Arye Rubinstein - Academia.edu (original) (raw)

Papers by Arye Rubinstein

Research paper thumbnail of In Reply: Thrombocytopenia and Pediatric Patients With AIDS

Research paper thumbnail of Improved brain delivery and in vitro activity of zidovudine through the use of a redox chemical delivery system

Aids, Mar 1, 1995

Improved therapy for AIDS dementia and related encephalopathies may be achieved through enhanced ... more Improved therapy for AIDS dementia and related encephalopathies may be achieved through enhanced delivery of effective antiretroviral agents to the central nervous system (CNS). A novel chemical delivery system (CDS) was used, which utilized redox trapping of drugs in the brain. This study was aimed at defining the pharmacokinetics of a zidovudine (ZDV)-CDS as well as establishing its in vitro antiviral efficacy against HIV in both lymphocytes and in a neural cell line. ZDV-CDS administered parenterally to rats produced significantly higher brain levels of ZDV [area under the curve (AUC), 425 micrograms x min/g] than equimolar ZDV (AUC, 13.5 micrograms x min/g). Native ZDV uptake was minimal after 1 h when analyzed in CEM lymphocytes and in SKNMC neuroblastoma cell line. By contrast, marked uptake of ZDV-CDS was followed by biochemical conversion of ZDV-CDS to its main metabolites (ZDV-CDS quaternary salt, ZDV-Q+, and native ZDV). These improved uptake profiles were associated with greater in vitro virucidal effect. ZDV-CDS at 0.5 microM was 80% more effective than ZDV in suppressing p24 production in a lymphocyte culture infected with 6000 median tissue culture infective doses (TCID50) of the HIV N1T strain and 50% more effective at 0.05 microM. Furthermore, syncytia formation was completely suppressed at a ZDV-CDS dose of 0.5 microM (600 TCID50) but native ZDV at the same dose was ineffective. Finally, while ZDV (at 0.5 microM) is not active in reducing viral replication in an SKNMC neural cell line, the ZDV-CDS complex significantly suppressed p24 synthesis. The ZDV-CDS complex is capable of delivering higher ZDV doses to lymphocytes and neural cells, with improved antiretroviral activity.

Research paper thumbnail of HIV Type 1 Infection of Human Cortical Neuronal Cells: Enhancement by Select Neuronal Growth Factors

Aids Res Hum Retrovirus, 1994

Neuronal cells in culture respond to neuronal growth factors by secondary cellular pathways simil... more Neuronal cells in culture respond to neuronal growth factors by secondary cellular pathways similar to those described for activation of lymphocytes and macrophages. In HIV-1-infected T lymphocytes and in macrophages, these pathways were shown to converge on nuclear factors that bind and stimulate the HIV-1 LTR and lead to enhancement of HIV-1 expression. In the current study we have investigated whether the same mechanisms also enhance HIV-1 production by neural cells. We have demonstrated that HIV/N1T replication in HCN-1A cells, a human cortical neuronal cell line, is enhanced threefold by nerve growth factor (NGF) and by fibroblast growth factor (FGF), but not by epidermal growth (EGF) factor, or phorbol ester. HCN-1A cells also responded to HIV/N1T infection with pronounced morphological changes, indicative of a differentiation-like process. The cells diminished in size and small neurites were observed.

Research paper thumbnail of Maternofetal Transmission of Human Immunodeficiency Virus-1: the Role of Antibodies to the V3 Primary Neutralizing Domain

Pediatric Research, Feb 1, 1993

Research paper thumbnail of Limbic encephalitis associated with anti-GAD antibody and common variable immune deficiency

