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Biomedical subjects

L Doll

Publications and source records attributed to L Doll.

At least 19 recordsLinked to original sources

Indinavir did not increase the short-term risk of adverse cardiovascular events relative to nucleoside reverse transcriptase inhibitor therapy in four phase III clinical trials.

A retrospective person-time analysis of the randomized and non-randomized extension phases of four phase III trials was performed to assess the incidence of adverse cardiovascular events in 2680 HIV-infected patients receiving indinavir or nucleoside reverse transcriptase inhibitor therapy, or both. The observed rate of cardiovascular events was not increased in patients receiving indinavir-based regimens compared with therapy without a protease inhibitor. Extrapolation of these findings is limited by the brief length of therapy and the small number of cases.

Anti-HIV Agents↗

Prevalence of sexual and drug-related HIV risk behaviors in the U.S. adult population: results of the 1996 National Household Survey on Drug Abuse.

CONTEXT: Data on the prevalence of HIV risk behavior that are representative of the general population are needed to help evaluate the effectiveness of prevention programs. OBJECTIVE: To use data from a large national interview survey to make estimates of the prevalence of sexual and drug-related HIV risk behaviors in the adult population of the United States. DESIGN: Nationally representative cross-sectional survey with in-person interviews collecting information on drug use and sexual behavior. SETTING AND PARTICIPANTS: 12,381 U.S. adults aged between 18 and 59 who were respondents to the 1996 National Household Survey on Drug Abuse, as part of sample of the noninstitutionalized population. Interviews took place in respondents homes using face-to-face interviewer-administered and self-administered questionnaires. RESULTS: In total, 2.8% of respondents were classified as having increased risk for HIV through sexual behavior; this represents 3.9 million persons. 1.7% reported some degree of risk through drug-related behaviors, representing 1.2 million persons. 3.5% of adults (5 million persons) were found to have some degree of HIV risk from sexual or drug-related behavior. Persons who were at risk through drug behavior were much more likely than others to be at risk through sexual behavior. Condom use was not related to HIV risk, although having a recent HIV test was found to be. Among those who reported some behaviors that placed them at increased risk for HIV infection, only 22% used a condom the last time they had sex with a regular partner. CONCLUSIONS: The high rate of sexual risk behavior on the part of drug users suggests increasing condom use for this group should be a priority goal for programs, especially condom use with main partners. Survey work needs to be continued and improved to make it possible to assess the impact of successful local prevention efforts on national rates of HIV risk behavior.

Adolescent↗

Detection of proviral human T-cell lymphotrophic virus type I DNA in mouthwash samples of HAM/TSP patients and HTLV-I carriers.

Human T-cell lymphotrophic virus type I (HTLV-I), is a member of the oncogenic retroviruses family endemic in several parts of the world and also recently identified in the Jewish Mashhadi population who immigrated from Iran to Israel. The virus is the causative agent of adult T-cell leukemia (ATL) and a chronic myelopathy known both as tropical spastic paraparesis (TSP) or HTLV-I associated myelopathy (HAM). The known modes of HTLV-I transmission are by sexual intercourse, from mother to child in breast milk, via blood transfusion, and by sharing of needles by parenteral drug users. In the present study we examined the presence of HTLV-I provirus genomic DNA by nested polymerase chain reaction (PCR) and by DNA hybridization in mouthwash samples obtained from 13 Mashhadi-born Iranian Jews with spastic paraparesis associated with HTLV-I, 4 Mashhadi-born Iranian Jews asymptomatic carriers for HTLV-I and 21 healthy controls. Proviral HTLV-I DNA was detected by mouthwash PCR in 12 of 17 HTLV-I infected subjects (71%) but in none of 21 controls. Proviral DNA was also detected in mouthwash samples using HTLV-I probe by dot blot hybridization assay. The presence of HTLV-I proviral DNA in whole saliva may suggest a possible transmission of the virus via saliva and explain the increased rate of infection in elderly Mashhadi-Jewish population.

Base Sequence↗

HIV/AIDS knowledge and high risk sexual practices among southern California Vietnamese.

OBJECTIVES: Vietnamese immigration to the U.S. since the conclusion of the Vietnam war has been substantial and in Orange County, CA, Vietnamese Americans comprise 3% of the population (the largest community in the US). Our objective was to collect data on the HIV/AIDS knowledge, attitudes and self-reported high risk behaviours within this community. METHODS: A survey instrument was administered anonymously in Vietnamese to 532 respondents in their homes. Individuals from three population strata were randomly sampled: men 18 to 35 years old (N = 193); men 36 to 45 years old (N = 137); and women 18 to 35 years old (N = 202). Data were gathered on: (1) degree of acculturation; (2) knowledge and attitudes towards HIV/AIDS; and (3) self-reported sexual and other high risk practices. RESULTS: Survey data indicated that 38% of respondents were very worried about themselves and 83% were worried about a family member getting AIDS. Knowledge about actual modes of HIV transmission was generally accurate, but a substantial minority still believed that HIV can be transmitted through casual contact, and 68% from needles used in hospitals. Women demonstrated less accurate knowledge than men on five key items. Quarantine of the HIV infected was agreed to by 45%. Twenty-nine percent did not believe that the epidemic would affect them personally, and 49% stated that they did not have enough information about AIDS to protect themselves. Regarding sexual practices, 31% reported never having had sex. Of the others, 8% had two or more sexual partners in the prior 12 months. No same sex behaviour was reported. Six percent of men had visited a female prostitute; of these, 24% had visited 2 or more in the prior 12 months; half of encounters in this time period were outside the US. Substantial percentages of sexually active, unmarried respondents indicated that they never use (17-40%) or only sometimes use (10-32%) condoms. Less than 1% had used injection drugs. CONCLUSIONS: Education should be targeted at the Vietnamese community of southern California to improve knowledge that HIV cannot be contracted through casual contact, to convey information about methods for self-protection, and to reduce high risk sexual practices such as unprotected sex, sex with multiple partners and sex with prostitutes.

