Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The majority of transmissions occur as a consequence of inapparent infection in the source contact, as asymptomatic viral excretion in individuals with recurrent infection. The development of type specific serological assays has allowed for a more accurate determination of herpes simplex virus (HSV) 2 prevalence and has revealed that the prevalence of HSV 2 in sexually transmitted disease clinic attenders varies from 8%-83%, in female prostitutes from 75%-96% and in antenatal clinic attenders from 6%-53%. The majority of individuals (+/-60%) exposed to HSV 2 do not develop any symptoms. Patients treated for primary genital herpes are likely to resume sexual intercourse earlier than those who do not. Long-term suppressive acyclovir will result in decrease in clinical symptoms and viral excretion and may decrease the opportunity for HSV transmission. Acyclovir is the drug of choice for the treatment of primary genital herpes and for long-term acyclovir suppression. Two new drugs, valaciclovir and famciclovir, are currently under investigation. Failure to respond to acyclovir may be due to inadequate dose, malabsorption, another condition, or resistance. Resistance is rare and occurs mainly in profoundly immunosuppressed individuals, and is usually due to the development of thymidine kinase deficient mutants. Treatment with intravenous foscarnet is usually successful. Patients with genital herpes have a number of emotional problems, particularly if the condition recurs. Recent studies suggest that emotional stress does not precipitate recurrences, but rather recurrences cause stress. Long-term acyclovir suppression can decrease psychological morbidity in patients with frequent recurrences.
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PMID:Recent advances in genital herpes. 884 93

Symptomatic human herpes simplex virus type 1 (HSV-1) infections are rather benign in immunocompetent individuals. The primary clinical manifestations of HSV-2 infection, which is mainly transmitted sexually, are anogenital lesions. Genital herpes affects one third of the world's population, and possibly 80% of those infected with HIV. HSV infections are especially severe and even life-threatening in people with AIDS. Only 20% of herpes seropositive persons have symptomatic infection, with the remainder asymptomatic but able to shed the virus. HSV infections are usually treated with nucleoside analogs such as acyclovir (ACV), but HSV eventually becomes resistant to ACV due to the loss or mutation of the viral thymidine kinase (TK) or changes in viral DNA polymerase. Gramicidin has recently been identified as a potent nontoxic anti-HIV agent 3-5 times more active than nonoxynol-9. Findings are reported from an assessment of the effect of gramicidin upon the replication of HSV-1 and HSV-2. Human WI-38 fibroblasts were inoculated with either HSV type in the presence of serial dilutions of gramicidin, while reduction in viral yield was measured by ELISA. The 50% inhibitory dose (IC50) of gramicidin against 3 HSV-1 and 4 HSV-2 isolates was equal to 0.3 mcg/ml and was comparable to the efficacy of ACV. The IC50 of gramicidin required to protect WI-38 from the cytolytic effect of HSV was 10 mcg/ml at day 5 postinfection, indicating that gramicidin was less active than ACV. Gramicidin nonetheless suppressed the replication of ACV-resistant thymidine kinase and DNA polymerase HSV mutants at doses effective against ACV-sensitive strains. These results suggest that gramicidin could be used against STDs and to prevent sexually transmitted HIV and HSV infections.
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PMID:The effect of gramicidin, a topical contraceptive and antimicrobial agent with anti-HIV activity, against herpes simplex viruses type 1 and 2 in vitro. 967 88

Dehydroepiandrosterone sulfotransferase (STD) is a hydroxysteroid sulfo-conjugating enzyme with preferential substrate specificity for C-19 androgenic steroids and C-24 bile acids. STD is primarily expressed in the liver, intestine and adrenal cortex. Earlier studies have shown that androgens inhibit the rat Std promoter function through a negative androgen response region located between -235 and -310 base pair positions (Song, C. S., Jung, M. H., Kim, S. C., Hassan, T., Roy, A. K., and Chatterjee, B. (1998) J. Biol. Chem. 273, 21856-21866). Here we report that the primary bile acid chenodeoxycholic acid (CDCA) also acts as an important regulator of the Std gene promoter. CDCA is a potent inducer of the Std gene, and its inducing effect is mediated through the bile acid-activated farnesoid X receptor (FXR), a recently characterized member of the nuclear receptor superfamily. The ligand-activated FXR acts as a heterodimer with the 9-cis-retinoic acid receptor (RXR) and regulates the Std gene by binding to an upstream region at base pair positions -169 to -193. This specific binding region was initially identified by bile acid responsiveness of the progressively deleted forms of the Std promoter in transfected HepG2 hepatoma and enterocyte-like Caco-2 cells. Subsequently, the precise RXR/FXR binding position was established by protein-DNA interaction using in vitro footprinting and electrophoretic mobility shift analyses. Unlike all other previously characterized FXR target genes, which contain an inverted repeat (IR) of the consensus hexanucleotide half-site (A/G)G(G/T)TCA with a single nucleotide spacer (IR-1), the bile acid response element of the Std promoter does not contain any spacer between the two hexanucleotide repeats (IR-0). A promoter-reporter construct carrying three tandem copies of the IR-0 containing -169/-193 element, linked to a minimal thymidine kinase promoter, can be stimulated more than 70-fold in transfected Caco-2 cells upon CDCA treatment. Autoregulation of the STD gene by its bile acid substrate may provide an important contributing role in the enterohepatic bile acid metabolism and cholesterol homeostasis.
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PMID:Dehydroepiandrosterone sulfotransferase gene induction by bile acid activated farnesoid X receptor. 1153 40