Developmental Medicine and Child Neurology, Feb 1, 2009

Research paper thumbnail of HIV-1 infection of human fetal thymocytes

Journal of Acquired Immune Deficiency Syndromes, Feb 1, 1992

Some neonates with congenital human immunodeficiency virus type 1 (HIV-1) infection exhibit immun... more Some neonates with congenital human immunodeficiency virus type 1 (HIV-1) infection exhibit immune dysregulation. This suggests that fetal CD4+ cells, possibly thymocytes, may be infected during gestation. If thymocytes are infected, this may result in a disruption of T-cell differentiation. To examine this hypothesis, normal human fetal thymocytes were established in tissue culture, characterized, and then exposed to HIV-1. On initial isolation, fetal thymocytes were analyzed for phenotypic markers by flow cytometry and assessed for T-cell function by mitogen-stimulated thymidine incorporation. The thymocytes comprised greater than 70% double positive (CD4+, CD8+) cells and responded to T- but not to B-cell mitogens. Thereafter, thymocytes were incubated in either tissue culture medium containing infectious HIV-1 or in control (HIV-free) medium. Infection of fetal thymocytes was determined by light and electron microscopy in combination with immunocytochemistry, molecular hybridization, and an infectious cell center (ICC) assay. After 1 week in culture, the thymocytes exposed to HIV-1 were positive by immunocytochemistry for the HIV-1-associated protein gp41. In addition, the presence of HIV-1 DNA was detected by molecular hybridization confirming infection of these cells. The ICC assay demonstrated the production of infectious HIV-1 particles and budding of mature virions was observed by electron microscopy. These studies demonstrate that human fetal thymocytes can be infected with HIV-1 in vitro and that this infection results in production of infectious virions. These results support the hypothesis that vertical transmission of HIV-1 in vivo may result in the infection of fetal thymocytes, which may contribute to postnatal HIV-1-associated pathologic conditions.

Research paper thumbnail of Cigarette smoking, premature rupture of membranes, and vertical transmission of HIV-1 among women with low CD4+ levels

Jaids Journal of Acquired Immune Deficiency Syndromes, Jun 30, 1994

To examine the possible influence of obstetric factors, substance use during pregnancy, and other... more To examine the possible influence of obstetric factors, substance use during pregnancy, and other maternal factors on the relationship between a low maternal CD4+ level and vertical transmission of human immunodeficiency virus type 1 (HIV-1), data were analyzed from the Mothers and Infants Cohort Study, a prospective cohort followed for up to 4 years between 1986 and 1992 in Brooklyn and the Bronx, New York. The overall transmission rate for the cohort was 25.1% (95% confidence interval (CI) = 19.0-31.3). Prenatal CD4+ lymphocyte measurements were available for 162 HIV-seropositive mothers of infants with known infection outcomes. Among mothers who smoked cigarettes after the first trimester, those whose mean prenatal CD4+ level was < 20% had more than a threefold increased risk of transmitting their infection to their infants [relative risk (RR) = 3.30; 95% CI = 1.46-7.44; p = 0.004]. Among mothers who developed premature rupture of membranes, those with a low CD4+ level had a similarly increased risk of vertical transmission (RR = 4.33; 95% CI = 1.78-10.5; p = 0.003). These relative risks were much higher than those for mothers who did not smoke after the first trimester (RR = 1.14; 95% CI = 0.48-2.70; p = 0.76) or have premature rupture of membranes (RR = 1.29; 95% CI = 0.61-2.74; p = 0.50), indicating that these factors modified the effect of CD4+ level on transmission. Among all mothers without regard to CD4+ level, those who experienced preterm premature rupture of membranes were also at greater risk of transmission (RR = 2.24; 95% CI = 1.07-4.69; p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Research paper thumbnail of Pediatric acquired immunodeficiency syndrome. Neurologic syndromes

American Journal of Diseases of Children, 1988

ABSTRACT

Research paper thumbnail of Hematologic Manifestations in Pediatric HIV Infection: Severe Anemia as a Prognostic Factor

The American Journal of Pediatric Hematology Oncology, Feb 1, 1990

The hematologic profile of 100 symptomatic children infected by the human immunodeficiency virus ... more The hematologic profile of 100 symptomatic children infected by the human immunodeficiency virus (HIV) was evaluated and compared to HIV uninfected infants with transplacentally acquired maternal anti-HIV antibodies, and to HIV-negative infants born to i.v. drug-abusing HIV uninfected mothers. Anemia was present in 94% of HIV-infected infants and was a major predictor of disease progression. In 91% of patients having a hematocrit (HcT) less than 25%, the disease course was rapidly fatal. Leukopenia and thrombocytopenia occurred in 47 and 33% of HIV infected patients, respectively. Neutropenia was most severe in children with opportunistic infections. There was no evidence of suppression of any component of hematopoiesis by passively acquired antibodies to HIV.

