alpha-Spectrin is required for ovarian follicle monolayer integrity in Drosophila melanogaster

To understand the role of the spectrin-based membrane skeleton in generating epithelial polarity, we characterized the distribution of membrane skeletal components in Drosophila ovarian follicle cells and in somatic clones of mutant cells that lack alpha-spectrin. Immunolocalization data reveal that wild-type follicle cells contain two populations of spectrin heterodimers: a network of alphabeta heterodimers concentrated on the lateral plasma membrane and an alphabetaH population targeted to the apical surface. Induction of somatic clones lacking alpha-spectrin leads to follicle cell hyperplasia. Surprisingly, elimination of alpha-spectrin from follicle cells does not appear to prevent the assembly of conventional beta-spectrin and ankyrin at the lateral domain of the follicle cell plasma membrane. However, the alpha-subunit is essential for the correct localization of betaH-spectrin to the apical surface. As a consequence of disrupting the apical membrane skeleton a distinct sub population of follicle cells undergoes unregulated proliferation which leads to the loss of monolayer organization and disruption of the anterior-posterior axis of the oocyte. These results suggest that the spectrin-based membrane skeleton is required in a developmental pathway that controls follicle cell monolayer integrity and proliferation.     

Coronal fracture of the hamate body

Three patients presented with an acquired green discoloration of their scalp hair. History revealed that all of them swam regularly in private swimming pools. Examination of the hair by atomic emission spectroscopy showed that the green discoloration was caused by an excessively high copper content of the hair. This exogeneous discoloration is characteristically related to the uptake of copper from private swimming pools.     

Using nursing diagnoses to achieve desired outcomes for hemodialysis clients

OBJECTIVE: To identify impediments to the successful transfer and implementation of packaged information systems through large, divisionalized health services. DESIGN: A case analysis of the failure of an implementation of a critical application in the Public Health System of the State of New South Wales, Australia, was carried out. This application had been proven in the United States environment. MEASUREMENTS: Interviews involving over 60 staff at all levels of the service were undertaken by a team of three. The interviews were recorded and analyzed for key themes, and the results were shared and compared to enable a continuing critical assessment. RESULTS: Two components of the transfer of the system were considered: the transfer from a different environment, and the diffusion throughout a large, divisionalized organization. The analyses were based on the Scott-Morton organizational fit framework. In relation to the first, it was found that there was a lack of fit in the business environments and strategies, organizational structures and strategy-structure pairing as well as the management process-roles pairing. The diffusion process experienced problems because of the lack of fit in the strategy-structure, strategy-structure-management processes, and strategy-structure-role relationships. CONCLUSION: The large-scale developments of integrated health services present great challenges to the efficient and reliable implementation of information technology, especially in large, divisionalized organizations. There is a need to take a more sophisticated approach to understanding the complexities of organizational factors than has traditionally been the case.     

Illegitimate recombination leading to allelic loss and unbalanced translocation in p53-mutated human lymphoblastoid cells

Allelic loss and translocation are critical mutational events in human tumorigenesis. Allelic loss, which is usually identified as loss of heterozygosity (LOH), is frequently observed at tumor suppressor loci in various kinds of human tumors. It is generally thought to result from deletion or mitotic recombination between homologous chromosomes. In this report, we demonstrate that illegitimate (nonhomologous) recombination strongly contributes to the generation of allelic loss in p53-mutated cells. Spontaneous and X-ray-induced LOH mutations at the heterozygous thymidine kinase (tk) gene, which is located on the long arm of chromosome 17, from normal (TK6) and p53-mutated (WTK-1) human lymphoblastoid cells were cytogenetically analyzed by chromosome 17 painting. We observed unbalanced translocations in 53% of LOH mutants spontaneously arising from WTK-1 cells but none spontaneously arising from TK6 cells. We postulate that illegitimate recombination was occurring between nonhomologous chromosomes after DNA replication, leading to allelic loss and unbalanced translocations in p53-mutated WTK-1 cells. X-ray irradiation, which induces DNA double-strand breaks (DSBs), enhanced the generation of unbalanced translocation more efficiently in WTK-1 than in TK6 cells. This observation implicates the wild-type p53 protein in the regulation of homologous recombination and recombinational DNA repair of DSBs and suggests a possible mechanism by which loss of p53 function may cause genomic instability.     

