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1.
Am J Epidemiol ; 153(9): 912-20, 2001 May 01.
Article in English | MEDLINE | ID: mdl-11323323

ABSTRACT

Between the time that two large, national surveys were conducted, the Second National Health and Nutrition Examination Survey (1976-1980) and the Third National Health and Nutrition Examination Survey (1988-1994), prevalence of herpes simplex virus type 2 (HSV-2) infection in the United States increased by 30%. From these survey data, the authors estimated the incidence of HSV-2 infection in the civilian, noninstitutionalized population aged > or = 12 years by means of a mathematical model that allowed overall incidence to increase linearly with time but required the shape of the age-specific incidence curve to remain constant. From 1970 to 1985, annual incidence of HSV-2 infection in HSV-2-seronegative persons increased by 82%, from 4.6 per 1,000 (95% confidence interval: 4.2, 5.0) to 8.4 per 1,000 (95% confidence interval: 7.7, 9.1). Incidence in 1985 was higher in women than in men (9.9 vs. 6.9 per 1,000), higher in Blacks than in Whites (20.4 vs. 6.3 per 1,000), and highest in the group aged 20-29 years (14.6 and 22.5 per 1,000 in men and women, respectively). Thus, by 1985, approximately 1,640,000+/-150,000 persons (730,000 men and 910,000 women) were being infected annually with HSV-2.


Subject(s)
Herpes Genitalis/epidemiology , Herpesvirus 2, Human , Models, Statistical , Adolescent , Adult , Black or African American/statistics & numerical data , Age Distribution , Aged , Child , Ethnicity , Female , Health Surveys , Herpes Genitalis/ethnology , Herpes Genitalis/immunology , Herpesvirus 2, Human/immunology , Humans , Incidence , Male , Middle Aged , Prevalence , Risk Assessment , Seroepidemiologic Studies , Sex Distribution , United States/epidemiology , White People/statistics & numerical data
2.
J Med Primatol ; 30(6): 291-8, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11990527

ABSTRACT

Macaque monkeys are frequently used in models for studies of infectious diseases, immunity, transplantation and vaccine development. Such use is largely due to the conservation of functionally important cell surface molecules and the phylogenetic proximity of their immune systems to that of humans. Some monoclonal antibodies (mAb) raised against human leukocyte antigens can be utilized in the monkey. Until recently, many primate centers have utilized the CD2 monoclonal antibody to enumerate T lymphocytes. We have evaluated the anti-human CD3 mAb in macaques and sooty mangabeys. Using this monoclonal antibody, pigtailed macaques were found to have a much higher proportion of CD2+ CD3- CD8+ cells as compared with rhesus macaques and sooty mangabeys. Such cells comprised approximately one-half of all CD8+ cells in the pigtailed macaque, but only one-quarter of CD8+ cells in the rhesus, and one-fifth in the sooty mangabey. Use of the CD2 monoclonal antibody as the T-cell marker resulted in underestimating CD4/CD8 ratios compared with using the CD3 mAb in pigtailed macaques. Phenotypic characterization of this subset of CD3- CD8+ cells indicated that they are CD16+, CD45RA+, CD11b+, CD69+ and CD28-. This would indicate that these cells represent an activated natural killer cell subset.


Subject(s)
Antibodies, Monoclonal/immunology , CD3 Complex/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cercocebus/immunology , Macaca mulatta/immunology , Macaca nemestrina/immunology , Animals , Antibody Specificity , Antigens, Differentiation, T-Lymphocyte/immunology , CD4-CD8 Ratio , CD4-Positive T-Lymphocytes/classification , CD4-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/classification , CD8-Positive T-Lymphocytes/cytology , Cross Reactions , Female , Flow Cytometry , Humans , Immunophenotyping , Lymphocyte Subsets/classification , Lymphocyte Subsets/cytology , Lymphocyte Subsets/immunology , Male
3.
Am J Epidemiol ; 152(8): 716-26, 2000 Oct 15.
Article in English | MEDLINE | ID: mdl-11052549

