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S M Samson

Publications and source records attributed to S M Samson.

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Declining efficacy of AIDS case list cross-referencing in human immunodeficiency virus look-back: 1981 through 1992.

BACKGROUND: The impact of AIDS case list cross-referencing in human immunodeficiency virus look-back was assessed. STUDY DESIGN AND METHODS: Post-1977 blood donations from former donors identified by 11 collaborating health departments as having developed AIDS have been traced at Irwin Memorial Blood Centers since 1983. To assess the changing efficacy of AIDS case list cross-referencing in identifying infected donors and recipients, trends in cases reported through December 1992 were analyzed. RESULTS: Previous donors (n = 638) were identified from 21,917 AIDS case listings, for an overall match rate of 2.9 percent. The rate of detection of previous donors from listings of AIDS cases declined from a peak of 5.3 percent in 1985 to 1.6 percent in 1992. Overall, 86 percent (1824/2122) of donations by persons later reported on AIDS case lists were made prior to January 1983 when risk exclusion measures were initiated. Of the 212 known infected recipients linked to AIDS case list donors, 87 (41%) were previously identified by other look-back approaches. The rate of identification of infected recipients detected exclusively through AIDS case listings declined from a mean of 21 per year from 1984 to 1987 to a mean of 3 per year from 1990 to 1992. No transmissions have been documented from donations prior to 1979. CONCLUSION: These findings demonstrate the declining yield of AIDS case list cross-referencing as a trigger for human immunodeficiency virus look-back. Continued reevaluation of look-back programs is essential so that their various components may be curtailed when justified.

Acquired Immunodeficiency Syndrome↗

Heterosexual transmission of human immunodeficiency virus type 1 from transfusion recipients to their sex partners.

Using lookback procedures and other methods, we identified and then prospectively followed human immunodeficiency virus type 1 (HIV-1)-infected transfusion recipients and their sex partners to determine AIDS incidence and risks of heterosexual transmission of HIV-1. At enrollment, 7 of 32 (21.9%) female partners of male recipients were themselves infected with HIV-1, as compared with none of 14 male partners of female recipients (p = 0.08). No additional episodes of transmission were observed. The prevalence of advanced immunodeficiency at enrollment was similar in male and female recipients. Male recipients with advanced immunodeficiency (CD4+ lymphocyte count < or = 0.20 x 10(9)/L or a history of clinical AIDS) at enrollment were more likely to have infected their female partners (odds ratio = 7.9; p = 0.03) than men with neither condition. Similarly, AIDS-free survival, as estimated by the product-limit method, was lower among male transmitters than among male nontransmitters (p = 0.01). Transmission was not associated with frequency of unprotected vaginal intercourse. Our data suggest that HIV-1-infected men who develop immunodeficiency rapidly are more likely to infect their sex partners and that the greater efficiency of male-to-female HIV-1 transmission is not explained by a greater number of sexual contacts or more advanced immunodeficiency in index subjects.

Adult↗

Risk of human immunodeficiency virus (HIV) transmission by blood transfusions before the implementation of HIV-1 antibody screening. The Transfusion Safety Study Group.

Little information is available regarding the risk of human immunodeficiency virus type 1 (HIV-1) infection for patients transfused before routine anti-HIV-1 screening of blood donors was instituted in March 1985. A model was developed for estimating both the proportion and the number of transfusion recipients in the San Francisco Bay area who were infected by HIV-1 during each of the 7 years preceding routine donor screening for anti-HIV-1. The model is based on analysis of 1) donation histories of HIV-1-infected donors identified at the regional blood center; 2) HIV-1 seroprevalence estimates for homosexual and bisexual men in San Francisco; and 3) HIV-1 infection and survival rates for recipients traced by the Transfusion Safety Study and Irwin Memorial Blood Centers' Look Back Program. The incidence of transfusion-associated HIV-1 infection is estimated to have risen rapidly from the first occurrence in 1978 to a peak in late 1982 of approximately 1.1 percent per transfused unit. The decrease after 1982 coincided with the implementation of high-risk donor deferral measures. It is estimated that, overall, approximately 2135 transfusion recipients were infected with HIV-1 in the San Francisco region alone. This number suggests a higher prevalence of transfusion-associated HIV-1 infection than has been generally recognized and indicates the need for continued tracing of potentially exposed recipients. The data also strongly support the effectiveness of early donor education and self-exclusion measures and emphasize the importance of continued research and development in this area.

