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Biomedical subjects

N Okabe

Publications and source records attributed to N Okabe.

At least 19 recordsLinked to original sources

Nonsteroidal anti-inflammatory drugs induce hypermotilinemia and disturbance of interdigestive migrating contractions in instrumented dogs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) induce gastric ulcers due to inhibition of prostaglandin production. Prostaglandins have an influence on physiological gastrointestinal motility, but the relationships between NSAID-induced gastric ulcer, gastrointestinal motility and motilin are unknown. Fifteen dogs were allocated randomly to three groups in which either gelatin, meloxicam or indomethacin was administered. Fecal occult blood and gastrointestinal motility were monitored continuously for 6 days. In addition, analyses of the plasma motilin concentration, gastrointestinal endoscopy and gastric emptying, and detection of motilin cells were performed. Gastrointestinal motility was disturbed in the indomethacin group, presenting as disappearance of interdigestive migrating contractions (IMCs) 3 days before gastric ulcers were detected. Delayed gastric emptying and hypermotilinemia were observed significantly more often in the indomethacin group compared with the other groups. Motilin cell-crypt/villi ratio in the indomethacin group significantly decreased in the duodenum and jejunum, compared with the other groups. No significant changes in any tests were observed in the meloxicam group, when compared with the gelatin group. These findings suggest that the disturbance of IMCs caused by hypermotilinemia, with changes in motilin cell distribution, and delayed gastric emptying induced by indomethacin may contribute to the development of gastric ulcers.

Animals↗

Development of reformative surgery method using partial freezing for the liver.

To minimize surgical stresses including blood loss and operation time to the patients during hepatic resection, we studied the feasibility of a combination of a partial liver freezing technique and shape-memory alloy, which also enables a free-designed resection curve. In this surgical procedure, the region surrounding a tumor in the liver is frozen to excise and prevent hemorrhage. The liver was frozen by a Peltier module. The effects of cooling rate and freezing temperature on the excision force that arise between a scalpel and the liver are carried out experimentally as a basic research for partial freezing surgical procedures. A porcine liver was used as a liver sample. The physical properties were estimated by using the finite element method based on the heat transfer characteristics of the liver. Isolation of the liver was conducted using a scalpel attached to the end-effector of a 3 degrees of freedom robot. In the experiments, the minimum excision force was obtained at a temperature between 272 K and 275 K; therefore, it is preferable that the liver be excised within this temperature range. Lowering of the cooling rate decreases the excision force even if the temperature of the liver remains unchanged. The lower the temperature of the liver is, the larger the increment rate of excision force is with regard to the cooling rate.

Animals↗

Experimental surveillance using data on sales of over-the-counter medications--Japan, November 2003-April 2004.

OBJECTIVES: This report describes a study to explore the possibility of using data on sales of over-the- counter (OTC) medications as part of a routine syndromic surveillance system aimed at early detection of infections of public health concern. A retrospective evaluation was conducted of sales of OTC medications used to treat the common cold. This report discusses the correlation of these data to influenza activity in Japan during the 2003-04 influenza season and evaluates the potential of using such data to predict influenza epidemics. METHODS: Data from approximately 1,100 pharmacies throughout Japan collected during November 2003-April 2004 were analyzed. OTC sales data were compared with influenza incidence data (one weekly and two daily data sets) to determine correlations and predictability. Adjusted R-square was used as an index of goodness of-fit in the estimation. Data reflecting daily influenza activity were obtained from the National Surveillance of Daily Influenza Outpatients and the Mailing List-Based Influenza Epidemic Database. National sentinel surveillance data for influenza from approximately 5,000 sites nationwide also were analyzed. RESULTS: Although a correlation was demonstrated between sales of OTC medications used to treat the common cold and concurrent influenza activity, analysis of sales data alone was not sufficient to determine influenza activity in advance even when sales promotion effects were excluded from the analysis. CONCLUSION: Because visiting a health-care provider costs more than purchasing OTC medications, the hypothesis was formed that an ill person will purchase OTC medications first and visit a physician only if the condition does not resolve or worsens. The results of this study do not provide any clear evidence to support this hypothesis. For this reason, OTC sales do not appear to be a good candidate for a national real-time detection system for influenza epidemics in Japan.

Commerce↗

Gallbladder wall thickening associated with infectious mononucleosis.

Acute infectious mononucleosis is a typical self-limited lymphoproliferative illness characterized by fever, tonsillar pharyngitis, and lymphadenopathy in adolescents and young adults. Thickening of the gallbladder wall is rarely observed. We report a case of infectious mononucleosis in which marked thickening of the gallbladder wall was detected by ultrasonography and computed tomography.

