Ataxia-telangiectasia (A-T) is an autosomal recessive neurodegenerative disorder with multisystem involvement and cancer predisposition, caused by mutations in the A-T mutated (ATM) gene. To study genotype-phenotype correlations, we evaluated the clinical and laboratory data of 51 genetically proven A-T patients, and additionally measured ATM protein expression and kinase activity. Patients without ATM kinase activity showed the classical phenotype. The presence of ATM protein, correlated with slightly better immunological function. Residual kinase activity correlated with a milder and essentially different neurological phenotype, absence of telangiectasia, normal endocrine and pulmonary function, normal immunoglobulins, significantly lower X-ray hypersensitivity in lymphocytes, and extended lifespan. In these patients, cancer occurred later in life and generally consisted of solid instead of lymphoid malignancies. The genotypes of severely affected patients generally included truncating mutations resulting in total absence of ATM kinase activity, while patients with milder phenotypes harbored at least one missense or splice site mutation resulting in expression of ATM with some kinase activity. Overall, the phenotypic manifestations in A-T show a continuous spectrum from severe classical childhood-onset A-T to a relatively mild adult-onset disorder, depending on the presence of ATM protein and kinase activity. Each patient is left with a tremendously increased cancer risk.

Some of the genes for the variant surface glycoproteins of trypanosomes are located close to a discontinuity in the DNA, presumably a chromosome end. We show here that DNA fragments containing these telomeres increase in length in multiplying trypanosomes at a rate of about 10 base pairs per division. We argue that chromosome growth may not be restricted to trypanosomes and could explain the heterogeneity of telomeric DNA fragments observed in some other organisms.

The current volume of pediatric guidelines categorized as evidence based in popular databases is large. Overall, these guidelines scored well, compared with other studies on guideline quality in fields outside pediatrics, when assessed for quality with the AGREE instrument. This holds especially for guidelines published or endorsed by the American Academy of Pediatrics or registered in the National Guideline Clearinghouse.

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P‐glycoproteins can cause multidrug resistance in mammalian tumor cells by active extrusion of cytotoxic drugs. The natural function of these evolutionarily conserved, membrane‐bound ATP binding transport proteins is unknown. In mammals, P‐glycoproteins are abundantly present in organs associated with the digestive tract. We have studied the tissue‐specific expression of Caenorhabditis elegans P‐glycoprotein genes pgp‐1 and pgp‐3 by transformation of nematodes with pgp‐lacZ gene fusion constructs in which the promoter area of the pgp genes was fused to the coding region of lacZ. Expression of pgp‐1 and pgp‐3, as inferred from pgp‐lacZ transgenic nematodes, was confined to the intestinal cells. The expression patterns of both genes were virtually indistinguishable. Quantitative analysis of pgp mRNA levels during development showed that pgp‐1, −2, and −3 were expressed throughout the life cycle of C.elegans, albeit with some variation indicating developmental regulation. The expression of P‐glycoprotein genes in intestinal cells is an evolutionarily conserved feature of these genes, consistent with the hypothesis that P‐glycoproteins provide a mechanism of protection against environmental toxins.