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Biomedical subjects

Hitoshi Kamiya

Publications and source records attributed to Hitoshi Kamiya.

18 recordsLinked to original sources

Leukotriene D4 induces production of transforming growth factor-beta1 by eosinophils.

Eosinophils may play an important role in the pathogenesis of airway remodeling in asthma through the production of various fibrogenic cytokines such as transforming growth factor-beta1 (TGF-beta1). Cysteinyl leukotrienes are also suggested to be involved in remodeling with their potential to induce proliferation of airway smooth muscle cells. Since massive eosinophil infiltration and the release of cysteinyl leukotrienes in airway secretions are often seen in asthma, we hypothesized that cysteinyl leukotrienes may be involved in airway remodeling through induction of TGF-beta1 from eosinophils. Peripheral blood eosinophils were cultured with leukotriene D(4) (LTD(4)) and/or interleukin-5 (IL-5) or granulocyte colony-stimulating factor (GM-CSF) for 16 h and gene expression of TGF-beta1 was quantified with real-time PCR. A combination of LTD(4) and IL-5 or LTD(4) and GM-CSF synergistically induced TGF-beta1 expression in eosinophils although stimulation with single factor, LTD(4), IL-5 or GM-CSF did not induce the gene expression. LTD(4) also induced significant gene expression in eosinophils cultured in an intercellular adhesion molecule-1-coated plate. The results suggested that CysLTs stimulate eosinophils to induce TGF-beta1 production in allergic inflammation where IL-5 and GM-CSF are abundant and may be involved in the pathogenesis of airway remodeling.

Asthma↗

Delirious behavior in children with influenza: its clinical features and EEG findings.

The clinical characteristics and electroencephalogram (EEG) findings in delirious behavior in children with influenza were studied in order to differentiate it from influenza-associated encephalitis/encephalopathy. Fifteen consecutive children with delirious behavior associated with influenza were investigated. Their clinical courses were investigated using medical records. EEG was obtained during the delirious behavior, when possible. The body temperature during the delirious behavior was 39.0 degrees C or higher in 13 children. A subtle reduction of consciousness was observed in 10 children. Seizures were observed in five children. EEG revealed some mildly abnormal findings in 13 children, including mild slowing of the background activity, insertion of semirhythmic high voltage slow waves, and appearance of relatively high voltage semirhythmic theta waves. The EEG findings normalized after the delirious behavior had disappeared. EEG revealed transient and mild abnormalities in children with delirious behavior but without encephalitis/encephalopathy, and thus might be useful for diagnostic evaluation in such condition.

Adolescent↗

Poor immune responses to influenza vaccination in infants.

Twenty-two and 37 infants and young children received two doses of influenza HA vaccine before the 2001-2002 influenza season and before the 2002-2003 season, respectively. Two or three serial specimens were obtained, before and 1 month after the first vaccination as well as 1 month after the second vaccination. Infants showed a significantly poor HI antibody rise and lymphocyte response compared with young children aged > or =12 months. Time kinetics of the lymphoproliferative responses to influenza antigen among young children varied whereas their activities in infants were typically negative before immunization and increased after vaccination. Infants responded poorly to HA influenza vaccine compared with young children.

Adult↗

Impairment of IL-12-dependent STAT4 nuclear translocation in a patient with recurrent Mycobacterium avium infection.

We examined the immunological abnormality in a patient with recurrent Mycobacterium avium infection. T cells from the patient showed decreased ability both to produce IFN-gamma and to proliferate in response to IL-12. Despite decreased expression of IL-12R beta1 and beta2 chains in the patient's PHA-activated T cells, there was no difference in IL-12-induced tyrosine and serine phosphorylation of STAT4 in PHA-activated T cells between the patient and healthy subjects, suggesting that IL-12R signals are transmitted to STAT4 in the patient's PHA-activated T cells. Using EMSA, confocal laser microscopy, and Western blotting, we demonstrated that the nuclear translocation of STAT4 in response to IL-12 is reduced in PHA-activated T cells from the patient when compared with those from healthy subjects. Leptomycin B was used to examine whether nuclear export of STAT4 is increased in the patient's T cells. However, leptomycin B treatment did not reverse impaired IL-12-induced nuclear accumulation of STAT4. Although the exact mechanism responsible for the impaired STAT4 nuclear translocation in this patient remains unclear, the absence of mutation in the IL-12Rbeta1, IL-12Rbeta2, STAT4, and STAT4-binding sequence of the IFN-gamma gene and preservation of STAT4 tyrosine and serine phosphorylation suggest the existence of a defective STAT4 nuclear translocation. This defect is likely responsible for the impaired STAT4 nuclear translocation in IL-12-stimulated T cells, leading to impairment of both IFN-gamma production and cell proliferation. To the best of our knowledge, this is the first report of a patient with atypical mycobacterial infection associated with impairment of STAT4 nuclear translocation.