ABSTRACT

The authors assessed risk factors for cervical intraepithelial neoplasia (CIN) among southwestern American Indian women using case-control methods. Cases were New Mexico American Indian women with biopsy-proven grade I (n = 190), grade II (n = 70), or grade III (n = 42) cervical lesions diagnosed between November 1994 and October 1997. Controls were American Indian women from the same Indian Health Service clinics with normal cervical epithelium (n = 326). All subjects underwent interviews and laboratory evaluations. Interviews focused on history of sexually transmitted diseases, sexual behavior, and cigarette smoking. Laboratory assays included polymerase chain reaction-based tests for cervical human papillomavirus infection, tests for gonorrhea and chlamydia, wet mounts, and serologic assays for antibodies to Treponema pallidum, herpes simplex virus, and hepatitis B and C viruses. In multiple logistic regression analysis, the strongest risk factors for CIN II/III among American Indian women were human papillomavirus type 16 infection (adjusted odds ratio (OR) = 7.6; 95% confidence interval (CI): 2.4, 23.2), any human papillomavirus infection (OR = 5.8; 95% CI: 3.3, 10.0), low income (OR = 3.3; 95% CI: 1.7, 6.2), and history of any sexually transmitted disease (OR = 2.0; 95% CI: 1.1, 3.5). Unlike previous research, this study found no strong associations between CIN and sexual activity or cigarette smoking.


Subject(s)
Indians, North American , Papillomaviridae/isolation & purification , Papillomavirus Infections/complications , Tumor Virus Infections/complications , Uterine Cervical Dysplasia/ethnology , Adolescent , Adult , Case-Control Studies , Female , Humans , Logistic Models , Marital Status , Middle Aged , New Mexico/epidemiology , Papillomavirus Infections/ethnology , Polymerase Chain Reaction , Risk Factors , Severity of Illness Index , Sexual Behavior , Sexually Transmitted Diseases/complications , Sexually Transmitted Diseases/ethnology , Smoking/adverse effects , Tumor Virus Infections/ethnology , Uterine Cervical Dysplasia/classification , Uterine Cervical Dysplasia/etiology
4.
J Virol ; 74(16): 7442-50, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10906197

ABSTRACT

The repertoire of functional CD4(+) T lymphocytes in human immunodeficiency virus type 1-infected individuals remains poorly understood. To explore this issue, we have examined the clonality of CD4(+) T cells in simian immunodeficiency virus (SIV)-infected macaques by assessing T-cell receptor complementarity-determining region 3 (CDR3) profiles and sequences. A dominance of CD4(+) T cells expressing particular CDR3 sequences was identified within certain Vbeta-expressing peripheral blood lymphocyte subpopulations in the infected monkeys. Studies were then done to explore whether these dominant CD4(+) T cells represented expanded antigen-specific cell subpopulations or residual cells remaining in the course of virus-induced CD4(+) T-cell depletion. Sequence analysis revealed that these selected CDR3-bearing CD4(+) T-cell clones emerged soon after infection and dominated the CD4(+) T-cell repertoire for up to 14 months. Moreover, inoculation of chronically infected macaques with autologous SIV-infected cell lines to transiently increase plasma viral loads in the monkeys resulted in the dominance of these selected CDR3-bearing CD4(+) T cells. Both the temporal association of the detection of these clonal cell populations with infection and the dominance of these cell populations following superinfection with SIV suggest that these cells may be SIV specific. Finally, the inoculation of staphylococcal enterotoxin B superantigen into SIV-infected macaques uncovered a polyclonal background underlying the few dominant CDR3-bearing CD4(+) T cells, demonstrating that expandable polyclonal CD4(+) T-cell subpopulations persist in these animals. These results support the notions that a chronic AIDS virus infection can induce clonal expansion, in addition to depletion of CD4(+) T cells, and that some of these clones may be SIV specific.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Complementarity Determining Regions , Simian Acquired Immunodeficiency Syndrome/immunology , Simian Immunodeficiency Virus/immunology , Animals , CD4 Lymphocyte Count , Clone Cells , Enterotoxins/immunology , Flow Cytometry , Immunoglobulin Variable Region/genetics , Macaca mulatta , Receptors, Antigen, T-Cell, alpha-beta/immunology , Staphylococcus/immunology , Staphylococcus/metabolism , Superantigens/immunology , T-Lymphocyte Subsets/immunology
5.
AIDS ; 14(16): 2429-36, 2000 Nov 10.
Article in English | MEDLINE | ID: mdl-11101052

