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Biomedical subjects

S E Read

Publications and source records attributed to S E Read.

At least 19 recordsLinked to original sources
PubMed1996

Characteristics of HIV-infected pregnant women in the Bahamas.

The Commonwealth of the Bahamas has one of the highest rates of acquired immunodeficiency syndrome (AIDS) in the English-speaking Caribbean. A seroprevalence study of pregnant women attending antenatal clinics in New Providence in 1990-91 showed that of 3,914 pregnant women tested, 2.9% were human immunodeficiency virus (HIV) infected. Women born in the Bahamas constituted 79.2% of the women tested; 17.7% were born in Haiti. The rate of HIV infection was 2.5% in the Bahamian women as compared with 4.5% in those born in Haiti. The highest incidence was in women aged 25-34 years and in women who had multiple pregnancies. There was a significant association with a history of crack cocaine use by the Bahamian women. There was also a significant association between a lack of education and HIV infection in this group. There was a lower rate of condom use among women with less education and also among women in common-law relationships, but the association of lack of condom use and HIV infection did not reach statistical significance.

Adolescent↗
PubMed1996

Screening for cytomegalovirus retinitis in children.

OBJECTIVES: To identify immunosuppressed children who are at risk of cytomegalovirus (CMV) retinitis developing and to evaluate the use of laboratory results for identifying this risk. DESIGN: Prospective cohort and retrospective case-control series. SETTING: University hospital pediatric referral center. PATIENTS: Fifty-six consecutive immunocompromised children (ie, the prospective group) with laboratory evidence consistent with acute or recently acquired CMV infection, which was defined as CMV cultured from the blood, urine, nasopharynx, or biopsy specimen, recent seroconversion, a 4-fold increase in the CMV antibody titer, or an antibody titer of 1:512 or greater. Ninety-three immunocompromised children (ie, the retrospective group) with acute CMV or previous CMV exposure, which was defined as a CMV titer of 1:4 or greater and less than 1:512. MAIN OUTCOME MEASURE: Occurrence of CMV retinitis. RESULTS: Cytomegalovirus retinitis developed in 3 children in the prospective group and in 4 children in the retrospective group. The causes of immunosuppression were severe combined immunodeficiency syndrome (n = 2), severe combined immunodeficiency syndrome status post bone marrow transplantation (n = 1), acquired immunodeficiency syndrome (n = 1), and acquired immunodeficiency syndrome status post bone marrow transplantation for leukemia (n = 1), renal transplantation (n = 1), and chemotherapy for leukemia (n = 1). Cytomegalovirus retinitis was associated with a positive CMV culture result from the urine (P = .03) or nasopharynx (P < .001) in the retrospective group. In the retrospective group, one child with congenital CMV infection and CMV retinitis was excluded from analysis because laboratory tests for CMV were not obtained prior to ganciclovir therapy. CONCLUSIONS: Cytomegalovirus retinitis is uncommon in children compared with adults; it occurred in 5% of the children in our series. A screening ophthalmologic examination should be considered in immunocompromised children with positive CMV laboratory results, particularly positive results of urine or nasopharynx cultures.

Adolescent↗
PubMed1996

HIV infection in vitro enhances the activity of src-family protein tyrosine kinases.

OBJECTIVE: We examined the effect of HIV infection on src-family protein tyrosine kinase (PTK) activity to determine if alterations in src-family PTK activity could contribute to the HIV-related chronic immune system activation observed in patients infected with HIV. METHODS: Jurkat, a CD4+ human T lymphocyte cell line was infected with HIV IIIB. Kinase activity was determined by in vitro immune complex kinase assays using antibodies specific for the src-family PTKs, p56lck, p59fyn and p60c-src expressed in T lymphocytes. PTK protein and total phosphotyrosine levels were assessed by Western blotting. The role of the gp120-CD4-Lck interaction in HIV-related PTK activation was determined using gp 120-treated Jurkat cells and HIV-infection of JCaM 1.6 cells, a Jurkat-derived cell line that lacks p56lck. RESULTS: Cells infected with HIV for 24 h exhibited increased levels of total tyrosine phosphorylation and enhanced src-family PTK activity without altered levels of expression of src-family kinases. The activity of Lck and Fyn was enhanced within 30 min of infection. HIV-related src-family PTK activation was not a function of the gp120-CD4-Lck interaction and occurred in the presence of 10 mmol/l zidovudine indicating that reverse transcriptase and activation of the HIV genome is not required. CONCLUSIONS: HIV-related activation of src-family PTK is a response of the cell to early stages of the virus life cycle, possibly either membrane fusion or viral uncoating. These results indicate that endogenous src-family PTKs may play a role in HIV-related immune activation and dysfunction. Moreover, activation of src-family PTK may be a mechanism used by the virus to facilitate some aspect of its own life cycle.