Research paper thumbnail of Platelet-Associated IgG in Pediatric HIV Infection

Pediatric Hematology and Oncology, 1991

Hematologic abnormalities, including thrombocytopenia, are seen in HIV infection. We have previou... more Hematologic abnormalities, including thrombocytopenia, are seen in HIV infection. We have previously reported elevated platelet-associated IgG (PAIgG) in thrombocytopenia in children associated with human immunodeficiency virus (HIV). In this study we prospectively monitored 40 HIV-infected infants and children to determine the significance of elevated PAIgG levels as they relate to thrombocytopenia. We also examined platelet eluates for the presence of HIV antibody and antigen. Of 16 patients with thrombocytopenia, 15 (93.7%) had elevated PAIgG. Of 24 patients with normal platelet counts, 21 (87.5%) had elevated PAIgG. On follow-up, none of the children with normal platelet counts and elevated PAIgG levels developed thrombocytopenia. Examination of the platelet eluates was negative for HIV antibody or P24 antigen. Although the sensitivity of an elevated PAIgG level in predicting thrombocytopenia is 93%, its specificity is only 13%. Elevated PAIgG levels are therefore not causally related to the development of thrombocytopenia in children.

Research paper thumbnail of Human T-cell lymphotropic virus type III (HTLV-III) embryopathy. A new dysmorphic syndrome associated with intrauterine HTLV-III infection

American journal of diseases of children (1960), 1986

Twenty infants and children with positive serologic tests for the human T-cell lymphotropic virus... more Twenty infants and children with positive serologic tests for the human T-cell lymphotropic virus type III (HTLV-III) were noted to have similar features including growth failure (75%), microcephaly (70%), and craniofacial abnormalities consisting of ocular hypertelorism (50%); prominent box-like appearance of the forehead (75%); flat nasal bridge (70%); mild upward or downward obliquity of the eyes (65%); long palpebral fissures with blue sclerae (60%); short nose with flattened columella and well-formed, triangular philtrum (65%); and patulous lips (60%). These features constitute a new and distinct dysmorphic syndrome, the HTLV-III embryopathy.

Research paper thumbnail of Vertical Transmission of Human Immunodeficiency Virus is Correlated with the Absence of High-Affinity/Avidity Maternal Antibodies to the gp120 Principal Neutralizing Domain

Proceedings of The National Academy of Sciences, 1990

Many, but not all, infants born to mothers infected with the human immunodeficiency virus (HIV) a... more Many, but not all, infants born to mothers infected with the human immunodeficiency virus (HIV) are infected in utero. We have now shown that mothers who have high-affinity/avidity antibodies directed toward the principal neutralizing domain (PND) of gp120 are less likely to transmit HIV to their children. An ELISA that preferentially measures the level of the biologically functioning, high-affinity/avidity antibodies

Research paper thumbnail of Human T-Cell Lymphotropic Virus Type III (HTLV-III) Embryopathy

Obstetric Anesthesia Digest, 1986

Twenty infants and children with positive serologic tests for the human T-cell lymphotropic virus... more Twenty infants and children with positive serologic tests for the human T-cell lymphotropic virus type III (HTLV-III) were noted to have similar features including growth failure (75%), microcephaly (70%), and craniofacial abnormalities consisting of ocular hypertelorism (50%); prominent box-like appearance of the forehead (75%); flat nasal bridge (70%); mild upward or downward obliquity of the eyes (65%); long palpebral fissures with blue sclerae (60%); short nose with flattened columella and well-formed, triangular philtrum (65%); and patulous lips (60%). These features constitute a new and distinct dysmorphic syndrome, the HTLV-III embryopathy.

Research paper thumbnail of Mitogenic induction of macrophage and neutrophil proliferation in human tonsils

Clinical immunology and immunopathology, 1978

Research paper thumbnail of Sexual behavior and injection drug use during pregnancy and vertical transmission of HIV-1

Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association, 1997

We evaluated maternal sexual behavior and injection drug use practices as possible risk factors f... more We evaluated maternal sexual behavior and injection drug use practices as possible risk factors for vertical transmission of human immunodeficiency virus type 1 (HIV-1). Data were analyzed from the Mothers and Infants Cohort Study, a prospective study in Brooklyn and the Bronx, New York. A total of 207 mother-infant sets were enrolled between 1986 and 1991 and followed for up to 4 years after the enrollment visit during pregnancy. HIV-1 transmission occurred in 49 of 201 mother-infant sets, yielding an overall transmission rate of 24.4% (95% confidence interval (CI) = 18.7% to 31.0%). Increased frequency of vaginal intercourse after the first trimester of pregnancy was positively associated with vertical transmission of HIV-1 (trend p = 0.03). A lifetime history of injection drug use was not associated with vertical transmission. However, a history of combined cocaine and heroin injection after the first trimester of pregnancy was associated with vertical HIV-1 transmission, particu...