ABSTRACT

OBJECTIVE: HIV infections in children are characterized by high viral load and, in some perinatally infected newborns, delayed appearance of viral markers. Both phenomena may be related to different levels of immune activation affecting viral replication. This study was designed to investigate the relationship between immune activation and viral replication in pediatric HIV infection, and the role of pre-existent immune activation in facilitating HIV transmission to the fetus/newborn. DESIGN: Plasma levels of soluble L-selectin (s-LS), an immune activation marker, were determined in 100 infants with perinatally transmitted HIV infection, compared with 106 age-matched HIV-exposed uninfected controls. Included in the analysis were samples from 31 HIV-infected (10 PCR+ and 21 PCR-) and 35 uninfected newborns aged < 2 days. METHODS: To determine s-LS levels, a solid phase ELISA was performed on plasma samples of patients and controls. RESULTS: s-LS levels in uninfected children were higher than those in normal adults. HIV-infected patients had more rapidly increasing values in the first 6 months of life compared with uninfected infants. Plasma s-LS levels correlated with HIV viral loads (r, 0.50). Among newborns in the first 2 days of life, s-LS levels were lowest in those with negative PCR tests, compared with PCR-positive or uninfected infants. CONCLUSIONS: These results suggest that higher immune activation in children contributes to higher viral loads, and that the level of pre-existent immune activation may have a role in determining which infants have detectable virus in peripheral blood at birth.


Subject(s)
HIV Infections/immunology , HIV-1/physiology , L-Selectin/blood , Viral Load , Child, Preschool , HIV Infections/virology , HIV-1/isolation & purification , Humans , Infant , Infant, Newborn , RNA, Viral/blood
6.
J Med Primatol ; 28(4-5): 174-80, 1999.
Article in English | MEDLINE | ID: mdl-10593483

ABSTRACT

T-cell receptor (TCR) complementarily determining region 3 (CDR3) spetratyping analysis was employed to assess the ability of an AIDS virus to disrupt CD4 + T-cell repertoires during the primary infection. Rhesus and pig-tailed macaques infected with simian immunodeficiency virus (SIV)mac 251 and SIVsmmFGb, respectively, were evaluated. Following SIV infection, the macaques exhibited an apparent decline of CD4 + peripheral blood lymphocyte (PBL) counts, which was associated with a change in CDR3 profiles from multiple-length distribution to one- or two-length dominance in the selected TCR Vbeta-expressing CD4 + PBL subpopulations. Molecular analysis of the perturbed cell subpopulations suggested that the CD4 + T cells bearing the dominant CDR3 length were clonally expanded. These results indicate that SIV infection can induce a disruption of macaque CD4 + T-cell repertoires during the primary infection. The finding in this study, therefore, suggests that the virus-induced clonal dominance can contribute to the disruption of CD4 + T-cell repertoires.


Subject(s)
CD4 Antigens/immunology , Simian Acquired Immunodeficiency Syndrome/immunology , Simian Immunodeficiency Virus/immunology , T-Lymphocyte Subsets/immunology , Animals , CD4 Lymphocyte Count , Clone Cells , Lymphocyte Activation , Macaca mulatta , Macaca nemestrina , Simian Acquired Immunodeficiency Syndrome/physiopathology , Simian Immunodeficiency Virus/pathogenicity
7.
Sex Transm Dis ; 26(8): 426-30, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10494932

ABSTRACT

BACKGROUND: Specific serologic assays for syphilis cannot differentiate current infections from past infections and are inefficient to monitor efficacy of antibiotic therapy. GOAL: To develop a new immunologic assay for the identification of active Treponema pallidum infection during the various stages of syphilis. STUDY DESIGN: Peripheral blood mononuclear cells obtained from patients with syphilis in an STD clinic were tested for T. pallidum-specific circulating antibody-secreting cells (ASC) by an enzyme-linked immunospot assay (ELISPOT). RESULTS: Specific ASC were demonstrated in all six patients with primary syphilis and in 14 of 16 patients diagnosed with secondary syphilis. ASCs were undetectable in five patients 8 to 16 days after appropriate therapy, but persisted in one case that was considered treatment failure. Among the 13 patients diagnosed with latent syphilis, six (46%) demonstrated ASC, reflecting antigenic stimulation. CONCLUSION: The ELISPOT assay is effective for the diagnosis of primary and secondary syphilis. The presence of circulating ASC suggests persistent active infection in some patients during the latent disease stage.


