Application of genetic markers to the identification of recrudescent Plasmodium falciparum infections on the northwestern border of Thailand

PATIENTS AND METHODS: The role of cerebral magnetic resonance imaging (MRI) in the diagnosis of growth hormone (GH) deficiency in children has been studied in 100 children. The diagnosis of GH deficiency was assessed at a mean age of 6.7 +/- 4.1 years: morphological abnormalities of the hypothalamic-pituitary (HP) region have been studied in three different groups: in the first group (70 cases), the neurohypophysis was present and normally located; in the second group (ten cases) it was missing; in the third group (20 cases) the neurohypophysis was ectopic (truncated stalk syndrome with ectopic neurohypophysis, small antehypophysis, thin or non-visualized stalk). RESULTS: In the majority of cases, children presenting with only one morphological abnormality of the HP region (ectopic neurohypophysis or small antehypophysis or non-visualized or thin stalk) had an isolated GH deficiency. When multiple morphological abnormalities were present, anterior pituitary deficiency was multiple in more than half the cases. Cerebral midline anomalies (above all Chiari I malformation and basipharyngeal canal) had been observed in 20% of the children presenting with GH deficiency. In the majority of cases (95%), these anomalies were associated with one or more abnormalities of the HP region. A familial case is reported: morphological anomalies of the HP region were different for both siblings. Genetic factors are evoked. CONCLUSION: The severity of the hormone deficiency is correlated to the ectopic location of the neurohypophysis, the thin appearance or non visibility of the pituitary stalk and the associated midline anomalies.     

A porous silicon-based optical interferometric biosensor

A biosensor has been developed based on induced wavelength shifts in the Fabry-Perot fringes in the visible-light reflection spectrum of appropriately derivatized thin films of porous silicon semiconductors. Binding of molecules induced changes in the refractive index of the porous silicon. The validity and sensitivity of the system are demonstrated for small organic molecules (biotin and digoxigenin), 16-nucleotide DNA oligomers, and proteins (streptavidin and antibodies) at pico- and femtomolar analyte concentrations. The sensor is also highly effective for detecting single and multilayered molecular assemblies.     

Injury control in practice. Home radiator burns in inner-city children

OBJECTIVE: To describe thermal burns from radiators in the homes of children in the inner city and an intervention to decrease the risk for this pediatric injury. SETTING: Academic medical center in Chicago. PATIENTS: Case series of 10 radiator-related burns. RESULTS: The burns described were found to be clustered in an area of a public housing project served by steam radiators. No burns were associated with hot water radiators. Just 14% of housing units with young children had adequate radiator covers and radiator pipe insulation. Radiator covers and insulation have now been replaced or repaired in all units of the 11 housing project buildings served by steam radiators. CONCLUSIONS: Steam radiators in the home represent a particular childhood burn hazard. Community-based clinicians are in a unique position to recognize local patterns of injury and work with other agencies in injury control efforts.     

The number of glutamate transporter subtype molecules at glutamatergic synapses: chemical and stereological quantification in young adult rat brain

The role of transporters in shaping the glutamate concentration in the extracellular space after synaptic release is controversial because of their slow cycling and because diffusion alone gives a rapid removal. The transporter densities have been measured electrophysiologically, but these data are from immature brains and do not give precise information on the concentrations of the individual transporter subtypes. Here we show by quantitative immunoblotting that the numbers of the astroglial glutamate transporters GLAST (EAAT1) and GLT (EAAT2) are 3200 and 12,000 per micrometer3 tissue in the stratum radiatum of adult rat hippocampus (CA1) and 18,000 and 2800 in the cerebellar molecular layer, respectively. The total astroglial cell surface is 1.4 and 3.8 m2/cm3 in the two regions, respectively, implying average densities of GLAST and GLT molecules in the membranes around 2300 and 8500 micrometer-2 in the former and 4700 and 740 micrometer-2 in the latter region. The total concentration of glial glutamate transporters in both regions corresponds to three to five times the estimated number of glutamate molecules in one synaptic vesicle from each of all glutamatergic synapses. However, the role of glial glutamate transporters in limiting synaptic spillover is likely to vary between the two regions because of differences in the distribution of astroglia. Synapses are completely ensheathed and separated from each other by astroglia in the cerebellar molecular layer. In contrast, synapses in hippocampus (stratum radiatum) are only contacted by astroglia and are often found side by side without intervening glial processes.     

Expression of deletion-containing dystrophins in mdx muscle: implications for gene therapy and dystrophin function

The expression of full-length dystrophin and various dystrophin deletion mutants was monitored in mdx mouse muscle after intramuscular injection of dystrophin-encoding plasmid DNAs. Recombinant dystrophin proteins, including those lacking either the amino terminus, carboxyl terminus, or most of the central rod domain, showed localization to the plasma membrane. This suggests that there are multiple attachment sites for dystrophin to the plasma membrane. Only those constructs containing the carboxyl terminus were able to stabilize dystrophin-associated proteins (DAP) at the membrane, consistent with other studies that suggest that this domain is critical to DAP binding. Colocalization with DAP was not necessary for membrane localization of the various dystrophin molecules. However, stabilization and co-localization of the DAP did seem to be a prerequisite for expression and/or stabilization of mutant dystrophins beyond 1 wk and these same criteria seemed important for mitigating the histopathological consequences of dystrophin deficiency.     

