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1.
S Shuman E M Kane S G Morham 《Proceedings of the National Academy of Sciences of the United States of America》1989,86(24):9793-9797
Site-directed mutagenesis of the vaccinia virus gene encoding a type I DNA topoisomerase implicates Tyr-274 as the active-site residue that forms a covalent adduct with DNA during cycles of DNA-strand breakage and reunion. Replacement of Tyr-274 by phenylalanine results in loss of the ability of the enzyme to relax negatively supercoiled DNA as well as to form the covalent DNA-protein intermediate. Substitution of phenylalanine for tyrosine at nine other sites in the protein has no apparent effect on enzyme activity. Amino acid sequence alignment reveals Tyr-274 to be homologous to Tyr-727 and Tyr-771, respectively, of the type I topoisomerases from Saccharomyces cerevisiae and Saccharomyces pombe; Tyr-727 and Tyr-771 have been shown to represent the active-site tyrosines of those enzymes. Sequence comparison of the active-site regions defines a motif Ser-Lys-Xaa-Xaa-Tyr common to the viral and cellular type I topoisomerases, including the human enzyme. 相似文献
2.
D S Rao R Antonelli K R Kane J E Kuhn C Hetnal 《Henry Ford Hospital medical journal》1991,39(1):41-44
Coexistent primary hyperparathyroidism and monoclonal gammopathy, although rare, has been reported previously by a number of investigators. We report four patients with such an occurrence who were seen between 1976 and 1988. Another patient with primary hyperparathyroidism also had multiple myeloma and was in remission for 12 years. These patients represent approximately 1% of the 386 patients with primary hyperparathyroidism seen during the same 12-year period. Although several mechanisms have been proposed to explain this concurrence, we believe it is the result of a chance occurrence. A review of the literature, an estimate of the chance occurrence of coincidental monoclonal gammopathy, benign or malignant, in patients with primary hyperparathyroidism, and some practical implications of this interesting coexistence are presented. 相似文献
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Both cyproterone acetate (CPA) and the gonadotrophin-releasing hormone
agonist (GnRHa) have been shown to be effective for the treatment of
hirsutism. We wished to compare the effectiveness of CPA in two standard
doses with GnRHa and add-back therapy and to compare the length of
remission after these treatments. A total of 60 hirsute hyperandrogenic
women was assigned to the following treatment groups: CPA 2 mg with 35
microg of ethinylestradiol for 21 days each month (Diane group), CPA 50 mg,
days 5-15, and ethinylestradiol 50 microg, days 5-25, each month (CPA
group) or Decapeptyl 3.75 mg i.m. every 28 days with the addition of
conjugated oestrogen 0.625 mg, days 1-21, and medroxyprogesterone acetate
10 mg, days 12-21 (GnRHa group). Hirsutism was graded by the
Ferriman-Gallwey-Lorenzo (FGL) index and anagen hair shaft diameters and
serum luteinizing hormone (LH) and testosterone were assessed before and
every 3 months during and after treatment. All women were treated for 1
year with 1 year follow-up. At baseline hirsutism and endocrine patterns
were similar in all groups. After one year of treatment, hirsutism
decreased in all groups but the changes were greater (P <0.05) in the
CPA and GnRHa groups than in the Diane group. Serum LH and testosterone
were lowest in the GnRHa group. After withdrawal, hirsutism increased
rapidly in the Diane and CPA groups and after 6 months, FGL scores and hair
shaft diameters were similar to pretreatment values. In the GnRHa group,
hirsutism increased more gradually and after 1 year of withdrawal, FGL
scores and hair diameters were significantly (P <0.05) less than
pretreatment values. Serum LH and testosterone increased rapidly in all
three groups reaching pretreatment values by 6 months. These data suggest
equal efficacy of the GnRHa and the high dose CPA regimen for the treatment
of hirsutism in hyperandrogenic women. GnRHa with add-back treatment
appears to result in a longer remission of hirsutism in comparison with
CPA.
相似文献
5.
Maxillary sinusitis in adults: an evaluation of placebo-controlled double-blind trials 总被引:1,自引:0,他引:1
BACKGROUND: In general practice, acute sinusitis is frequently diagnosed
and treated with antibiotics. OBJECTIVE: This study aimed to determine the
evidence for the effectiveness of antibiotic treatment in acute maxillary
sinusitis in adults by assessing the methodological quality of
placebo-controlled double-blind randomized trials. METHOD: An evaluation by
four raters through a 35-item scoring-scale for internal and external
validity of all placebo-controlled double-blind randomized trials on acute
sinusitis found between January 1966 and July 1996. RESULTS: Eighty-five
trials were excluded because they were not placebo-controlled,
double-blind, randomized, or were carried out in patients with chronic
sinusitis or in children. The three remaining trials were performed in
different populations (one in general practice) between 1973 and 1978. Only
one study claimed superiority of antibiotic treatment. Different inclusion
criteria and major outcome measures were used by the authors. The
reliability of major outcome events was reported poorly or not at all and
in two studies outcome measures were clinically inappropriate. The studies
scored 30-62% of the maximum attainable score for internal validity and
10-20% for external validity. CONCLUSION: The effectiveness of antibiotic
treatment in acute maxillary sinusitis in a general practice population is
not based sufficiently on evidence.
相似文献
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BACKGROUND: There are obvious advantages to increasing donor retention. However, for reasons of blood safety, certain donors may, in fact, be more desirable to retain than others. “Safe” donors are defined as those who provided a blood donation that was negative on all laboratory screening tests and who subsequently reported no behavioral risks in response to an anonymous survey. This study identifies the most important factors affecting the intention of “safe” donors to provide another donation. STUDY DESIGN AND METHODS: An anonymous survey asking about donation history, sexual history, injecting drug use, and recent donation experience was mailed to 50,162 randomly selected allogeneic donors (including directed donors) who gave blood from April through July or from October through December 1993 at one of the five United States blood centers participating in the Retrovirus Epidemiology Donor Study. Before mailing, questionnaires were coded to designate donors with nonreactive laboratory screening tests at their most recent donation. RESULTS: A total of 34,726 donors (69%) responded, with substantially higher response among repeat donors. According to reported intentions only, the vast majority of “safe” donors indicated a high likelihood of donating again within the next 12 months. Only 3.4 percent reported a low likelihood of donating again. A comparison of those likely to return and those unlikely to return reveals significant differences in demographics and in ratings of the donation experience. A higher proportion of those unlikely to return were first-time donors, minority-group donors, and donors with less education. The highest projected loss among “safe” donors was seen for those who gave a fair to poor assessment of their treatment by blood center staff or of their physical well-being during or after donating. CONCLUSION: These data suggest that efforts to improve donors' perceptions of their donation experience, as well as attention to the physical effects of blood donation, may aid in the retention of both repeat and first-time donors. 相似文献