Subject(s)
Syphilis Serodiagnosis/standards , Syphilis/diagnosis , Treponema pallidum/immunology , Adolescent , Adult , Antibodies, Bacterial/blood , Enzyme-Linked Immunosorbent Assay , Female , Humans , Leukocyte Count , Leukocytes, Mononuclear , Male , Middle Aged , Sensitivity and Specificity , Syphilis/blood , Syphilis/pathology
8.
J Infect Dis ; 178(3): 680-5, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9728535

ABSTRACT

The effect of human immunodeficiency virus (HIV)-induced thymic dysfunction (TD) on mortality was studied in 265 infected infants in the CDC Perinatal AIDS Collaborative Transmission Study. TD was defined as both CD4 and CD8 T cell counts below the 5th percentile of joint distribution for uninfected infants within 6 months of life. The 40 HIV-infected infants with TD (15%) had a significantly greater mortality than did the 225 children without TD (44% vs. 9% within 2 years). Infants with TD infected in utero had higher mortality than did those infected intrapartum (70% vs. 37% within 2 years), while no significant difference was noted between infants without TD with either mode of transmission. The TD profile was independent of plasma virus load. Virus-induced TD by particular HIV strains and the time of transmission are likely to explain the variation in pathogenesis and patterns of disease progression and suggest the need for early aggressive therapies for HIV-infected infants with TD.


Subject(s)
HIV Infections/mortality , HIV Infections/physiopathology , HIV-1 , Thymus Gland/physiopathology , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/pathology , Cohort Studies , HIV Infections/virology , HIV-1/genetics , Humans , Infant, Newborn , Polymerase Chain Reaction , Predictive Value of Tests , Prospective Studies , Time Factors
9.
Epidemiol Infect ; 120(2): 179-86, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9593488

ABSTRACT

A seroepidemiologic study of herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) was performed on Japanese adults. Serum samples collected between 1985-9 from a total of 536 healthy adults, female prostitutes, males with sexually transmitted diseases (STD), homosexual men, and pregnant women were studied by immunodot assays using HSV type-specific antigens, glycoproteins G (gG1 and gG2). HSV-1 infections correlated mostly with age and was widely prevalent among subjects < 40 years. HSV-2 prevalence varied greatly among subgroups defined by sexual activity and was associated with risk behaviours for prostitution, infection with STD, and homosexual activity. HSV-2 seroprevalence was highest among prostitutes (80%), lowest among pregnant women (7%), and intermediate in STD patients (23%) and homosexuals (24%). Because HSV-1 infection during childhood has been decreasing, primary genital HSV-2 infection, with its higher frequency of clinical manifestations, will become a greater burden to the public health in Japan.


Subject(s)
Herpes Genitalis/epidemiology , Herpes Simplex/epidemiology , Herpesvirus 1, Human , Herpesvirus 2, Human , Adult , Antigens, Viral/blood , Blood Donors , Female , Herpes Genitalis/blood , Herpes Genitalis/virology , Herpes Simplex/blood , Herpes Simplex/virology , Herpesvirus 1, Human/immunology , Herpesvirus 2, Human/immunology , Homosexuality, Male , Humans , Japan/epidemiology , Male , Population Surveillance , Pregnancy , Prevalence , Risk Factors , Seroepidemiologic Studies , Sex Work , Sexual Behavior
10.
Nature ; 391(6667): 594-7, 1998 Feb 05.
Article in English | MEDLINE | ID: mdl-9468138

