Chemokine receptors: structure, function and role in microbial pathogenesis

The chemokine superfamily is composed of at least 20 different leukocyte chemoattractants that act by binding to a family of G protein-coupled receptors. Leukocyte subtypes respond preferentially to unique but overlapping subsets of chemokines as determined by the receptor distribution, yet the receptors appear to signal through a common Gi-type G protein. Since chemokines appear to play major roles in inflammatory pathology, their receptors may be good targets for developing leukocyte selective anti-inflammatory drugs. Two chemokine receptors, CC CKRS and ONCC, function pathologically as cell entry factors respectively for human immunodeficiency virus 1, the cause of AIDS, and Plasmodium vivax, the major cause of malaria.     

Prenatal cocaine delays astroglial maturation: immunodensitometry shows increased markers of immaturity (vimentin and GAP-43) and decreased proliferation and production of the growth factor S-100

Exposure to cocaine during fetal development has been demonstrated to produce a variety of brain and behavioral changes. Cocaine is a potent releaser of a variety of neurotransmitters, such as serotonin, which act as developmental signals. Since serotonin plays an important role in astroglial maturation, migration, and growth factor production (e.g. S-100 beta), we proposed that these properties of astroglial cells will be altered in a brain prenatally exposed to cocaine. To observe cocaine's effects on astroglial development, we performed immunocytochemical analyses of a variety of developmental protein makers including BrdU, Gap-43, vimentin, and S100 beta. Our results demonstrate that prenatal cocaine administration produces decreased cell proliferation as measured by BrdU staining, retarded neurite outgrowth as ascertained by increased Gap-43 immunoreactivity, increased density of vimentin-positive radial glial cells, and diminished tissue S100 beta immunoreactivity. Overall, these results suggest that cocaine delays astroglial development. This delay would have profound effects on neuronal development and outgrowth and, thus, development of the entire brain.     

Transconductance and mobility of Si:B delta MOSFETs

Delta-doped MOSFETs have been fabricated in MBE-grown silicon using for the first time boron as the dopant within the delta layer. Current-voltage characteristics have been measured, and secondary ion mass spectrometry (SIMS) is used to confirm the location of the delta layer and the extent of layer broadening by diffusion during processing. Precise threshold voltages of the devices are difficult to determine since the devices (which all operate in depletion mode) take several volts to switch off. Transconductances of the devices have been measured, and it is shown how analysis of these results can yield estimates of the carrier mobility for transport along the delta layers despite the uncertainty in the threshold voltage. A clear transition is observed in the results which is attributed to the formation of a parasitic surface-channel field-effect transistor, providing conclusive evidence that the devices are conducting along a delta channel for part of the measured range of applied gate biases     

Computerized determination of proliferating cell nuclear antigen expression in meningiomas. A comparison with non-automated method

Proliferating cell nuclear antigen (PCNA) expression has been proven to be a significant marker of cell proliferation in meningiomas, which correlates with growth rate and, as shown by several authors, possibly provides prognostic information concerning biologic behavior. However, the current method for determining PCNA labeling index (LI) is tedious and time consuming like all the nonautomated methods for evaluating cell kinetics, presenting high interobserver and interlaboratory variability and low reproducibility. In the present study, we introduce a semi-automated computer-assisted image analysis method for determining PCNA LI in 38 meningiomas, in parallel with the current nonautomated method. Image analysis technique permits unbiased cell counting, standardizes the degree of staining intensity and provides instant results. By calculating coefficient of variability, the method proved to be highly reproducible. The correlation between the results provided by the nonautomated and the semiautomated image analysis method showed a high agreement between them, with a correlation coefficient, r, of 0.82. In conclusion, we consider that image analysis contributes to the accuracy, reproducibility, and practicality of PCNA LI determination so that along with other useful parameters this significant marker may serve to predict the clinical behavior in meningiomas.     

Epitope cleavage by Leishmania endopeptidase(s) limits the efficiency of the exogenous pathway of major histocompatibility complex class I-associated antigen presentation

The activation of CD8+ T cell responses is commonplace during infection with a number of nonviral pathogens. Consequently, there has been much interest in the pathways of presentation of such exogenous antigens for major histocompatibility complex class I-restricted recognition. We had previously shown that Leishmania promastigotes transfected with the ovalbumin (OVA) gene could efficiently target OVA to the parasitophorous vacuole (PV), with subsequent recognition by class II-restricted T cells. We now report the results of studies aimed at evaluating the PV as a route of entry into the exogenous class I pathway. Bone marrow-derived macrophages can present soluble OVA (albeit at high concentrations) to the OVA(257-264)-specific T cell hybridoma 13.13. In contrast, infection with OVA-transfected Leishmania promastigotes failed to result in the stimulation of this hybridoma. This appeared unrelated to variables such as antigen concentration, parasite survival, and macrophage activation status. These results prompted an analysis of the effects of promastigotes on class I peptide binding using RMA-S cells and OVA(257-264). Our data indicate that the major surface protease of Leishmania, gp63, inhibits this interaction by virtue of its endopeptidase activity against the OVA(257-264) peptide. The data suggest that this activity, if maintained within the PV, would result in loss of the OVA(257-264) epitope. Although we can therefore draw no conclusions from these studies regarding the efficiency of the PV as a site of entry of antigen into the exogenous class I pathway, we have identified a further means by which parasites may manipulate the immune repertoire of their host.     

Mal de Meleda: a report of four cases from the United Arab Emirates

Scanning electron microscopy was used to study the effect of cyclophosphamide (Cy) on molar development in 18 Sprague-Dawley rats from 15 to 48 days of age after birth. Doses of 30 mg/kg body weight of Cy dissolved in 1 ml 0.9% NaCl were given to the rats at 10 and 13 days of age. Eighteen control rats had injections of 1 ml 0.9% NaCl at the same ages. The most obvious changes in the experimental teeth were found in the developing roots of the first and second molars and in both the crown and roots of the third molar. The roots of the first and second molars were short and showed apical closure in the experimental rats. In addition to the disturbances in crown and root formation, the third molars were also significantly reduced in total size as compared with the third molars in the control rats.     

Antiserum against Escherichia coli J5 contains antibodies reactive with outer membrane proteins of heterologous gram-negative bacteria

The binding of IgG in antiserum to Escherichia coli J5 to the surface of Enterobacteriaceae and to cell wall fragments released from serum-exposed bacteria was studied in a search for potentially protective epitopes other than lipopolysaccharide (LPS). IgG titers to multiple heterologous gram-negative smooth bacteria increased following incubation of the bacteria in serum and decreased following absorption with serum-exposed heterologous bacteria. IgG eluted from absorbing bacteria bound to at least three conserved bacterial outer membrane proteins (OMPs), but not LPS, as assessed by immunoblotting. The same OMPs were present in LPS-containing macromolecular cell wall fragments released by incubation of heterologous gram-negative bacteria in human serum. Part of the protection offered by J5 antiserum could be from binding of IgG to conserved OMPs at the bacterial surface or to OMPs in cell-wall fragments released from dying bacteria.     

Amitriptyline in the treatment of interstitial cystitis

Limited data and an accumulated body of anecdotal experience with the tricyclic class of antidepressants suggest that this group of drugs (especially amitriptyline) may be an effective treatment modality in nonulcerative interstitial cystitis. Both the ease of administration and the relatively rapid onset of relief make these types of drugs appropriate to consider for first-line therapy after bladder distention has failed.