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J J Goedert

Publications and source records attributed to J J Goedert.

At least 109 records · Page 6Linked to original sources
PubMed1997

Parvovirus B19 quiescence during the course of human immunodeficiency virus infection in persons with hemophilia.

To detect and characterize parvovirus B19 infection during the course of progressive immune deficiency from human immunodeficiency virus (HIV), ten subjects enrolled in the Multicenter Hemophilia Cohort Study were followed for 6.4 to 15 years from HIV seroconversion through extreme immune deficiency. Four to five sera or plasma samples from each subject, collected at predetermined CD4+ lymphocyte levels, were tested for immunoglobulin G (IgG) and M (IgM) B19 antibodies and DNA. All 42 samples were positive for B19 IgG antibodies, and three were weakly positive for IgM antibodies. Only one sample, collected coincident with HIV seroconversion, was unequivocally positive for B19 DNA. No persistent hematologic adverse effects of B19 infection were observed. Thus, although B19 IgG antibodies are highly prevalent among HIV-infected persons with hemophilia or related disorders, B19 viremia and its hematologic consequences were not detected, even with severe depletion of CD4+ lymphocytes. If primary B19 infection occurs after immune deficiency, however, the consequences may be more adverse.

Adolescent↗
PubMed1997

Detection of serum antibodies to a Kaposi's sarcoma-associated herpesvirus-specific peptide.

Kaposi's sarcoma (KS)-associated herpesvirus/human herpesvirus type 8 (KSHV/HHV-8) may play an etiologic role in the pathogenesis of KS. In an attempt to assess KSHV/HHV-8 infection, an ELISA was developed using an 18-amino acid peptide from a putative minor capsid protein of KSHV/HHV-8 conjugated to bovine serum albumin. Overall, sera from human immunodeficiency virus type 1 (HIV-1)-positive patients with KS had a higher reactivity in the assay than did sera from HIV-1-positive patients without KS (P = .018). Of 35 HIV-1-positive patients with KS, 60% were antibody positive, compared with 27% of 33 HIV-1-positive patients without KS. Of 30 healthy blood donors, 20% were antibody positive. The ELISA responses did not correlate with antibody titers to Epstein-Barr virus. Given the homology and antigenic relatedness between KSHV/HHV-8 and Epstein-Barr virus, serologic assays involving unique KSHV/HHV-8 peptides may prove to be valuable in defining the epidemiology and clinical expression of this virus.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Investigation of human urine for genomic sequences of the primate polyomaviruses simian virus 40, BK virus, and JC virus.

Recent reports of the detection of simian virus 40 (SV40) nucleotide sequences in ependymomas, choroid plexus tumors, osteosarcomas, and mesotheliomas have raised the possibility that SV40, which naturally infects Asian macaques, is circulating among humans. This possibility was examined by performing polymerase chain reaction assays on urine samples of 166 homosexual men, 88 of them human immunodeficiency virus (HIV)-seropositive, for genomic sequences of SV40 as well as of human polyomaviruses BK virus (BKV) and JC virus (JCV). Tests with masked urine specimens spiked with SV40-transformed cells were included to monitor the SV40 assay. SV40, BKV, and JCV sequences were identified, respectively, in 0, 14%, and 34% of the urine specimens. JCV viruria was far more common (37%) than BKV viruria (5%) in HIV-seronegative persons. HIV infection and more severe immunosuppression were associated with a higher frequency of BKV viruria. In summary, SV40 viruria was not detected among homosexual men who shed human polyomaviruses at a high frequency.

AIDS-Related Opportunistic Infections↗
PubMed1997

Influence of other maternal variables on the relationship between maternal virus load and mother-to-infant transmission of human immunodeficiency virus type 1.

To assess the relationship between maternal human immunodeficiency virus (HIV) type 1 RNA level, other important covariates, and mother-to-infant (vertical) transmission of HIV-1, third trimester repository specimens from 160 HIV-1-seropositive women enrolled in the Mothers and Infants Cohort Study between 1986 and 1991 were assayed in batch for HIV-1 RNA. A significant association between peripheral blood HIV-1 RNA level and vertical transmission remained after controlling for CD4 cell level, duration of ruptured membranes, "hard" drug (cocaine and heroin) use, and frequency of sexual activity during pregnancy. However, the association was attenuated among women with advanced HIV infection and those with a high frequency of sexual activity during pregnancy. In these settings, interventions that target risk factors other than virus load may be particularly important for preventing vertical transmission of HIV-1.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Vertical transmission of human immunodeficiency virus type 1: seroreactivity by maternal antibodies to the carboxy region of the gp41 envelope glycoprotein.