ABSTRACT

There is considerable genetic diversity among viruses of different subtypes (designated A to J) in the major group of human immunodeficiency virus type 1 (HIV-1), the form of HIV that is dominant in the global epidemic. If available, HIV-1 sequences pre-dating the recognition of AIDS could be crucial in defining the time of origin and the subsequent evolution of these viruses in humans. The oldest known case of HIV-1 infection was reported to be that of a sailor from Manchester who died of an AIDS-like illness in 1959; however, the authenticity of this case has not been confirmed. Genetic analysis of sequences from clinical materials obtained from 1971 to 1976 from members of a Norwegian family infected earlier than 1971 showed that they carried viruses of the HIV-1 outlier group, a variant form that is mainly restricted to West Africa. Here we report the amplification and characterization of viral sequences from a 1959 African plasma sample that was previously found to be HIV-1 seropositive. Multiple phylogenetic analyses not only authenticate this case as the oldest known HIV-1 infection, but also place its viral sequence near the ancestral node of subtypes B and D in the major group, indicating that these HIV-1 subtypes, and perhaps all major-group viruses, may have evolved from a single introduction into the African population not long before 1959.


Subject(s)
Disease Outbreaks/history , HIV Infections/history , HIV Infections/virology , HIV-1/genetics , Democratic Republic of the Congo/epidemiology , Evolution, Molecular , HIV Infections/blood , HIV Infections/epidemiology , HIV-1/classification , HIV-1/isolation & purification , History, 20th Century , Humans , Male , Molecular Sequence Data , Phylogeny , Polymerase Chain Reaction , RNA, Viral/blood , Sequence Alignment
11.
Am J Med Sci ; 315(2): 64-75, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9472905

ABSTRACT

Predictions that infectious diseases would be eliminated as a major threat to human health have been shattered by emerging and reemerging infections, among them acquired immunodeficiency syndrome (AIDS), hemorrhagic fevers, marked increases in infections caused by antimicrobial-resistant bacteria, and the resurgence of tuberculosis and malaria. Understanding the dynamics of emerging and reemerging infections is critical to efforts to reduce the morbidity and mortality of such infections, to establish policy related to preparedness for infectious threats, and for decisions on where to use limited resources in the fight against infections. In order to offer a multidisciplinary perspective, 23 infectious disease specialists, epidemiologists, geneticists, microbiologists, and population biologists participated in an open forum at Emory University on emerging and reemerging infectious diseases. As summarized below, the group addressed questions about the definition, the identification, the factors responsible for, and multidisciplinary approaches to emerging and reemerging infections.


Subject(s)
Communicable Diseases/epidemiology , Research/organization & administration , Acquired Immunodeficiency Syndrome/epidemiology , Bacteria/genetics , Bacterial Infections/epidemiology , Biological Evolution , Communicable Diseases/transmission , Humans , Malaria/epidemiology , Models, Theoretical , Research Design , Tuberculosis/epidemiology , Virulence , Virus Diseases/epidemiology , Viruses/genetics
13.
Scand J Immunol ; 46(3): 281-3, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9315117

ABSTRACT

The authors evaluated the lymphocyte subsets in eight children with the DiGeorge anomaly, compared with 48 age-matched control infants. Of particular interest was the finding that the percentage and number of CD5+ B lymphocytes were decreased in seven of the eight cases. This observation may provide insight into thymic function and the interaction of the B and T cell systems in some forms of congenital and acquired immunodeficiencies.


Subject(s)
B-Lymphocytes/immunology , CD5 Antigens/immunology , DiGeorge Syndrome/immunology , Antigens, CD19/immunology , Child, Preschool , Flow Cytometry , Humans , Infant , Infant, Newborn , Lymphocyte Count , Lymphocyte Subsets
14.
N Engl J Med ; 337(16): 1105-11, 1997 Oct 16.
Article in English | MEDLINE | ID: mdl-9329932

