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Biomedical subjects

S K Tyring

Publications and source records attributed to S K Tyring.

At least 91 records · Page 5Linked to original sources
PubMed1997

Lack of mda-6/WAF1/CIP1-mediated inhibition of cyclin-dependent kinases in interferon-alpha resistant murine B16 melanoma cells.

Previously we demonstrated that IFN-alpha augments mda-6/WAF1 and inhibits cyclin-dependent kinases in a p53-independent fashion in B 16 murine melanoma cells. On the other hand, IFN-gamma activates p53 expression without affecting the mda-6/WAF1 system. Combination of the two IFNs is additive. B16 cells acquire IFN-alpha resistant but IFN-gamma sensitive phenotype after long term IFN-alpha treatment (B16alpha cells). Here we demonstrate the absence of mda-6/WAF1-associated repression of cyclin-dependent kinases, but the existence of p53-dependent c-myc inhibition in IFN-gamma-treated B16alpha cells. Clearly, selective desensitization of IFN-alpha related growth regulation does not influence the IFN-gamma associated pathway. Our results further support the coexistence of distinct growth regulatory mechanisms in B16 cells that can be activated by different IFN-types independently of each other.

Animals↗
PubMed1997

Detection and cloning of epidermal zinc-alpha 2-glycoprotein cDNA and expression in normal human skin and in tumors.

Zinc-alpha 2-glycoprotein (Zn alpha 2gp) is almost ubiquitous in body fluids, and its antibody labels the corresponding secretory epithelia. We have found that Zn alpha 2gp is also expressed in human epidermis. We cloned the Zn alpha 2gp cDNA by screening our cDNA library, derived from epidermal keratinocytes, with a probe for prostate Zn alpha 2gp. It had complete nucleic acid sequence homology with that from prostate, including the signal peptide. Just as Zn alpha 2gp expression is higher in more differentiated breast tumors, so in skin tumors the highest mRNA levels occurred in the normal controls, the lowest in basal cell carcinomas (the least differentiated epidermal tumor type), and intermediate levels in squamous cell carcinomas and Merkel cell carcinomas. A similar increase in Zn alpha 2gp gene expression with differentiation was observed when epidermal keratinocytes were cultured in media that varied in cellular maturation potential.

Amino Acid Sequence↗
PubMed1997

Interferon regulates expression of mda-6/WAF1/CIP1 and cyclin-dependent kinases independently from p53 in B16 murine melanoma cells.

Interferons (IFNs) induce growth arrest and terminal differentiation through regulation of proliferative genes in a variety of cell types including tumor cells. Growth of melanoma cells is believed to be controlled by the cyclin-dependent kinase inhibitor, mda-6/WAF1/CIP1 gene. IFNs affect the expression of WAF1 in several cell types, including human melanomas. In our earlier reports we demonstrated the antitumor and anticellular activities of different IFN-types on B16 murine melanoma cells. The present study aimed to demonstrate the involvement of mda-6/WAF1 and related cyclin-dependent kinases in antitumor action of different IFN-types in B16 melanoma cells. IFN-alpha has been proven to be a potent inducer of mda-6/WAF1, also inhibiting cyclin-dependent kinases, such as cdc2- and cdk2-kinase. This induction is p53-independent. However, IFN-gamma affects B16 cells differently, it induces p53 activity without inducing WAF1. The combination of IFN-alpha plus IFN-gamma is additive rather than synergistic. Our data demonstrate differential effects of different IFNs on murine B16 melanoma cells which may have relevance in nonsurgical treatment of melanomas.

Animals↗
PubMed1997

Oral famciclovir for suppression of recurrent genital herpes simplex virus infection in women. A multicenter, double-blind, placebo-controlled trial. Collaborative Famciclovir Genital Herpes Research Group.

