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R Coutinho

Publications and source records attributed to R Coutinho.

At least 19 recordsLinked to original sources
PubMed2006

Discrete time piecewise affine models of genetic regulatory networks.

We introduce simple models of genetic regulatory networks and we proceed to the mathematical analysis of their dynamics. The models are discrete time dynamical systems generated by piecewise affine contracting mappings whose variables represent gene expression levels. These models reduce to boolean networks in one limiting case of a parameter, and their asymptotic dynamics approaches that of a differential equation in another limiting case of this parameter. For intermediate values, the model present an original phenomenology which is argued to be due to delay effects. This phenomenology is not limited to piecewise affine model but extends to smooth nonlinear discrete time models of regulatory networks. In a first step, our analysis concerns general properties of networks on arbitrary graphs (characterisation of the attractor, symbolic dynamics, Lyapunov stability, structural stability, symmetries, etc). In a second step, focus is made on simple circuits for which the attractor and its changes with parameters are described. In the negative circuit of 2 genes, a thorough study is presented which concern stable (quasi-)periodic oscillations governed by rotations on the unit circle - with a rotation number depending continuously and monotonically on threshold parameters. These regular oscillations exist in negative circuits with arbitrary number of genes where they are most likely to be observed in genetic systems with non-negligible delay effects.

Algorithms↗
PubMed2005

[Human Immunodeficiency Virus type 1 seroincidence estimate among a group of drug users: a new approach].

INTRODUCTION: Estimating Human Immunodeficiency Virus type 1 (HIV-1) infection remains one of the great challenges of the epidemiologic surveillance of HIV-1 epidemics. WHO has recently approved a laboratory based strategy that enables the identification of recent infections. OBJECTIVES: To identify the number of recent (incident) infections and estimate the seroincidence of HIV-1, using for the first time in Portugal, a new methodology based on the Avidity Index of HIV-1 antibodies. METHODS: Cross-sectional study of a HIV-1 positive group selected within drug users admitted in a Low Threshold Methadone Program in Lisbon during a one-year period. Avidity Index is calculated by testing a sample from each participant on the automated AxSYM HIV 1/2gO assay (Abbott) following a specific protocol. HIV-1 infections are classified as recent or established according to the Avidity Index value. RESULTS: The Low Threshold Methadone Program admitted 714 drug users and 175 were HIV-1 infected at admission (proportion of 24.5%; 95% confidence interval (CI): 21.3-27.7). Twenty recent infections were identified and the seroincidence of HIV-1 estimated as 3.58% (IC 95%, 2.0-5.1) (six-month value), which corresponds to an annual projection of 7.16% (IC 95%, 5.0-9.3). Comparative analysis between groups identified independent associations between incident HIV-1 infections and race/ethnicity (p=0.047), educational level (p=0.006) and presence of HBsAg (p=0.028). In the present study no association was found between incident HIV-1 infections and ever injected or syringe sharing. Independent determinants were found in logistic regression associated to HIV-1 incident infection: presence of HBsAg (odds-ratio (OR)=5.0; 95% CI 1.3-19.1) and race/ethnicity other than Caucasian (OR=4.0; 95% CI 1.1-14.7). CONCLUSION: The avidity index methodology is simple and rapid, allowing the identification of recent infections. So far, there are no published national or international studies, allowing us to assess our annual projection of HIV-1 seroincidence, due to the recent introduction of this methodology.

Adult↗
PubMed2002

Field experimental evaluation of secondary metabolites from marine invertebrates as antifoulants.

The crude organic extracts of the endemic gorgonian Phyllogorgia dilatata and two sponge species Aplysina fulva and Mycale microsigmatosa were evaluated for anti-fouling properties through field experiments. To investigate this property in ecologically meaningful conditions, crude extracts from these invertebrates were incorporated at concentrations naturally found in these marine organisms into a stable gel used as a substratum for fouling settlement. Crude extract from A. fulva showed no significant anti-fouling property at the natural concentrations used in the field experiments. In fact, fouling organisms settled significantly more on gels treated with A. fulva extract than on the control gel. On the other hand, both M. microsigmatosa and P. dilatata yielded crude extracts that exhibited a selective action inhibiting only the settlement of barnacles. The evidences obtained here by means of field experiments can provide a basis for future development of one kind of natural antifoulant technology to prevent marine biofouling.

Analysis of Variance↗
PubMed2001

Surrogate markers for disease progression in treated HIV infection.