ABSTRACT

BACKGROUND: Herpes simplex virus type 2 (HSV-2) infection is usually transmitted sexually and can cause recurrent, painful genital ulcers. In neonates the infection is potentially lethal. We investigated the seroprevalence and correlates of HSV-2 infection in the United States and identified changes in HSV-2 seroprevalence since the late 1970s. METHODS: Serum samples and questionnaire data were collected during the National Health and Nutrition Examination Surveys (NHANES) II (1976 to 1980) and III (1988 to 1994). HSV-2 antibody was assessed with an immunodot assay specific for glycoprotein gG-2 of HSV-2. RESULTS: From 1988 to 1994, the seroprevalence of HSV-2 in persons 12 years of age or older in the United States was 21.9 percent (95 percent confidence interval, 20.2 to 23.6 percent), corresponding to 45 million infected people in the noninstitutionalized civilian population. The seroprevalence was higher among women (25.6 percent) than men (17.8 percent) and higher among blacks (45.9 percent) than whites (17.6 percent). Less than 10 percent of all those who were seropositive reported a history of genital herpes infection. In a multivariate model, the independent predictors of HSV-2 seropositivity were female sex, black race or Mexican-American ethnic background, older age, less education, poverty, cocaine use, and a greater lifetime number of sexual partners. As compared with the period from 1976 to 1980, the age-adjusted seroprevalence of HSV-2 rose 30 percent (95 percent confidence interval, 15.8 to 45.8 percent). The seroprevalence quintupled among white teenagers and doubled among whites in their twenties. Among blacks and older whites, the increases were smaller. CONCLUSIONS: Since the late 1970s, the prevalence of HSV-2 infection has increased by 30 percent, and HSV-2 is now detectable in roughly one of five persons 12 years of age or older nationwide. Improvements in the prevention of HSV-2 infection are needed, particularly since genital ulcers may facilitate the transmission of the human immunodeficiency virus.


Subject(s)
Antibodies, Viral/blood , Herpes Genitalis/epidemiology , Herpesvirus 2, Human/immunology , Adolescent , Adult , Age Distribution , Aged , Black People , Child , Female , Health Surveys , Herpes Genitalis/ethnology , Humans , Logistic Models , Male , Mexican Americans , Middle Aged , Multivariate Analysis , Prevalence , Seroepidemiologic Studies , Sex Distribution , United States/epidemiology , White People
15.
Clin Perinatol ; 24(2): 497-521, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9209815

ABSTRACT

This article conceptualizes the various balancing acts between the pregnant woman, the placenta, the fetus, and the infectious agents. Despite the very large number of infectious insults during pregnancy, the outcome of most interactions usually is a normal newborn. We have identified only one general immune defect of the fetus and neonate: The inability to respond to polysaccharide antigens; yet, a similar defect also is found with certain polysaccharides in older children and adults. The capacity of the neonate to control severe life-threatening diseases with most infectious agents and the ability of the fetus, when infected in utero, to mount sophisticated, immune responses make it conceptually advantageous to consider the older fetus and the newborn infant as "immunodelayed" rather than as immunodeficient or immature.


Subject(s)
Fetus/immunology , Immunity/physiology , Infections/immunology , Placenta/immunology , Pregnancy/immunology , Animals , Bacteria/immunology , Child , Female , Humans , Infant, Newborn , Infections/microbiology , Parasites/immunology , Viruses/immunology
16.
Microbiol Immunol ; 41(10): 823-7, 1997.
Article in English | MEDLINE | ID: mdl-9403510

ABSTRACT

Sixty-eight sera from the acute, recurrent, and provoked types of female genital herpes were compared for the seroprevalence of herpes simplex virus (HSV) types 1 and 2 by immunodot assay using HSV glycoprotein G. In the HSV-1-isolated patients, no HSV-2 antibodies were detected, whereas in the HSV-2-isolated patients, HSV-1 seroprevalence was 9% for the acute type, 89% for the provoked type (P < 0.005), and 55% for the recurrent type (P < 0.05). The natural history of female genital herpes and the possible protective role of pre-existing antibodies in preventing the acquisition or clinical manifestation of a subsequent HSV infection are discussed.


