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Biomedical subjects

Kazunori Oishi

Publications and source records attributed to Kazunori Oishi.

At least 19 recordsLinked to original sources

Strain-specific pulmonary defense achieved after repeated airway immunizations with non-typeable haemophilus influenzae in a mouse model.

Strain-specific immune responses may play a critical role in the acute exacerbation of chronic obstructive pulmonary disease (COPD) caused by Haemophilus influenzae (NTHi), and the outer membrane protein P2 is one of surface antigens of NTHi, which may contribute to the strain-specific protective immunity. We examined whether repeated airway immunizations with killed-NTHi strains bearing different P2 molecules were capable of inducing protective immunity against homologous or heterologous strains in the lungs of a mouse model. Three different strains of NTHi were used in this study. Three serial intratracheal (IT) immunizations of a single strain or three different strains of NTHi led to the production of cross-reactive immunoglobulins G and A in bronchoalveolar lavage fluids. Three serial IT immunizations with a single strain enhanced the bacterial clearance of the homologous strain in the lungs, but no enhancement of bacterial clearance was found with three serial IT immunizations of heterologous strains. The enhancement in bacterial clearance, therefore, appears to be primarily strain-specific. Enhanced bacterial clearance of a heterologous strain was also found after three serial IT immunizations of a single strain among two of the three strains employed for bacterial challenge. These findings suggest that P2 molecules and surface antigens other than P2 are involved in the development of pulmonary defense against NTHi in mice. Our data may explain, in part, why patients with COPD experience recurrent NTHi infections.

Amino Acid Sequence↗

Comparative immune responses of patients with chronic pulmonary diseases during the 2-year period after pneumococcal vaccination.

Antibody responses to a 23-valent pneumococcal vaccine for Streptococcus pneumoniae serotypes 6B, 14, 19F, and 23F in 84 patients with chronic pulmonary diseases over a 2-year period after vaccination were examined by using a third-generation enzyme-linked immunosorbent assay. Of these patients, 28 (31%) were low responders who had developed increases of at least twofold in the levels of serotype-specific immunoglobulin G (IgG) in sera for none of the four serotypes at 1 month after vaccination. Although no specific clinical features of low responders were evident, their prevaccination levels of IgG for all serotypes were higher than those of responders. In responders, the levels of IgG specific for serotypes 14 and 23F in sera were greatly increased 1 month after vaccination and those specific for serotypes 6B and 19F were moderately increased. In contrast, no significant increases in the levels of IgG specific for serotypes 6B, 19F, and 23F in the low responders during the same period were found, but the levels of IgG specific for serotype 14 did increase. Although a rapid decline in the levels of IgG for all serotypes in responders between 1 month and 6 months after vaccination was found, the levels of IgG specific for serotypes 14 and 23F in sera remained higher than the prevaccination levels for at least 2 years after vaccination. These data suggest the need for the revaccination of responders but not low responders among patients with chronic pulmonary diseases. Revaccination as early as 3 years postvaccination is recommended for responders to increase the reduced levels of IgG in sera, especially those specific for the weak vaccine antigens.

Antibodies, Bacterial↗

Dynamics of dendritic cell migration and the subsequent induction of protective immunity in the lung after repeated airway challenges by nontypeable Haemophilus influenzae outer membrane protein.

To determine the dynamics of dendritic cell (DCs) migration and their role in recurrent infections by nontypeable Haemophilus influenzae (NTHi), the migration of mature DC into pulmonary lymph nodes (LN) and the development of a P6-specific immune response and bacterial clearance in the lung were examined after repeated airway challenges with outer membrane protein (OMP) at 1-week intervals in mice. Although the migration of mature DC into the pulmonary LN is attenuated after repeated airway challenge with OMP, the in vitro P6-specific T cell proliferation in the cultured pulmonary LN cells was enhanced and was subsequently linked to the development of P6-specific IgA production and the development of protective immunity in the airway of mice.

Administration, Inhalation↗

A multicenter phase II study of carboplatin and paclitaxel with a biweekly schedule in patients with advanced non-small-cell lung cancer: Kyushu thoracic oncology group trial.