Maternal antibodies against the envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) have previously been suggested to be important in influencing the rate of vertical transmission. In this study, serum antibody responses in mothers who did or did not transmit HIV-1 infection to their children were measured against the carboxy region of the transmembrane envelope glycoprotein gp41. Results indicate significantly higher binding reactivity of nontransmitter mothers compared with transmitters to three peptides spanning amino acids 771-810 and 841-856. In addition, high neutralization titers in maternal sera against HIV-1(MN) were associated with a nontransmission status. This is the initial report demonstrating a correlation between maternal antibody binding to epitopes within the carboxy region of gp41 envelope glycoprotein and lack of vertical transmission. Immunodetection that identifies antibodies to these regions in gp41 could therefore be considered a strategy to assess the risk of vertical transmission of HIV-1.

Amino Acid Sequence↗
PubMed1997

Does umbilical cord blood polymerase chain reaction positivity indicate in utero (pre-labor) HIV infection?

OBJECTIVE: To compare risk factors for infants whose cord blood was positive for HIV DNA with those who were cord blood-negative but found to be HIV DNA-positive in early infancy. METHODS: In 1994, infants born to HIV-infected women were enrolled in a study in Blantyre, Malawi. Birth weight and transmission risk factors from cord blood-positive infants were compared with cord blood-negative/HIV-positive infants on their first postnatal visit (4-7 weeks of age). Testing for HIV DNA on cord and peripheral blood was performed by polymerase chain reaction. RESULTS: Of 249 HIV-infected infants (overall transmission rate, 26%), 83 (33%) were cord blood-positive and 166 were initially cord blood-negative. The mean birth weight was 2.1% (59 g) lighter in cord blood-positive infants than initially cord blood-negative infants; initially cord blood-negative infants were 2.8% (80 g) lighter than uninfected infants born to HIV-infected women. There were no significant differences in the risk factors for infection between HIV-infected cord blood-positive and -negative infants; when transmission was increased, both HIV-infected cord blood-positive and -negative infants contributed to the increase in a similar proportion. INTERPRETATION: It was concluded that umbilical cord blood positivity for HIV DNA did not identity a subset of in utero HIV-infected infants and suggested that HIV-infected cord blood-positive and -negative infants have similar timing and routes of HIV infection.

Adolescent↗
PubMed1997

Development of genetic vaccines for pathogenic genes: construction of attenuated vif DNA immunization cassettes.

OBJECTIVE: To develop a putative immunization cassette using HIV-1 vif accessory gene derived from HIV-1 clinical specimens as a component of a DNA vaccine for HIV-1. METHODS: vif genes were cloned from HIV-1-infected patients and the sequence variation present within the patients was analyzed. Prototypic genetic variants were selected and the ability of these clones to induce humoral and cellular immune responses was studied in animals. The selected protective genetic variants were biologically characterized through transcomplementation assays using primary cells infected with a vif-defective HIV-1 proviral clone. RESULTS: Analysis of vif variants from different patients revealed that vif is highly conserved with the open reading frame remaining intact in vivo. It was shown that attenuated vif clones from HIV-1-infected subjects can effectively induce both humoral and cellular responses against Vif protein in mice. Evaluation of the cellular responses in vitro using human cellular targets infected with a clinical HIV-1 isolate showed that vif clones could induce cellular responses capable of destroying the virus. CONCLUSIONS: The vif variants developed in this study exhibited non-productive phenotypes, yet were capable of inducing specific immune responses against HIV-1. These constructs could be used as part of a DNA vaccine strategy for HIV-1. This vaccine adaptation strategy could be used for the development of immunogens for any pathogen resulting in cross-reactive immunity and attenuated gene pathogenesis.

AIDS Vaccines↗
PubMed1997

Vertical transmission of human immunodeficiency virus type 1: insights from studies of multiple pregnancies.

Because twins share an in utero environment and genetic relationships, similarities and differences between them can provide insight into the epidemiology and natural history of infectious agents, especially human immunodeficiency virus type 1 (HIV-1). Three projects were summarized: HIV-1 transmission and AIDS-free survival in The International Registry of HIV-Exposed Twins; cloning and sequencing of HIV-1 proviral sequences in two sets of identical twins; and transmission and natural history of ovine lentivirus (OvLV) in twin lambs. Both HIV-1 and OvLV transmission were increased for first-born twins. With HIV-1, progression to AIDS appeared independent of zygosity. Development of pneumonitis with experimental OvLV infection was highly concordant in monozygotic lambs. Finally, the identical infected twins in one set had intermingling of each infant's HIV-1 quasispecies, whereas in the second set each twin had its own distinct cluster of quasispecies around a maternal sequence. The studies indicate that most transmission occurs during labor or delivery, and they suggest that immunogenetics may not affect susceptibility to different HIV-1 quasispecies but may affect the manifestations of specific opportunistic diseases.

Animals↗
PubMed1997

Epidemiology of squamous cell conjunctival cancer.