Catalysis↗
PubMed1995

Programmed cell death induced by HIV type 1 antigen stimulation is associated with a decrease in cytotoxic T lymphocyte activity in advanced HIV type 1 infection.

The immune competence of peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus-seropositive (HIV+) patients was studied by assessing cytotoxic T lymphocyte (CTL) activity following recall HIV antigen stimulation. Target cells were HLA-A-matched EBV-transformed B cells expressing HIV-1 antigen. In the presence of recombinant IL-2 (rIL-2, 2 or 10 U/ml), about 50% of PBMCs from HIV+ asymptomatic patients responded to HIV-1 antigen stimulation in vitro with increased cytotoxic activity. In contrast, PBMCs from patients with overt AIDS, cultured in medium containing rIL-2 (2 U/ml) and HIV-1 antigen, showed no increase in cytotoxic activity; in the presence of rIL-2 (10 U/ml) and HIV-1 antigen, an inhibitory effect on CTL activity was observed. This inhibitory effect was associated with programmed cell death (apoptosis) of CD8+ lymphocytes and cells of both gamma/delta TcR-positive and -negative phenotypes. However, prior to the apoptosis, different TcR phenotypes of T lymphocyte reacted differently to HIV-1 antigen stimulation. The HIV-1 antigen initially appeared to cause gamma/delta TcR-positive T lymphocytes to proliferate and/or differentiate and later induced cell death. Whereas, prior to the apoptosis, no proliferation of gamma/delta TcR-negative T lymphocytes induced by HIV-1 antigen was observed.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Quantitative measures of human immunodeficiency virus-specific antibodies predict progression to AIDS.

Studies examining specific antibodies directed against antigenic components of human immunodeficiency virus (HIV), as potential markers of progression to AIDS, have reported inconsistent results. We used reflectance densitometry and survival analysis to determine whether single quantitative measures of HIV-specific antibodies predicted progression to AIDS in a prospective cohort of 159 HIV-infected homosexual men. Lowered baseline levels of p24 antibody and p24/gp41 antibody ratio were independent predictors of progression to AIDS and retained statistical significance after simultaneously controlling for CD4:CD8 ratio, age, use of zidovudine, and clinical symptoms. Quantitative measures of p24 antibody and p24/gp41 antibody ratio warrant further study with regards to their clinical application as markers of HIV disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Lack of correlation between phenotype activation markers of CD8 lymphocytes and cytotoxic T lymphocyte (CTL) function in HIV-1 infection: evidence for rescue with rIL-2.

CTL activity against HIV-1 antigens expressed on HLA-A-matched EBV-transformed B target cells was detected in 33% (6/18) of freshly isolated PBMC (FPBMC) from patients in the early stages of HIV-1 infection (CDCII). No CTL activity was detected in FPMBC in patients with AIDS (CDCIV). However, the presence of CTL activity did not correlate with the expression of CTL activation markers. A dual-color flow cytometric examination revealed that the CD8+ lymphocytes bearing the memory (CD29) and activation (S6F1) surface molecules increased in number as the HIV-1 infection progressed. This functional and phenotypic discrepancy in memory CD8+ lymphocytes suggests that the memory CD8+ lymphocytes have lost cytotoxic function and become "paralyzed" as the HIV disease progresses. Incubation of PBMC of HIV(+) patients with rIL-2 reactivated predominantly HIV-specific CTL. However, rIL-2 stimulation also activated a "polyclonal or polyreactive" cytotoxic function. The reactivation of CTL function is rIL-2 dosage dependent and the amount of rIL-2 required for reactivation is associated with the severity of the disease. HIV antigen specific CTL in HIV(+) patients can be selectively expanded by HIV antigen stimulation in the presence of rIL-2. These results suggest that the in vivo IL-2 deficiency occurring in HIV-1 infection may be responsible in part for the "paralysis" of HIV specific CTL activity. Such activity can be rescued nonspecifically by exogenous rIL-2 stimulation and expanded specifically by HIV-1 antigen stimulation.

Antigens, Surface↗
PubMed1993

Ongoing high-risk sexual behaviors in relation recreational drug use in sexual encounters. Analysis of 5 years of data from the Toronto Sexual Contact Study.