PURPOSE: This multicenter phase II study was conducted to investigate the efficacy and safety of carboplatin in combination with paclitaxel administered according to a biweekly schedule as a first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligibility criteria included histologically or cytologically confirmed NSCLC (stage IIIb or IV), no prior treatment, and measurable or evaluable disease. Paclitaxel (140 mg/m(2)) was administered intravenously on day 1, in combination with carboplatin at an area under the concentration time curve (AUC) of 3, every 2 weeks. RESULTS: Seventy-four patients (45 men) with a median age of 62 years (range 40-74) and a median ECOG performance status of 1 (range 0-2) were enrolled. The response rate was 35.1% [95% confidence interval (CI): 24.4-47.1%], with 26 partial responses. The median survival was 357 days, and the median time to progression was 218 days. Toxicity was generally mild; National Cancer Institute-Common Toxicity Criteria (NCI-CTC) grades 3 and 4 neutropenia was observed in 50.0% of the patients, and grades 3 and 4 nausea/vomiting in 4.1%. CONCLUSIONS: Biweekly carboplatin combined with paclitaxel demonstrated anti-tumor activity in advanced NSCLC, with response and survival rates similar to those of carboplatin combined with paclitaxel administered every 3 weeks but with a more favorable toxicity profile, and the present data indicate that the regimen is suitable for use on an outpatient basis.

Adult↗

Epidemiological and clinical features of idiopathic pulmonary alveolar proteinosis in Japan.

Idiopathic pulmonary alveolar proteinosis (IPAP) is a rare disease characterized by excessive amounts of lipoproteinaceous material in the alveolus. This report presents an interim analysis of nationwide epidemiological data from Japanese patients with pulmonary alveolar proteinosis, and the roles of serum markers for IPAP. (i) The nationwide demographic data from 166 Japanese patients with IPAP are shown. The female to male ratio was 1:2, and the average age was 51 +/- 14 years old (age range: 15-79 years) at registration or diagnosis. A total of 30% of patients with IPAP have a poor clinical course. In total, 30% of patients were treated with whole lung lavage therapy (WLL). Under WLL, the patients significantly improved in the short term, but 40% of the patients who underwent WLL worsened again. A new strategy such as granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy for intractable PAP is required. (ii) The correlation of serum KL-6, carcinoembryonic antigen, surfactant proteins D and A, and LDH with disease severity suggests their potential as disease markers. In contrast, serum anti-GM-CSF antibody did not correlate with disease severity, but is a specific marker for the diagnosis of IPAP. The combined measurements of the serum markers may well prove very useful for both the diagnosis and the management of IPAP patients.

Adolescent↗

Drug-resistant genes and serotypes of pneumococcal strains of community-acquired pneumonia among adults in Japan.

BACKGROUND: A high frequency of drug-resistant pneumococci has been reported in Asian countries. Few data on the drug-resistance or serotype of pneumococcal strains responsible for community-acquired pneumonia (CAP), however, are available for the past two decades in Japan. METHODOLOGY: Susceptibility to antibiotics and the genotype of antibiotic-resistant genes and serotypes of Streptococcus pneumoniae isolates from 114 adult patients with CAP were examined in a nationwide study in Japan between 2001 and 2003. RESULTS: Most of the cases were non-bacteraemic pneumonia and the case fatality rate was 4.4%. The most frequent genotype of the pbp gene was pbp1a + 2x + 2b (gPRSP; 36.8%) followed by pbp 2x (28.1%) and of the macrolide-resistant gene, it was ermB (50.0%). The most common serotype was 19F (29.1%), followed by serotype 23F (13.2%), 6B (12.3%) and 3 (11.4%). The coverage of serotypes of isolates by a 23-valent pneumococcal polysaccharide vaccine (PPV) would be 82.5% in these patients with CAP. Most of strains with serotypes 19F and 23F were gPRSP. A cluster of serotype 3 strains associated with the pbp 2x and ermB gene was also noted. CONCLUSION: A high frequency of altered pbp gene mutations or of macrolide-related genes and a high serotype coverage by the 23-valent PPV found in our study of pneumococcal pneumonia facilitates attempts to increase the coverage rate of the 23-valent PPV in adults older than 65 years in Japan.

Adult↗

Significant reduction of nosocomial pneumonia after introduction of disinfection of upper airways using povidone-iodine in geriatric wards.