Subject(s)
Antibodies, Viral/blood , Herpes Genitalis/immunology , Herpesvirus 1, Human/immunology , Herpesvirus 2, Human/immunology , Acute Disease , Female , Humans , Recurrence , Viral Envelope Proteins/immunology
17.
J Immunol Methods ; 209(1): 93-104, 1997 Nov 10.
Article in English | MEDLINE | ID: mdl-9448038

ABSTRACT

A noninvasive perfusion method for the recovery of maternal placental (intervillous) blood for use in immunologic assays is described. 60% of the perfused blood samples tested for fetal red blood cell (RBC) contamination were found to be pure maternal blood; in the remainder, fetal RBC contamination, with a single exception, was less than 6%. The intervillous mononuclear cells (IVBMC) isolated from this blood were of predominantly maternal origin as demonstrated by a polymerase chain reaction-based DNA typing technique. The number of IVBMC obtained was within the range of 9 to 55 X 10(6) cells. Phenotypic analysis of IVBMC surface antigens revealed that 61% of the cells were CD3 + T-cells and 18% were CD19 + B-cells. The CD4 + and CD8 + T-lymphocyte subsets accounted for 28 and 26% of the IVBMC, respectively. The IVBMC were functionally competent as evidenced by in vitro lymphoproliferation and cytokine production in response to mitogen and PPD stimulation. This technique allows for rapid and safe isolation of large numbers of IVBMC which are functionally active up to 12 h post-delivery, thus representing a significant improvement over previously described methods. It should facilitate more vigorous research in the study of uteroplacental immunity and infectious disease research, particularly in field settings where sample collection and laboratory facilities are distant.


Subject(s)
Chorionic Villi/blood supply , Leukocytes, Mononuclear/cytology , Pregnancy/blood , Chorionic Villi/immunology , Chorionic Villi/metabolism , Cytokines/biosynthesis , DNA/analysis , Enzyme-Linked Immunosorbent Assay , Female , Fetal Hemoglobin/analysis , Humans , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Lymphocyte Activation , Perfusion , Phenotype , Pregnancy/immunology , Pregnancy/metabolism , Staining and Labeling
18.
N Engl J Med ; 335(19): 1431-6, 1996 Nov 07.
Article in English | MEDLINE | ID: mdl-8875920

ABSTRACT

BACKGROUND: Infants with congenital thymic deficiency (the DiGeorge syndrome) have immunodeficiency and a characteristic pattern of low CD4+ and CD8+ T-lymphocyte counts and low CD5+ B-lymphocyte counts. Because the thymus is essential for the generation of CD4+ cells, we sought evidence of thymus dysfunction in infants infected perinatally with the human immunodeficiency virus (HIV). METHODS: We studied the immunophenotypes of 59 infants with maternally transmitted HIV, 5 infants with the DiGeorge syndrome, and 168 infants exposed to HIV but not infected. The criteria for a presumed thymic defect were reductions in both the CD4+ and CD8+ T-cell subgroups during the first six months of life that were confirmed in a subgroup of infants by low counts of CD4+CD45RA+ and CD4+CD45RO+ T cells and CD5+ B cells. RESULTS: Of the 59 HIV-infected infants, 17 had immunophenotypes similar to those of infants with the DiGeorge syndrome. The risks of the acquired immunodeficiency syndrome (AIDS) by the ages of 12 and 24 months were 75 percent and 92 percent in these 17 infants, as compared with 14 and 34 percent in the other 42 infants (P<0.001). Nine of the HIV-infected infants with the DiGeorge-like immunophenotype (53 percent) died within six months of the progression to AIDS, as compared with only three of the other infants (7 percent, P=0.006). CONCLUSIONS: In some infants infected perinatally with HIV, a pattern of lymphocyte depletion develops that resembles the pattern in congenital thymic deficiency. Since HIV disease progresses rapidly in such infants, they may be candidates for early antiviral therapy and attempts at immune reconstitution.


Subject(s)
Acquired Immunodeficiency Syndrome/immunology , DiGeorge Syndrome/immunology , HIV Infections/immunology , Thymus Gland/immunology , Acquired Immunodeficiency Syndrome/mortality , Disease Progression , Female , HIV Infections/transmission , Humans , Immunophenotyping , Infant , Infectious Disease Transmission, Vertical , Lymphocyte Count , Male , Prospective Studies , Thymus Gland/physiopathology
19.
Sex Transm Dis ; 23(2): 138-44, 1996.
Article in English | MEDLINE | ID: mdl-8919741