Acquired Immunodeficiency Syndrome↗

AIDS, HIV infection, and illicit drug use within inner-city families and social networks.

OBJECTIVES: Drug use is commonly depicted and treated as an individual problem. This study describes the extent of drug use, human immunodeficiency virus (HIV) infection, and acquired immunodeficiency syndrome (AIDS) among drug users' sexual partners and family and household members in order to broaden considerations of risk. METHODS: Social network charts and structured interviews were administered to 126 women (predominantly African American and Latino) enrolled in methadone treatment. The charts elicited the prevalence of drug use and HIV infection among subjects' family and household members. RESULTS: Drug use and HIV/AIDS permeated subjects' sexual, familial, and household relationships. More than half of the women who resided with a sexual partner reported that their partners currently used drugs. Almost one third of the subjects' siblings were drug users. Of the 715 total siblings (all subjects plus their siblings), 69 (9.7%) were known to be HIV positive or to have an AIDS diagnosis. CONCLUSIONS: The sexual, familial, and household expressions of drug use underscore the notion that drug use and attendant risks, including but not limited to HIV infection, might be usefully viewed and treated as an inter- and intracommunity problem rather than as an exclusively individual one.

Acquired Immunodeficiency Syndrome↗

Cloning and sequencing of two new fli genes, the products of which are essential for Salmonella flagellar biosynthesis.

We have identified two new open reading frames downstream from fliC, which appear to encode 19- and 20-kDa proteins that are essential for flagellar formation. The nucleotide and the predicted amino acid sequences of the genes are presented. Both genes, termed fliU and fliV, are preceded by the flagellar-specific -10 consensus promoter DNA sequence, suggesting their expression in the earlier stages of flagellar-component biosynthesis.

Amino Acid Sequence↗

Spastic paraparesis associated with human T-lymphotropic virus type I: a clinical, serological, and genomic study in Iranian-born Mashhadi Jews.

The Mashhadi-Jewish community originating in Iran is a closed and ethnically segregated population with a unique history and a high rate of intrafamilial marriage among its members. A high risk of infection by human T-lymphotropic virus type I (HTLV-I) and of adult T-cell leukemia associated with such infection was found in this population. HTLV-I is also associated with a syndrome of progressive spastic paraparesis. We therefore evaluated the occurrence of HTLV-I infection and spastic paraparesis in Mashhadi-born Iranian Jews who immigrated to Israel. We examined 83 Mashhadi-born subjects (52 women, 31 men; mean age, 61 +/- 15.5 years) and 73 age-matched non-Mashhadi Iranian-born Jews. Blood samples were tested for HTLV-I antibodies by particle agglutination test. The polymerase chain reaction (PCR) was used to detect HTLV-I proviral DNA sequences from peripheral blood mononuclear cells. Fifteen Mashhadi-born Jews (18%) were both seropositive and PCR-positive for HTLV-I. Four HTLV-I-seronegative subjects were found to be positive for HTLV-I proviral DNA by PCR. Of the 19 HTLV-I-infected subjects (11 women, 8 men; mean age, 59 +/- 16 years), 13 (68%) had spastic paraparesis of varying severity. There were no signs of myelopathy in the Mashhadi-born subjects who were negative for HTLV-I proviral DNA by PCR. None of the non-Mashhadi Iranian Jews was seropositive or PCR-positive for HTLV-I proviral DNA, or had clinical signs of spastic paraparesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Poly(GTG)5-associated profiles of Salmonella and Shigella genomic DNA.

DNA hybridization with oligonucleotide probes is a powerful technique to study population genetics and structures. The use of probes which recognize ubiquitously interspersed DNA sequences has a distinct advantage over other techniques (e.g. the analysis of patterns of restriction fragment length polymorphism) in that many independent loci can be detected simultaneously. In this communication, we investigated the use of a trinucleotide repetitive DNA oligonucleotide, poly(GTG)5, in Southern blot analysis of Salmonella serotypes and Shigella species. The strains in this study were isolated over several years from widely disparate geographic locations and can therefore be considered to represent the structure of part of the natural populations of these organisms. In most of the Salmonella serotypes, the poly(GTG)5-associated profile (GTG profile) phenotypes appeared to be clonally stable; in cases where only one isolate of a serotype was tested, the GTG profile was distinct from the others. On the other hand, when GTG profile analysis was applied to Shigella strains, each of the 12 isolates, belonging to the four Shigella species, produced a unique pattern phenotype of both the chromosome and plasmid DNA.

