Fetal cervical hyperextension in arthrogryposis

Perhaps the most dramatic position of a newborn after delivery is when there is hyperextension of the neck and spine. It will have been presented in utero and today, almost always, such babies will have been delivered by C‐section. The associated anomalies are variable. The process(es) that can lead to cervical hyperextension is/are largely unknown. The outcome is variable from lethal to completely resolve. Individuals with arthrogryposis and in particular with Amyoplasia appear to have an increased frequency of neck, cervical, and spine hyperextension at birth. We present here 41 cases of arthrogryposis (mainly Amyoplasia) with fetal cervical hyperextension. The outlook is surprisingly good if spinal cord trauma does not occur. Ultrasound late in pregnancy when arthrogryposis is recognized prenatally should determine whether cervical hyperextension has developed, so that appropriate preventive measures can be taken.     

Differential effects of external pH alteration on intracellular pH in rat coronary and cardiac myocytes

Changes in extracellular pH (pH_o) induce changes in the intracellular pH (pH_i) of cardiac myocytes that are slow and attenuated. Little however is known about the effects of changing pH_o on the pH_i of the coronary smooth muscle cells. We have therefore directly compared the effects of altering pH_o on pH_i of both coronary and cardiac myocytes. Carboxy-SNARF was used in single cells to measure pH_i. Alteration of pH_o caused corresponding changes in pH_i that were large (70–80 % of pH_o) and rapid in coronary myocytes compared to cardiac myocytes. In contrast, changes of pH_i produced by weak acids or bases produced similar pH_i responses in both types of cells. It is suggested that the differential effects of pH_o on coronary and cardiac cells may be functionally significant, as it will allow rapid alteration of coronary perfusion to meet tissue needs, while maintaining cardiac output.Supported by the BHF and MRC     

Chondromyxoid fibroma resembles in vitro chondrogenesis, but differs in expression of signalling molecules

Chondromyxoid fibroma is a rare benign cartilaginous bone tumour characterized by morphological features that resemble different steps of chondrogenesis in terms of both cellular morphology, ranging from spindled to rounded cells, and the extracellular matrix formed, which ranges from fibrous to cartilaginous. The presence in chondromyxoid fibroma of signalling molecules that regulate the spatial expression of proteins involved in normal cartilage proliferation and differentiation was investigated in samples from 20 patients and compared with articular chondrocytes from 11 normal donors cultivated in 3D pellet culture. Sections were stained with safranin-O and H&E, and immunohistochemistry was performed for p16, cyclin D1, FGFR3, BCL2, p21, PTHLH, PTHR1 and N-cadherin. Expression patterns were analysed using hierarchical clustering. In chondromyxoid fibroma, specific morphological features correlated with a distinct pattern of expression. Comparison with normal chondrocytes in pellet culture showed a striking morphological resemblance, but with an unmistakably different pattern of expression. N-cadherin, PTHLH, and PTHR1 were expressed to a significantly higher level (p < 0.01) in articular chondrocyte pellets but, conversely, there was significantly lower expression of cyclin D1, p16 and BCL2 (p < 0.05) in these cells. Morphological similarities reflect common steps in cartilage differentiation, albeit driven by different molecular mechanisms. The proteins we have found to be differentially expressed seem crucial for neoplastic chondrogenesis.     

A multi-modal treatment program for childhood trauma recovery:Women Recovering from Abuse Program (WRAP).

This article describes the Women Recovering from Abuse Program (WRAP), an outpatient day-hospital program for women suffering from the sequelae of childhood abuse. WRAP was conceived in 1998 by clinicians who advocated for its development based on a growing need to provide women who had experienced childhood trauma an alternative to an inpatient program. WRAP draws from a Stage 1 treatment approach to address chronic interpersonal trauma and dissociation by incorporating psychopharmacology, individual and group psychotherapy. The program is structured into two phases: a preparatory Building Resources Group (BRG) and an intensive multimodal segment comprised of seven types of group therapy. Each group is described in terms of the treatment rationale and its structure and process. Two research studies to date support the effectiveness of WRAP.     

Psychiatric disorders associated with risk for the development of eating disorders during adolescence and early adulthood

Longitudinal data were used to investigate whether anxiety, depressive, disruptive, personality, or substance use disorders are associated with risk for the development of eating disorders during adolescence or early adulthood. Psychiatric disorders were assessed among 726 youths from a random community sample during adolescence and early adulthood. Depressive disorders during early adolescence were associated with elevated risk for the onset of eating disorders, dietary restriction, purging behavior, and recurrent weight fluctuations after preexisting eating problems and other psychiatric disorders were controlled statistically. Disruptive and personality disorders were independently associated with elevated risk for specific eating or weight problems. The present findings suggest that depressive disorders during early adolescence may contribute to the development of eating disorders during middle adolescence or early adulthood.     