The current study investigated the association between the use of recreational drugs at the time of sexual activity and high-risk sexual behavior in a Toronto cohort of 249 homosexual and bisexual men over a 5-year period commencing in 1984 to 1985 and concluding in 1989 to 1990. The main analysis was based on a total of 2536 visits. Univariate and multivariate Liang-Zeger regression models were used to relate the log of the sexual activity score (SARS) to the independent variables over the 20 follow-up visits while controlling for intercorrelations between variables from the same respondent. We found that there was a significant decline, over time, in the sexual activities that pose a higher risk of infection with human immunodeficiency virus. Recreational drugs still appear to be playing an important role in the continuation of higher-risk sexual activities. The use of poppers in conjunction with sex is a strong predictor of high-risk activity, as is use of alcohol and marijuana in conjunction with sex. Also, simultaneously strongly associated with higher-risk score is the Centers for Disease Control classification II. More emphasis needs to be placed on educating the population about the potential risks of combining reactional drugs with sexual activity.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Using serial observations to identify predictors of progression to AIDS in the Toronto Sexual Contact Study.

The Toronto Sexual Contact Study comprises a cohort of 249 male sexual contacts of men with HIV disease which has been followed every 3 months for almost 5 years. On enrollment 143 were seropositive and 16 seroconverted during the follow-up period. By 31 December 1989, 41 of the 159 seropositive cohort members had developed AIDS. Using Cox relative risk regression models, we investigated the association of a number of laboratory and clinical variables and progression to AIDS. Fixed covariate models examined laboratory variables from the enrollment visit of cohort members, with time calculated from this date. In models assessing time dependent covariates, time was calculated from the estimated date of HIV infection. In the univariate models of either fixed or time dependent covariates, many variables were significantly associated with risk of progression to AIDS (T4 cell count, T4/T8 ratio, blastogenic responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen, serum IgA, appearance of p24 antigen, and the development of oral hairy leukoplakia, thrush, or herpes zoster). Appearance of persistent generalized lymphadenopathy was not associated with increased risk of progression. In the multivariate model which evaluated fixed laboratory covariates, T4/T8 ratio, IgA level, and PHA response at enrollment were significantly associated with elevated risk.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Serodiagnosis↗
PubMed1992

The probability of progression to AIDS in a cohort of male sexual contacts of men with HIV disease.

In a cohort of 249 male sexual contacts of men with AIDS or an AIDS-related condition (ARC), 143 cohort members were seropositive on enrollment and 16 seroconverted during follow-up. A logistic Weibull mixture model was used to estimate the probability of progression to AIDS after HIV infection when infection was assumed to occur during the period of sexual contact with the primary case. Forty cohort members developed AIDS while under study. It appears that at least 50% of men with HIV disease will progress to AIDS and that the best estimate of this probability lies anywhere in the interval 70% to 100%.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Percutaneous injuries among health care workers. The real value of human immunodeficiency virus testing of 'donor' blood.

A decision analysis was conducted to examine whether health care workers should receive short-term (42 days) zidovudine treatment following percutaneous exposure to blood, as well as to determine the value of testing "donor" (patient's) blood. Three alternative options were analyzed: treat all, treat none, and test. In the treat all option, all health care workers receive short-term zidovudine therapy immediately after exposure; in the treat none option, no one receives zidovudine; and in the test option, donor blood is tested, and if it is human immunodeficiency virus (HIV) positive, zidovudine is given. Baseline variables were obtained from the literature. Each outcome was expressed as a utility; this is a method of quantifying the values that persons place on different health states. The results showed that the test option was preferred. Sensitivity analyses indicated that even if the risk of seroconversion were zero or the effectiveness of zidovudine were zero or the drug were withheld, this option was preferred, thus indicating some value of testing other than merely identifying health care workers who should receive zidovudine. In the baseline analysis, this was derived from the fact that approximately 95% of the health care workers would be reassured by a negative test; ie, only approximately 5% of donors are HIV positive. If the prevalence of HIV seropositivity exceeded 42%, the treat none option was preferred. This was found to be due to the fact that increased numbers of health care workers would be told that they were exposed to HIV-positive blood. The "worrying factor" associated with such an exposure was such that above 42% HIV seropositivity, the treat none option was preferred overall. Thus, the real value of testing donor blood is in identifying those persons (greater than 95%) who could be told that they were exposed to HIV-negative blood, that is, reducing their worrying factor to zero. Because acquired immunodeficiency syndrome is a fatal disease, and given that zidovudine is the only available therapeutic option at present, the drug has an important role to play if its effectiveness is greater than zero.