Acquired Immunodeficiency Syndrome↗

The natural history of transfusion-associated infection with human immunodeficiency virus. Factors influencing the rate of progression to disease.

Patients infected by the human immunodeficiency virus (HIV) as a result of blood transfusions are unique in that their dates of infection are well defined and their medical conditions before infection are known. To characterize the natural history of transfusion-associated HIV infection, we studied 694 recipients of blood from 112 donors in whom AIDS later developed and from 31 donors later found to be positive for HIV antibody. Of the recipients tested, 85 were seronegative, 116 were seropositive, and 19 had AIDS. Of 101 HIV-seropositive recipients followed for a median of 55 months after infection, 54 had Centers for Disease Control Class IV disease, including 43 with AIDS. Life-table analysis suggested that AIDS will develop in 49 percent of infected recipients (95 percent confidence limits, 36 to 62 percent) within seven years after infection. As compared with recipients without AIDS, the 43 recipients with AIDS had received more transfusions at the time of infection (median, 21 vs. 7; P = 0.01). HIV-infected blood donors in whom AIDS developed were grouped according to whether AIDS developed within 29 months (the median) after donation (Group 1) or 29 or more months after donation (Group 2). As compared with the 31 recipients of blood from Group 2 blood donors, the 31 recipients of blood from Group 1 donors were more likely to have AIDS four years after infection (49 percent vs. 4 percent; P = 0.005) and illnesses resembling acute retroviral syndrome (14 of 24 vs. 5 of 22; P = 0.03). We conclude that most recipients of HIV-infected blood become seropositive, that AIDS develops in about half these recipients within seven years, and that the risk may be higher when AIDS develops in the blood donor soon after donation.

Acquired Immunodeficiency Syndrome↗

Analysis of the role of cysteine residues in isopenicillin N synthetase activity by site-directed mutagenesis.

The predicted amino acid sequences of isopenicillin N synthetase from both Cephalosporium acremonium and Penicillium chrysogenum have two cysteine residues in analogous positions (Cys-106 and Cys-255 in the C. acremonium numbering). To examine the role of these cysteine residues in the activity of the C. acremonium enzyme, we used site-directed in vitro mutagenesis to change these cysteine residues to serine residues. Mutation of Cys-255 reduces specific activity approximately equal to 50%, whereas mutation of Cys-106 or mutation of both Cys-106 and Cys-255 reduces specific activity about 97%. This suggests that the cysteines are important but not essential for IPNS activity. Alkylation of IPNS also almost completely inactivated the enzyme, but residual activity could have been due to incomplete alkylation. Atomic substitution via genetic manipulation in this case is a more accurate means of assessing the role of sulfhydryl moieties in enzyme activity.

Acremonium↗

Isolation, sequence determination and expression in Escherichia coli of the isopenicillin N synthetase gene from Cephalosporium acremonium.

The enzyme isopenicillin N synthetase (IPS) catalyses the oxidative condensation of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (LLD-ACV) to isopenicillin N, which is a central reaction in the pathway to clinically important penicillins and cephalosporins. Here we report the cloning, characterization and expression in Escherichia coli of the gene encoding the IPS protein in Cephalosporium acremonium. The IPS gene was identified by purifying IPS protein, determining the first 23 amino-terminal amino acids, preparing a set of synthetic oligonucleotides encoding a portion of the determined amino-acid sequence, and probing a cosmid genome library with the mixed oligonucleotides. A cosmid hybridizing with the probe was isolated and the IPS gene was localized and sequenced. The IPS gene encodes a polypeptide of relative molecular mass (Mr) 38,416. When this open reading frame was cloned into an E. coli expression vector and inserted into E. coli, the recombinant E. coli produced a new protein co-migrating with authentic IPS as the major protein of the cell (approximately 20% of cell protein). Crude cell extracts condensed LLD-ACV to a penicillinase-sensitive molecule whose antibacterial activity indicated that it was isopenicillin N.

Acremonium↗