We investigated the efficacy of disinfection of the upper airway using povidone-iodine against nosocomial pneumonia in geriatric wards. Cases of nosocomial pneumonia were retrospectively analyzed between January 1991 and March 1995 in geriatric wards (190 beds). Moreover, the relationship concerning methicillin-resistant Staphylococcus aureus (MRSA) isolates between patient and environment was investigated using pulsed-field gel electrophoresis (PFGE) with the SmaI restriction enzyme. The incidence of nosocomial pneumonia decreased significantly (p < 0.05). Major causative organisms of nosocomial pneumonia were MRSA and Pseudomonas aeruginosa, which significantly decreased. PFGE studies showed that the patterns of MRSA isolates show a strong association between patient and environment. Our study indicates that disinfection of the upper airways by povidone-iodine is very important in the prevention of nosocomial pneumonia in geriatric wards.

Aged↗

Norepinephrine inhibits human immunodeficiency virus type-1 infection through the NF-kappaB inactivation.

Exercise or acute stress can exert significant effects on immune system as well as cardiovascular and respiratory systems through catecholamines. In this study, we investigated effects of norepinephrine (NE), a catecholamine neurotransmitter on human immunodeficiency virus type-1 (HIV-1) infection. NE inhibited in vitro HIV-1 infection of peripheral blood mononuclear cells (PBMC) from healthy donors and ex vivo HIV-1 replication in patients' PBMC. In transient expression assays, NE downregulated HIV-1 long terminal repeat, but site-directed mutagenesis on NF-kappaB-binding sites or cotreatment with H89 (a protein kinase A inhibitor) abrogated the NE-mediated effect. Gel-shift assays showed suppression of NF-kappaB activity in NE-treated cells. NE increased cytoplasmic levels of IkappaB-alpha, a natural inhibitor of NF-kappaB. Thus, NE apparently inhibits HIV-1 infection, at least in part through NF-kappaB inactivation.

Adult↗

Molecular analysis of intrafamiliar transmission of Moraxella catarrhalis.

The possible intrafamiliar transmission of Moraxella catarrhalis was evaluated in 3 pairs between children and their parents, and 8 pairs between siblings from 11 families. Of the 22 isolates, all were found producing beta-lactamase. Molecular typing by pulsed-field gel electrophoresis (PFGE) with Not I and Spe I showed that the PFGE patterns in 2 of 3 pairs between children and their parents, and 4 of 8 pairs between siblings were indistinguishable and those of the remaining pairs were different. These data indicate a possible high rate of intrafamiliar transmission of M. catarrhalis.

Adult↗

Invasive Haemophilus influenzae type B diseases in Bangladesh, with increased resistance to antibiotics.

OBJECTIVE: To determine the prevalence, age-group distribution, serotype, and antibiotic susceptibility patterns of invasive Haemophilus influenzae type b (Hib) isolates in Bangladeshi children because data regarding Hib diseases in developing countries are scarce, which has led to delay of the introduction of Hib vaccine in these countries. METHODS: Children diagnosed with meningitis (n = 1412) and pneumonia (n = 2434) were enrolled in this surveillance study for Hib invasive diseases. Cerebrospinal fluid (CSF) and blood specimens, and the subsequent isolates, were processed using standard procedures. RESULTS: During 1993 to 2003, 455 H influenzae strains were isolated from patients with meningitis (n = 425) and pneumonia (n = 30), and an additional 68 Hib meningitis cases were detected by latex agglutination (LA) testing. Overall, 35% of pyogenic meningitis cases were a result of H influenzae, 97.1% of which were Hib. Most (91.4%) cases occurred during the first year of life. Resistance to ampicillin, chloramphenicol, and cotrimoxazole was 32.5%, 21.5%, and 49.2%, respectively. There was a trend toward increasing resistance for all three drugs. Resistance to ampicillin and chloramphenicol was almost universally coexistent and was associated with increased sequelae compared with the patients infected with susceptible strains (31% [23/75] vs 11% [21/183]; P <.001). CONCLUSION: Hib is the most predominant cause of meningitis in young Bangladeshi children. Resistance to ampicillin and chloramphenicol and the high cost of third-generation cephalosporin highlight the importance of disease prevention through vaccination against Hib.

Age Factors↗

Pulmonary anisakiasis presenting as eosinophilic pleural effusion.