The etiology of squamous cell carcinoma of the conjunctiva (SCCC) is not well known. A possible role of UVB radiation is suggested by an excess of SCCC in tropical countries and by the association between squamous cell skin cancer and exposure to UVB. Human papillomavirus type 16 also may be involved, given that it has been detected in benign and malignant conjunctival lesions and is the primary etiological agent involved in carcinoma of the anogenital tract. To examine the relationship between UVB exposure and SCCC, population-based age-adjusted incidence rates of SCCC and of conjunctival melanoma and squamous cell cancer of the eyelid were plotted against the UVB insolation of each registry site. Incidence data were examined further for patterns of second primary cancers among people with SCCC. SCCC was rare in the United States, with an incidence rate of 0.03 per 100,000 persons, although the rate was approximately 5-fold higher among males and whites. Regression analysis suggested a link between UVB exposure and SCCC rates (beta = 2.25; r = 0.58) that was as strong as that for squamous cell carcinoma of the eyelid (beta = 2.73; r = 0.62) and much stronger than for conjunctival melanoma (beta = 0.28; r = 0.02). Risk of a second malignancy after SCCC was not increased overall (20 observed and 14.1 expected), although a significant excess of salivary gland cancer (4 observed and 0.03 expected) and a borderline excess of lung cancer (6 observed and 2.4 expected) were noted. These observations suggest that UV radiation likely contributes to SCCC development. Additional research is needed to define the other exposures and host susceptibility that likely interact with UV-related genetic damage in the multifactorial development of this rare neoplasm.

Carcinoma, Squamous Cell↗
PubMed1996

Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study.

The chemokine receptor 5 (CKR5) protein serves as a secondary receptor on CD4(+) T lymphocytes for certain strains of human immunodeficiency virus-type 1 (HIV-1). The CKR5 structural gene was mapped to human chromosome 3p21, and a 32-base pair deletion allele (CKR5Delta32) was identified that is present at a frequency of approximately0.10 in the Caucasian population of the United States. An examination of 1955 patients included among six well-characterized acquired immunodeficiency syndrome (AIDS) cohort studies revealed that 17 deletion homozygotes occurred exclusively among 612 exposed HIV-1 antibody-negative individuals (2.8 percent) and not at all in 1343 HIV-1-infected individuals. The frequency of CKR5 deletion heterozygotes was significantly elevated in groups of individuals that had survived HIV-1 infection for more than 10 years, and, in some risk groups, twice as frequent as their occurrence in rapid progressors to AIDS. Survival analysis clearly shows that disease progression is slower in CKR5 deletion heterozygotes than in individuals homozygous for the normal CKR5 gene. The CKR5Delta32 deletion may act as a recessive restriction gene against HIV-1 infection and may exert a dominant phenotype of delaying progression to AIDS among infected individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Serum HIV-1 RNA levels and time to development of AIDS in the Multicenter Hemophilia Cohort Study.

OBJECTIVE: To determine if the long-term incidence of the acquired immunodeficiency syndrome (AIDS) is related to human immunodeficiency virus type 1 (HIV-1) RNA levels measured early in HIV-1 infection. DESIGN: Epidemiologic cohort study. SETTING: Five hemophilia treatment centers in the United States. SUBJECTS: A total of 165 subjects with hemophilia and HIV-1 infection (age at HIV-1 seroconversion, 1-66 years) followed from 1979 to 1995. METHODS: The HIV-1 RNA level was measured by polymerase chain reaction over a range of 200 to 1 million or more HIV-1 RNA copies/mL in archived serum specimens collected 12 to 36 months (median, 27 months) after the estimated date of HIV-1 seroconversion. Kaplan-Meier methods were used to examine the risk of AIDS and proportional hazards models were used to estimate relative hazards. RESULTS: The HIV-1 RNA values were similar in subjects younger than 17 years at seroconversion (median, 5214 copies/mL) and those 18 to 34 years old (median, 4693 copies/mL), but higher in those 35 years or older (median, 12069 copies/mL) (P = .02 compared with each younger group). At 10 years after seroconversion, the proportions of subjects with AIDS were 72% among subjects with 100,000 or more HIV-1 RNA copies/mL measured 12 to 36 months after HIV-1 seroconversion (n = 9), 52% among subjects with 10,000 to 99,999 copies/mL (n = 55), 22% among subjects with 1000 to 9,999 copies/mL (n = 82), and 0% among subjects with fewer than 1000 copies/mL (n = 19) (P < .001). The age-adjusted relative hazard for AIDS for subjects with 10,000 or more copies/mL was 14.3 (95% confidence interval, 1.9-105.6) compared with subjects with fewer than 1000 copies/mL. CONCLUSIONS: The HIV-1 RNA level during early chronic HIV-1 infection is a strong, age-independent predictor of clinical outcome; low levels define persons with a high probability of long-term AIDS-free survival.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Kaposi's sarcoma (KS)-associated herpesvirus-like DNA sequences in peripheral blood mononuclear cells: association with KS and persistence in patients receiving anti-herpesvirus drugs.