Research paper thumbnail of Developmental abnormalities in children with acquired immunodeficiency syndrome (AIDS): a follow-up study

The International journal of neuroscience, 1987

Developmental abnormalities in 16 pediatric patients with AIDS or AIDS-Related Complex (ARC) were... more Developmental abnormalities in 16 pediatric patients with AIDS or AIDS-Related Complex (ARC) were previously described. Neurological deterioration was in evidence on follow-up in 9 of the children, 5 died since the original assessments were performed. Ten patients were reevaluated 14 months later by cognitive testing. Two showed greater progress than expected on the basis of earlier test results; 6 showed the expected level of developmental progress; and the remaining 2 showed regression in cognitive functioning. All patients who exhibited regression in their developmental course showed deterioration in their neurological examinations. Developmental progression was noted in some children who on follow-up serial examinations exhibited a clinically deteriorating neurological picture. Pediatric AIDS patients manifest variable neurodevelopmental courses. As a result, rehabilitative intervention services must be tailored to meet individual needs.

Research paper thumbnail of Transfer factor treatment in a patient with progressive tuberculosis

Clinical immunology and immunopathology, 1977

Research paper thumbnail of THYMULIN (FTS) AND THYMOSIN ??1 - DIAGNOSTIC CRITERIA FOR AIDS IN CHILDREN

Pediatric Research - PEDIAT RES, 1984

ABSTRACT

Research paper thumbnail of Human immunodeficiency virus-1 principal neutralizing domain peptide-toxin A conjugate vaccine

Vaccine, 1995

To enhance the potential efficacy of peptide-based vaccines for human immunodeficiency virus-1 (H... more To enhance the potential efficacy of peptide-based vaccines for human immunodeficiency virus-1 (HIV-1), a principal neutralizing domain (PND) peptide (KRIHIGPGRAFYT) (HIV-1MN) was covalently coupled to Pseudomonas aeruginosa toxin A (TA). Immunization of guinea-pigs with this conjugate vaccine, in the absence of an adjuvant, engendered a high-affinity antibody response to the homologous HIV-1MN PND peptide and to analogous peptides from variant strains of HIV-1. A substantial proportion of such antibodies was directed to the conserved GPGRAF motif. Anti-PND peptide antibodies were capable of neutralizing the homologous strain, HIV-1MN, in addition to two heterologous (RF, IIIB) variants, as determined either by inhibition of syncytia formation or by suppression of p24 antigen production in cultured cells. Therefore, the method of conjugation used preserved critical neutralizing epitopes expressed by the PND peptide. Monovalent or polyvalent PND-TA conjugates, which meet all safety criteria for human use, are a promising approach towards the development of an acquired immunodeficiency syndrome (AIDS) vaccine.

Research paper thumbnail of Inhibition of acute in vivo human immunodeficiency virus infection by human interleukin 10 treatment of SCID mice implanted with human fetal thymus and liver

Proceedings of the National Academy of Sciences, 1996

To improve the usefulness of in vivo mode for the investigation of the pathophysiology of human i... more To improve the usefulness of in vivo mode for the investigation of the pathophysiology of human immunodeficiency virus (HIV) infection, we modified the construction of SCID mice implanted with human fetal thymus and liver (thy/liv-SCID-hu mice) so that the peripheral blood of the mice contained significant numbers of human monocytes and T cells. After inoculation with HIV-1(59), a primary patient isolate capable of infecting monocytes and T cells, the modified thy/liv-SCID-hu mice developed disseminated HIV infection that was associated with plasma viremia. The development of plasma viremia and HIV infection in thy/liv-SCID-hu mice inoculated with HIV-1(59) was inhibited by acute treatment with human interleukin (IL) 10 but not with human IL-12. The human peripheral blood mononuclear cells in these modified thy/liv-SCID-hu mice were responsive to in vivo treatment with exogenous cytokines. Human interferon gamma expression in the circulating human peripheral blood mononuclear cells was induced by treatment with IL-12 and inhibited by treatment with IL-10. Thus, these modified thy/liv-SCID-hu mice should prove to be a valuable in vivo model for examining the role of immunomodulatory therapy in modifying HIV infection. Furthermore, our demonstration of the vivo inhibitory effect of IL-10 on acute HIV infection suggests that further studies may be warranted to evaluate whether there is a role for IL-10 therapy in preventing HIV infection in individuals soon after exposure to HIV such as for children born to HIV-infected mothers.