OBJECTIVE: To characterize the relationships among highly active antiretroviral therapy (HAART), HIV-1 RNA levels, immune system markers, and clinical outcome in a cohort of HIV-1-infected homosexual men. PATIENTS: A total of 123 men enrolled in the Amsterdam cohort study of HIV-1 infection and AIDS with a documented seroconversion for HIV-1 antibodies and known date of seroconversion were included in this study. METHODS: CD4 + /CD8 + T-cell counts and HIV-1 RNA levels in plasma were measured approximately every 6 months. Dates of starting and stopping antiretroviral therapy were also recorded. The relationship between HIV-1 RNA in plasma, CD4 + /CD8 + T-cell counts and HAART and their influence on clinical outcome were examined using a graphical chain modeling approach. Generalized estimating equations were used to examine correlations among the three disease markers. Hazards models with time-dependent covariates were used to examine the influence of HAART and the disease markers on progression to AIDS. RESULTS: HAART was significantly associated with reduced disease progression (relative hazard [RH] of AIDS, 0.20;, 95% confidence interval [CI], 0.05-0.85). The most recent HIV-1 RNA measurement and CD4 + T-cell count are independently associated with disease progression (adjusted RH for HIV-1 RNA 1.8 per log 10 increase; 95% CI, 1.2-2.6, p =.002; adjusted RH for CD4 + 0.48 per 100 x 10(6)/L increase; 95% CI, 0.40-0.58; p <.001). Depending on these measurements, HAART was no longer significantly associated with AIDS (adjusted RH, 0.81; 95% CI, 0.18-3.6; p =.78). CONCLUSIONS: HIV-1 RNA levels in plasma and CD4 + T-cell counts are currently considered as effective surrogate markers for the effect of HAART on disease progression in this cohort.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Increase in the share of steady partners as a source of HIV infection: a 17-year study of seroconversion among gay men.

OBJECTIVES: To examine the share of steady versus casual partners as the source of HIV infection in gay male seroconversions between 1984 and 2000 and the effect of age at seroconversion on the source of HIV transmission. METHODS: The sample consisted of 144 seroconverstors from the Amsterdam Cohort Study among Homosexual Men. Questionnaires and post-seroconversion interviews were used to determine the source of HIV transmission. RESULTS: Analysis revealed an interaction effect between calendar year and age at seroconversion (P < 0.05). Younger seroconverters had higher odds ratios [odds ratio, 11.33; 95% confidence interval, 1.77--72.13] to be infected by their steady partner late in the AIDS epidemic: 15% (three of 20) between 1984 and 1987 versus 67% (six of nine) between 1994 and 2000. No such time effect was present for older seroconverters who were consistently more likely to be infected by a casual partner: 79% (37 of 47) between 1984 and 1987, and 83% (15 of 18) between 1994 and 2000. CONCLUSIONS: Young gay seroconverters today are more likely to have contracted HIV from a steady partner than from a casual partner, compared with early in the AIDS epidemic and compared also with older gay seroconverters. There is a pressing need for preventive measures addressing sexual risk behaviour within steady relationships among younger gay men.

Adult↗
PubMed2001

Factors associated with HIV-1 infection among sex workers of Addis Ababa, Ethiopia.

OBJECTIVE: To study the prevalence and risk factors for HIV infection among sex workers of Addis Ababa, Ethiopia. DESIGN AND METHODS: Cross-sectional survey on socio-demographic characteristics, behaviours, and HIV serological status of sex workers attending two health centres of Addis Ababa. RESULTS: HIV prevalence among sex workers was 274 of 372 (73.7%). Several factors were significantly associated with an increased risk of being HIV-infected [among others, working in 'shared rooms', high number of clients, use of injectable hormones, and positive Treponema pallidum particle agglutination (TPPA) serology], and others with a decreased risk (being born in Addis Ababa, high level of education, peer education on sex work, condom use, use of oral pill, and use of condoms for contraception). Of interest, sex workers who were using condoms for contraception were, compared with others, more likely to use condoms consistently (65 versus 24%, respectively; P < 0.001), and less likely to be HIV-infected (55 versus 86%, respectively; P < 0.001). In multivariate analysis [log-binomial model, giving estimates of the prevalence ratio (PR)], being born in Addis Ababa (PR = 0.74; 95% confidence interval (CI), 0.61-0.91), using condoms for contraception (PR = 0.73; 95% CI, 0.64-0.85), and a positive TPPA serology (PR = 1.21; 95% CI, 1.09-1.36), remained significantly associated with HIV infection. CONCLUSIONS: HIV prevalence was remarkably high among sex workers of Addis Ababa. Condom use was higher, and HIV prevalence lower, in sex workers using condoms not only for prevention of HIV and sexually transmitted diseases, but also for contraceptive purpose. This finding is of particular interest for its implications for prevention strategies among sex workers in the developing world.

Adolescent↗
PubMed2001

Amplified fragment length polymorphism fingerprinting for identification of a core group of Neisseria gonorrhoeae transmitters in the population attending a clinic for treatment of sexually transmitted diseases in Amsterdam, The Netherlands.

