Interleukin-2 induced immune effects in human immunodeficiency virus-infected patients receiving intermittent interleukin-2 immunotherapy

To characterize the immunological effects of intermittent IL-2 therapy, which leads to selective increases in CD4+ T lymphocytes in HIV-infected patients, 11 patients underwent extensive immunological evaluation. While IL-2 induced changes in both CD4+ and CD8+ cell number acutely, only CD4+ cells showed sustained increases following discontinuation of IL-2. Transient increases in expression of the activation markers CD38 and HLA-DR were seen on both CD4+ and CD8+ cells, but CD25 (a chain of the IL-2 receptor) increased exclusively on CD4+ cells. This increase in CD25 expression was sustained for months following discontinuation of IL-2, and was seen in naive as well as memory cells. IL-2 induced cell proliferation, but tachyphylaxis to these proliferative effects developed after 1 week despite continued IL-2 administration. It thus appears that sustained CD25 expression selectively on CD4+ cells is a critical component of the immunological response to IL-2, and that intermittent administration of IL-2 is necessary to overcome the tachyphylaxis to IL-2-induced proliferation.     

Extensive transmission of Mycobacterium tuberculosis from a child

BACKGROUND AND METHODS: Young children rarely transmit tuberculosis. In July 1998, infectious tuberculosis was identified in a nine-year-old boy in North Dakota who was screened because extrapulmonary tuberculosis had been diagnosed in his female guardian. The child, who had come from the Republic of the Marshall Islands in 1996, had bilateral cavitary tuberculosis. Because he was the only known possible source for his female guardian's tuberculosis, an investigation of the child's contacts was undertaken. We identified family, school, day-care, and other social contacts and notified these people of their exposure. We asked the contacts to complete a questionnaire and performed tuberculin skin tests. RESULTS: Of the 276 contacts of the child whom we tested, 56 (20 percent) had a positive tuberculin skin test (induration of at least 10 mm), including 3 of the child's 4 household members, 16 of his 24 classroom contacts, 10 of 32 school-bus riders, and 9 of 61 day-care contacts. A total of 118 persons received preventive therapy, including 56 young children who were prescribed preventive therapy until skin tests performed at least 12 weeks after exposure were negative. The one additional case identified was in the twin brother of the nine-year-old patient. The twin was not considered infectious on the basis of a sputum smear that was negative on microscopical examination. CONCLUSIONS: This investigation showed that a young child can transmit Mycobacterium tuberculosis to a large number of contacts. Children with tuberculosis, especially cavitary or laryngeal tuberculosis, should be considered potentially infectious, and screening of their contacts for infection with M. tuberculosis or active tuberculosis may be required.     

Simple and efficient method for the detection of diethylenetriaminepentaacetic acid

Diethylenetriaminepentaacetic acid (DTPA) is a commonly used chelating agent. Its antiviral, antibacterial and immunomodulatory effects are well documented. DTPA forms a highly stable complex with lead (II) with an increased absorption coefficient and a bathochromic shift of the absorption maximum compared to pure DTPA. Based on this complex a high-performance liquid chromatographic method for the quantitative detection of DTPA in biological fluids was developed. A calibration curve was prepared and linearity was shown in the concentration range between 10 mg l(-1) and 1000 mg l(-1) DTPA. The recovery in water and in human plasma showed the method to be suitable for routine use.     

Trisomy 8 in primary esthesioneuroblastoma.

Esthesioneuroblastoma is a rare malignancy believed to be derived from neuroectodermal stem cells within the olfactory epithelium. We have obtained the karyotype of a primary esthesioneuroblastoma following brief (7-day) in vitro culture, and have determined that the only observable cytogenetic anomaly is the presence of an additional chromosome 8. Previously, the karyotypes of two cell lines established from metastatic esthesioneuroblastomas have been reported to contain the equivalent of three copies of chromosome 8, in addition to other chromosomal aberrations, including the reciprocal translocation, t(11;22)(q24;q12). Examination of the cytogenetic literature suggests that an extra copy of chromosome 8 is a common occurrence in undifferentiated small round cell tumors frequently observed to carry the t(11;22), including esthesioneuroblastoma, Ewing's sarcoma, peripheral neuroepithelioma, Askin's tumor, and rhabdomyosarcoma. These data, combined with our report of a small round cell tumor with the karyotype 47,XY, +8, indicate that trisomy 8 may be a common phenomenon in these tumors, and may also provide some sort of selective advantage to these tumor types.     

A murine TSPY

Sequences homologous to human and bovine TSPY were isolated from M. musculus testicular cDNA, and a nearly full-length gene was polymerase chain reaction (PCR) amplified from mouse genomic DNA. This gene is apparently non-functional. Contrary to the situation encountered in species along the primate and artiodactyl lineages, in which TSPY is moderately repetitive, murine Tspy appears to be single copy. Murine Tspy is located on Yp, i.e. in the same syntenic group as in man. Sequence comparisons of murine, human and bovine TSPY exons suggest that TSPY became non-functional during rodent evolution.     

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP)

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.      

Mikrokallusformationen der Spongiosa Ein bisher unterschätzter reparativer Mechanismus des Skelettsystems

Zusammenfassung Mikrokallusformationen lassen sich in nahezu allen Skelettabschnitten der Spongiosa nachweisen. Mikrokallus besteht aus Geflechtknochen, der sich an lokal überbelasteten Stellen in der Spongiosa bildet. Mit Hilfe einer speziellen Pr?parationstechnik wurden 26 skelettgesunde und 11 Wirbels?ulen von F?llen mit Osteoporose untersucht. Mikrokallusformationen finden sich bevorzugt bei Frauen ?lter als 45 Jahre in den unteren Wirbels?ulenabschnitten. Dabei hat die Mikroarchitektur der Spongiosa (TBPf) einen st?rkeren Einflu? auf die Anzahl der Mikrokalli, als individuelle Trabekelparameter (Tb.N, BV/TV und Tb.Th). Nur in 33 % der Formationen lassen sich Frakturspalten nachweisen. Mikrokallusformationen k?nnen nichtinvasive Knochenmassemessungen verf?lschen. Auch wenn Mikrokallusformationen Indikatoren für eine Instabilit?t der Spongiosa sind, tragen sie zur Knochenregeneration bei, und die Entstehung neuer Trabekel ist durch sie m?glich. Die Vorstellung, da? Osteoporose das Resultat einer verminderten Mikrokallusbildung ist, trifft nicht zu.