Haplotype analysis of the BRCA2 9254delATCAT recurrent mutation in breast/ovarian cancer families from Spain

A frame-shift 9254del5 mutation was independently identified in 12 families, eleven of them with Spanish ancestors, in a BRCA2 screening performed in 841 breast and/or ovarian cancer families and in 339 women with breast cancer diagnosed before the age of 40 at different centers in France and Spain. We sought to analyze in detail the haplotype and founder effects of the 9254del5 and to estimate the time of origin of the mutation. Eight polymorphic microsatellite markers and two BRCA2 polymorphisms were used for the haplotype analyses. The markers were located flanking the BRCA2 gene spanning a region of 6.1 cM. Our results suggest that these families shared a common ancestry with BRCA2 9254del5, which is a founder mutation originating in the Northeast Spanish, with an estimated age of 92 (95% CI 56-141) generations.     

Chromosome abnormalities in chronic lymphocytic leukemia revealed by TPA as a mitogen

Bone marrow and peripheral blood cultures of chronic lymphocytic leukemia patients were mitogenically stimulated with TPA (12-0-tetradecanylphorbol-13-acetate). Clonal cytogenetic abnormalities were detected in frequencies varying from 15% to 100%, in five of the six patients studied. Parallel studies with pokeweek mitogen showed a much lower level of stimulation and only two abnormal clones were detected. The chromosome abnormalities described in this study are similar to those reported in CLL by other authors, particularly with respect to trisomy 12 and deletion 11q. A significant frequency of hypodiploidy and chromosome deletion was also detected in this study, and further studies are underway to determine the significance of these findings.     

Localization of IFN-gamma-activated Stat1 and IFN regulatory factors 1 and 2 in breast cancer cells.

The aim of the present work was to evaluate the induction and localization of Stat1, interferon (IFN) regulatory factor-1 (IRF-1), and IRF-2 after IFN-gamma exposure of human breast cancer cell lines, SKBR3, MDA468, MCF7, and BT20. Results from growth assays, Western staining, electrophoretic mobility shift assay (EMSA), and immunohistochemical staining were collated to test our hypothesis that immunohistochemical analysis of Stat1, IRF-1, and IRF-2 would provide additional information about the functionality of the IFN-gamma signaling pathway in human tumor lines. EMSA results showed that in each of four cell lines, Stat1 expression was increased and demonstrated functional activity after IFN-gamma stimulation. Western and EMSA analysis showed upregulation of IRF-1 but not IRF-2 in each cell line. Confocal microscopy of cells stained for Stat1, IRF-1, and IRF-2 confirmed the results and also provided novel information about the intracellular localization of proteins and intercellular variations in responses. The proportion of cells with IRF-1 stimulation and translocation was positively correlated with the IFN-gamma growth suppression in vitro. In conclusion, using four independent assays, we have demonstrated that heterogeneity in IFN-gamma-mediated upregulation of signal transduction proteins can be detected in vitro and that these differences can explain distinct cellular growth effects.     

Urban adolescents' perceptions of their neighborhoods: An examination of spatial dependence

Spatial dependence exists when the variation between observations is dependent on spatial location. In the present study, geostatistical methods were used to examine spatial dependence in adolescents' perceptions of their neighborhoods: whether adolescents living in close proximity perceived their neighborhoods more similarly than adolescents living further apart. Participants included 343 adolescents (53% male; 91% African American) enrolled in sixth grade, residing in Baltimore City, with geocoded home addresses. These addresses were used in combination with a measure of perceived neighborhood disorder and disadvantage to compute variogram plots, a geostatistical technique used to evaluate spatial dependence. Results indicated that perceptions of youth residing in close geographic proximity were more similar than perceptions of youth residing further apart. Adjusting for census‐level characteristics, but not individual and family characteristics, resulted in decreased variation among participants but did not eliminate the spatial dependence. Findings highlight the utility of geostatistical methods for social science research. © 2004 Wiley Periodicals, Inc. J Comm Psychol 32: 277–293, 2004.     

Mapping nondominant voices into understanding stress-coping mechanisms

This study reports key findings from a research project, which examined the stress and coping mechanisms of several nondominant groups of individuals. The groups were based in Winnipeg, Manitoba, Canada and included (a) Aboriginal individuals with diabetes, (b) individuals with disabilities, and (c) gays and lesbians. Our analyses of personal narratives and life stories have led to develop an interpretive map of findings that depicts mechanisms of how stress and coping operate. Specifically, the interpretive map consists of personal and structural stressors, meanings of stress, and personal and structural resources, as well as of two constructs termed intersectionality and social exclusion. Not only are nondominant voices and lived experiences recognized and incorporated into an emergent interpretive map, but this map also articulates the complex ways in which multiple identities intersect (i.e., intersectionality) and the realities of being excluded socioeconomically, culturally, and politically among nondominant groups (i.e., social exclusion). © 2008 Wiley Periodicals, Inc.