Adolescent↗

Vibrio vulnificus septicaemia in Japan: an estimated number of infections and physicians' knowledge of the syndrome.

Questionnaire surveys were implemented to study the incidence and physicians' knowledge of Vibrio vulnificus infections in Japan. Registered emergency physicians were selected by stratified random sampling for a questionnaire survey. A total of 235 out of 386 physicians (61%) responded to the questionnaire and 12 V. vulnificus septicaemia cases were reported from 10 respondents. The annual estimated number of V. vulnificus septicaemia was calculated as 425 (95 % CI 238-752). The study also revealed that only 15.7 % (95 % CI 11.3-21.0) of responding physicians had a basic knowledge of V. vulnificus infection. Education for both physicians and people in the high-risk group for developing the infection (e.g. immunocompromised, chronic liver disease) will be necessary for the prevention, early diagnosis and appropriate treatment of the disease.

Clinical Competence↗

Salmonella Enteritidis outbreak associated with a school-lunch dessert: cross-contamination and a long incubation period, Japan, 2001.

A Salmonella Enteritidis (SE) outbreak in Japan was investigated with an observational study, analytical epidemiology and bacteriological examination (including phage typing). The outbreak occurred among 96 schoolchildren, and was caused by SE phage type 1. The outbreak source was dessert buns served at a school lunch (RR 42.55, 95 % CI 5.93-305.11, P < 0.001). The buns were probably cross-contaminated from eggs from a factory with a history of SE-contaminated products. The incubation period was longer than usual (3-16 days, median 8 days). A low contaminating dose may account for the long incubation period and low attack rate. Outbreak detection was hampered by the absence of routine Salmonella surveillance in Japan. The investigation was complicated by concurrent illnesses from other SE phage types. It was successful, in part, because adequate food samples were available for microbiological testing.

Child↗

Serological and genetic characterisation of a unique strain of adenovirus involved in an outbreak of epidemic keratoconjunctivitis.

AIMS: To characterise a novel strain of adenovirus (Ad) type Ad8 (genome type Ad8I) involved in an epidemic keratoconjunctivitis (EKC) outbreak in Hiroshima city using serological testing and sequence analysis of the fibre and hexon gene. METHODS: A neutralisation test (NT) was performed in microtitre plates containing a confluent monolayer of A549 cells using 100 tissue culture infectious doses of virus and type specific antisera. The haemagglutination inhibition test was also carried out in microtitre plates with rat erythrocytes using four haemagglutination units of virus and twofold dilutions of serum. The fibre gene was sequenced by generating overlapping polymerase chain reaction products or by direct sequencing of genomic DNA. Primer selection was based on alignment of the fibre genes of human adenovirus serotypes Ad8, Ad19, Ad37, Ad9, and Ad15 available from Gene Bank. RESULTS: The virus strain was specifically neutralised by anti-Ad8 antibodies, although there was a major crossreaction with anti-Ad9 antibodies. Haemagglutination was equally inhibited by anti-Ad8 and anti-Ad9 antibodies. The predicted amino acid sequences of the hypervariable regions (HVRs) of the Ad8I hexon gene showed higher homology with Ad9 (83.3%) than with Ad8 (62.0%). However, the Ad8I fibre knob was more homologous to Ad8 (94.4%) than to Ad9 (91.6%). CONCLUSIONS: Ad8I is a unique strain of adenovirus because of its lower genomic homology with Ad8, major crossreactivity with Ad9 in NT, and mixed genetic organisation of HVRs of the hexon gene. These factors may have enabled the virus to circumvent acquired immunity, resulting in the outbreak.

Adenovirus Infections, Human↗

Heterogeneity of the fibre sequence in subgenus C adenoviruses.

AIMS: To determine the nucleotide sequences of adenovirus (Ad) types 1 and 6 fibre genes; to clarify the molecular basis of the distinct haemagglutination properties of subgenus C Ads and their phylogenetic relations. METHODS: Human Ad1 and Ad6 fibre genes were sequenced from genomic DNA by direct sequencing. Primer selection was based on alignment of the fibre gene of human Ad serotypes Ad2 and Ad5. Fibre based subgenus C specific polymerase chain reaction (PCR) was performed to check for deletions in field isolates of Ad6, as revealed by sequence analysis of the Ad6 prototype. A phylogenetic tree was constructed from the predicted amino acid (AA) sequences of the fibre gene of important Ads. RESULTS: Ad1 and Ad6 comprise 1746 and 1584 nucleotides, encoding 582 and 528 AA, respectively. Ad6 showed deletions in motifs 15-17 (51 AA) of the shaft when compared with Ad1, Ad2, and Ad5. Subgenus C specific PCR with both prototype and field isolates also showed deletions in Ad6. In the shaft and knob, AA homology was 58.82-72.91% and 68.89-74.59%, respectively. The tail was 100% conserved. Phylogenetically, Ad1 and Ad6, including Ad2 and Ad5, formed a subgenus specific cluster, like other serotypes. CONCLUSIONS: The fibre gene (including the knob region) of subgenus C Ads is heterogeneous, providing the molecular basis for lack of crossreactivity in the haemagglutination inhibition test. This heterogeneity could be helpful in fibre based genotyping of subgenus C field isolates. Phylogeny might be useful for subgenus specific identification of important field strains.