Research paper thumbnail of In Reply: Thrombocytopenia and Pediatric Patients With AIDS

Research paper thumbnail of Improved brain delivery and in vitro activity of zidovudine through the use of a redox chemical delivery system

Aids, Mar 1, 1995

Improved therapy for AIDS dementia and related encephalopathies may be achieved through enhanced ... more Improved therapy for AIDS dementia and related encephalopathies may be achieved through enhanced delivery of effective antiretroviral agents to the central nervous system (CNS). A novel chemical delivery system (CDS) was used, which utilized redox trapping of drugs in the brain. This study was aimed at defining the pharmacokinetics of a zidovudine (ZDV)-CDS as well as establishing its in vitro antiviral efficacy against HIV in both lymphocytes and in a neural cell line. ZDV-CDS administered parenterally to rats produced significantly higher brain levels of ZDV [area under the curve (AUC), 425 micrograms x min/g] than equimolar ZDV (AUC, 13.5 micrograms x min/g). Native ZDV uptake was minimal after 1 h when analyzed in CEM lymphocytes and in SKNMC neuroblastoma cell line. By contrast, marked uptake of ZDV-CDS was followed by biochemical conversion of ZDV-CDS to its main metabolites (ZDV-CDS quaternary salt, ZDV-Q+, and native ZDV). These improved uptake profiles were associated with greater in vitro virucidal effect. ZDV-CDS at 0.5 microM was 80% more effective than ZDV in suppressing p24 production in a lymphocyte culture infected with 6000 median tissue culture infective doses (TCID50) of the HIV N1T strain and 50% more effective at 0.05 microM. Furthermore, syncytia formation was completely suppressed at a ZDV-CDS dose of 0.5 microM (600 TCID50) but native ZDV at the same dose was ineffective. Finally, while ZDV (at 0.5 microM) is not active in reducing viral replication in an SKNMC neural cell line, the ZDV-CDS complex significantly suppressed p24 synthesis. The ZDV-CDS complex is capable of delivering higher ZDV doses to lymphocytes and neural cells, with improved antiretroviral activity.

Research paper thumbnail of HIV Type 1 Infection of Human Cortical Neuronal Cells: Enhancement by Select Neuronal Growth Factors

Aids Res Hum Retrovirus, 1994

Neuronal cells in culture respond to neuronal growth factors by secondary cellular pathways simil... more Neuronal cells in culture respond to neuronal growth factors by secondary cellular pathways similar to those described for activation of lymphocytes and macrophages. In HIV-1-infected T lymphocytes and in macrophages, these pathways were shown to converge on nuclear factors that bind and stimulate the HIV-1 LTR and lead to enhancement of HIV-1 expression. In the current study we have investigated whether the same mechanisms also enhance HIV-1 production by neural cells. We have demonstrated that HIV/N1T replication in HCN-1A cells, a human cortical neuronal cell line, is enhanced threefold by nerve growth factor (NGF) and by fibroblast growth factor (FGF), but not by epidermal growth (EGF) factor, or phorbol ester. HCN-1A cells also responded to HIV/N1T infection with pronounced morphological changes, indicative of a differentiation-like process. The cells diminished in size and small neurites were observed.

Research paper thumbnail of Maternofetal Transmission of Human Immunodeficiency Virus-1: the Role of Antibodies to the V3 Primary Neutralizing Domain

Pediatric Research, Feb 1, 1993

Research paper thumbnail of Limbic encephalitis associated with anti-GAD antibody and common variable immune deficiency