Herpesvirus-like DNA sequences (KSHV/HHV-8) have recently been described in AIDS-associated Kaposi's sarcoma (KS) lesions. Many questions remain regarding the role of this virus in KS and the therapeutic implications of this finding. In the current study, KSHV/HHV-8 DNA was detected in peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus (HIV)-infected patients with KS (34/98) more often than in HIV-infected individuals without KS (12/64, P = .03). The detection of KSHV/HHV-8 DNA did not correlate with the CD4 lymphocyte count. Five patients demonstrated KSHV/HHV-8 DNA in their PBMCs during administration of intravenous foscarnet and/or ganciclovir. The continued detection of KSHV/HHV-8 DNA in the PBMCs of patients receiving these anti-herpesvirus drugs has potential implications regarding the virus-cell relationship of KSHV/HHV-8, as well as for the value of these drugs in treating or preventing KS, but additional studies are needed.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Perinatal intervention trial in Africa: effect of a birth canal cleansing intervention to prevent HIV transmission.

BACKGROUND: Perinatal transmission of human immunodeficiency virus (HIV) type 1 contributes significantly to infant mortality. Exposure in the birth canal may account for some transmission. We examined the efficacy of a birth canal washing procedure in reducing perinatal transmission in Malawi. METHODS: The infection status of infants of 3327 control women (conventional delivery procedures) was compared with that of 3637 infants of intervention-delivered women. The infants' HIV status was determined by polymerase chain reaction on dried blood spots collected at 6 and 12 weeks of age. The intervention consisted of manual cleansing of the birth canal with a cotton pad soaked in 0.25% chlorhexidine, which was done on admission in labour and every 4 h until delivery. FINDINGS: No adverse reactions to the intervention procedure were seen. 2094 (30%) of the enrolled women were HIV-infected, and 59% of their infants were seen in follow-up. Among 982 vaginal vertex singleton deliveries to HIV-infected women, 269 (27%) infants were infected. The intervention had no significant impact on HIV transmission rates (27% in 505 intervention women compared with 28% in 477 control women), except when membranes were ruptured more than 4 h before delivery (transmission 25% in the intervention group vs 39% in the control group). INTERPRETATION: If birth canal exposure is an important risk factor, different or additional methods to reduce the risk of perinatal HIV transmission should be tested. Alternatively, perhaps birth canal exposure is not a major contributor to perinatal infection risk.

Adult↗
PubMed1996

Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection.

Major histocompatibility complex (MHC) genes (HLA in humans) regulate the immune response to foreign antigens. Molecular and serologic techniques were used to identify products of HLA class I, class II and transporter (TAP) genes (also part of the MHC) in homosexual seroconverters to human immunodeficiency virus type 1 (HIV-1). Comprehensive statistical analysis produced an HLA profile that predicted time from HIV-1 infection to the onset of AIDS. The profile was developed in a cohort of 139 men and evaluated in a second unrelated cohort of 102 men. In the evaluation cohort, the profile discriminated a sixfold difference between groups with the shortest and longest times to AIDS (P = 0.001). These findings support current theory about control of antigen processing by HLA genes and have implications for immunopathogenesis of HIV-1 and other infections.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Analysis of genetic heterogeneity, antigenicity, and biological characteristics of HIV-1 in a maternal transmitter and nontransmitter patient pair.

To obtain insight into the factors involved in vertical transmission, we compared the sequence diversity, seroreactivity, and biological characteristics of human immunodeficiency virus type 1 (HIV-1) derived from a transmitter and nontransmitter mother pair. Forty-two clones from the transmitter and 20 from the nontransmitter, spanning the principal neutralization determinant (PND) of the env gene, were sequenced and analyzed. The intrapatient sequence variation in transmitter and nontransmitter viruses was 12% and 36%, respectively, and the interpatient variation was 38%. In an effort to correlate immune responses to viral genetics, we analyzed the sera from these patients against a number of V3 peptides from known HIV-1 isolates. We observed that (i) both the transmitter and nontransmitter sera demonstrated higher binding to V3 peptides based on SF-2 and MN sequences than to IIIB and Z6 isolates; (ii) the vertical transmission of HIV-1 is correlated with the absence of high maternal antibody responses to the PND; and (iii) the high-affinity binding of the sera to SF-2 and MN V3 peptides correlated with the sequence analysis, indicating that the V3 sequences from both patients are more closely related to ADA, SF-162, and MN than to IIIB or Z6. Biological analysis of the viruses from these patients demonstrate that the transmitters' viruses infect a number of T-cell lines in vitro, whereas the nontransmitter viruses do not infect cell lines or the primary lymphocytes.

Amino Acid Sequence↗