The entorhinal cortex: an examination of cyto- and myeloarchitectonic organization in humans

The entorhinal cortex (ERC) has been implicated in the pathophysiology of Alzheimer's disease, schizophrenia and other disorders affecting cognitive functions. While powerful anatomical and histochemical methods (immunohistochemistry, in situ hybridization, etc.) may be applied (although with limitations) to postmortem human brain, each analysis should utilize a cytoarchitectonic approach to provide appropriate comparisons within the subdivisions of the ERC. Accordingly, we describe here the normal cyto- and myeloarchitecture of the human ERC as a prerequisite for the accompanying study of this region in schizophrenia. Our parcellation of this cortex differs from previous treatments in three ways. First, we adopted specific criteria of inclusion to define each subdivision of the region. Although distinctive ERC features are most prominent in the intermediate portion of this region, at least one of these features was considered the minimum necessary criterion to include adjacent tissue in the entorhinal area. Second, we used morphometric measurements (neuronal size and density as well as subdivisional volume and laminar thickness) to support our qualitative evaluation. Third, we have applied to the human ERC the conventional cytoarchitectonic nomenclature of the entorhinal cortex used previously in studies of non-human primates. This allows a more accurate extrapolation of the available numerous experimental anatomical, physiological and psychological data on this region to the human. As in the monkey, the five main subareas were recognized in the human (prorhinal, lateral, intermediate, sulcal and medial) but three required further subdivision (intermediate, sulcal and medial). The morphometric results obtained suggested a progression of the human entorhinal cortex from the peripheral to the central subareas, with the intermediate subarea (281) as the most complete entorhinal subdivision. Compared with non-human primates, the human ERC not only retains the basic periallocortical organization but also demonstrates further evolution. Taken together with available experimental data on the connectivity of this brain region, these results provide an anatomical basis for evaluating the ERC in human behavior.     

Regional hepatic CYP1A1 and CYP1A2 induction with 2,3,7,8-tetrachlorodibenzo-p-dioxin evaluated with a multicompartment geometric model of hepatic zonation

A physiologically based pharmacokinetic (PBPK) model for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was combined with a five-compartment geometric model of hepatic zonation to predict both total and regional induction of CYP450 proteins within the liver. Three literature studies on TCDD pharmacokinetics and protein induction in female rats were analyzed. In simulating low-dose behavior for mRNA in whole liver and, particularly, in representing immunohistochemical observations, the five-compartment model was more successful than conventional homogeneous one-compartment liver models. The five-compartment liver model was used with the affinity of TCDD for the Ah receptor (AhR) held constant across all the liver (Kb = 0.2 nM). The presumed affinities of the AhR-TCDD complex for TCDD responsive elements in the CYP1A1 (Kd1) and CYP1A2 (Kd2) genes varied between adjacent compartments by a factor of 3. This parameterization leads to predicted 81-fold differences in affinities between the centrilobular and the periportal regions. The affinities used for AhR-TCDD complex binding to TCDD response elements for CYP1A2 in compartment 3 (the midzonal area) ranged from 0.08 to 1.0 nM in the three studies modeled. For CYP1A1 the corresponding dissociation constant in compartment 3 varied from 0.6 to 2.0 nM. In each compartment, the Hill coefficient for induction had to be 4 or greater to match the immunohistochemical results. This multi-compartment liver model is consistent with data on protein and mRNA induction throughout the liver and on the regional distribution of these proteins. No previous model has incorporated regional variations in induction. The PBPK analysis based on the multicompartment liver model suggests that the low-dose behavior for hepatic CYP1A1/CYP1A2 induction by TCDD is highly non-linear.