BACKGROUND: The Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) is essential for replication and maintenance of circular EBV genomes in latently infected B lymphocytes and is the only EBV protein expressed in nearly all cells carrying the virus. EBNA-1 is suggested to be oncogenic in vivo since its expression induces B-cell neoplasia in transgenic mice. PATIENTS, MATERIALS AND METHODS: EBV wild-type isolates from ten malignant tumors and from 15 children with various benign EBV-associated disorders were examined for the presence of EBNA-1 variant strains by PCR and sequencing. RESULTS: One isolate harbored both the B95-8-like and a variant sequence within the C-terminus of the EBNA-1 gene. All other isolates (n = 24) revealed clustered nucleic acid sequence alterations within the EBNA-1 gene, which led to amino acid exchanges at positions 524, 563, 574, 585, 594 and 595. Few isolates exhibited additional amino acid exchanges at positions 564, 571 or 588. CONCLUSIONS: The observed EBNA-1 sequence variation pattern seems not to be restricted to a certain EBV-associated disease or tumor type. The EBNA-1 variant strains reported here may reflect the most prevalent EBV strains in the exposed population. In none of all the cases studied so far did the sequence alteration affect any known functionally crucial amino acids in the core domain of EBNA-1. This suggests that strict conservation of most of the C-terminal portion of EBNA-1 sequence may be essential for survival of EBV in the infected host.

Base Sequence↗

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Herpes simplex virus glycoprotein immunotherapy of recurrent genital herpes: factors influencing efficacy.

Recombinant herpes simplex virus type 1 (HSV-1) glycoproteins B (gB) and D (gD) were used as immunotherapeutic agents for the treatment of recurrent genital herpes in guinea pigs. Administration of a gBgD vaccine eight to 21 days after intravaginal HSV-2 inoculation significantly increased the titer of anti-HSV antibodies (P less than 0.005) while significantly reducing the frequency of subsequent herpetic recurrences (P less than 0.05). The effectiveness of gBgD immunotherapy was influenced by both the co-administration of adjuvant, the type of adjuvant, and by the timing and route of administration. These data demonstrate that recurrent HSV disease in animals with established latent infection may be favorably altered by the administration of immunogenic viral proteins.

Animals↗

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How many EF-Tu molecules participate in aminoacyl-tRNA binding?

The stoichiometry of the EF-Tu-GTP-aminoacyl-tRNA complex has been re-determined by a variety of methods, viz gel filtrations, fluorescence titrations, as well as hydrolysis and RNase protection experiments. The results of these experiments clearly demonstrate that one aminoacyl-tRNA interacts with only one EF-Tu-GTP molecule, in agreement with the established view and in contrast to the recently published results by Ehrenberg et al [6].

Binding Sites↗

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Pharmacokinetics of alprazolam in elderly patients with multiple diseases.

The pharmacokinetics of alprazolam (1 mg p.o.) were investigated (using a new developed HPLC-assay) in 10 multimorbid elderly patients (five female, five male; mean age 72.8 +/- 8.2 years, creatinine clearance 63.6 +/- 25.9 ml/min, weight 68.9 +/- 13.9 kg). Compared with young and elderly volunteers from other studies peak plasma concentrations of alprazolam were decreased while peak time and elimination half-life were increased. 'Second peak' plasma levels (correlated with age and creatinine clearance) occurred in eight of 10 elderly patients. The variability associated with the pharmacokinetic parameters in the multimorbid elderly patients was far greater than that observed in young and old healthy volunteers. Mean alprazolam concentrations in multimorbid patients aged 72 years or more were elevated as compared to 'younger' patients (age range: 63-71 years). Dose reduction should be considered in the older multimorbid patients.

Journal Article↗

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Sentinel node biopsy in vulvar malignancies: a preliminary feasibility study.

Sentinel lymph node biopsies (SLNB) were investigated in 8 cases (6 squamous cell carcinomas, 2 melanomas) of vulvar malignancy. The sentinel node was detected by patent blue dye injection (1 case), pre operative lymphoscintigraphy with intra-operative gamma hand-held probe (2 cases), and combined techniques (5 cases). The procedure was successful in all cases but one (1 invasive squamous cell carcinoma) in which there was medial groin recurrence at 6 months. Nodal invasion was observed in only one case and was confined to the sentinel node. No specific morbidity related to the SLNB procedure occurred. SLNB appears to be a feasible and promising technique, however, requiring further evaluation before being considered as a reliable method to spare inguinofemoral lymphadenectomy in early-stage patients free of sentinel node metastasis, or to be substituted in screening elderly clinically node-negative females.

Adult↗

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Methotrexate for the treatment of patients with multiple episodes of acute cardiac allograft rejection.

Of 142 cardiac allograft recipients who underwent transplantation from December 1985 to January 1991, four women and seven men (mean age, 41 +/- 14 years) required multiple (10.5 +/- 3.3) courses of antirejection treatment over a total follow-up period of 30 +/- 15 months. The underlying heart disease was cardiomyopathy in six patients and coronary disease in five patients. These patients were treated with methotrexate (10 mg/wk for 6 weeks). Rejection treatment before methotrexate therapy included six courses of OKT3, one course of antithymocyte globulin, 33 courses of high-dose steroids, and 45 courses of low-dose steroids for the entire group. The average number of rejection treatments per patient before methotrexate therapy was 8.7 +/- 3.5 treatments or 0.90 +/- 0.51 treatments per month of follow-up. After methotrexate therapy the average number of rejection treatments fell to 1.7 +/- 1.1 treatments or 0.11 +/- 0.08 treatments per month of follow-up (p = 0.0002). Seven patients responded to a single course of methotrexate therapy; three patients required two courses (second course, 20 mg/wk for 6 weeks), and one patient required three courses of methotrexate therapy. The only complication associated with methotrexate therapy was one patient in whom cytomegalovirus interstitial pneumonitis developed while on therapy. Methotrexate was well tolerated and appeared to be effective in halting repeated episodes of rejection in this subset of patients who have had multiple episodes of acute rejection.

Adult↗

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Disinfection and sterilization.

Explore the source record for details and available documents.

Disinfection↗