Biomedical subjects

G J Adams

Publications and source records attributed to G J Adams.

15 recordsLinked to original sources

PubMed2001

Networks and tuberculosis: an undetected community outbreak involving public places.

After decades of decline in developed countries, there was a resurgence of tuberculosis in the mid-1980s accompanied by increased recognition that this infectious disease has long remained a major public health problem at the global level. New methods from molecular biology, in particular DNA 'fingerprinting' (of Mycobacterium tuberculosis), made it clear that current transmission and recent infection (in contrast to reactivation of earlier, latent infection) were much more significant than previously believed. Studies of tuberculosis outbreaks using these new tools pointed to complex networks through which infection was spreading and highlighted the need for new approaches to outbreak investigation and disease control. In the study reported here a new approach--combining methods from molecular biology, epidemiology and network analysis--was used to examine an outbreak of tuberculosis in Houston, Texas. Initial investigation using conventional strategies revealed few contacts among 37 patients with identical (six-band) DNA (IS6110-based) fingerprints but subsequent research uncovered over 40 places (including many gay bars) to which patients in this outbreak could be linked. Network methods were used to reconstruct an outbreak network and to quantify the relative importance (here, 'betweenness' centrality) of different actors (persons and places) playing a role in the outbreak. The multidisciplinary work provides the basis for a new approach to outbreak investigation and disease control.

AIDS-Related Opportunistic Infections↗

PubMed2001

Developmental, family, and ethnic influences on adolescent alcohol usage: a growth curve approach.

The influence of the developmental process of individuation, family conflict and cohesion, and ethnicity on adolescent alcohol use was examined in a 3-year longitudinal study. Participants included non-Hispanic White, Mexican American, and African American adolescents (n = 6,522) from 6th, 7th, and 8th grades. They were surveyed annually for 3 years. Depending on which aspect of individuation was measured, hierarchical linear modeling indicated that changes in adolescent individuation were related to either increases or decreases in alcohol use over the 3-year period. Separation and family conflict were related to increases in alcohol use, and intergenerational individuation and family cohesion were related to decreases in alcohol use. White and Mexican American adolescents had a faster rate of increase in alcohol use than did African American youth. Separation and family process similarly influenced adolescent alcohol use from different ethnic groups. Implications for prevention and intervention programs are discussed.

Adolescent↗

PubMed2001

Interactive effects of individuation, family factors, and stress on adolescent alcohol use.

A prospective, school-based study of increasing alcohol use in a multi-ethnic sample of 7,540 adolescents showed that the effects of stress, family conflict, and parental monitoring were differentially moderated by two modes of individuation. The effects of stress were moderated by ethnic status and individuation. Implications for prevention and intervention are discussed.

Adolescent↗

PubMed2001

The contribution of ethnicity to Mycobacterium tuberculosis strain clustering.

OBJECTIVE: Descriptive study of molecular epidemiologic patterns of tuberculosis cases among ethnic minorities in Houston, Texas. DESIGN: Population-based, prospective, active surveillance, and molecular epidemiology study. PATIENTS: Tuberculosis cases reported to the City of Houston Tuberculosis Control Office between October 1995 and September 1998. RESULTS: During the study period, 1,139 culture-positive patients were enrolled for whom isolates of their culture specimen were available. Of these, 910 were part of an ethnic minority. Molecular characterization identified 689 of 1,139 isolates to be clonally related. Factors significantly associated with tuberculosis strain clustering in a multivariable logistic regression analysis were: birth in the United States, a history of homelessness, infection with the human immunodeficiency virus (HIV), pulmonary disease, infection with a tuberculosis strain from principal genetic group 1 or 3, living in a residence with five or more persons present, and use of public transportation more than once weekly. Asian ethnicity and increasing age were associated with decreased odds of clustering. CONCLUSIONS: Ethnicity was not a significant covariate for strain clustering after adjustments for factors related to socio-economic status.

Adult↗

PubMed2000

Epidemiologic differences between United States- and foreign-born tuberculosis patients in Houston, Texas.

The proportion of foreign-born tuberculosis patients in the United States is increasing. To analyze the epidemiology of tuberculosis in foreign-born people, culture-positive patients with tuberculosis in Houston, Texas, were interviewed from October 1995 through September 1998, and their isolates were molecularly characterized. Of the 1131 patients included in the study, 795 (70.3%) were US born and 336 (29.7%) were foreign born. The decrease in tuberculosis case rate among US-born people was 3.5 times that of foreign-born people. Significantly more US-born than foreign-born patients belonged to strain clusters (71.3% vs. 29.5%; P<.001). Risk factors associated with strain clustering were as follows: black ethnicity, low income, and homelessness in US-born patients and homelessness in foreign-born patients. Isolates from foreign-born patients were more likely to be resistant to >/=1 drug (15.4% vs. 8.4%; P=.001) and to be multidrug resistant (2.4% vs. 0.7%; P=.027) than isolates from US-born patients. These observations warrant increased emphasis on this distinct subpopulation of tuberculosis patients.

Adolescent↗

PubMed2000

Human immune response to streptococcal inhibitor of complement, a serotype M1 group A Streptococcus extracellular protein involved in epidemics.

