Takao Samukawa

Immune responses to specific antigens of Streptococcus pneumoniae and Moraxella catarrhalis in the respiratory tract.

ABSTRACT Streptococcus pneumoniae and Moraxella catarrhalis are two common respiratory pathogens, colonizing as many as 54 and 72% of children, respectively, by 1 year of age. The immune responses to surface protein A of S. pneumoniae(PspA) and the high-molecular-weight outer membrane protein of M. catarrhalis (UspA) in the sera of various age groups in the general population and in the nasopharynges of 30 children monitored from birth through 1 year of age were evaluated. Immunoglobulin G (IgG) was the dominant serum antibody to PspA and UspA. Whereas the serum antibody response to PspA peaked in childhood, the antibody response to UspA peaked in adulthood. In the first 2 years of life, comparable amounts of IgM and IgG antibodies to both proteins were observed. In older persons, IgG antibodies to both antigens predominated over IgM antibodies. The levels of IgA antibody to these antigens in serum remained low during the first 2 years of life. The levels of IgM antibody to the two antigens in serum exceeded the levels of IgA antibody to the same two antigens throughout life. Although IgA was the dominant antibody to PspA and UspA in airway secretions, it was detected in a minority of the children (3 of 15 for PspA and 0 of 15 for UspA). Even the majority of the children previously colonized with these pathogens lacked antibody to them in their secretions.

Treatment and outcome of severe and non-severe acute otitis media

To determine outcomes in acute otitis media (AOM) according to severity of disease and to assess different initial treatment regimens, 308 with AOM were enrolled and divided into severe ( n =277; 89.9%) and non-severe ( n =31; 10.1%) groups based on symptoms and tympanic membrane changes. Children in the severe group were initially managed with amoxicillin (AMPC) whereas children in the non-severe group were initially managed without antibiotics. Children were monitored on days 1, 5, 10, 14 and 28. Five outcome measures were assessed: disappearance of symptoms at day 5, resolution of tympanic membrane changes by day 28, disappearance of middle ear effusions by day 28, recurrence of acute symptoms prior to day 28, and need to change treatment regimens. Children with severe disease were more often male (57% versus 36%, P <0.05) and more often colonized with pathogens (77% versus 55%, P <0.05 than children with non-severe disease. The two groups were similar with respect to age and day care attendance. Despite differences in initial treatment regimens between the two groups, symptoms improved at the same rate for severe and non-severe disease, 94% by day 5. In contrast, tympanic membranes returned to normal in 69% of the severe and 81% of the non-severe groups by day 28; however, as early as day 5, 10% of the severe and 55% of the non-severe groups demonstrated normal tympanic membranes. Middle ear effusions similarly disappeared more slowly in the severe group, 52% versus 74% by day 14 and 76% versus 84% by day 28. Recurrence rates of acute symptoms occurred with equal frequency in the severe, 15%, and non-severe groups, 10%. Failure of the symptoms or the tympanic membranes to improve led to antibiotic changes in 59.9% of the severe group and to the addition of antibiotics in 51.6% of the non-severe group. Children in the severe group who failed to improve with an initial course of amoxicillin were younger (40.2 months versus 45.8 months, P <0.05), had higher tympanic membrane scores (4.5 versus 4.1, P <0.05), and were more often colonized with penicillin-resistant Streptococcus pneumoniae (33.8% versus 6.5%, P <0.01) than children who responded to AMPC. In a similar manner, children with non-severe disease who failed to improve without antibiotics were younger (40.7 months versus 54.8 months, P <0.05) and more often colonized with pathogens (75.0% versus 33.4%, P <0.05). Conclusion:Severe disease occurred more often among males and among children colonized with pathogens. Response to treatment was impaired in younger children and in children colonized with pathogens, especially penicillin-resistant Streptococcus pneumoniae.