Active Transport, Cell Nucleus↗

Enhancement of immunity against VZV by giving live varicella vaccine to the elderly assessed by VZV skin test and IAHA, gpELISA antibody assay.

The enhancement of immunity against varicella-zoster vaccine (VZV) by subcutaneous injection of a live varicella vaccine was assessed by the VZV skin test for cell-mediated immunity (CMI), and immunoadherence hemagglutination assay (IAHA) and gpELISA antibody assays in the elderly people of 50-79 years of age. A total of 127 subjects were examined: 79 aged 50-59, 25 aged 60-69, and 25 aged 70-79. All were seropositive by the gpELISA assay (one was seronegative in the IAHA antibody assay). In contrast, a notable decline was observed in the VZV skin test with increasing age. Negative reaction was observed in 16/79 (20.2%) of the subjects in their 50s, 12/25 (48.0%) in their 60s and 14/25 (56.0%) in the 70s. After the vaccination, the results of the VZV skin test changed from negative to positive in 15/16 (91.8%) of subjects in their 50s, 11/12 (91.7%) in their 60s and 12/14 (85.7%) in their 70s. The mean antibody titer in the IAHA and the gpELISA increased approximately two-fold after the vaccination in each group. Immunity to VZV in 35 elderly subjects who were vaccinated previously was followed up for 4 years. All were positive by the VZV skin test after the previous vaccination. After 4 years, 31 (88.6%) were positive by the skin test, 4 were negative and became positive after revaccination. Although this study was uncontrolled open study, the results suggest that administering live varicella vaccine to the elderly is effective for enhancing immunity, particularly CMI to VZV.

Aged↗

Polio eradication.

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Health Promotion↗

[Efficacy of influenza vaccine for young children in Mie Prefecture in the 1999/2000 prevalent season].

PURPOSE: The purpose of this survey was to investigate the efficacy and safety of influenza HA vaccine for children between 1 and 6 years of age in Mie Prefecture during the 1999/2000 prevalent season. METHODS: We surveyed clinical data for children aged between 1 to 6 who visited five clinics in Mie Prefecture. Dividing them into vaccinated and non-vaccinated groups, we surveyed their basic properties, disease histories and manifestation of symptoms. The survey was performed with the consent of parents who were informed of the purpose. We also surveyed the adverse effects within 48 hours after vaccination. The serum HI titers of the vaccinated children were sampled three times: before the first vaccination and after the first and second vaccinations. The data were analysed with the chi-squared test and a multiple logistic model. RESULTS: The frequency of febrile episodes above 38 degrees C was significantly lower in the vaccinated than the non-vaccinated group. While the relative risk for the entire survey period was 0.79, it declined to 0.62 during the peak period of the epidemic. Furthermore, the odds ratio was 0.42 by the multiple logistic model. Among the vaccinated group, the pattern in the increase of HI titer after vaccination varied depending on the species of vaccine antigen. In addition, the frequency of febrile episodes above 38 degrees C was significantly lower in the group which had an HI titer to A/Sydney antigen of 1:40 or more than in these with values below 1:40. CONCLUSION: The relative risk of febrile episodes above 38 degrees C during the influenza prevalent season was 0.62 or below, and vaccine efficacy was 38 percent or above. Considering the significant difference in the frequency of febrile episodes between the groups with HI titers above and below 1:40, it is necessary to study strategies for those with a low response.

Child↗

Presence of high contents of thymus and activation-regulated chemokine in platelets and elevated plasma levels of thymus and activation-regulated chemokine and macrophage-derived chemokine in patients with atopic dermatitis.