Amplified fragment length polymorphism analysis seems well suited for studying the epidemiology of isolates of Neisseria gonorrhoeae obtained from patients attending the Sexually Transmitted Disease Outpatient Clinic in Amsterdam, The Netherlands. It shows potential to identify the core group of transmitters.

Adult↗
PubMed1998

Presence of the variant mannose-binding lectin alleles associated with slower progression to AIDS. Amsterdam Cohort Study.

OBJECTIVE: To examine the association between mannose-binding lectin (MBL) polymorphism and progression to AIDS and death in HIV-1 infection. DESIGN AND METHODS: In 131 HIV-1-infected homosexual seroconverters, survival analyses were performed to determine both the association between MBL genotype and time from HIV-1 seroconversion to AIDS and death, and time from AIDS to death. RESULTS: Of the 131 seroconverters, of whom 61 developed AIDS, 76 were typed as homozygous wild-type and 55 as carriers of variant alleles (52 heterozygous and three homozygous variant alleles). A Survival analyses suggested that HIV-1-infected men with the variant alleles progressed somewhat slower to AIDS [relative hazard (RH), 0.62; 95% confidence interval (CI), 0.36-1.10] and death (RH, 0.73; 95% CI, 0.42-1.25). Interestingly, CD4+ T-cell count determined at the moment of AIDS was found to be significantly lower among persons with the mutation (97 x 10(6)/l versus 204 x 10(6)/l; P=0.03). Furthermore, when AIDS-free times before the diagnosis of an opportunistic infection were compared with those preceding a diagnosis of Kaposi's sarcoma, Kaposi's sarcoma diagnosis was more postponed than that of an opportunistic infection (RH, 0.21; 95% CI, 0.05-0.95; versus RH, 0.67; 95% CI, 0.35-1.27). CONCLUSION: Indications for a weak pre-AIDS protective effect of variant MBL alleles were demonstrated.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Identification of a site for a cohort study on natural history of HIV infection in Ethiopia.

A cross-sectional survey was carried out in a sugar estate in central Ethiopia to identify a subgroup for a cohort study on the natural history of HIV infection. HIV prevalence was 2.8% (95% confidence interval [CI], 1.7%-3.9%) in 957 adults aged 15 to 54 years randomly selected for the initial survey. A follow-up survey including only factory workers of the estate aged 18 to 45 years (n = 280) showed a higher HIV prevalence in male factory workers (n = 262) compared with the male estate workers of the same age of the initial survey (n = 484; 8.8% versus 3.1 %; p < .05). Factors independently associated with HIV infection in male factory workers were number of lifetime sexual partners, positive syphilis serology, higher income, and absence of travel outside the residential area. Among male estate workers, only older age was associated with HIV infection. Both factory workers and male estate workers were stable residents and were willing to participate in a long-term study on HIV/ AIDS. However, because of the higher HIV prevalence in factory workers and the higher prevalence of behaviors associated with an increased risk for HIV infection, factory workers were selected for the long-term cohort study on the natural history of HIV infection.

Adolescent↗
PubMed1998

Smoke-induced inhalation injury: effects of retinoic acid and antisense oligodeoxynucleotide on stability and differentiated state of the mucociliary epithelium.

Rabbit tracheal explants, exposed to burning pine wood smoke, were cultured in a chemically defined medium with and without retinoic acid (+/- RA). Exposures of 15-20 minute led to RA-independent degeneration of the mucociliary epithelial sheath. In 10 minute exposures tissue integrity was retained, but epithelial morphology changed from normal pseudostratified columnar to the flattened appearance typical of the squamous phenotype. Despite the dramatic shift in morphology, explants exhibited normal RA-dependent mucin gene expression characteristic of the mucociliary phenotype. Furthermore, electron micrographs showed continued presence of both secretory granules and cilia. RA(+) cultures also showed a normal pattern of adherent epithelial cells. In RA(-) cultures, however, there were prominent intercellular spaces indicating an RA dependence for maintaining adhesive contacts following smoke exposure. An 18-mer mucin antisense oligomer that suppressed mucin gene expression also unexpectedly blocked the smoke induced metaplasia in RA(+) cultures, but the sense oligomer had no effect.

Animals↗
PubMed1998

Emergence of syncytium-inducing human immunodeficiency virus type 1 variants coincides with a transient increase in viral RNA level and is an independent predictor for progression to AIDS.