Allied Health Personnel↗
PubMed1991

Regulation of tumor necrosis factor receptor expression by acid-labile interferon-alpha from AIDS sera.

High levels of an unusual acid-labile interferon (IFN) alpha in sera of patients with human immunodeficiency virus (HIV) infection are associated with disease progression to acquired immunodeficiency syndrome (AIDS). Since IFNs have been shown to enhance the cytotoxic actions of tumor necrosis factor (TNF), a potent mediator of inflammation and cachexia, a study was undertaken to investigate whether the acid-labile IFN alpha produced in AIDS can regulate TNF receptor expression. The expression of TNF receptors was determined by studying the interaction of [125I]TNF with cellular receptors. The results show the acid-labile IFN alpha present in AIDS sera is capable of inducing the expression of cellular receptors for TNF. The extent of induction of TNF receptors depends on the concentration of the acid-labile IFN alpha in the AIDS sera. There is no significant induction of TNF receptors when the AIDS sera are preneutralized with polyclonal anti-IFN alpha antibodies. It is also shown that the synthesis of TNF by peripheral blood monocytes (PBM) from patients with HIV infection is enhanced during the progression of HIV infection in vivo. Thus, the TNF system is activated in patients with HIV infection. This activation may be a contributing factor to some of the physiological disturbances including the wasting syndrome observed in AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Comparison of saliva and blood for human immunodeficiency virus prevalence testing.

Testing saliva for the detection of human immunodeficiency virus (HIV) antibodies has many potential advantages for epidemiologic surveillance. A commercial ELISA kit and a standardized in-house immunoblot (IB) system were slightly modified to enhance antibody detection in saliva. Frozen saliva specimens from Toronto Sexual Contact Study participants (including sequential saliva specimens collected during seroconversion) were tested as were fresh saliva samples collected from a population of street-based intravenous drug users (IVDUs). HIV antibody results on saliva were compared with HIV serostatus determined by ELISA and IB on serum or dried blood spots. The overall sensitivity was 98.3% (117/119) for the kit and 99.2% (118/119) for IB; the specificity was 100% (429/429). In the IVDU population, compliance in the voluntary submission of specimens increased from 69% agreeing to provide blood samples to 89% agreeing to provide blood, saliva, or both. Saliva specimens can be easily collected under difficult field conditions with minimal training and provide a valuable alternative to testing blood for HIV-seroprevalence studies.

Cohort Studies↗
PubMed1991

Inhibition of human immunodeficiency virus type 1 multiplication by antisense and sense RNA expression.

Human immunodeficiency virus type 1 (HIV-1) primarily infects CD4+ lymphocytes and macrophages and causes AIDS in humans. Retroviral vectors allowing neomycin phosphotransferase (npt) gene expression were engineered to express 5' sequences of HIV-1 RNA in the antisense or sense orientation and used to transform the human CD4+ lymphocyte-derived MT4 cell line. Cells expressing antisense or sense RNA to the HIV-1 tat mRNA leader sequence, as part of the 3' untranslated region of the npt mRNA, remained sensitive to HIV-1 infection. In contrast, resistance to HIV-1 infection was observed in cells expressing antisense RNA to the HIV-1 primer-binding site or to the region 5' to the primer-binding site as part of the 3' region of the npt mRNA. Cells expressing the tat mRNA leader sequence in the sense orientation as a precise replacement of the 5' untranslated region of npt mRNA were also resistant to HIV-1. These results indicate that sense and antisense approaches can be used to interfere with HIV-1 multiplication.

Base Sequence↗
PubMed1991

Resistance to human immunodeficiency virus type 1 (HIV-1) infection in human CD4+ lymphocyte-derived cell lines conferred by using retroviral vectors expressing an HIV-1 RNA-specific ribozyme.