Autoradiography↗

fliU and fliV: two flagellar genes essential for biosynthesis of Salmonella and Escherichia coli flagella.

The possible functions of two recently described flagellar genes, fliU and fliV, have been examined. Introduction of gene fliC, encoding the bacterial flagellin protein, into a number of flagellin-deficient Salmonella and Escherichia coli strains failed to complement the mutations in these strains, and the FliC flagellin was accumulated in the bacterial cytoplasm. Complementation with fliU and fliV, which map downstream of fliC, restored motility to some of the mutants which became flagellated. After inactivation of either fliU or fliV, such complementation no longer occurred and the flagellin protein accumulated in the cytoplasm, which suggested that both genes are required for the secretion of flagellin and expression of motility. Expression of these genes from high copy number plasmids resulted in the synthesis of exceptionally long flagella and in detection of the FliV protein on polyacrylamide gels.

Bacterial Proteins↗

Mono- and bi-phasic Salmonella typhi: genetic homogeneity and distinguishing characteristics.

Several lines of evidence indicate a relatively low genetic heterogeneity in the natural Salmonella typhi population. However, some S. typhi isolates found in Indonesia express, instead of the usual fliC-d flagellin gene, a different flagellar gene fliC-j. In addition, Indonesian strains may have a second flagellar antigen fliC-z66. We have previously suggested, on the basis of the flagellar antigen constitution, that S. typhi evolved in an isolated human population in Indonesia. In order to test this hypothesis, we have gathered S. typhi isolates from around the world and tested the genetic heterogeneity among them. In general, polymorphism was greater in isolates from the Far East, as was indicated by Southern hybridizations with rDNA and fliC DNA probes. Gene fliC-j was not found in S. typhi isolates, other than those from Indonesia. However, the one-clone origin of S. typhi was indicated by a common DNA fingerprint pattern and by the occurrence, in the 5' end region of the fliC gene, of 10 scattered nucleotides that differ from the corresponding 10 nucleotides in other fliC alleles studied. These nucleotides were present in all isolates tested but did not change the amino acid sequence of the flagellin polypeptide.

Africa↗

No evidence for female-to-female HIV transmission among 960,000 female blood donors. The HIV Blood Donor Study Group.

The frequency of female-to-female HIV transmission was assessed among 960,000 female blood donors at 20 large U.S. blood centers during 1990. Of 144 HIV-seropositive women identified, 106 were interviewed. None of the interviewed women reported sex exclusively with women since 1978. Three seropositive women reported sex contact with women as well as with either bisexual men or men who had used i.v. drugs. In this large population, we identified no woman who was infected with HIV from sexual contact with another woman.

Adolescent↗

Lipid dependence of surface conformations of protein kinase C.

The change of conformation of protein kinase C interacting with the surface of a mercury electrode directly from a solution or through a lipid monolayer was inferred from the number of cystine residues exposed and reduced on the electrode and from their reduction potentials. Soluble protein kinase C was estimated to have 5-6 disulfide bonds which could potentially react with the mercury electrode. Two major reduction peaks of cystine at different microenvironments within the protein molecule adsorbed to a mercury surface. They were observed in a.c. polarograms and cyclic voltamograms at two distinct potentials. The potential of these peaks became more negative as the pH of the solution increased, which was consistent with relaxation or decrease in alpha-helicity (ordered structure) of the protein as determined by circular dichroism (CD) estimations of secondary structure. The peak at the more positive potentials (-0.46 V relative to NAg/AgCl electrode at pH 7.4) tended to vanish upon cyclic reduction and reoxidation of the cystine, while the more negative peak (-0.62 V at pH 7.4) was enhanced. Addition of Mg2+ or Ca2+ had no significant effect on the potential but there was a reduction in their amplitude which appeared to affect the disappearance of these peaks upon pH adjustment. This suggests that the tertiary structure of the molecule is stabilized by Ca2+ and Mg2+, as substantiated by CD spectral analysis of secondary structures. Protein kinase C penetrated lipid monolayers to some extent. Addition of diacylglycerol or phorbol ester to the lipid monolayers facilitated this penetration. These compounds stabilized the protein surface conformation by destabilizing the monolayer at more positive potentials, resulting in an enhanced reduction peak at -0.42 V. This phenomenon was not significantly affected by Mg2+ or by Ca2+. The region of the protein kinase C (PKC) sequence which penetrated the monolayer contains cysteines and a primary amine(s), and may have homology to a region of phospholipase A2 which has been proposed as a phospholipid binding site for the two enzymes. Additionally, these polarographic studies suggest that PKC associates with and penetrates monolayers in a divalent cation-independent manner in agreement with our previous physical analyses of PKC interactions with lipid bilayers.

Adsorption↗