Biomedical subjects

Jama M Darling

Publications and source records attributed to Jama M Darling.

5 recordsLinked to original sources

PubMed2006

Optimizing treatment regimens in hepatitis C.

Scientists and clinicians have made tremendous advances in understanding the pathogenesis of hepatitis C virus (HCV) infection and have developed impressive strategies for treating this hepatotropic virus in the short time since its discovery in 1989. This article goes beyond the current guidelines for the treatment of HCV infection to examine the use of multiple pretreatment factors to predict response; the use of viral kinetics to guide length of treatment; higher dose ribavirin in genotype 1 infection; retreatment of non responders and relapsers; and improving adherence to therapy.

Antiviral Agents↗

PubMed2006

Management and treatment of hepatitis C viral infection: recommendations from the Department of Veterans Affairs Hepatitis C Resource Center program and the National Hepatitis C Program office.

Chronic hepatitis C virus (HCV) infection affects approximately 1.3% of the general U.S. population and 5-10% of veterans who use Department of Veterans Affairs medical services. Chronic HCV is clearly linked to the development of cirrhosis, hepatocellular carcinoma (HCC), and end-stage liver disease requiring liver transplantation. The consequences of HCV infection constitute a significant disease burden and demonstrate the need for effective medical care. Treatment of chronic HCV is aimed at slowing disease progression, preventing complications of cirrhosis, reducing the risk of HCC, and treating extrahepatic complications of the virus. As part of a comprehensive approach to HCV management, antiviral therapy with peginterferon alfa combined with ribavirin is the current standard of care. Antiviral therapy should be provided to those individuals who meet criteria for treatment and who are at greatest risk for progressive liver disease. Many of these patients may have comorbid medical and psychiatric conditions, which may worsen while on antiviral therapy. Current antiviral regimens are associated with significant adverse effects that can lead to noncompliance, dose reduction, and treatment discontinuation. To overcome these barriers and to address these issues, it has become crucial to facilitate a multidisciplinary team who can respond to and provide HCV-specific care and treatment. Screening for HCV, preventing transmission, delaying disease progression, ensuring appropriate antiviral therapy, and managing treatment-related adverse effects can improve patient quality of life, treatment adherence, and ultimately, improve patient outcomes.

Antiviral Agents↗

PubMed2004

Immune responses in hepatitis C: is virus or host the problem?

PURPOSE OF REVIEW: Hepatitis C virus is an RNA virus that usually establishes persistent infection in its host. As an important cause of cirrhosis and hepatocellular carcinoma worldwide, hepatitis C is a growing public health concern. Despite recent advances in therapy, most people infected with the virus can expect lifelong infection. In the minority of those exposed and who spontaneously clear virus, a robust hepatitis C virus-specific T cell response of T helper 1 type correlates with resolution. The longevity of this response in the recovered state and the potential for hepatitis C virus-specific T cells to protect against future infection are critical parameters for vaccine design. RECENT FINDINGS: The literature of the past year dissected components of protective immunity to hepatitis C and emphasized the importance of the CD4 helper response in both the expansion and maintenance of hepatitis C virus-specific CD8(+) T cells. Other important studies examined how the virus interacts with immune cells to subvert both innate and adaptive immune responses in acute and chronic infection. SUMMARY: Defining the essential components of protective immunity against a highly mutable virus like hepatitis C underpins successful vaccine design. By understanding viral and host factors which influence hepatitis C virus-specific T cell maintenance and function, we are better equipped to devise immunomodulatory therapies and vaccines which induce robust and lasting immunity.

CD4-Positive T-Lymphocytes↗

PubMed2003

Keratin 8 and 18 mutations are risk factors for developing liver disease of multiple etiologies.

Keratin 8 and 18 (K8K18) mutations are found in patients with cryptogenic cirrhosis, but the role of keratin mutations in noncryptogenic cirrhosis and the incidence of keratin mutations in the general population are not known. We screened for K8K18 mutations in genomic DNA isolated from 314 liver explants of patients who primarily had noncryptogenic cirrhosis, and from 349 blood bank volunteers. Seven unique K8K18 mutations were found in 11 independent patients with biliary atresia, hepatitis BC, alcohol, primary biliary cirrhosis, and fulminant hepatitis. Seven of the 11 patients had mutations previously described in patients with cryptogenic cirrhosis: K8 Tyr-53 --> His, K8 Gly-61 --> Cys, and K18 His-127 --> Leu. The four remaining patients had mutations at one K8 and three other K18 new sites. Of the 349 blood bank control samples, only one contained the Tyr-53 --> His and one the Gly-61 --> Cys K8 mutations (P < 0.004 when comparing cirrhosis versus control groups). Two additional mutations were found in both the liver disease and blood bank groups and, hence, likely represent polymorphisms. Livers with keratin mutations had cytoplasmic filamentous deposits that were less frequent in livers without the mutations (P = 0.03). Therefore, K8K18 are likely susceptibility genes for developing cryptogenic and noncryptogenic forms of liver disease.

Cohort Studies↗

PubMed2002

A blood-borne antigen induces rapid T-B cell contact: a potential mechanism for tolerance induction.

Understanding the difference between the development of a productive T-cell response and tolerance is central to discerning how the immune system functions. Intravenous injection of soluble protein is thought to mimic the presentation of self-serum and orally introduced antigens. It is generally toleragenic. The current view is that this outcome reflects the failure of 'immunogenic' dendritic cells to relocate to the T-cell zone of the secondary lymphoid tissues. Here, using a peptide/I-Ek tetramer and antibodies to stain splenic sections, we showed that antigen-specific T cells were activated in the spleen within hours of injection or feeding of protein. The activated T cells were found to be located at the T-B junction, the bridging zone and the B-cell area, interacting directly with B cells. In addition, B cells gain the ability to present antigen. Our results suggest a way for T cells to be stimulated by blood-borne antigen presented by naïve B cells, a potential mechanism of tolerance induction.

Animals↗