OBJECTIVE: To evaluate the efficacy and safety of oral famciclovir in the suppression of genital herpes. METHODS: In this randomized, double-blind, placebo-controlled trial that was performed at 11 university and 9 private ambulatory care referral centers, 375 women who were 18 years of age or older and had a history of 6 or more episodes of genital herpes during 12 of the last 24 months in the absence of suppressive therapy were treated for 4 months with oral famciclovir, 125 mg once daily or twice daily, 250 mg once daily or twice daily, 500 mg once daily, or placebo. The primary outcome measures included the time to first clinically and virologically confirmed recurrences, and safety as measured by clinical laboratory tests and adverse experiences. RESULTS: The median time to first recurrence was 82 days in the placebo group, 114 days in those receiving famciclovir, 125 mg once daily, and more than 120 days in the other treatment groups. When compared with placebo recipients, the time to the first clinical recurrence was significantly prolonged in subjects who received famciclovir, 125 mg twice daily (hazard ratio, 1.8; 95% confidence interval, 1.0-3.0; P = .03), and in those who received famciclovir, 250 mg twice daily (hazard ratio, 3.6; 95% confidence interval, 1.9-6.9; P < .001). Treatment was well tolerated, and there was no evidence of emergence of resistance during or after suppressive famciclovir therapy. CONCLUSIONS: Oral famciclovir, 250 mg, given twice daily for 4 months is an effective, well-tolerated treatment for the suppression of genital herpes in women with frequent recurrences, but single daily doses produced less complete suppression of genital herpes.

2-Aminopurine↗
PubMed1997

The effect of sorivudine on dihydropyrimidine dehydrogenase activity in patients with acute herpes zoster.

OBJECTIVE: Bromovinyl-uracil (BVU) is the principal metabolite of sorivudine, a potent anti-zoster nucleoside. BVU binds to, and irreversibly inhibits, the enzyme dihydropyrimidine dehydrogenase (DPD). The objective of this study was to assess the time course of recovery of DPD activity after oral administration of sorivudine in patients with herpes zoster and to correlate restoration of DPD activity and levels of uracil with the elimination of sorivudine and its metabolite BVU from the circulation. METHODS: Sorivudine was given orally as 40 mg once-daily doses for 10 consecutive days to a total of 19 patients with herpes zoster. Serum sorivudine, BVU, and circulating uracil and DPD activity in peripheral blood mononuclear cells (PBMCs) were determined before, during, and after administration of sorivudine. RESULTS: BVU was eliminated from the circulation within 7 days after the last sorivudine dose. DPD activity in PBMCs, which was completely suppressed in 18 of the 19 subjects and markedly suppressed in the remaining subject during administration of sorivudine, recovered to baseline levels within 19 days after the last dose of sorivudine in all subjects and within 14 days in all but one of the subjects. The restoration of DPD activity was temporally associated with elimination of BVU from the circulation. The elevated uracil concentrations produced by inhibition of DPD activity fell rapidly after cessation of sorivudine administration and also were temporally associated with elimination of BVU from the circulation. The time course of recovery of DPD activity in three patients with renal impairment was similar to that of the other subjects. CONCLUSIONS: This study indicates that sorivudine therapy is associated with a profound depression of DPD activity. Recovery of DPD activity occurred within 4 weeks of the completion of sorivudine therapy, which indicates that fluorinated pyrimidines may be safely administered 4 weeks after completion of sorivudine therapy.

Acute Disease↗
PubMed1997

Mastication of verruca vulgaris associated with esophageal papilloma: HPV-45 sequences detected in oral and cutaneous tissues.

Human papillomaviruses (HPVs) are double-stranded, circular, epitheliotropic DNA viruses of which nearly 70 types have been identified. Specific HPV types exhibit a predilection to infect certain sites; however, occurrence is not unique or restricted to these sites. HPV typing may also be helpful in determining the oncogenic potential of HPV lesions. The most common HPV types, 6 and 11, are associated with benign mucosal lesions, whereas types 18, 16, 31, and 33 are thought to confer a high rate of malignant transformation. We describe a patient with both palmar verrucae and esophageal papillomatosis that proved to be HPV type 45 by polymerase chain reaction. HPV 45 has a high homology to HPV 18 and is a member of the relatively new "high-risk" mucosal HPV family in terms of cervical oncogenic potential. To our knowledge, HPV 45 has never been reported in cutaneous warts or esophageal lesions.