BACKGROUND: T(H)2 cells and eosinophils selectively express CC chemokine receptor 4 and CCR3, respectively, and their chemokine ligands are likely to play important roles in the pathogenesis of atopic dermatitis (AD). OBJECTIVE: The purpose of this study was to demonstrate the presence of thymus and activation-regulated chemokine (TARC) in platelets and its release during clotting and to evaluate the circulating levels of TARC, macrophage-derived chemokine (MDC), and eotaxin in control subjects and patients with AD. METHODS: We compared plasma and serum contents of TARC, MDC, and eotaxin. We measured TARC contents in platelet lysates. We analyzed the correlation of plasma levels of TARC, MDC, and eotaxin with various clinicolaboratory parameters in patients with AD. RESULTS: Serum contents of TARC rapidly increased during clotting, whereas those of MDC and eotaxin increased only slightly. We demonstrated that platelets contained TARC, and its levels were dramatically elevated in patients with AD. Platelets also released TARC on stimulation with thrombin. We therefore evaluated circulating levels of these chemokines in control subjects and patients with AD by using plasma samples. Plasma TARC levels were significantly increased in patients with AD (P <.0001) and showed significant correlations with severity scoring of atopic dermatitis (SCORAD) index (r = 0.665, P <.00001), serum lactate dehydrogenese levels (r = 0.696, P =.00001), eosinophil counts (r = 0.381, P =.007), and platelet counts (r = 0.562, P <.0001). Similarly, plasma MDC levels were significantly increased in patients with AD (P <.0001) and showed significant correlations with SCORAD index (r = 0.727, P <.0001), serum lactate dehydrogenese levels (r = 0.861, P <.0001), eosinophil counts (r = 0.505, P =.005), and platelet counts (r = 0.370, P =.01). On treatment, plasma TARC and MDC levels were dramatically decreased in accordance with improved SCORAD scores (P =.0012 and P =.0007, respectively). On the other hand, plasma eotaxin levels did not show any significant increase or correlation with any of the clinical parameters in patients with AD. CONCLUSION: Platelets from patients with AD contain high levels of TARC. Thus platelets might play an important role in AD pathogenesis by releasing T(H)2-attracting TARC on activation. Furthermore, circulating levels of TARC and MDC, but not those of eotaxin, correlate well with the disease activity of AD.

Adolescent↗

Measles outbreak among non-immunized children in a Japanese hospital.

We experienced an outbreak of measles in which our hospital played an unfortunate role as a vector for the transmission of the disease. Most patients had never been vaccinated and an investigation into the reasons for this revealed a need to more widely promote awareness of measles vaccination in Japan.

Adolescent↗

Synergistic effect of theophylline and procaterol on interleukin-5-induced degranulation from human eosinophils.

Inhibiting the release of toxic granule proteins from eosinophils is a possible means of treating allergic inflammation. This study was performed to examine whether procaterol and theophylline, commonly used bronchodilators in asthma, inhibit eosinophil degranulation induced by interleukin (IL)-5. Purified eosinophils from patients with asthma were incubated with IL-5 for 24 hr in the presence of theophylline, procaterol, combinations of theophylline and procaterol, or dexamethasone. Levels of eosinophil-derived neurotoxin (EDN) in the supernatants were measured with radioimmunoassay. Theophylline inhibited IL-5-induced release of EDN in a concentration-dependent manner. Procaterol inhibited degranulation only at high concentrations. However, procaterol at 10(-9) M and 10(-8) M, which are physiologic concentrations, together with theophylline at 10(-5) M, which is a concentration commonly found in the serum of patients receiving low-dose theophylline, inhibited degranulation by 43.8%. This finding indicates that theophylline and procaterol have synergistic effects. The inhibition was comparable to that with dexamethasone at 10(-9) M. Our results suggest that a combination of low-dose theophylline and procaterol exhibits antiinflammatory effects in asthma by inhibiting eosinophil-effector functions.

Bronchodilator Agents↗

[Field trial of combined measles and rubella live attenuated vaccine].

We investigated the antibody responses and clinical adverse reactions after immunization with live combined measles and rubella vaccine (HF vaccine) in 442 healthy children, aged 12-90 months of age. We obtained 368 paired sera. Among them, 363 were initially sero-negative against measles virus and 343 (94.5%) became sero-positive after immunization. Sero-conversion against rubella virus was demonstrated in 349 (96.7%) of 361 initially sero-negatives against rubella virus. We investigated the clinical adverse reactions in 406 recipients. In 102 (25.1%) recipients, febrile reaction (> 37.5 C) developed on the day 6.7 of vaccination on average, with a mean duration of 2.2 days. Only two (0.5%) developed high body temperature over 39.5 C. Skin rash was noted in 87 (21.4%) on day 7.1 of vaccination on average, with a mean duration of 4.8 days. Lymphoadenopathy was demonstrated in 12 (3.0%). Thus, measles and rubella combined vaccine was safe and sufficiently immunogenic as well as each monovalent one, having clinical advantage in immunization practice.