Developmental Medicine and Child Neurology, Feb 1, 2009

Research paper thumbnail of HIV-1 infection of human fetal thymocytes

Journal of Acquired Immune Deficiency Syndromes, Feb 1, 1992

Some neonates with congenital human immunodeficiency virus type 1 (HIV-1) infection exhibit immun... more Some neonates with congenital human immunodeficiency virus type 1 (HIV-1) infection exhibit immune dysregulation. This suggests that fetal CD4+ cells, possibly thymocytes, may be infected during gestation. If thymocytes are infected, this may result in a disruption of T-cell differentiation. To examine this hypothesis, normal human fetal thymocytes were established in tissue culture, characterized, and then exposed to HIV-1. On initial isolation, fetal thymocytes were analyzed for phenotypic markers by flow cytometry and assessed for T-cell function by mitogen-stimulated thymidine incorporation. The thymocytes comprised greater than 70% double positive (CD4+, CD8+) cells and responded to T- but not to B-cell mitogens. Thereafter, thymocytes were incubated in either tissue culture medium containing infectious HIV-1 or in control (HIV-free) medium. Infection of fetal thymocytes was determined by light and electron microscopy in combination with immunocytochemistry, molecular hybridization, and an infectious cell center (ICC) assay. After 1 week in culture, the thymocytes exposed to HIV-1 were positive by immunocytochemistry for the HIV-1-associated protein gp41. In addition, the presence of HIV-1 DNA was detected by molecular hybridization confirming infection of these cells. The ICC assay demonstrated the production of infectious HIV-1 particles and budding of mature virions was observed by electron microscopy. These studies demonstrate that human fetal thymocytes can be infected with HIV-1 in vitro and that this infection results in production of infectious virions. These results support the hypothesis that vertical transmission of HIV-1 in vivo may result in the infection of fetal thymocytes, which may contribute to postnatal HIV-1-associated pathologic conditions.

Research paper thumbnail of Cigarette smoking, premature rupture of membranes, and vertical transmission of HIV-1 among women with low CD4+ levels

Jaids Journal of Acquired Immune Deficiency Syndromes, Jun 30, 1994

To examine the possible influence of obstetric factors, substance use during pregnancy, and other... more To examine the possible influence of obstetric factors, substance use during pregnancy, and other maternal factors on the relationship between a low maternal CD4+ level and vertical transmission of human immunodeficiency virus type 1 (HIV-1), data were analyzed from the Mothers and Infants Cohort Study, a prospective cohort followed for up to 4 years between 1986 and 1992 in Brooklyn and the Bronx, New York. The overall transmission rate for the cohort was 25.1% (95% confidence interval (CI) = 19.0-31.3). Prenatal CD4+ lymphocyte measurements were available for 162 HIV-seropositive mothers of infants with known infection outcomes. Among mothers who smoked cigarettes after the first trimester, those whose mean prenatal CD4+ level was < 20% had more than a threefold increased risk of transmitting their infection to their infants [relative risk (RR) = 3.30; 95% CI = 1.46-7.44; p = 0.004]. Among mothers who developed premature rupture of membranes, those with a low CD4+ level had a similarly increased risk of vertical transmission (RR = 4.33; 95% CI = 1.78-10.5; p = 0.003). These relative risks were much higher than those for mothers who did not smoke after the first trimester (RR = 1.14; 95% CI = 0.48-2.70; p = 0.76) or have premature rupture of membranes (RR = 1.29; 95% CI = 0.61-2.74; p = 0.50), indicating that these factors modified the effect of CD4+ level on transmission. Among all mothers without regard to CD4+ level, those who experienced preterm premature rupture of membranes were also at greater risk of transmission (RR = 2.24; 95% CI = 1.07-4.69; p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Research paper thumbnail of Pediatric acquired immunodeficiency syndrome. Neurologic syndromes

American Journal of Diseases of Children, 1988

ABSTRACT

Research paper thumbnail of Hematologic Manifestations in Pediatric HIV Infection: Severe Anemia as a Prognostic Factor

The American Journal of Pediatric Hematology Oncology, Feb 1, 1990

The hematologic profile of 100 symptomatic children infected by the human immunodeficiency virus ... more The hematologic profile of 100 symptomatic children infected by the human immunodeficiency virus (HIV) was evaluated and compared to HIV uninfected infants with transplacentally acquired maternal anti-HIV antibodies, and to HIV-negative infants born to i.v. drug-abusing HIV uninfected mothers. Anemia was present in 94% of HIV-infected infants and was a major predictor of disease progression. In 91% of patients having a hematocrit (HcT) less than 25%, the disease course was rapidly fatal. Leukopenia and thrombocytopenia occurred in 47 and 33% of HIV infected patients, respectively. Neutropenia was most severe in children with opportunistic infections. There was no evidence of suppression of any component of hematopoiesis by passively acquired antibodies to HIV.