DNA, Viral↗
PubMed1997

Identification of HHV-8 DNA in the skin lesions of Kaposi's sarcoma in an immunosuppressed patient with bullous pemphigoid.

Kaposi's sarcoma rarely occurs as an opportunistic tumor in iatrogenically immunosuppressed patients. We describe the clinical presentation, treatment of Kaposi's sarcoma skin lesions in an immunosuppressed patient with bullous pemphigoid. Using the polymerase chain reaction, HHV-8 DNA was detected in two separate Kaposi's sarcoma lesions but not in control tissues. The amplified DNA fragments derived from our patient's Kaposi's sarcoma skin lesions contained unique point mutations that distinguished the virus isolated from Kaposi's sarcoma lesions derived from other patients. This is the first demonstration that HHV-8 DNA is associated with Kaposi's sarcoma skin lesions in an HIV-negative, immunosuppressed patient with bullous pemphigoid. HHV-8 is probably a common latent herpesvirus that is activated by immunosuppressive therapy in genetically predisposed patients and may be involved in the pathogenesis of Kaposi's sarcoma.

Aged↗
PubMed1997

Therapeutic approaches to papillomavirus infections.

Human papillomaviruses (HPVs) cause benign tumors (i.e., warts) and are occasionally responsible for malignant tumors such as squamous-cell carcinomas. Therapy for most warts is commonly via surgical or cytodestructive methods. Presently, only one antiviral/immunomodulatory drug is available for wart therapy; this agent, interferon alpha (IFN alpha), is approved only for genital warts (condylomata acuminata) and is expensive, relatively difficult to use, associated with systemic side effects, and somewhat slow acting. Two new antiviral/immunomodulatory drugs, imiquimod and cidofovir, have been proved to be effective and able to overcome many of the shortcomings of IFN alpha. While these two agents are pending approval, other treatments are being evaluated, such as antisense oligonucleotides and therapeutic HPV vaccines. In contrast to surgical and cytodestructive therapies, the goal of these new antiviral/immunomodulatory agents is not just to remove the tumor but also to reduce sufficiently the amount of latent and subclinical HIV so as to reduce the rate of recurrence.

Female↗
PubMed1997

Current antiretroviral therapy in the treatment of HIV infection.

Since the introduction of the first antiretroviral agent, zidovudine (AZT) in 1987, much progress has been made in the chemotherapy of the human immunodeficiency virus (HIV). Currently nine antiretroviral agents are approved for the treatment of individuals infected with HIV or with the acquired immune deficiency syndrome (AIDS). These medications are routinely divided into three categories: nucleoside analogues, non-nucleoside analogues, and most recently, protease inhibitors. As our knowledge of the pathogenesis of HIV increases, new antiretroviral agents become available, and advanced techniques develop to more accurately assess the degree of viral burden in an individual's blood, recommendations regarding treatment initiation and choice of antiviral agents are continually changing. The current general consensus is to "hit early" and "hit hard." Early initiation of treatment with multidrug therapy in all individuals infected with HIV is recommended by most experts with the common goal of reducing viral load to a nondetectable level. Numerous studies have shown the increased efficacy of multidrug therapy over monotherapy, however trials are still continuing to determine combination therapies which will provide the maximum benefit.

Anti-HIV Agents↗
PubMed1997

Cutaneous verruca with genital human papillomavirus in a 2-year-old girl.

