VA Palo Alto Healthcare System

About: VA Palo Alto Healthcare System is a healthcare organization based out in Palo Alto, California, United States. It is known for research contribution in the topics: Population & Health care. The organization has 2548 authors who have published 4605 publications receiving 209938 citations.

Chronic hepatitis, hepatocyte fragility, and increased soluble phosphoglycokeratins in transgenic mice expressing a keratin 18 conserved arginine mutant.

Abstract: The two major intermediate filament proteins in glandular epithelia are keratin polypeptides 8 and 18 (K8/18). To evaluate the function and potential disease association of K18, we examined the effects of mutating a highly conserved arginine (arg89) of K18. Expression of K18 arg89-->his/cys and its normal K8 partner in cultured cells resulted in punctate staining as compared with the typical filaments obtained after expression of wild-type K8/18. Generation of transgenic mice expressing human K18 arg89-->cys resulted in marked disruption of liver and pancreas keratin filament networks. The most prominent histologic abnormalities were liver inflammation and necrosis that appeared at a young age in association with hepatocyte fragility and serum transaminase elevation. These effects were caused by the mutation since transgenic mice expressing wild-type human K18 showed a normal phenotype. A relative increase in the phosphorylation and glycosylation of detergent solubilized K8/18 was also noted in vitro and in transgenic animals that express mutant K18. Our results indicate that the highly conserved arg plays an important role in glandular keratin organization and tissue fragility as already described for epidermal keratins. Phosphorylation and glycosylation alterations in the arg mutant keratins may account for some of the potential changes in the cellular function of these proteins. Mice expressing mutant K18 provide a novel animal model for human chronic hepatitis, and for studying the tissue specific function(s) of K8/18.

Treatments for Patients With Dual Diagnosis: A Review

Abstract: Background: Comorbid substance use and mental illness is prevalent and often results in serious consequences. However, little is known about the efficacy of treatments for patients with dual diagnosis. Methods: This paper reviews both the psychosocial and medication treatments for those diagnosed with a substance-related disorder and one of the following disorders: (a) depression, (b) anxiety disorder, (c) schizophrenia, (d) bipolar disorder, (e) severe mental illness, and (f) nonspecific mental illness. We made no restriction of study design to include all published studies, due to the dearth of studies on treatments of patients with dual diagnosis. Results: Fifty-nine studies were identified (36 randomized-controlled trials; RCT). Limited number of studies, especially RCTs, have been conducted within each comorbid category. This review did not find treatments that had been replicated and consistently showed clear advantages over comparison condition for both substance-related and other psychiatric outcomes. Conclusions: Although no treatment was identified as efficacious for both psychiatric disorders and substance-related disorder, this review finds: (1) existing efficacious treatments for reducing psychiatric symptoms also tend to work in dual-diagnosis patients, (2) existing efficacious treatments for reducing substance use also decrease substance use in dually diagnosed patients, and (3) the efficacy of integrated treatment is still unclear. This review provides a critique of the current state of the literature, identifies the directions for future research on treatment of dual-diagnosis individuals, and calls for urgent attention by researchers and funding agencies to conduct more and more methodologically rigorous research in this area.