Streptococcal inhibitor of complement (Sic) is a highly polymorphic extracellular protein made by serotype M1 group A Streptococcus strains that contributes to bacterial persistence in the mammalian upper respiratory tract. New variants of the Sic protein arise very rapidly by positive selection in human populations during M1 epidemics. The human antibody response to Sic was analyzed. Of 636 persons living in diverse localities, 43% had anti-Sic serum antibodies, but only 16.4% had anti-M1 protein serum antibody. Anti-Sic antibody was also present in nasal wash specimens in high frequency. Linear B cell epitope mapping showed that serum antibodies recognized epitopes located in structurally variable regions of Sic and the amino terminal hypervariable region of the M1 protein. Phage display analyses confirmed that the polymorphic regions of Sic are primary targets of host antibodies. These results support the hypothesis that selection of Sic variants occurs on mucosal surfaces by a mechanism that involves acquired host antibody.

Adolescent↗

PubMed1999

Complex transmission dynamics of clonally related virulent Mycobacterium tuberculosis associated with barhopping by predominantly human immunodeficiency virus-positive gay men.

Limited data suggest that measures to reduce tuberculosis transmission should be based on locations rather than on personal contacts. Molecular epidemiologic methods (analysis of IS6110 patterns, spoligotypes, variable numbers of tandem DNA repeats, and automated DNA sequence data) identified a cohort of 48 persons who were infected with progeny of the same Mycobacterium tuberculosis strain. Epidemiologic investigation documented that a large proportion of the patients were gay white human immunodeficiency virus-positive men. Most practiced barhopping, an activity that involved patronizing many bars in the same neighborhood each night. Few subjects were directly linked to more than 1 or 2 other persons by conventional investigation methods, which shows that the transmission dynamics were unusually complex compared with most previously described episodes of strain spread. The data support the concept that identification of locations where pathogen dissemination likely occurs may provide additional strategies for targeted tuberculosis control.

Alcohol Drinking↗

PubMed1999

Extracellular cysteine protease produced by Streptococcus pyogenes participates in the pathogenesis of invasive skin infection and dissemination in mice.

The role of an extracellular cysteine protease encoded by the speB gene in group A Streptococcus (GAS) skin infection was studied with a mouse model. Mice were injected subcutaneously with a wild-type GAS serotype M3 strain or a cysteine protease-inactivated isogenic derivative grown to stationary phase. The mortality rate of mice injected with the M3 speB mutant strain was significantly decreased (P < 0.0008) compared to that of animals injected with the wild-type parental organism. The abscesses formed in animals infected with the cysteine protease mutant strain were significantly smaller (P < 0.0001) than those caused by the wild-type organism and slowly regressed over 3 to 4 weeks. In striking contrast, infection with the wild-type GAS isolate generated necrotic lesions, and in some animals the GAS disseminated widely from the injection site and produced extensive cutaneous damage. All of these animals developed bacteremia and died. GAS dissemination was accompanied by severe tissue and blood vessel necrosis. Cysteine protease expression in the infected tissue was identified by immunogold electron microscopy. These data demonstrate that cysteine protease expression contributes to soft tissue pathology, including necrosis, and is required for efficient systemic dissemination of the organism from the initial site of skin inoculation.

Animals↗

PubMed1994

Vaccination with streptococcal extracellular cysteine protease (interleukin-1 beta convertase) protects mice against challenge with heterologous group A streptococci.

Virtually all clinical isolates of group A streptococci secrete a highly conserved extracellular cysteine protease that cleaves human fibronectin and vitronectin, and converts IL-1 beta precursor to biologically active IL-1 beta. Based on the high degree of gene conservation within the species and its role in host pathogenicity, it was postulated that antibodies to the cysteine protease would confer protective immunity against S. pyogenes infection. To test this hypothesis, Swiss CD1 mice were intraperitoneally administered either saline, rabbit IgG, or IgG from rabbits immunized with the protease, and challenged with a highly virulent (minimum lethal dose approximately 10 cfu) clinical isolate of S. pyogenes expressing a heterologous cysteine protease. The results indicate that mice administered IgG from rabbits immunized with purified cysteine protease had significantly enhanced survival when compared with mice given either non-specific rabbit IgG (log rank test; chi 2; p = 0.0195) or saline (log rank test; chi 2; p = 0.0002). Moreover, mice actively immunized with the cysteine protease had a significantly longer time to death than the control group (log rank test; chi 2; p = 0.0418). The results show that the cysteine protease elicits non-type-specific immunity to challenge with heterologous S. pyogenes.

Animals↗

PubMed1989

The pro-peptide is not necessary for active renin secretion from transfected mammalian cells.

Cultured mouse myeloma cells were transfected with expression vectors encoding the aspartyl proteinase, human renin. The full construct, encoding the renin precursor prorenin, allows transfected cells to secrete the enzymically inactive pro-protein. Activity is detectable only following trypsin treatment which mimics the physiological activation step. Accordingly, it appears that myeloma cells do not contain detectable levels of an appropriate activating proteinase. However, when these cells are transfected with a construct from which the pro-peptide coding sequence has been deleted, they secrete an apparently fully active enzyme which is indistinguishable from mature renin. We conclude that expression of the pro-peptide is not necessary to allow correct folding of the molecule and its passage through the secretory pathway.

Amino Acid Sequence↗

PubMed1989