Topographical organization in the early postnatal corticopontine projection: a carbocyanine dye and 3-D computer reconstruction study in the rat

We have explored basic rules guiding the early development of topographically organized projections, employing the rat corticopontine projection as a model system. Using anterograde in vivo tracing with 1,1',dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI), we studied the distribution of labelled fibers in the pontine nuclei in relation to cortical site of origin during the first postnatal week. Labelled corticopontine fibers enter the pontine nuclei in distinct, sharply defined zones. The putative terminal fibers typically occupy lamella-like subspaces. Related to changes in cortical site of origin, we describe mediolateral, internal to external, and caudorostral distribution gradients in the pontine nuclei. Fibers originating in the anterolateral cortex occupy an internal central core, while implantations at increasing distance from the anterolateral cortex produce 1) more externally located lamellae, and 2) a caudal to rostral shift in fiber location. Previous investigations have shown that pontocerebellar neurons migrate into the ventral pons in a temporal sequence (Altman and Bayer [1987] J. Comp. Neurol. 257:529). The earliest arriving neurons occupy the central core and later arriving neurons settle in more externally and rostrally located subspaces. We hypothesize that the earliest arriving corticopontine fibers grow into the then only available zone of pontocerebellar neurons (central core), attracted by a diffusible chemotropic cue. Later arriving fibers grow into correspondingly later and more externally and rostrally located contingents of pontocerebellar neurons. Thus, we propose that the topographical organization in the early postnatal corticopontine projection is determined by simple temporal and spatial gradients operative within source (cerebral cortex) and target region (pontine nuclei).     

The validity of two versions of the GHQ in the WHO study of mental illness in general health care

BACKGROUND: In recent years the 12-item General Health Questionnaire (GHQ-12) has been extensively used as a short screening instrument, producing results that are comparable to longer versions of the GHQ. METHODS: The validity of the GHQ-12 was compared with the GHQ-28 in a World Health organization study of psychological disorders in general health care. Results are presented for 5438 patients interviewed in 15 centres using the primary care version of the Composite International Diagnostic Instrument, or CIDI-PC. RESULTS: Results were uniformly good, with the average area under the ROC curve 88, range from 83 to 95. Minor variations in the criteria used for defining a case made little difference to the validity of the GHQ, and complex scoring methods offered no advantages over simpler ones. The GHQ was translated into 10 other languages for the purposes of this study, and validity coefficients were almost as high as in the original language. There was no tendency for the GHQ to work less efficiently in developing countries. Finally gender, age and educational level are shown to have no significant effect on the validity of the GHQ. CONCLUSIONS: If investigators wish to use a screening instrument as a case detector, the shorter GHQ is remarkably robust and works as well as the longer instrument. The latter should only be preferred if there is an interest in the scaled scores provided in addition to the total score.     

Prevalence of obesity

Numerical values for prevalence of obesity are highly dependent on the criteria used to identify the condition and its gradations of severity. Prevalence is also affected by the makeup of the surveyed population. Recently, national surveys of prevalence of obesity in the United States and some European countries have been reported in terms of criteria that permit direct comparison of the findings. When the prevalence of a body mass index is 30 kg/m2 or more in US adults is compared with findings in adults in the United Kingdom, France, the Netherlands, and Italy, the differences are striking, with prevalence ratios ranging from approximately 1.5 (US versus UK) to 3.0 (US versus France).     

Staphylococcus aureus nasal colonization in HIV-seropositive and HIV-seronegative drug users

Five cases of adenoid basal carcinoma (ABC) of the uterine cervix were examined for the presence of p53 tumor suppressor gene, K-ras-2 oncogene, and human papillomavirus (HPV). A topographic genotyping approach was used to search for point mutations in K-ras-2 (exon 1 and 2) and p53 (exons 5 to 8) in archival formalin-fixed tissue blocks. Minute target sites were selected from polymerase chain reaction (PCR) amplified and directly sequenced tissue sections. Tissue sections were additionally subjected to immunohistochemical staining for p53 and WAF-1 protein. Because wild type p53 induces WAF-1 gene expression, immunohistochemical staining for WAF-1 protein using monoclonal antibodies may serve as an indirect means to test for p53 mutational damage. Mutational genotype was compared to histopathologic features and immunohistochemical staining. To study the role of HPV, L1 region consensus primers were used to amplify topographic samples, followed by HPV genotyping by direct sequencing and comparison to known viral strains. ABC was found to contain HPV in all cases, proven by genotyping to be HPV type 16 in each case. The virus showed no evidence of genomic variation from prototype HPV type 16 in the L1 segment examined. No K-ras-2 point mutations were identified. p53 immunopositivity was present in all tumors, being weak and focal in 4 and strong and diffuse in 1. WAF-1 immunostaining was positive in two tumors showing weak focal p53 immunopositivity. The single strong and diffuse p53 immunopositive tumor was negative for WAF-1 and was shown to contain a missense p53 point mutation (exon 7-codon 248 tryptophan). In conclusion, ABC is characterized by the presence of HPV type 16. K-ras-2 point mutation appears to play no role in the development of this tumor. p53 gene alterations are common including wild type hyperexpression (weak focal p53 immunopositivity, WAF-1 positivity, no mutational change) and p53 point mutational damage.     

Induction of CYP1A1 by GABA receptor ligands

The induction of CYP1A1 is mediated via the aromatic hydrocarbon (Ah) receptor. Studies from our laboratory show CYP1A1 induction by picrotoxin and phenobarbital which prompted us to examine if other ligands of the gamma-aminobutyric acid (GABA) receptor could also induce CYP1A1. Here we report the nuclear translocation of the Ah receptor and its DNA binding activity to radiolabeled double-stranded synthetic xenobiotic response elements (XREs) in nuclear extracts, increased accumulation of CYP1A1 mRNA, and alterations in intracellular calcium concentrations in cells exposed to GABA receptor ligands.