Toward gene therapy for the treatment of human immunodeficiency virus type 1 (HIV-1) infections in AIDS, Moloney murine leukemia virus-derived retroviral vectors were engineered to allow constitutive and tat-inducible expression of an HIV-1 5' leader sequence-specific ribozyme (Rz1). These vectors were used to infect the human CD4+ lymphocyte-derived MT4 cell line. The stable MT4 transformants expressing an HIV-1 RNA-specific ribozyme, under the control of the herpes simplex virus thymidine kinase (tk) promoter, were found to be somewhat resistant to HIV-1 infection as virus production was delayed. In cells allowing ribozyme expression under control of the simian virus 40 or cytomegalovirus promoter, the rate of HIV-1 multiplication was slightly decreased, and virus production was delayed by about 14 days. The highest level of resistance to HIV-1 infection was observed in MT4 cells transformed with a vector containing a fusion tk-TAR (trans activation-responsive) promoter to allow ribozyme expression in a constitutive and tat-inducible manner; no HIV-1 production was observed 22 days after infection of these cells. These results indicate that retroviral vectors expressing HIV-1 RNA-specific ribozymes can be used to confer resistance to HIV-1 infection.

Base Sequence↗
PubMed1991

Colchicine: a state-of-the-art review.

Colchicine is an ancient drug that is attracting renewed interest because of its actions at a subcellular level. Specifically, it interferes with microtubule growth and therefore affects mitosis and other microtubule-dependent functions. Various mechanisms have been proposed to account for the action of colchicine in acute gouty arthritis, its interaction with cellular membrane and cyclic 3',5'-adenosine monophosphate, and its action in amyloidosis. Pharmacokinetic studies have been relatively limited and their results somewhat contradictory, with mean terminal elimination half-lives of 19 minutes to 9 hours being reported. Some of these differences may be attributed to assay difficulties. Colchicine can cause gastrointestinal side effects and should be used with care to protect patients from toxic doses. Colchicine-induced myopathy and neuropathy may be more frequent than previously recognized, and therefore patients receiving long-term therapy should be monitored carefully. Bone marrow depression has been reported, primarily in cases of acute colchicine intoxication, and intravenous administration of the drug has been associated with severe pancytopenia and death. Colchicine intoxication causes multiple organ failure. Because of its cytogenic effects and reported association with Down's syndrome, the agent should not be used by pregnant women.

Amyloidosis↗
PubMed1991

Comparison of three HIV antigen detection kits in sequential sera from a cohort of homosexual men.

HIV antigen detection kits are available from a number of commercial sources. Abbott, Coulter, and Du Pont antigen kits were used to test 661 sera collected sequentially from 65 members of the Toronto Sexual Contact Study (TSCS). The sera had been collected at 3-month intervals over 4 years from nine persistently HIV-seronegative men, 14 seroconverters, and 42 seroprevalent participants. Antigen was not detected in any seronegative men. Two of 14 seroconverters were antigen positive in the specimen immediately preceding seroconversion (by all kits). Antigen was detected in 22 of 56 seropositive participants; of these, 16 of 22 demonstrated the emergence of antigen during observation. Discrepancies were noted in the time of detection of antigen (ranging from 3 months to more than 3 years) in nine participants. Although overall concordance among all kits for all specimens appears high (95.4%), when the bias introduced by testing multiple specimens from the same patient is removed, the lower bound of concordance among all three kits is estimated to be 80%. Similarly, after correction, the upper and lower bound of estimates of sensitivity are Abbott 96, 92%; Coulter 88, 63%; and Du Pont 88, 58%. There are significant differences in the performance characteristics of these commercial products for the detection of HIV antigen in serum.

AIDS-Related Complex↗
PubMed1990

Erythema infectiosum and pregnancy-related complications.

Erythema infectiosum, an acute, communicable viral disease with a highly distinctive exanthem, follows the usual course of a self-limiting benign disease. In pregnant women, however, it may be associated with fetal death and nonimmune hydrops fetalis. Because of the association of human parvovirus (HPV) B19 infection with fetal damage we reviewed the current knowledge of the clinical aspects of erythema infectiosum, focusing on pregnancy and fetal outcome, to determine the magnitude of fetal risk and offer recommendations for management. Among 180 infected pregnant women 44 fetal deaths (24%) occurred, 1 to 12 weeks after the infection was noted. Pregnant women should be advised that (a) because of the high prevalence (up to 65%) of anti-HPV B19 IgG antibody among adults most of them are not at risk and (b) if maternal infection does occur therapeutic abortion is not indicated since intrauterine infection causes fetal death more often than abnormal development. Infection should be suspected in pregnant women who exhibit the symptoms of erythema infectiosum with or without arthropathy. They should be monitored for an elevated serum alpha-fetoprotein level (indicating fetal aplastic crisis) and undergo serial ultrasonography for the detection of hydrops fetalis. Although the incidence of congenital malformation is no higher than the expected rate in the general population (3% to 5%), the precise incidence of fetal adverse outcomes remains unknown and requires investigation in larger, prospective studies.

Erythema↗