To study the dynamics of human immunodeficiency virus (HIV)-1 RNA level around the time of conversion from non-syncytium-inducing (NSI) to syncytium-inducing (SI) phenotype and to study the predictive value of the SI phenotype for progression to AIDS, sequential samples from 123 HIV-infected homosexual men with documented intervals of seroconversion were evaluated. The NSI-to-SI phenotype conversion coincided with a 3-fold increase in median RNA level, which was not observed in matched controls in whom a viral phenotype conversion did not occur. This increase in virus was followed by a decrease to a higher steady-state RNA level than before the switch. After adjusting for RNA level and CD4 T cell count, SI phenotype was an independent marker for progression to AIDS. Hence, phenotype determination will contribute to optimal staging of HIV-infected persons in addition to virus load measurements and CD4 T cell count.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Relation of parental birth weights to infant birth weight among African Americans and whites in Illinois: a transgenerational study.

The authors used a transgenerational data set of Illinois vital records to ascertain the relation between parental birth weights and infant birth weight. The infant generation consisted of all African Americans and whites born in Illinois during 1989-1991. The parent generation included the mothers and fathers who were also born in Illinois between 1956 and 1975. In the infant cohort, the rate of low birth weight (LBW) (<2,500 g) was 11.7% for African Americans (n = 15,287) versus 5.0% for whites (n = 117,708) (relative risk (RR) = 2.3, 95% confidence interval (CI) 2.2-2.5). For African Americans, the LBW rate was 17.9% among those born to LBW mothers (n = 1,943) compared with 10.8% among those born to non-LBW mothers (n = 13,344) (RR = 1.8, 95% CI 1.6-1.9). For whites, the LBW rate was 8.5% among those born to LBW mothers (n = 2,174) compared with 4.8% among those born to non-LBW mothers (n = 115,534) (RR = 1.7, 95% CI 1.6-2.0). A weaker association was observed between paternal birth weight and infant birth weight. The authors conclude that parental birth weights are important risk factors for LBW in both African Americans and whites.

Adult↗
PubMed1997

Differentiation of respiratory epithelium: the effects of retinoic acid and carcinogens on the expression of mucociliary vs. squamous phenotype.

Changes in ultrastructural characteristics and mucin gene expression were examined in rat tracheal explants cultured in a synthetic medium +/- retinoic acid (RA), benzo[a]pyrene (B[a]P) and N-methyl-N-nitrosourea (NMNU). In the RA(+) cultures, no changes in either ultrastructural features or mucin gene expression were detected after 48 h incubation. After 96 h incubation, however, the ultrastructural features associated with the squamous phenotype were characteristics of cultures containing the two carcinogens and the mucin gene expression was slightly reduced. Thus, in the presence of retinoic acid, the carcinogen induced changes in cytology to the squamous phenotypes were not matched by a marked loss of mucin gene expression. Explants cultured for 48 h without RA and +/- carcinogens showed none of the cytological changes associated with onset of the squamous phenotype. While mucin mRNA was still detected, it was clearly reduced compared to 48 h cultures in RA(+) medium. However, 48 h later, all explants exhibited pronounced squamous metaplasia and the mucin message decreased to trace levels. Thus, the results of these experiments with B[a]P and NMNU in RA(+) and RA(-) media indicates that at least the early carcinogen induced changes may be distinct from those associated with the retinoid pathway controlling expression of the mucin component of the mucociliary epithelium.

Animals↗
PubMed1997

AIDS prognosis based on HIV-1 RNA, CD4+ T-cell count and function: markers with reciprocal predictive value over time after seroconversion.

OBJECTIVE: HIV-1 RNA levels in peripheral blood are strongly associated with progression to AIDS, CD4+ T-cell decline, or death. Their predictive value is reportedly independent of the predictive value of CD4+ T-cell counts. Because the interrelations between these parameters of HIV-1 infection are poorly understood, we studied the kinetics and predictive value of serum HIV-1 RNA levels, CD4+ T-cell counts, and T-cell function. DESIGN AND METHODS: HIV RNA levels, CD4+ T-cell counts, and T-cell function were measured from seroconversion to AIDS in 123 homosexual men who seroconverted during a prospective study and were followed over 10 years. RESULTS: Two patterns of median HIV-1 RNA levels were found during infection: a steady-state and a 'U-shaped' curve. Steady-state high RNA levels were related to rapid disease progression. For the U-shaped curve, there were groups with high and low RNA levels related to disease progression. At 1 year after seroconversion, RNA level was the only marker that was strongly predictive. Furthermore, decreasing RNA levels in the first year following seroconversion were related to better prognosis than stable low levels. Low CD4+ T-cell count and T-cell function became predictive of progression to AIDS at 2 and 5 years after seroconversion, respectively. CONCLUSIONS: With ongoing infection, the predictive value of low CD4+ T-cell count and T-cell function increases, whereas the predictive value of high HIV-1 RNA level decreases. These findings reflect the observation that infection with HIV progressively leads towards immune deficiency, which in later stages is most predictive of disease progression.

Acquired Immunodeficiency Syndrome↗