Antibodies, Viral↗

[Contamination of oyster sea farm with the Norwalk virus: mechanisms and control].

The Norwalk virus(NV) is widely known as a cause of nonbacterial food poisoning, infant diarrhea, and acute gastroenteritis in the winter months between November and March. While it is strongly suspected that NV that is excreted by humans flows into coastal seawaters via rivers and wastewater treatment facilities to contaminate oysters that are grown in farms in the area, light has yet to be shed on the behavior of this virus in the natural environment. We therefore conducted a polymerase chain reaction (PCR) survey of NV levels in the aquatic environment of the oyster bed area of the Shima region in Mie Prefecture, whereupon the NV was detected in marine sediment, oysters, and mule clams even during the summer months, when food poisoning is infrequent. In order to assess their similarity to human-derived strains, the detected viruses and their human-derived counterparts were subjected to genetic analysis, whereupon some of the detected viruses were found to be remarkably similar to those that were previously detected in humans infected with NV. In the interests of examining methods for decontaminating NV-contaminated oysters, we also conducted an assessment on a system of virus decontamination that focuses on seawater temperature and oyster metabolism, using Poliovirus Sabin strain. The decontamination system mentioned above was a closed loop, water circulating system, built on the same principles as those actually in use at oyster farms. Our experiment indicated that at seawater temperatures of both 10 degrees C and 20 degrees C, virus placed into the water tank was rapidly incorporated into the midgut glands of the oysters. Thereafter, when seawater irradiated with UV was circulated, the virus count in the oysters fell from 1/1,000 to 1/10,000 within 6 hours. These results indicated the utility of this system for virus decontamination, suggesting the possibility of significantly alleviating the risk of NV infection in humans by using this system to maintain the seawater temperature within the decontamination tank above a certain temperature, and to perform decontamination with an adequate water flow.

Animals↗

Human rotavirus subgroups and severity of associated diarrhoea in Ghana.

In a 12 month study of children with acute diarrhoea seeking medical care in 2 hospitals in Accra, Ghana, 16.3% were found to be infected with human rotaviruses (HRV). Vomiting and diarrhoea were the main symptoms observed. HRV infection was frequently associated with severe diarrhoea. Vomiting was however less frequent in HRV associated diarrhoea than in non HRV diarrhoea. No significant association was observed between the severity of dehydration and HRV infection. Subgroup II HRV was the predominant subgroup identified with the dominant serotypes being HRV serotypes 1 and 4. Poly-acrylamide gel electrophoresis of HRV RNAs isolated from 40 positive stool samples revealed the existence of 7 distinct electrophoretic migration patterns in the study population.

Journal Article↗

Plasma levels of Th1 and Th2 cytokines in Ghanaian children with vaccine-modified measles.

To understand the pathogenesis of vaccine-modified measles (VMM), we measured plasma levels of IFN-gamma and IL-2 (Th1 cytokines), IL-4 and IL-10 (Th2 cytokines), IL-12, TNF-alpha and TGF-beta1 in children with uncomplicated measles, who had anti-measles IgG antibodies and with a history of immunization on admission (day 0), day 14 and day 60. We compared these to levels in healthy, age-matched, immunized children. Plasma levels of IFN-gamma, IL-2 and IL-12 were significantly higher in VMM patients on day 0 compared to healthy controls (p = 0.023; p = 0.018; p = 0.001) respectively. In contrast, plasma IL-4 was lower in VMM patients on day 0 when compared to the controls (p = 0.009). Plasma levels of IL-12 remained consistently high on days 14 and 60 (p = 0.001; p = 0.04), whilst IL-10 levels fell significantly on the same days (p = 0.002; p = 0.001) respectively. Kinetically, IFN-gamma and IL-10 levels decreased consistently from day 0 to days 14 and 60 in VMM patients. In contrast, IL-4 levels increased from day 0 to day 14 and day 60. Our results therefore suggest that VMM is associated with an early up-regulation of Th1 cytokine production and a down-regulation of Th2 cytokine production. The strong Th1 response may be associated with the induction of IL-12 and memory cells, thus contributing to the early resolution of the infection and lack of complications.

Child↗