Human papillomavirus (HPV) is the etiologic agent of warts and condyloma acuminatum (CDA). Condyloma acuminatium is believed to result from sexual transmission of HPV types 6 and 11 in adults. In contrast, nonsexual transmission of CDA occurs frequently between children and caregivers. Nonsexual-CDA are present almost exclusively in the mucosal epithelium in children. The authors analyzed a rapidly growing cutaneous wart on the thigh of a two-year-old girl for the presence of oncogenic and nononcogenic HPV types by in situ hybridization. This cutaneous wart was found to have the HPV types commonly found in CDA, namely types 6 and/or 11. This is an unusual finding and suggests that verruca vulgaris may result from papillomavirsuses other than HPV 2 in children.

Child, Preschool↗
PubMed1997

Acceptability of genital herpes immunization. The role of health beliefs and health behaviors.

BACKGROUND AND OBJECTIVES: Little is known about the acceptability of vaccines for prevention of sexually transmitted diseases (STDs). The purpose of this study was to examine potential predictors of genital herpes simplex virus type 2 (HSV-2) vaccine acceptability. GOALS: To evaluate the relationship of health beliefs and health behaviors to HSV-2 vaccine acceptability. STUDY DESIGN: Three hundred twenty-one subjects participating in two phase III clinical trials for an HSV-2 vaccine completed surveys addressing health beliefs, health behaviors, and acceptability of hypothetical HSV-2 vaccines. RESULTS: Bivariate analyses found that perceived benefits of vaccination, seatbelt use, a healthy diet, and having had cholesterol levels checked were associated with higher acceptability. Perceived limitations of HSV-2 immunization, alcohol use, and exercise were associated with lower acceptability. Multiple regression analysis identified perceived benefits of vaccination, decreased exercise, and lower alcohol use as significant independent predictors of greater HSV-2 vaccine acceptability. CONCLUSIONS: In groups of high-risk individuals who had completed participation in HSV-2 clinical trials, health beliefs and health behaviors influenced acceptability of hypothetical HSV-2 vaccination. The findings support the need to understand determinants of acceptance of vaccines for HSV-2 and other STDs.

Adult↗
PubMed1997

Development of intralesional therapy with fluorouracil/adrenaline injectable gel for management of condylomata acuminata: two phase II clinical studies.

OBJECTIVES: To evaluate a sustained release chemotherapy for treating condylomata acuminata with an injectable gel containing fluorouracil and adrenaline (5-FU/adrenaline gel). Study 1-- To assess contributions of the components of 5-FU/adrenaline gel to efficacy. Study 2--To assess therapeutic contribution of adrenaline and safety and efficacy of the formulations. DESIGN: Randomised, double blind, placebo controlled studies. SETTING: Private practices and university clinics in the United States. PATIENTS: Men and women with new, recurrent, or refractory external condylomata acuminata. INTERVENTION: Six injections over 8 weeks; follow up visits at weeks 1, 4, 8, and 12. MAIN OUTCOME MEASURES EFFICACY: patient/wart response, times to complete response, recurrence rates. SAFETY: injection reactions, tissue conditions, other adverse events, laboratory studies. RESULTS: Study 1: 132 evaluable patients. Complete response (CR) rate was highest for the 5-FU/adrenaline gel group, followed by the 5-FU/adrenaline solution group, then the 5-FU gel group. 5-FU, adrenaline, and the collagen gel vehicle (in the presence of 5-FU) significantly affected CR and strongly influenced time to CR. The effects of 5-FU and adrenaline were statistically significant. Cutaneous reactions were mild to moderate. Study 2: 187 evaluable patients. Patients treated with 5-FU/adrenaline gel had a significantly higher CR rate and lower cumulative 90 day recurrence rate than those treated with 5-FU gel without adrenaline. Treatments were generally well tolerated, with only three treatment related, serious adverse events. CONCLUSION: 5-FU/adrenaline gel is safe and efficacious for treatment of condylomata acuminata, and when compared with individual or various combinations of components, this formulation provided the greatest therapeutic advantage.

Adolescent↗