Adenoviruses, Human↗

Characterisation of hexon and fibre genes of a novel strain of adenovirus involved in epidemic keratoconjunctivitis.

AIMS: To characterise a novel strain (M86) of adenovirus (Ad) involved in epidemic keratoconjunctivitis (EKC). METHODS/RESULTS: The virus strain was neutralised by antisera to both Ad35 and Ad11. Restriction endonuclease analysis of genomic DNA showed 98% and 88% homology with Ad11 and Ad35, respectively. The deduced amino acid sequence of the hypervariable regions of (HVRs) of the hexon gene showed a higher homology with Ad35 (94.4%) than with Ad11 (83.7%). However, it was 100% homologous to Ad35 in HVRs 1, 2, 3, and 6 and to Ad11 in HVRs 4 and 6. In the fibre knob, the isolate was more homologous to Ad11 (99.4%) than to Ad35 (29.1%). CONCLUSION: This novel strain of adenovirus showed similarities with both Ad11 and Ad35. The isolation of a novel strain like Ad35+11 is important because of its association with EKC.

Adenovirus Infections, Human↗

Genetic characterisation of adenovirus type 8 isolated in Hiroshima city over a 15 year period.

AIMS: To investigate the genetic differences among the strains of adenovirus type 8 (Ad8) circulating in Hiroshima city, Japan, and to study their circulation pattern. METHODS: One hundred and twenty nine strains of adenovirus type 8 (Ad8) were isolated in Hiroshima City over a 15 year period (1983-97) from patients with keratoconjunctivitis, and analysed with six restriction enzymes-BamHI, HindIII, PstI, SacI, SalI, and SmaI-to investigate possible relations among the isolates and their genetic variability. Seven hypervariable regions of the hexon gene that carry the type specific epitope were also sequenced to investigate the variation among the genome types. RESULTS: Restriction endonuclease analyses yielded three known genome types (Ad8A, 13 samples; Ad8B, seven samples; and Ad8E, 35 samples) and a novel genome type (Ad8I, 74 samples). Ad8A, Ad8B, and Ad8E were closely related, with 96% homology, whereas Ad8I had only 71% homology. Ad8A, Ad8B, and Ad8E shared 91.8% and 96.4% homology with regard to their amino acid and nucleotide sequences, respectively, with the isolate 1127 (accession no X74663). However, when compared with Ad8A, Ad8B, Ad8E, and isolate 1127, Ad8I shared only 62.7% and 69.9% homology with regard to amino acid and nucleotide sequences, respectively. Ad8A, Ad8B, and Ad8E had a unique 31 amino acid deletion in the hypervariable region 1 of the hexon gene, whereas Ad8I had a 33 residue deletion. The Ad8E strain that circulated from 1984 to 1995 was stable among the study population. Ad8I was isolated from an outbreak of epidemic keratoconjunctivitis in 1995 and was also isolated from sporadic cases until 1997. CONCLUSIONS: These results confirmed that genetic variability occurs in Ad8 in the microenvironment and revealed the emergence of a new genome type (Ad8I).

Adenoviruses, Human↗

Comparative analysis of host responses related to immunosuppression between measles patients and vaccine recipients with live attenuated measles vaccines.