Research paper thumbnail of Platelet-Associated IgG in Pediatric HIV Infection

Pediatric Hematology and Oncology, 1991

Hematologic abnormalities, including thrombocytopenia, are seen in HIV infection. We have previou... more Hematologic abnormalities, including thrombocytopenia, are seen in HIV infection. We have previously reported elevated platelet-associated IgG (PAIgG) in thrombocytopenia in children associated with human immunodeficiency virus (HIV). In this study we prospectively monitored 40 HIV-infected infants and children to determine the significance of elevated PAIgG levels as they relate to thrombocytopenia. We also examined platelet eluates for the presence of HIV antibody and antigen. Of 16 patients with thrombocytopenia, 15 (93.7%) had elevated PAIgG. Of 24 patients with normal platelet counts, 21 (87.5%) had elevated PAIgG. On follow-up, none of the children with normal platelet counts and elevated PAIgG levels developed thrombocytopenia. Examination of the platelet eluates was negative for HIV antibody or P24 antigen. Although the sensitivity of an elevated PAIgG level in predicting thrombocytopenia is 93%, its specificity is only 13%. Elevated PAIgG levels are therefore not causally related to the development of thrombocytopenia in children.

Research paper thumbnail of Human T-cell lymphotropic virus type III (HTLV-III) embryopathy. A new dysmorphic syndrome associated with intrauterine HTLV-III infection

American journal of diseases of children (1960), 1986

Twenty infants and children with positive serologic tests for the human T-cell lymphotropic virus... more Twenty infants and children with positive serologic tests for the human T-cell lymphotropic virus type III (HTLV-III) were noted to have similar features including growth failure (75%), microcephaly (70%), and craniofacial abnormalities consisting of ocular hypertelorism (50%); prominent box-like appearance of the forehead (75%); flat nasal bridge (70%); mild upward or downward obliquity of the eyes (65%); long palpebral fissures with blue sclerae (60%); short nose with flattened columella and well-formed, triangular philtrum (65%); and patulous lips (60%). These features constitute a new and distinct dysmorphic syndrome, the HTLV-III embryopathy.

Research paper thumbnail of Vertical Transmission of Human Immunodeficiency Virus is Correlated with the Absence of High-Affinity/Avidity Maternal Antibodies to the gp120 Principal Neutralizing Domain

Proceedings of The National Academy of Sciences, 1990

Many, but not all, infants born to mothers infected with the human immunodeficiency virus (HIV) a... more Many, but not all, infants born to mothers infected with the human immunodeficiency virus (HIV) are infected in utero. We have now shown that mothers who have high-affinity/avidity antibodies directed toward the principal neutralizing domain (PND) of gp120 are less likely to transmit HIV to their children. An ELISA that preferentially measures the level of the biologically functioning, high-affinity/avidity antibodies

Research paper thumbnail of Human T-Cell Lymphotropic Virus Type III (HTLV-III) Embryopathy

Obstetric Anesthesia Digest, 1986

Twenty infants and children with positive serologic tests for the human T-cell lymphotropic virus... more Twenty infants and children with positive serologic tests for the human T-cell lymphotropic virus type III (HTLV-III) were noted to have similar features including growth failure (75%), microcephaly (70%), and craniofacial abnormalities consisting of ocular hypertelorism (50%); prominent box-like appearance of the forehead (75%); flat nasal bridge (70%); mild upward or downward obliquity of the eyes (65%); long palpebral fissures with blue sclerae (60%); short nose with flattened columella and well-formed, triangular philtrum (65%); and patulous lips (60%). These features constitute a new and distinct dysmorphic syndrome, the HTLV-III embryopathy.

Research paper thumbnail of Mitogenic induction of macrophage and neutrophil proliferation in human tonsils

Clinical immunology and immunopathology, 1978

Research paper thumbnail of Sexual behavior and injection drug use during pregnancy and vertical transmission of HIV-1

Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association, 1997

We evaluated maternal sexual behavior and injection drug use practices as possible risk factors f... more We evaluated maternal sexual behavior and injection drug use practices as possible risk factors for vertical transmission of human immunodeficiency virus type 1 (HIV-1). Data were analyzed from the Mothers and Infants Cohort Study, a prospective study in Brooklyn and the Bronx, New York. A total of 207 mother-infant sets were enrolled between 1986 and 1991 and followed for up to 4 years after the enrollment visit during pregnancy. HIV-1 transmission occurred in 49 of 201 mother-infant sets, yielding an overall transmission rate of 24.4% (95% confidence interval (CI) = 18.7% to 31.0%). Increased frequency of vaginal intercourse after the first trimester of pregnancy was positively associated with vertical transmission of HIV-1 (trend p = 0.03). A lifetime history of injection drug use was not associated with vertical transmission. However, a history of combined cocaine and heroin injection after the first trimester of pregnancy was associated with vertical HIV-1 transmission, particu...