Longitudinal studies of immune function in cattle experimentally infected with bovine immunodeficiency-like virus and/or bovine leukemia virus

The effects of single or dual infection with bovine immunodeficiency-like virus (BIV) and/or, bovine leukemia virus (BLV) on bovine immune function were examined over a 4 year period. Holstein calves were infected with BIV (four calves), BLV (five calves), BIV and BLV (five calves), or sham inoculated (three calves). Lymphocyte blastogenesis to mitogens, seven tests of neutrophil function, and mononuclear cell subset analysis by flow cytometry (BoCD4, BoCD8, BoCD2, BoWC1, sIgM+, and monocytes) were performed at regular intervals to 49 months post-infection. These data were analyzed for main effects of each virus and interaction as a 2 x 2 factorial. BIV infected cattle had lower neutrophil antibody-dependent cell-mediated cytotoxicity and iodination responses during 2 of the 4 years post-infection (P < 0.05). BIV infection was not associated with any long-term significant changes in lymphocyte blastogenesis to mitogens or changes in mononuclear cell subset numbers in blood. There was a tendency for animals infected with BIV alone to have decreased lymphocyte blastogenic responses to mitogens, but this was not statistically significant. BLV infection caused an increase in total mononuclear cells with no dramatic shift in the relative proportions of the various subsets. Co-infection with BIV and BLV did not consistently cause a different response than either virus did individually. One BIV infected animal died of non-BLV lymphosarcoma 7 months after infection. All other animals had no unusual clinical signs. In summary, infection with BIV caused a significant, temporary decrease in neutrophil function with no consistent statistically significant alteration in lymphocyte blastogenesis or mononuclear cell numbers during the first 4 years after infection. BLV infection caused an increase in lymphocyte numbers, and there appeared to be no synergism between the viruses.     

Cellular localization of the chemokine receptor CCR5. Correlation to cellular targets of HIV-1 infection

The chemokine receptor CCR5 has recently been described as a co-receptor for macrophage-tropic strains of human immunodeficiency virus (HIV)-1. In this study, using a panel of monoclonal antibodies specific for human CCR5, we show by immunohistochemistry and flow cytometry that CCR5 is expressed by bone-marrow-derived cells known to be targets for HIV-1 infection, including a subpopulation of lymphocytes and monocyte/macrophages in blood, primary and secondary lymphoid organs, and noninflamed tissues. In the central nervous system, CCR5 is expressed on neurons, astrocytes, and microglia. In other tissues, CCR5 is expressed on epithelium, endothelium, vascular smooth muscle, and fibroblasts. Chronically inflamed tissues contain an increased number of CCR5+ mononuclear cells, and the number of immunoreactive cells is directly associated with a histopathological correlate of inflammatory severity. Collectively, these results suggest that CCR5+ cells are recruited to inflammatory sites and, as such, may facilitate transmission of macrophage-tropic strains of HIV-1.     

Extent of radial sarcomere coupling revealed in passively stretched cardiac myocytes

We report a simple method, the PinPoint assay, for detecting and identifying single-base variations (polymorphisms) at specific locations within DNA sequences. An oligonucleotide primer is annealed to the target DNA immediately upstream of the polymorphic site and is extended by a single base in the presence of all four dideoxynucleotide triphosphates and a thermostable DNA polymerase. The extension products are desalted, concentrated, and subjected to delayed-extraction MALDI-TOF mass spectrometry. The base at the polymorphic site is identified by the mass added onto the primer. Heterozygous targets produce two mass-resolved species that represent the addition of both bases complementary to those at the polymorphic site. The assay is suitable for double-stranded PCR products without purification or strand separation. More than one primer can be simultaneously extended and then mass-analyzed. The mass spectrometric method thus shows promise for high-volume diagnostic or genotyping applications.     

Staphylococcal culture supernates stimulate human phagocytes

c-fos induction was investigated as a potential component in the avian photic entrainment pathway and as a possible means of locating the central pacemaker in birds. In both quail (Coturnix coturnix japonica) and starlings (Sturnus vulgaris) exposure to 1 h of light induced Fos-lir in the visual suprachiasmatic nucleus but not in the medial suprachiasmatic nucleus. However, the degree of c-fos induction in the visual suprachiasmatic nucleus was similar at different circadian times despite the fact that the light pulses caused differential phase shifts in the locomotor rhythm. For golden hamsters the same experiment resulted in significantly different levels of Fos-lir in the suprachiasmatic nucleus, as well as different phase shifts. Starlings and hamsters were also entrained to T-cycles that caused a large daily phase shift (T = 21.5 h in starlings, T = 22.67 hours in hamsters), or no daily phase shift (T = free running period). No difference in the induced levels of Fos-lir in the visual suprachiasmatic nucleus region was observed between the two groups of starlings, but in hamsters there were significantly different levels of Fos-lir in the suprachiasmatic nucleus between the two groups.