A 63-year-old man developed a pleural effusion with marked eosinophilia, which was more prominent in the pleural fluid than in the peripheral blood. The pleural effusion spontaneously disappeared 7 days after admission. A multiple dot enzyme-linked immunosorbent assay for anisakiasis was strongly positive for both the serum and pleural fluid. The serum IgG titre for Anisakis simplex gradually decreased over 7 months. It is suspected that Anisakis larvae can penetrate the alimentary canal, and then migrate into the pleural cavity through the diaphragm. Screening with a serological test is useful in the diagnosis of this condition; human pulmonary anisakiasis.

Animals↗

Usefulness of the Japanese Respiratory Society guidelines for community pneumonia: a retrospective analysis of community-acquired pneumonia between 2000 and 2002 in a general hospital.

OBJECTIVE: The aim of this study was to investigate the causative organisms of community-acquired pneumonia (CAP) diagnosed between 2000 and 2002 and to evaluate the Japanese Respiratory Society (JRS) guidelines. METHODOLOGY: A total of 124 cases of CAP diagnosed during the study period were analyzed, and the results were compared with those of a previous study by the authors' research group. Determination of the causative organisms of CAP was based on Gram stain, morphology of colonies, quantitative culture of sputum, identification of bacterial isolates, and serological tests. RESULTS: During the study period, the causative organisms were identified in 42 cases (33.8%). Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were the major causative organisms. Patients were classified into three groups based on the severity of CAP according to the JRS guidelines. The survival rates of patients with moderate and severe CAP were significantly lower than those of the mild group as evaluated by the Kaplan-Meier method (moderate vs mild, 70% vs 100%; severe vs mild, 40% vs 100%; P < 0.001 for both). Seven patients died during the study, and the risk factors were old age, bedridden status with cerebral infarction, and microaspiration, which was associated with recurrent pneumonia within 17 days. CONCLUSION: This study indicates that the JRS guidelines for CAP are useful for treating patients with CAP in Japan.

Adolescent↗

Comparative molecular analysis of Haemophilus influenzae isolates from young children with acute lower respiratory tract infections and meningitis in Hanoi, Vietnam.

Thirty-seven Haemophilus influenzae strains from nasopharyngeal swabs (NP) and 44 H. influenzae strains from cerebrospinal fluid (CSF) were investigated. Of the 37 H. influenzae isolates from NP, the serotypes of 30 isolates were nontypeable, 4 were type b, 2 were type c, and 1 was type a, whereas all of the 44 isolates from CSF were type b. The MICs of 16 antibiotics for the H. influenzae isolates from NP and CSF were similar, and no beta-lactamase-negative ampicillin-resistant strain was found. Molecular typing by pulsed-field gel electrophoresis (PFGE) showed that the 37 H. influenzae strains from NP had 22 PFGE patterns, with none predominating, and the 44 H. influenzae strains from CSF had 9 PFGE patterns, with patterns alpha (22 isolates) and beta (12 isolates) predominating. Our results indicate that two predominant types of H. influenzae type b strains have the potential to spread among children with meningitis in Hanoi, Vietnam.

Antibodies, Bacterial↗

Molecular characterization of the transmission between the colonization of methicillin-resistant Staphylococcus aureus to human and environmental contamination in geriatric long-term care wards.

OBJECTIVE: Transmission between human and environmental contamination from colonized methicillin-resistant Staphylococcus aureus (MRSA) remains a controversial issue. We, therefore, investigated the differences between MRSA types which colonize in humans and in the environment. METHODS: A 4-week prospective culture survey for MRSA was performed for 12 patients as well as for the environment of the room of MRSA carriers in quarantine in the geriatric long-term care ward of a 270-bed hospital. RESULTS: A total of 97 S. aureus strains (80 MRSA and 17 methicillin-sensitive Staphylococcus aureus [MSSA]) was isolated during the periods of September 8 to 10, 23 to 25 and October 5 to 7, 1998; 25 strains were from the respiratory tract, 4 strains from feces and 11 strains from decubitus ulcers. Fifty-seven strains were from the patients' environment. Molecular typing by pulsed-field gel electrophoresis (PFGE) with the Sma I restriction enzyme demonstrated that the predominant type of MRSA isolated from the environment changed by the minute. The patterns of 42 MRSA strains isolated from the environment were identical in 26 (61.9%), closely related in 15 (35.7%) and possibly related in 1 (2.4%) of the cases of those isolated from patients simultaneously. There was no correlation between patients and the environment with the 17 MSSA isolates. CONCLUSION: Our results demonstrated that MRSA from patients can contaminate the environment, whereas MRSA from the environment might be potentially transmitted to patients via health care workers under unsatisfactory infection control.

