Proximal femoral focal deficiency: radiologic analysis of 49 cases

Proximal femoral focal deficiency, an uncommon congenital anomaly, necessitates early radiologic classification for surgical planning and treatment. Objective radiographic criteria, including femoral length index, acetabular depth index, acetabular angle index, and shape of the proximal femur were determined in 49 patients before cartilaginous ossification of the femoral capital epiphysis; final classification was based on follow-up radiographs or findings at arthrography or surgery. These parameters were analyzed to determine the accuracy and contributions of each in classification. Correct classification into one of three groups was possible in 86% of cases with use of three of the parameters: femoral length index, acetabular depth index, and shape of the proximal femur. The acetabular angle was found to contribute insignificantly to classification. Magnetic resonance imaging, used in only one case, depicted the nonossified cartilaginous femoral capital epiphysis, thus obviating the need for invasive diagnostic procedures and facilitating early classification.     

Reporting bias and mode of interview in a study of adverse pregnancy outcomes and water consumption.

In an earlier publication, it was shown that consumption of tapwater during the first trimester of pregnancy was associated with a risk of spontaneous abortion among women who attended three prenatal clinics located in northern California between September 1981 and June 1982. Evidence for biased recall was presented. This report demonstrates that the association is limited to women interviewed by telephone and is not observed among those who completed a mail questionnaire. The possibility that the association among women interviewed by telephone is causal and that the lack of association among mail respondents is due to bias, confounding, or apparently chance fluctuations is shown to be unlikely. For instance, the probability is low that, among mail respondents, cases underreported exposure as compared with controls or that random errors were common enough to camouflage a true effect. Demographic differences between mail and telephone respondents also do not explain the results. Interviewers were, however, aware of the outcome of the pregnancy, suggesting that differential reporting of exposure may have been stimulated in the nonblind telephone interview. The pattern of heterogeneity between mail and telephone respondents was also observed for reportable anomalies and tapwater consumption. The data on heterogeneity support the previously published conclusion that differential reporting (biased recall) of this common exposure, tapwater consumption, is the likely explanation for its observed association with the risk of spontaneous abortion. That this association is limited to telephone respondents elucidates the mechanism that apparently produced the bias: that is, the medium of nonblind telephone interviews.     

Adherence of Salmonella typhimurium to Caco-2 cells: identification of a glycoconjugate receptor.

The mechanism by which Salmonella species adhere to the epithelium of the intestine is not well understood. To identify components on intestinal epithelial cells that may be involved in the initial adherence of Salmonella typhimurium, we correlated patterns of adherence to well-differentiated Caco-2BBe cell monolayers with expression of brush border membrane components and lectin binding sites. This cloned cell line shows heterogeneous expression of sucrase-isomaltase and most lectin receptors. S. typhimurium adhered to a subpopulation of living or formaldehyde-fixed cells with a high multiplicity (up to 150 bacteria per cell). Bacterial binding to selected cells was not correlated with expression of the brush border hydrolases dipeptidyl-peptidase IV and sucrase-isomaltase or with binding of 10 of the 12 lectins tested. However, binding was correlated with the presence of binding sites for peanut agglutinin (PNA) [specific for Gal beta (1-3) GalNAc] and soybean agglutinin (specific for terminal GalNAc). Preincubation of live and fixed Caco-2BBe monolayers with PNA inhibited bacterial binding, while preincubation with soybean agglutinin did not. Electron microscopic analysis demonstrated that the initial adherence of S. typhimurium to Caco-2 cells in vitro involved peripheral components of the glycocalyx on apical microvilli. These results suggest that a Gal beta (1-3)GalNAc epitope recognized by PNA and located in the glycocalyx is involved in the early recognition events between S. typhimurium and Caco-2 cells and that differences in glycosylation patterns among individual epithelial cells may be a determinant in cell-selective adherence of S. typhimurium.     

Life expectancy in British Marfan syndrome populations

A total of 206 patients with Marfan syndrome were ascertained throughout genetic clinics in Wales and Scotland during the period 1970–1990. There were 45 deaths representing 22% of the cohort. Mean age at death was 45.3 ± 16.5 years. 50% median cumulative survival in the total cohort (n = 206) was 53 years for males and 72 years for females. Multivariate analysis confirmed severity as the best independent indicator of survival. These findings and survival curves will assist in the counselling of British families and individuals with Marfan syndrome.     

Human MSH2 binds to trinucleotide repeat DNA structures associated with neurodegenerative diseases

The expansion of trinucleotide repeat sequences is associated with several neurodegenerative diseases. The mechanism of this expansion is unknown but may involve slipped-strand structures where adjacent rather than perfect complementary sequences of a trinucleotide repeat become paired. Here, we have studied the interaction of the human mismatch repair protein MSH2 with slipped-strand structures formed from a triplet repeat sequence in order to address the possible role of MSH2 in trinucleotide expansion. Genomic clones of the myotonic dystrophy locus containing disease-relevant lengths of (CTG)n x (CAG)n triplet repeats were examined. We have constructed two types of slipped-strand structures by annealing complementary strands of DNA containing: (i) equal numbers of trinucleotide repeats (homoduplex slipped structures or S-DNA) or (ii) different numbers of repeats (heteroduplex slipped intermediates or SI-DNA). SI-DNAs having an excess of either CTG or CAG repeats were structurally distinct and could be separated electrophoretically and studied individually. Using a band-shift assay, the MSH2 was shown to bind to both S-DNA and SI-DNA in a structure- specific manner. The affinity of MSH2 increased with the length of the repeat sequence. Furthermore, MSH2 bound preferentially to looped-out CAG repeat sequences, implicating a strand asymmetry in MSH2 recognition. Our results are consistent with the idea that MSH2 may participate in trinucleotide repeat expansion via its role in repair and/or recombination.