuclear fraction with high salt. These observations suggest that the so-called dominant interfering effect of PEBPbeta/CBFbeta-SMMHC on PEBP2/CBF occurs inside the nucleus. In addition, we could detect PEBP2beta/CBFbeta-SMMHC in the cytoplasmic membrane fraction as well. The function of this membrane-located PEBP2beta/CBFbeta-SMMHC, if any, appears to be unrelated to that of Runt protein homologs.

Binding Sites↗
PubMed2000

Meeting review--Helicobacter pylori: basic mechanisms to clinical cure 2000.

The meeting Helicobacter pylori: Basic Mechanisms to Clinical Cure 2000, held in Bermuda from March 26 to 29, 2000, gathered physicians and scientists from all corners of the world. State-of-the-art reviews and the most recent developments in the field were presented. This article summarizes the highlights of this meeting, including important scientific and clinical developments.

Animals↗
PubMed2000

From bench to bedside to bug: an update of clinically relevant advances in the care of persons with Helicobacter pylori- associated diseases.

In-depth meetings of the XIth International Workshop on Gastroduodenal Pathology and Helicobacter pylori led to the presentation and discussion of extensive new data on H. pylori and its diseases. The mode of transmission of H. pylori remains unclear, and it remains unknown why only a small proportion of infected individuals develop duodenal or gastric ulcer disease and even fewer develop gastric cancer. The role of H. pylori eradication in persons with uninvestigated dyspepsia remains controversial. New clinical trials of H. pylori treatment show symptom relief and improvement in the quality of life of persons with functional dyspepsia, especially in those with ulcer-like or reflux-like dyspepsia. Clearly the move is toward symptom-based management of persons with dyspepsia, with fewer endoscopies being needed in the otherwise healthy young dyspeptic patients. It remains controversial whether eradicating H. pylori in duodenal ulcer or functional dyspepsia increases the risk of subsequent development of gastroesophageal reflux disease. The one-week proton pump inhibitor-based triple regimens remain the gold standard of H. pylori therapy, but some of the ranitidine bismuth citrate plus two antibiotic regimens also achieve an 80% H. pylori eradication rate on an intention-to-treat basis. While the urea breath test remains the noninvasive test of choice, interesting new data are available on the use of stool antigen testing to diagnose H. pylori infection. The number of H pylori-associated gastroduodenal diseases grows to include possible liver, vascular, immune and skin conditions.

Anti-Bacterial Agents↗
PubMed2000

Effects of in vitro antibiotic resistance on treatment: bismuth-containing regimens.

Bismuth compounds remain useful for Helicobacter pylori eradication therapy. These include colloidal bismuth subcitrate (CBS), bismuth subsalicylate (BSS) and, most recently, ranitidine bismuth citrate (RBC). CBS appears to prevent the development of imidazole resistance when coadministered with nitroimidazoles. Traditional triple therapy with bismuth, metronidazole and tetracycline or amoxicillin (BMT/A) only partially overcomes metronidazole resistance. However, the addition of a PPI to bismuth triple therapy largely overcomes established metronidazole resistance if treatment is given for at least one week or more. When RBC rather than PPI is used with clarithromycin, this dual regimen appears to be more effective in preventing the development of secondary clarithromycin resistance. The triple combination of RBC, metronidazole and clarithromycin appears to be effective against metronidazole resistant strains of H pylori. Thus, overall, there is some evidence that bismuth compounds may prevent the development of antibiotic resistance and that existing antibiotic resistance may at least be partially overcome in vitro and in vivo. With the growing emergence of H pylori resistance to metronidazole and clarithromycin, further research to clarify the role of bismuth compounds is required.

Anti-Bacterial Agents↗
PubMed2000

Omeprazole once or twice daily with clarithromycin and metronidazole for Helicobacter pylori.

BACKGROUND: Triple therapy for one week with omeprazole, clarithromycin and metronidazole (OCM) is accepted worldwide as a first line therapy for Helicobacter pylori eradication. It is unclear whether omeprazole needs to be given once or twice daily. OBJECTIVES: To assess the efficacy and safety of these regimens in a single-centre, Canadian practice. METHODS: Histologically proven H pylori-positive patients were treated for seven days with clarithromycin 250 mg bid and metronidazole 500 mg bid, and randomly allocated to omeprazole 20 mg either once or twice daily in this open, cohort study. Endoscopy with histology (two antrum and two body biopsies, Giemsa stain) was done four weeks or longer after the pills were completed to assess H pylori eradication. RESULTS: Whether omeprazole was given once or twice daily, eradication was high and the same in both arms. All-patients-treated eradication was 85% (39 of 46 in the omeprazole once daily group and 41 of 48 in the omeprazole twice daily group) and intent-to-treat eradication was 80% (39 of 49 in the omeprazole once daily group and 41 of 51 in the omeprazole twice daily group). Side effects were frequently seen, suffered by 65% to 69% of patients treated. However, these were mild and compliance was high, with 94% of patients taking all of their pills. Mild side effects included loose stools, taste disturbance, nausea, headache and upper or lower gastrointestinal gas. Only one patient (1%) from the omeprazole once daily arm stopped taking metronidazole due to excessive perspiring. CONCLUSIONS: In this community practice, OCM triple therapy was effective whether omeprazole was given once or twice daily. For those with financial constraint, omeprazole 20 mg once daily can be considered. The regimens were well tolerated without serious adverse events.

Anti-Bacterial Agents↗
PubMed2000

What determines the heart rate response to exercise in patients with atrial fibrillation?

We evaluated the factors that determine the heart rate response to exercise in 60 patients with atrial fibrillation (25 men and 35 women, with a mean age of 61+/-10 years) who underwent symptom limited cardiopulmonary exercise testing with blood sampling of atrial natriuretic peptide (ANP), 2-dimensional echocardiography and cardiac catheterization. Atrial muscles resected during the Maze operation were examined histologically in 12 patients. The heart rate response to exercise depended on the severity of the atrial organic injury, which was expressed as left atrial diameter, ANP secretion during the maximal exercise testing and the histological findings of atrial tissue. Conversely, we believe that the severity of the atrial injury can be predicted from the heart rate response to exercise in patients with atrial fibrillation.

Aged↗