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B Cullen

Publications and source records attributed to B Cullen.

At least 19 recordsLinked to original sources

The relationship between obsessive-compulsive disorder and anxiety and affective disorders: results from the Johns Hopkins OCD Family Study.

OBJECTIVE: This study investigates the relationship of specific anxiety and affective disorders to obsessive-compulsive disorder (OCD) in a blind, controlled family study. METHOD: Eighty case and 73 control probands, as well as 343 case and 300 control first-degree relatives of these probands, participated in the study. Subjects were examined by psychologists or psychiatrists using the Schedule for Affective Disorder and Schizophrenia-Lifetime Anxiety version (SADS-LA). Two experienced psychiatrists independently reviewed all clinical materials, and final diagnoses were made according to DSM-IV criteria, by consensus procedure. RESULTS: Except for bipolar disorder, all anxiety and affective disorders investigated were more frequent in case than control probands. Substance dependence disorders were not more frequent. Generalized anxiety disorder (GAD), panic disorder, agoraphobia, separation anxiety disorder (SAD) and recurrent major depression were more common in case than control relatives. These disorders occurred more frequently if the relative was diagnosed with OCD. Only GAD and agoraphobia were more frequent in case relatives independent of OCD. CONCLUSION: GAD and agoraphobia share a common familial aetiology with OCD. The other anxiety and affective disorders, when comorbid with OCD, may emerge as a consequence of the OCD or as a more complex syndrome.

Adolescent↗

Complex segregation analysis provides compelling evidence for a major gene underlying obsessive-compulsive disorder and for heterogeneity by sex.

Evidence from twin and family studies supports a genetic etiology for obsessive-compulsive disorder (OCD). The purpose of this study was to test whether a major gene is implicated in a proportion of families with OCD. Complex segregation analyses of 153 families (80 case and 73 control), ascertained in the Johns Hopkins OCD Family Study, provided strong evidence for a major gene. A Mendelian-dominant model, with significant sex effects and with residual familial effects, best explained the observed data. Stratification of the sample by the sex of probands provided further evidence of heterogeneity with respect to familial aggregation. Segregation analyses of 86 families with a female proband and of the 67 families with a male proband suggested that a Mendelian-dominant model with familial residual effects was the most parsimonious model explaining the inheritance of OCD in both subgroups.

Adolescent↗

Y2K: are you ready?

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Chronology as Topic↗

Molecular mechanism of desensitization of the chemokine receptor CCR-5: receptor signaling and internalization are dissociable from its role as an HIV-1 co-receptor.

The chemokine receptor, CCR-5, a G protein-coupled receptor (GPCR) which mediates chemotactic responses of certain leukocytes, has been shown to serve as the primary co-receptor for macrophage-tropic human immunodeficiency virus type 1 (HIV-1). Here we describe functional coupling of CCR-5 to inhibition of forskolin-stimulated cAMP formation via a pertussis toxin-sensitive G(i) protein mechanism in transfected HEK 293 cells. In response to chemokines, CCR-5 was desensitized, phosphorylated and sequestered like a prototypic GPCR only following overexpression of G protein-coupled receptor kinases (GRKs) and beta-arrestins in HEK 293 cells. The lack of CCR-5 desensitization in HEK 293 cells in the absence of GRK overexpression suggests that differences in cellular complements of GRK and/or beta-arrestin proteins could represent an important mechanism determining cellular responsiveness. When tested, the activity of CCR-5 as an HIV-1 co-receptor was dependent neither upon its ability to signal nor its ability to be desensitized and internalized following agonist stimulation. Thus, while chemokine-promoted cellular signaling, phosphorylation and internalization of CCR-5 may play an important role in regulation of chemotactic responses in leukocytes, these functions are dissociable from its HIV-1 co-receptor function.

Arrestins↗

The differential regulation and secretion of proteinases from fetal and neonatal fibroblasts by growth factors.

One of the major differences between fetal and adult wound repair is the unique ability of fetal wounds to heal without scarring. Since scar formation is a function of extracellular matrix deposition, the regulation of this component is fundamental in tissue remodeling. In this study, we have characterized the differences in the secretion of matrix-degrading proteases, namely urokinase plasminogen activator and gelatinase A and B, from fetal and neonatal fibroblasts. In addition, we examined the modulation of these protease levels by growth factors known to be important in wound repair. The results indicate that the secretion of these proteases differ significantly between the two cell types. The levels of urokinase plasminogen activator and its inhibitor were notably higher in media conditioned by neonatal fibroblasts in comparison to fetal samples. In contrast, the basal level of gelatinase A was comparable in both cell types, whilst the level of gelatinase B was elevated in the fetal fibroblasts. Transforming growth factor-beta 1 reduced the level of urokinase plasminogen activator and stimulated the secretion of plasminogen activator inhibitor-1 and progelatinase B in both neonatal and fetal fibroblasts. However, only progelatinase A and an activated form of gelatinase B were significantly elevated in fetal fibroblasts. In contrast, platelet-derived growth factor stimulated urokinase plasminogen activator, its inhibitor and both gelatinase A and B, an effect which was more apparent in fetal fibroblasts. This difference in protease regulation may be reflected in the differing rate and quality of tissue remodeling observed during adult vs fetal wound repair.

Adult↗

Priorities in assessment and intervention in trauma victim medical care.

There is substantial evidence that with better investment of human and capital resources, better evacuation procedures, and more timely delivery of trauma victims to trauma centres, that mortality and morbidity from trauma will be reduced. The integration of these advances in care, as well as the need to avoid mistakes, requires sound decisions. Thankfully, a clear consensus of the priorities in assessment and intervention is available to guide caregivers as they make these decisions. Repeated examination of the patient and concerted use of these priorities, together with data collection to monitor their use will benefit patients.

Caregivers↗