Measles virus infection induces a profound immunosuppression. We analyzed in a time-dependent manner peripheral bloods of one to two-year-old children immunized with live attenuated measles vaccines, compared with age-matched measles patients, for immunosuppression. In contrast to transient severe lymphopenia with measles patients, primarily due to extensive apoptosis of a broad spectrum of uninfected lymphocytes, neither apoptosis nor lymphopenia occurred with measles vaccine recipients. Increase in number and activation of NK cells, which might compensate for the lymphopenia in measles patients, were not found with the vaccinees. While cell surface expression of apoptosis-related molecules such as TNF-related apoptosis-inducing ligand (TRAIL), TRAIL-receptors, CD95(Fas) and Fas-ligand, and plasma interferon-gamma were increased for measles patients, they remained unchanged after vaccination. Plasma interleukin (IL)-18, which is responsible for inducing apoptosis in several infectious diseases, was increased predominantly with measles patients, whereas the increase remained marginal with the vaccinees. IL-10 was elevated transiently in both measles patients and vaccinees. Decrease in plasma IL-12, which is often correlated with T cell suppression, was not found for both cases. Serum IgM and IgG antibodies to measles virus were induced at lower titers in the vaccinees than measles patients. These results indicate that in contrast to wild-type measles virus, live measles vaccines hardly provoked host cytokine responses that lead to apoptotic cytolysis of uninfected lymphocytes, lymphopenia and immunosuppression, and thereby induced weaker immune responses to the virus.

Antibodies, Viral↗

Use of antiserum-coated latex particles for serotyping Streptococcus pneumoniae.

The Quellung reaction provides a standard means for serotyping Streptococcus pneumoniae, but it requires microscopic examination with skillful technique. We have developed an improved agglutination method with anti-rabbit IgG-coated latex particles, which are sensitized with pooled antisera for serotyping/serogrouping S. pneumoniae. Our method is as specific and sensitive as the Quellung test, and much easier to perform.

Animals↗

[Field epidemiological investigation on an outbreak of Chlamydia pneumoniae infection--first recognized incidence in a nursing home for elderly in Japan].

Chlamydia pneumoniae (C. pneumoniae) is an emerging pathogen recognized in 1989. Although C. pneumoniae infection is known to give a great impact on public health in western countries, many aspects remain unclarified in Japan. During December 1999 and March 2000, respiratory symptoms among residents and employees in a nursing home for elderly implicated an outbreak of C. pneumoniae infection. Field epidemiological investigation confirmed that this is the first outbreak recognized in a nursing home setting in Japan, involving 31/59 (15 confirmed) residents and 9/41 (2 confirmed) employees. Fifteen residents developed severe C. pneumoniae infections including one fatal outcome with pneumonia. Epidemiological analysis did not identify risk factors which induce infection or severe illness by C. pneumoniae for the residents. However, for the employees, frequent contact with the residents was demonstrated as a significant risk factor for the infection. None of 13 employees who had no contact with the residents presented C. pneumoniae infection, while nine out of 28 employees who had frequent contact developed C. pneumoniae infections (RR infinite, P = 0.04). These results indicated that C. pneumoniae infection spread gradually by human-to-human droplet transmission without specific risk factors. This study raised current problems in diagnosing and treating the C. pneumoniae infection and the need to enhance the awareness of this disease.

Aged↗

The pathogenesis of Crohn's disease.

Although much progress has been made in understanding the pathogenesis of Crohn's disease, the precise etiology of Crohn's disease still remains unknown. In our serial studies on Crohn's disease, we found a decrease in NK and ADCC activities as well as a decrease in the phagocytic activity by monocytes, whereas an increased superoxide production activity by monocytes was evident. On the other hand, the characterization of lymphocyte subsets has demonstrated no abnormalities. According to these findings, I would like to propose a new tentative hypothesis for the pathogenesis of Crohn's disease. It has been suggested that impaired killing system activities, such as phagocytic as well as NK and ADCC activities, are primarily responsible for the promotion and perpetuation of chronic inflammation and ulceration. When our attention is directed to the common target substances of these protective mechanisms, viral antigens appear as the most likely causative organism. Therefore, a lot of attention must be focused on viral infection as a causative factor. Furthermore, effects of psychological and physical stress on the disease onset or the recurrence of inflammatory bowel disease are also discussed.

Antigens, Viral↗

Analysis of Japanese encephalitis epidemic in Western Nepal in 1997.

We conducted an epidemiological study of a Japanese encephalitis (JE) outbreak in the southwestern part of Nepal in 1997. A high density of JE infections was found and it was estimated that 27.9% the total population were infected with JE virus in the study area. The fatality rate was 13.2% and there was no difference in the fatality rate between males and females over 5 years old. However, the case fatality rate was 2.1 times higher in females than in males (14.6% vs. 6.9%) among children under 5 years of age. Fifty-three blood samples were collected from suspected JE cases during the epidemic period in 1998. Findings for JE specific IgM revealed that clinical diagnoses of JE were serologically confirmed in an average 78% (70-93%) of patients in three collaborating hospitals. These studies demonstrated that JE was highly prevalent in the area and clinical diagnoses were reliable. Effective preventive measures should be taken against this vaccine-preventable disease.

Adolescent↗