Targets of the nuclear factor I regulon involved in early and late development of postmitotic cerebellar granule neurons

Recent studies have shown that the nuclear factor I (NFI) family controls multiple stages of the postmitotic differentiation of cerebellar granule neurons (CGNs). Regulation of cell–cell signaling is an integral part of this NFI program, which involves expression of the cell adhesion molecules N cadherin and ephrin B1 throughout postmitotic CGN development. Here, we identify two additional downstream targets of NFI that are involved in extracellular CGN interactions. The cell adhesion molecule Tag‐1 is highly enriched in CGNs undergoing parallel fiber formation and is down‐regulated prior to onset of radial migration. We found that Tag‐1 expression was strongly reduced by NFI dominant repression in immature primary CGNs and in the cerebella of E18 Nfib‐null mice. Transient transfection and chromatin immunoprecipitation suggested that the Tag‐1 gene is directly regulated by NFI. Furthermore, functional, Nfi knockout and chromatin immunoprecipitation studies implicated Wnt7a as a direct target of NFI in maturing CGNs. Wnt7a is secreted by developing CGNs and is required for maturation of mossy fiber–CGN synaptic rosettes. Consistent with this, synapsin I was greatly reduced within the internal granule cell layer of P17 Nfia‐null mice. These findings indicated that NFI controls CGN postmitotic maturation through a combination of extracellular signaling molecules that operate either continuously to regulate multiple stages of development (N cadherin and ephrin B1) or primarily at early (Tag‐1) or late (Wnt7a) maturation steps. They also illustrate the importance of NFI as a critical link between cell‐intrinsic mechanisms and cell–cell interactions in the development of the mouse cerebellum. © 2009 Wiley‐Liss, Inc.     

Percutaneous fluoroscopic removal of a knotted Swan–Ganz catheter in a patient with a persistent left‐sided superior vena cava

Knotting of intravascular catheters is an uncommon but a well‐recognized occurrence. The Swan–Ganz catheter (SGC) is the one that knots most commonly. A case of a knotted SGC is described in a patient with a persistent left‐sided superior vena cava, and we propose that the presence of a left‐sided superior vena cava is a risk factor for knot formation not previously reported. We review the published work on the risk factors for knot formation and on the techniques used to remove knotted SGC. We describe a technique using a gooseneck snare and Omni Flush catheter (Angiodynamics, Queensbury, NY, USA) to loosen and untie a knotted SGC.     

Comorbidity of bulimia nervosa and alcohol use disorders: results from the National Women's Study

OBJECTIVE: The nature of the relationship between bulimia nervosa (BN) and alcohol abuse/alcohol dependence (AA/AD) and the extent to which women with BN+AA differ from women with BN-AA were examined in a national sample of women (N = 3,006). METHOD: The sample of was generated by multistage geographic sampling and interviews were conducted by telephone. RESULTS: AA was higher in women with BN compared to women without BN or binge eating disorder, only when the influence of major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) was controlled. Prevalence rates of AA and AD were similar in women with BN, MDD, and PTSD. Analyses indicated that the relationship between BN and AA/AD may be indirect and influenced by associations with MDD and PTSD. Women with BN+AA did not differ from those with BN-AA on most variables concerning victimization, family of origin, and disordered eating. DISCUSSION: Evaluation of MDD and PTSD in women presenting for treatment of BN and/or alcohol use disorders (AUDs) is recommended.     

Which comes first in the pathogenesis of bulimia nervosa: dieting or bingeing?

OBJECTIVE: Clinical experience has indicated that dieting usually precedes the onset of binge eating in the development of bulimia nervosa (BN). However, data confirming this in nonclinical, representative samples are lacking. METHOD: Using results obtained from the National Women's Study (NWS), we were able to determine the chronological relationship between age of onset of significant dieting (attempting to lose 15 lbs) and onset of bingeing in 85 respondents who met DSM-III-R criteria for BN. These respondents were a subset of over 3,000 female adult U.S. women who completed a random telephone interview (averaging 40 min and including screenings for rape, sexual molestation, aggravated assault, posttraumatic stress disorder [PTSD], and BN). RESULTS: We found that the age of first serious attempt to diet preceded the age of first binge in 46% of cases. There were no significant differences in histories of victimization experiences among the groups. First binge preceded first serious diet in 37% of cases, and these behaviors occurred during the same age in 17% of cases. DISCUSSION: These data confirm that dieting is more likely to precede binge eating, although binge eating precedes significant dieting in a substantial proportion of bulimic respondents.     

Defining a conceptual framework for near-miss maternal morbidity

Maternal mortality is the major indicator used to monitor maternal health in the United States. For every woman who dies, however, many suffer serious life-threatening complications of pregnancy. Yet relatively little attention has been given to identifying a general category of morbidities that could be called near misses. Characterizing near-miss morbidity is valuable for monitoring the quality of hospital-based obstetric care and for assessing the incidence of life-threatening complications. Cases of near-miss morbidity also provide an appropriate comparison group both for dinical case review and for epidemiologic analysis. This paper presents an initial framework and a process for the definition and identification of near-miss morbidity that minimizes loss of information yet has practical utility. A clinical review team classified 22 of 186 women as near misses and 164 as other severe morbidity. A quantitative score classified 28 women as near misses and 156 as other severe morbidity. Precise classification of near-miss morbidity is the first step in analyzing factors that may differentiate survival from death on the continuum from morbidity to mortality. Ultimately, a methodology for the identification and analysis of near-miss morbidity will allow for integrated morbidity and mortality reviews that can then be institutionalized. The results will serve as important models for other researchers, state health agencies, and regionalized perinatal systems that are engaged in morbidity and mortality surveillance.     

Treatment of experimental autoimmune encephalomyelitis with antisense oligonucleotides against the low affinity neurotrophin receptor

Upregulated expression of the low-affinity neurotrophin receptor (p75) in the central nervous system (CNS) during experimental autoimmune encephalomyelitis (EAE) has recently been demonstrated. To investigate whether p75 plays a role in disease pathogenesis, we adopted a gene therapy approach, utilizing antisense oligonucleotides to downregulate p75 expression during EAE. Phosphorothioate antisense oligonucleotides (AS), nonsense oligonucleotides (NS) or phosphate buffered saline (PBS) were injected daily for 18 days after immunization of SJL/J (H-2s)-mice with myelin proteolipid protein (PLP) peptide 139-151. In the AS group, there was a statistically significant reduction in both the mean maximal disease score (1.85 in the AS, 2.94 in the NS and 2.75 in the PBS-groups, respectively, P < 0.025) and in the cumulative disease incidence ( approximately 60% in the AS group and approximately 90% in the control groups). Histological and immunohistochemical analysis showed reduced inflammation and demyelination, as well as reduced p75 expression at the blood-brain barrier (BBB) in the AS-treated mice in comparison with both control groups. There was no difference, however, in p75 expression on neural cells within the CNS between the three groups of mice. We conclude that p75 could play a proactive role in the pathogenesis of EAE and may exert its effect at the level of the BBB.