Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neopterin is a pyrazino-pyrimidine compound which is biosynthesized by macrophages. Increased concentrations of neopterin have been reported in conditions causing stimulation of cellular immunity, such as viral and other infections, graft versus host disease, autoimmune diseases and different malignancies. Recently, increased urinary neopterin levels have been found in patients with acute viral hepatitis and NANB chronic hepatitis. In the present study, neopterin serum levels were measured in 23 cirrhotic patients (6 HBV related, 7 alcoholic and 10 cryptogenetic cirrhosis) and in 24 normal subjects. Mean values of serum neopterin were statistically increased in cirrhotics (3.92 +/- 3.28 ng/mL versus 1.24 +/- 0.51 ng/mL in controls, p less than 0.01). Serum neopterin values were not statistically different either in cirrhotics assessed in three different classes according to Child's classification or in cirrhotics with or without serological findings of active disease. In fact, in cirrhotic patients, serum neopterin levels did not correlate with serum aspartate and alanine aminotransferases, alkaline phosphatase, gamma-glutamyltransferase and gammaglobulins values. These data show that increased levels of serum neopterin occur in cirrhotic patients, but there is no relation between serum neopterin values and the histological activity or the clinical severity of the disease. The results are consistent with the hypothesis that activated macrophages are involved in all forms and in all stages of liver cirrhosis.
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PMID:[Blood levels of neopterin in patients with liver cirrhosis]. 248 6

Neopterin is a pyrazino-pyrimidine compound which is biosynthesized by macrophages. Increased concentrations of neopterin have been reported in conditions causing a stimulation of cellular immunity, such as viral and other infections, graft versus host disease, autoimmune disease and different malignancies. Recently, urinary neopterin levels have been found increased in patients with acute viral hepatitis and NANB chronic hepatitis. In the present study, neopterin serum levels have been measured in 23 cirrhotic patients (6 HBV related, and 17 cryptogenetic cirrhosis, 7 of them occurring in alcoholic subjects) and in 24 normal subjects. Mean values of serum neopterin were significantly increased in cirrhotics (3.92 +/- 3.28 ng/ml versus 1.24 +/- 0.51 ng/ml in controls, p less than 0.01). Serum neopterin values were not found to be significantly different in cirrhotics assessed in three different clinical classes according to Child's classification and in cirrhotics with and without serological findings of active disease. In fact, in cirrhotic patients, serum neopterin levels did not correlate with the values of serum AST, ALT, ALP, GGT and gamma-globulin. These data show that increased levels of serum neopterin occur in cirrhotic patients, but there is no relation between serum neopterin values and the activity or the clinical severity of the disease. The results are consistent with the hypothesis that activated macrophages are involved in all stages of liver cirrhosis irrespective of its aetiology.
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PMID:Serum neopterin levels in liver cirrhosis. 263 48

Tumor necrosis factor-alpha (TNF-alpha) is a highly pleiotropic cytokine produced mainly by activated macrophages. This cytokine has been found to mediate the growth of certain tumors, the replication of HIV-1, septic shock, cachexia, graft-versus-host disease, and autoimmune diseases. The binding of TNF-alpha to the p55 tumor necrosis factor receptor type I (TNFRI) is considered one of the initial steps responsible for the multiple physiologic effects mediated by TNF-alpha. The role of TNF-alpha as an inflammatory mediator through TNFRI makes both of these genes attractive targets for intervention in both acute and chronic inflammatory diseases. We have designed antisense oligodeoxynucleotides (ODNs) containing chemically modified purine and pyrimidine bases that specifically inhibit TNFRI expression and functions. These ODNs were designed to hybridize to the 3'-polyadenylation signal region of the TNFRI gene. In cell-based assays, gene-specific antisense inhibition occurred in a dose-dependent fashion at submicromolar concentrations in the presence of cellular uptake enhancing agents. Within ODN sets with a common pattern of stabilizing backbone substitution, the inhibition of the gene expression is found to be correlated with the affinity of the ODNs for their cognate mRNA target sites, providing direct evidence for an antisense mechanism of action. In addition, events triggered by the binding of TNF-alpha to TNFRI, such as the production of IL-6 and IL-8, were significantly reduced by treatment of cells with the anti-TNFRI ODN. Therefore, antisense ODNs can be used to control biologic processes mediated by TNF-alpha and may be useful as therapeutic agents to treat conditions resulting from overproduction of TNF-alpha.
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PMID:Sequence-specific inhibition of the tumor necrosis factor-alpha receptor I gene by oligodeoxynucleotides containing N7 modified 2'-deoxyguanosine. 936 4

The specific combination for conditioning regimens in hematopoietic stem cell transplantation continues to be a premier area of focus in research. Although conditioning regimens have significantly evolved over time, obstacles continue to persist, including regimen-related toxicities, graft-versus-host disease, and disease relapse. Gemcitabine (2',2'-difluoro 2'-deoxycytidine, dFdC) is a pyrimidine nucleoside analog that distinguishes itself from other agents in the class by possessing a favorable pharmacokinetic and cytotoxic profile, while maintaining acceptable toxicities. Given the desirable properties, gemcitabine has garnered much attention and been assessed in several conditioning regimens. In this article, we review the pharmacology of gemcitabine with other nucleoside analogs and report the findings of pivotal trials conducted in both autologous and allogeneic transplantation. The positive results suggest a potential future role for gemcitabine and necessitate the need to conduct studies to further define its role.
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PMID:The emerging role of gemcitabine in conditioning regimens for hematopoietic stem cell transplantation. 2481 80