Interpreting the correlation coefficient when one of the variables is discrete

The effect on the correlation coefficient of discretizing data was investigated in two ways. First, the theoretical effect of dichotomizing data was calculated, and it was shown that the resulting correlation coefficient is considerably less than that between the underlying bivariate normally distributed variables. Second, computer simulations were performed of a model in which a continuous variable (measured with some error) gives rise to a counting variable through a mechanism in which the count is zero below a certain threshold value for the continuous variable and then increases linearly as the continuous variable increases. It was shown that the correlation coefficient between the observed values of the continuous and counting variables decreased as (a) the measurement error increased, (b) the slope of the relationship decreased, and (c) the number of counts decreased. It is concluded that caution is required when interpreting correlation coefficients when one or both of the variables consist of a few (say only four or five) discrete scores.     

Growth factor responsiveness of human retinal pigment epithelial cells

Growth factor effects on DNA synthesis in density-arrested human retinal pigment epithelial cells were assessed by [3H]-thymidine incorporation. Acidic and basic fibroblast growth factor and epidermal growth factor were potent stimulators, whereas platelet-derived growth factor, insulinlike growth factor-1, and insulin were weak or modest stimulators when used alone. When used in combination, each of the above growth factors caused a significant enhancement of [3H]-thymidine incorporation regardless of its effect when used alone. The combination of all four growth factors was significantly more effective than all other combinations, demonstrating synergism in their action. Similar results were found in cell proliferation assays. In contrast to this, transforming growth factor-beta inhibited the ability of each of the other growth factors and serum-containing media to stimulate [3H]-thymidine incorporation. These data suggest that DNA synthesis in human retinal pigment epithelial cells can be modulated by several growth factors, some in a stimulatory or synergistic manner and at least one in an inhibitory manner. A better understanding of these complex interactions may provide insights relevant to normal and abnormal ocular wound healing.     

Psychological Disturbance and its Associations in the Children of the Gujarati Community

The infrequent referral of Asian children to child psychiatry clinics was noted. By administering Rutter's scale A2 to samples of Gujarati and English parents with children between the ages of 4 and 7 years a lower rate of disturbance was demonstrated among the Asian sample providing an explanation for the original observation. Family and child-rearing factors associated with disturbance were identified.     

Comparative performance of three viral load assays on human immunodeficiency virus type 1 (HIV-1) isolates representing group M (subtypes A to G) and group O: LCx HIV RNA quantitative, AMPLICOR HIV-1 MONITOR version 1.5, and Quantiplex HIV-1 RNA version 3.0

The performance of the LCx HIV RNA Quantitative (LCx HIV), AMPLICOR HIV-1 MONITOR version 1.5 (MONITOR v1.5), and Quantiplex HIV-1 RNA version 3.0 (bDNA v3.0) viral load assays was evaluated with 39 viral isolates (3 A, 7 B, 6 C, 4 D, 8 E, 4 F, 1 G, 4 mosaic, and 2 group O). Quantitation across the assay dynamic ranges was assessed using serial fivefold dilutions of the viruses. In addition, sequences of gag-encoded p24 (gag p24), pol-encoded integrase, and env-encoded gp41 were analyzed to assign group and subtype and to assess nucleotide mismatches at primer and probe binding sites. For group M isolates, quantification was highly correlated among all three assays. In contrast, only the LCx HIV assay reliably quantified group O isolates. The bDNA v3.0 assay detected but consistently underquantified group O viruses, whereas the MONITOR v1.5 test failed to detect group O viruses. Analysis of target regions revealed fewer primer or probe mismatches in the LCx HIV assay than in the MONITOR v1.5 test. Consistent with the high level of nucleotide conservation is the ability of the LCx HIV assay to quantify efficiently human immunodeficiency virus type 1 group M and the genetically diverse group O.     

A galE via (Vi antigen-negative) mutant of Salmonella typhi Ty2 retains virulence in humans.

We have recently described the construction of a galE derivative of Salmonella typhi Ty2 (Ty2H1) which had a 0.4-kilobase deletion in the galE gene and was sensitive to galactose-induced lysis when cultured with greater than or equal to 0.06 mM galactose (D. M. Hone, R. Morona, S. Attridge, and J. Hackett, J. Infect. Dis. 156:167-174, 1987). We now report the selection of a rifampin-resistant, via derivative of Ty2H1, EX462. Compared with the Ty2 parent strain, EX462 was serum sensitive and highly attenuated in the mouse mucin virulence assay. When four human volunteers ingested 7 X 10(8) viable EX462, two became ill and developed a typhoidlike disease with fever and bacteremia. Blood isolates from these individuals were indistinguishable from the vaccine strain by a variety of criteria. We concluded that, even in a via background, the galE mutation was not attenuating for S. typhi in humans.     

The shufflon of Salmonella enterica serovar Typhi regulates type IVB pilus-mediated bacterial self-association

Previously, it was shown that type IVB pili encoded by the Salmonella enterica serovar Typhi pil operon are used to facilitate bacterial entry into human intestinal epithelial cells in vitro and that such entry is inhibited by purified prepilin (pre-PilS) protein (X.-L. Zhang, I. S. M. Tsui, C. M. C. Yip, A. W. Y. Fung, D. K.-H. Wong, X. Dai, Y. Yang, J. Hackett, and C. Morris, Infect. Immun. 68:3067-3073, 2000). The pil operon concludes with a simple shufflon, and a recombinase gene product (Rci) inverts DNA in the C-terminal region of the pilV gene to allow synthesis of two distinct PilV proteins, PilV1 and PilV2, which are presumptive minor pilus proteins. We show here that the type IVB pili mediate bacterial self-association, but only when the PilV1 and PilV2 proteins are not expressed. This may be achieved in wild-type serovar Typhi by rapid DNA inversion activity of the shufflon. We show that the inversion activity inhibits the expression of genes inserted between the 19-bp inverted repeats used for Rci-mediated recombination and that the activity of Rci increases when DNA is supercoiled. The data suggest that serovar Typhi self-associates under conditions (such as low oxygen tension in the gut) that favor DNA supercoiling. These results explain (i) the function of the serovar Typhi shufflon and (ii) why there are only two possible shufflon states, in contrast to the many possible states of other shufflon systems. The data further indicate that a very early step in serovar Typhi pathogenesis may be type IVB pilus-mediated self-association of bacteria in the anaerobic human small intestine prior to invasion of the human gut epithelium. The suggested type IVB pilus-dependent step in typhoid fever pathogenesis may partially explain the enhanced invasiveness of serovar Typhi for humans.     

Expression of VE-cadherin in zebrafish embryos: a new tool to evaluate vascular development.

We have identified the zebrafish homologue of VE-cadherin and documented its expression in the developing vascular system. The zebrafish VE-cadherin gene is specifically expressed in the vascular endothelial cell lineage beginning with the differentiation and migration of angioblasts and persists throughout vasculogenesis, angiogenesis, and endocardium development. Staining zebrafish embryos by whole-mount in situ hybridization with the VE-cadherin probe provides a method to screen embryos for vascular defects. To illustrate this utility, we used VE-cadherin expression to demonstrate a conservation of vascular endothelial growth factor-A (VEGF-A) function. The morpholino antisense oligonucleotide knockdown of VEGF-A function in zebrafish embryos results in a loss of angiogenic blood vessels, as indicated by the lack of VE-cadherin expression in the intersegmental vasculature. This loss can be restored in embryos supplemented with either zebrafish or human VEGF-A, the latter indicating that genes crucial to angiogenesis have highly conserved functional activities in vertebrates.