Interleukin-8 in Otitis Media with Effusion

Interleukin-8 induces chemotaxis of neutrophils, basophils and T-lymphocytes, releases intracellular enzymes from neutrophils and histamine from basophils, and regulates the adhesion of neutrophils. In this study, using an enzyme-linked immunosorbent assay, we evaluated 33 middle ear effusions (MEEs) for levels of IL-8. The mean level of IL-8 in MEEs from children with OME was 616.7 +/- 211.0 pg/mgTP, while that of adults was 197.4 +/- 66.7 pg/mgTP. With respect to MEE types, the mean level of IL-8 in serous effusion was lower than that in two other types of MEEs (mucoserous and serous). These results suggest that inflammatory reaction in the middle ear cavity of children with OME is different from that of adults and that the pathogenesis of OME in children may differ from that in adults. Determination of IL-8 concentration in MEEs may help to illuminate the pathogenesis of OME.

Immune Response to Surface Protein A of Streptococcus pneumoniae and to High—Molecular-Weight Outer Membrane Protein A of Moraxella catarrhalis in Children with Acute Otitis Media

The immune response was evaluated in 11 children with Streptococcus pneumoniae and in 9 children with Moraxella catarrhalis otitis media. The age of the children had a range of 4-32 months. The mean IgG, IgM, and IgA antibody responses to surface protein A (PspA) of S. pneumoniae in sera from children at the acute and convalescent stages were 4864 versus 5831 ng/mL, P<.05, 1075 versus 3752 ng/mL, P<.05, and 67 versus 93 ng/mL, nonsignificant (NS), respectively. The mean IgG, IgM, and IgA antibody responses to the high-molecular-weight outer membrane protein (UspA) of M. catarrhalis in sera from children at acute and convalescent stages were 710 versus 935 mg/mL, NS; 1895 versus 2646 ng/mL, NS; and 121 versus 204 ng/mL, P<.05, respectively. These data show that PspA and UspA are immunogenic in children after otitis media.

Analysis of Viral Infection in Patients with IgA Nephropathy

We investigated viral infections in the tonsils, pharynx and renal tissues of patients with IgA nephropathy using cell culture, polymerase chain reaction (PCR) and immuno-fluorescent techniques, and measured antibody titers against numerous types of viruses. Neutralization tests found no significant inhibition of growth of adenovirus-1, 2, 3, 4, 5, 6, 7, 11 or 19, Coxsackie virus-A7, A9, A16, B1, B2, B3, B4, B5 or B6, or RS virus. Swabs of the oral cavity of patients with IgA nephropathy were cultured with Hel cells, MDCK cells, FL cells, BHK-21 cells and RD-18S cells. No cytopathic effect was detected in any of these cell cultures. We failed to detect the presence of herpes simplex virus-1 and -2, varicella-zoster virus, cytomegalovirus and Epstein-Barr virus (EBV)-1 and -2 in tonsils, renal tissues and mouthwashings from patients with IgA nephropathy. On the other hand, EBV alone was detected with the PCR technique, in mouthwashings from 6 out of 14 patients with IgA nephropathy (42%). Immunohistological and serological analyses were done to examine the relationship between EBV and IgA nephropathy. No evidence was obtained that EBV-infected B lymphocytes were producing IgA. It seems unlikely that the viral infections examined in this study play a significant role in the pathogenesis of IgA nephropathy.

Clarithromycin(CAM) Treatment for Chronic Sinusitis and Change in the Bacterial Flora.

Sixteen children with severe chronic sinusitis were treated with the low-dose long-term clarithromycin (CAM) administration. Patients showed marked improvement in the following symptoms; 66.7% for mucosal swelling, 60.0% for volume of rhinorrhea, 60.0% for quality of rhinorrhea and 73.3% for postnasal drip.Bacterial examinations were also performed before and after treatment. The incidence of H. influenzae was lower during the CAM therapy than erythromycin (EM) therapy, but the ratio of CAMresistant bacteria increased after treatment.

Treatment of Tinnitus with LipoPGE1.

Severe tinnitus in 32 patients wtih senile deafness was treated with Lipoprostaglandin E1 10μg i. v. once a week. The tinnitus score was significantly decreased from 10 to 3.9±2.4. Slight to marked improvement was recorded in 90.6% of the patients. Early treatment, within 4 weeks of the onset of tinnitus, was more effective than later treatment. There were 4 patterns of improvement. No severe side effect was observed.The results of this study suggest that Lipoprostaglandin E1 is very useful in the treatment of tinnitus.