Genetic defect in human X-linked agammaglobulinemia impedes a maturational evolution of pro-B cells into a later stage of pre-B cells in the B-cell differentiation pathway.

Surrogate light chains (lambda 5/VpreB) are selectively expressed in early precursors of B cells. B-cell defects in X-linked agammaglobulinemia (XLA) are caused by mutations in the gene for Bruton's tyrosine kinase. To elucidate the nature of early B-lineage cells in bone marrow (BM), samples from 13 XLA patients and 24 healthy controls of different ages were comparatively analyzed using an antihuman VpreB monoclonal antibody. Expression of surrogate light (SL) and mu-heavy chains were examined after cell membrane permeabilization because they are mainly expressed in the cytoplasm of early B-lineage cells. A flow cytometric analysis of normal BM identified 5 discrete cell types of B cells: mu(-)SL(++) (pro-B [B-cell progenitor]), mu(low)SL(++) (pre-B1a), mu(low)SL(+) (pre-B1b), mu(low)SL(- )(pre-B2), and mu(high)SL(- )(B). The large cells, presumably in cycling states, were enriched in pre-B1a cells. The frequencies of B-lineage cells in BM were higher in young children, and declined with advancing age. In contrast, XLA showed a profound reduction in BM B-lineage cells. In XLA BM, an expansion of pro-B cells with some small pre-B1a cells was marked, but other cells were negligible. These observations illustrate a B-cell maturation defect in XLA as well as a normal human B-cell differentiation pathway. The results suggest that the genetic defect in XLA may impede the evolution of pro-B cells beyond the earlier pre-B stage into the later stage of pre-B cells in B-cell development. (Blood. 2000;96:610-617)

Therapeutic effect of clarithromycin for respiratory-tract infections in children caused by Chlamydia pneumoniae. Research Group of Sapporo for Pediatric Chlamydial Infections.

Children infected with Chlamydia pneumoniae sometimes experience lower respiratory tract infections such as pneumonia and bronchitis. Although numerous anti-microbial compounds have been reported to be active against the organism, most of them have not been in a clinical trial in infants and children with C. pneumoniae infection. Clarithromycin has been shown to express anti-chlamydial effects in vitro. In this study, we evaluated the clinical anti-C. pneumoniae properties of clarithromycin in children with mainly lower respiratory tract infection. We administered clarithromycin orally to 21 infants and children at a dose of 10-15 mg/kg/day divided into two or three doses for 4-21 days. Clinical symptoms, roentgenographic and laboratory abnormal findings improved. The overall clinical efficacy rate was 85.7% (18 of 21 cases). Administration of clarithromycin was considered to be a suitable treatment for improving lower respiratory infections in infants and children caused by C. pneumoniae.

Reduced passive measles immunity in infants of mothers who have not been exposed to measles outbreaks.

Natural measles infection usually confers life-long immunity which is transferred from mothers to their offspring, protecting them from natural measles until the age of about 12 months. Recently, however, natural measles has been observed with increased frequency in infants under the age of 12 months. Natural measles outbreaks in the city of Sapporo have been suppressed by widely applied measles vaccination. Passive measles immunity in 160 neonates (cord blood), born during the last 17 y in Sapporo, Japan was determined by a neutralization (NT) antibody test. The mothers of these infants had had natural measles infection during childhood. Geometric mean titres (GMTs) of cord blood NT antibodies gradually decreased after 1989 and the GMTs of the most recently born infants were significantly lower than those of infants born in the first few years of the study. These observations suggest that even in mothers who experienced natural measles in childhood, recurrent exposure to natural measles is necessary in order to maintain adequate antibody levels for effective passive immunity of their infants.

Immunochromatography test for rapid diagnosis of adenovirus respiratory tract infections: comparison with virus isolation in tissue culture.

The sensitivity and the specificity of a new commercial rapid 10-min adenovirus antigen immunochromatography (IC) test were determined by comparison with the sensitivity and specificity of virus isolation. Of 169 pharyngeal swabs from children with suspected adenovirus respiratory tract infections, 95 (56%) were culture positive for adenovirus. The IC test was sensitive (detecting 69 of these 95 infections [72.6%]) and completely specific (identifying 74 of 74 specimens [100%]) when it was compared with cell culture. The test detected adenovirus serotypes 1, 2, 3, 5, and 7 with almost equal sensitivities. This test is not only rapid and easy to perform but also sensitive and specific for adenovirus respiratory tract infections. The test is sufficiently rapid to be used at the bedside or in an outpatient clinic, with the result being available during a patient's first examination.

Cytotoxicities of sodium benzoate in primary culture of hepatocytes from adult rat liver.

The cytotoxicities of sodium benzoate was studied using primary culture of hepatocytes established from adult rat liver by a collagenase perfusion technique and maintained as a monolayer in serum-free culture medium. The activities of ornithine transcarbamylase (as a marker of mitochondria) and tyrosine aminotransferase (as a marker of cytosol) were clearly suppressed by sodium benzoate at concentration in excess of 500 micrograms/ml. Intracellular protein synthesis and DNA synthesis were also suppressed, and the suppression of DNA synthesis was observed even with a lower concentration of benzoate (100 micrograms/ml).