ABSTRACT

BACKGROUND AND OBJECTIVES: Few published data describe the seroprevalence of antibodies to herpes viruses and hepatitis viruses among Southwestern minority women. GOALS: To determine the prevalence of antibodies to herpes simplex virus type-1 and type-2, hepatitis B, and hepatitis C among 595 southwestern Hispanic and non-Hispanic white patients seeking gynecologic care; and to investigate risk factors associated with seropositivity. STUDY DESIGN: Analysis of serologic and interview data. Antibody assays were based on purified glycoprotein assays (herpes simplex virus), and commercial assays for hepatitis B virus and hepatitis C virus. RESULTS: Hispanic ethnicity was a risk factor for herpes simplex virus type-1 (age-adjusted odds ratio, 3.1; 95% confidence interval, 1.8-5.3) but was not associated with antibodies to herpes simplex virus type-2, hepatitis B virus, or hepatitis C virus. Risks associated with seropositivity to herpes simplex virus type-2 included a high lifetime number of sex partners, history of any sexually transmitted disease, and increasing age. Among all patients with herpes simplex virus type-2 antibodies, only 11.1% gave histories of genital herpes infection. For women with antibodies to hepatitis B virus, 31.1% gave histories of hepatitis during adulthood. CONCLUSIONS: The seroprevalence of antibodies to herpes simplex virus type-1 and herpes simplex virus type-2 was high in this clinic population; the prevalence of antibodies to herpes simplex virus type-1 was significantly higher in Hispanics than in non-Hispanic whites. Antibodies to herpes simplex virus type-2 and hepatitis B virus were associated with most indicator of sexual behavior. The high prevalence of antibodies to herpes simplex virus type-2 and the infrequent reporting of histories of genital herpes suggest that asymptomatic infection with herpes is common among these clinic patients.


Subject(s)
Hepatitis B/epidemiology , Hepatitis C/epidemiology , Herpes Simplex/epidemiology , Hispanic or Latino , Adult , Age Distribution , Case-Control Studies , Female , Hepatitis B/complications , Hepatitis B/prevention & control , Hepatitis C/complications , Hepatitis C/prevention & control , Herpes Simplex/complications , Herpes Simplex/prevention & control , Herpesvirus 1, Human/immunology , Herpesvirus 2, Human/immunology , Humans , Logistic Models , New Mexico/epidemiology , Odds Ratio , Prevalence , Risk Factors , Seroepidemiologic Studies , Uterine Cervical Dysplasia/epidemiology , Uterine Cervical Neoplasms/epidemiology
20.
Placenta ; 17(1): 57-68, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8710814

ABSTRACT

An improved method for long-term perfusion of the isolated human term placental lobule has been developed to investigate the maternofetal transfer of infectious agents, in particular the human immunodeficiency virus (HIV). The purpose of this paper is to describe those modifications that allow for substantially prolonged perfusions in in a biohazard environment. The method described has been adapted from previous models. The perfusion apparatus has been modified for use within a biohazard hood, and, intravenous bags contain the medium for circulation of perfusates in closed circuits. A Mera Silox-S 0.3 membrane oxygenator delivers more oxygen to the tissue, and, Electromedic Cardioplegia heat exchangers warm the perfusate prior to oxygenation. Viability criteria (glucose consumption, lactate production, de novo production of human placental lactogen (hPL), volume loss, flow, temperature, pressure, oxygen transfer, carbon dioxide production, absence of IgM transfer and light and electron microscopy) demonstrate that the placental tissue remains in a functional state throughout the perfusion. Oxygen and glucose consumption are both stable over time; lactate levels remain constant; and hPL continues to be produced. These significant modifications of the perfusion system have permitted the investigators to increase the duration of perfusion to 48 h while preserving normal metabolic function of ultrastructurally intact tissue as demonstrated by ultra structural observations. This perfusion model device provides biohazard precautions and may be applied to other studies of placental physiology.


Subject(s)
Infections/transmission , Maternal-Fetal Exchange , Oxygen Consumption , Perfusion , Placenta/metabolism , Carbon Dioxide/blood , Chorionic Villi/blood supply , Chorionic Villi/ultrastructure , Female , Glucose/metabolism , Humans , Immunoglobulin M/metabolism , Kinetics , Microscopy, Electron , Oxygen/blood , Oxygenators , Placental Lactogen/biosynthesis , Pregnancy , Virus Diseases/transmission
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