Aged↗

Comparison of clinical features and hematologic abnormalities between dengue fever and dengue hemorrhagic fever among children in the Philippines.

To demonstrate the differences of clinical features and hematologic abnormalities between dengue fever (DF) and dengue hemorrhagic fever (DHF), 359 pediatric patients admitted St. Luke's Medical Center in Quezon City, between 1999 and 2001 in Metro Manila, and adjoining provinces the Philippines, with a laboratory-confirmed dengue virus infection were evaluated. One third of the patients had DHF, and most of these patients were without shock. Restlessness, epistaxis, and abdominal pain were more associated with DHF. The platelet count was significantly lower in the DHF group than in the DF group before and after defervescence. In the DHF patients, the hematocrit was significantly increased before defervescence, and decreased the day after due to administration of intravenous fluid. Coagulation abnormalities associated with most DHF patients were thrombocytopenia and an increased fibrinolysis, but not disseminated intravascular coagulation. We present recent data on readily obtained clinical and laboratory data that can be used for early diagnosis and consequently earlier appropriate treatment of dengue virus infections.

Adolescent↗

Identification of a host gene subset related to disease prognosis of HIV-1 infected individuals.

Although plasma-virus-RNA level and CD4-positive-T-cell count are useful to monitor clinical status of the human immunodeficiency virus (HIV)-infected individuals, clinical course is often varied among patients and sometimes difficult to predict. To identify additional parameters associated with disease progression, we examined by cDNA microarray the expression profiles of 731 immune-response-related genes in the peripheral blood mononuclear cells (PBMCs) from 21 HIV-positive individuals in Uganda. The analysis enabled the patients to be classified into three distinct groups on the basis of the gene expression patterns. Notably, these groups, clusters I, II and III, were highly associated with clinical status of the patients defined by CDC classification, categories A, B, and C, respectively. Statistical analysis identified 40 genes whose expressions were significantly up- or down-regulated in the cluster III patients (p<0.05). Up- and down-regulated genes included ones involved in immature T lymphocytes differentiation, apoptosis signaling, and active HIV replication, suggesting that the levels of active destruction and regeneration of mature T lymphocytes associated with enhanced HIV-1 replication is related to the disease progression. Follow-up study showed that the cluster classification improved prediction of disease prognosis with the CDC classification. These findings provide new clues for studying perturbation of host immunity, pathogenesis, and disease prognosis of HIV-infected individuals.

Adult↗

Graves' hyperthyroidism and the hygiene hypothesis in a mouse model.

Graves' hyperthyroidism is an organ-specific autoimmune disease mediated by stimulatory autoantibodies against the TSH receptor (TSHR; thyroid-stimulating antibodies), causing thyroid hyperplasia and hyperthyroidism. Development of this ailment is well known to be under polygenic and environmental control. For example, we recently demonstrated that parasite helminth Schistosoma mansoni infection suppressed a T helper cell type 1 (Th1)-type anti-TSHR immune response and prevented disease development in our mouse model of Graves' disease using adenovirus coding for the TSHR. In the present study we examined the outcome of infection with Mycobacterium bovis bacillus Calmette-Guerin (BCG), a Th1-promoting infectious pathogen, on Graves' disease. Our results show that prior infection with M. bovis BCG differentiates the TSHR-specific immune response toward a Th1 phenotype, as demonstrated by enhanced secretion of a Th1 cytokine interferon-gamma and impaired production of a Th2 cytokine IL-10 from splenocytes stimulated in vitro with TSHR antigen. M. bovis BCG also significantly suppressed disease induction. These data together with our recent report that coinjection of adenovirus expressing the Th1 cytokine IL-12 induced a Th1-polarized, TSHR-specific immune response without affecting disease development support the hygiene hypothesis, rather than Th1-mediated disease suppression. Thus, some infectious pathogens may influence the development of Graves' disease regardless of their ability to modify the Th1/Th2 balance.

Animals↗