Research paper thumbnail of Developmental abnormalities in children with acquired immunodeficiency syndrome (AIDS): a follow-up study

The International journal of neuroscience, 1987

Developmental abnormalities in 16 pediatric patients with AIDS or AIDS-Related Complex (ARC) were... more Developmental abnormalities in 16 pediatric patients with AIDS or AIDS-Related Complex (ARC) were previously described. Neurological deterioration was in evidence on follow-up in 9 of the children, 5 died since the original assessments were performed. Ten patients were reevaluated 14 months later by cognitive testing. Two showed greater progress than expected on the basis of earlier test results; 6 showed the expected level of developmental progress; and the remaining 2 showed regression in cognitive functioning. All patients who exhibited regression in their developmental course showed deterioration in their neurological examinations. Developmental progression was noted in some children who on follow-up serial examinations exhibited a clinically deteriorating neurological picture. Pediatric AIDS patients manifest variable neurodevelopmental courses. As a result, rehabilitative intervention services must be tailored to meet individual needs.

Research paper thumbnail of Transfer factor treatment in a patient with progressive tuberculosis

Clinical immunology and immunopathology, 1977

Research paper thumbnail of THYMULIN (FTS) AND THYMOSIN ??1 - DIAGNOSTIC CRITERIA FOR AIDS IN CHILDREN

Pediatric Research - PEDIAT RES, 1984

ABSTRACT

Research paper thumbnail of Human immunodeficiency virus-1 principal neutralizing domain peptide-toxin A conjugate vaccine

Vaccine, 1995

To enhance the potential efficacy of peptide-based vaccines for human immunodeficiency virus-1 (H... more To enhance the potential efficacy of peptide-based vaccines for human immunodeficiency virus-1 (HIV-1), a principal neutralizing domain (PND) peptide (KRIHIGPGRAFYT) (HIV-1MN) was covalently coupled to Pseudomonas aeruginosa toxin A (TA). Immunization of guinea-pigs with this conjugate vaccine, in the absence of an adjuvant, engendered a high-affinity antibody response to the homologous HIV-1MN PND peptide and to analogous peptides from variant strains of HIV-1. A substantial proportion of such antibodies was directed to the conserved GPGRAF motif. Anti-PND peptide antibodies were capable of neutralizing the homologous strain, HIV-1MN, in addition to two heterologous (RF, IIIB) variants, as determined either by inhibition of syncytia formation or by suppression of p24 antigen production in cultured cells. Therefore, the method of conjugation used preserved critical neutralizing epitopes expressed by the PND peptide. Monovalent or polyvalent PND-TA conjugates, which meet all safety criteria for human use, are a promising approach towards the development of an acquired immunodeficiency syndrome (AIDS) vaccine.

Research paper thumbnail of Inhibition of acute in vivo human immunodeficiency virus infection by human interleukin 10 treatment of SCID mice implanted with human fetal thymus and liver

Proceedings of the National Academy of Sciences, 1996

To improve the usefulness of in vivo mode for the investigation of the pathophysiology of human i... more To improve the usefulness of in vivo mode for the investigation of the pathophysiology of human immunodeficiency virus (HIV) infection, we modified the construction of SCID mice implanted with human fetal thymus and liver (thy/liv-SCID-hu mice) so that the peripheral blood of the mice contained significant numbers of human monocytes and T cells. After inoculation with HIV-1(59), a primary patient isolate capable of infecting monocytes and T cells, the modified thy/liv-SCID-hu mice developed disseminated HIV infection that was associated with plasma viremia. The development of plasma viremia and HIV infection in thy/liv-SCID-hu mice inoculated with HIV-1(59) was inhibited by acute treatment with human interleukin (IL) 10 but not with human IL-12. The human peripheral blood mononuclear cells in these modified thy/liv-SCID-hu mice were responsive to in vivo treatment with exogenous cytokines. Human interferon gamma expression in the circulating human peripheral blood mononuclear cells was induced by treatment with IL-12 and inhibited by treatment with IL-10. Thus, these modified thy/liv-SCID-hu mice should prove to be a valuable in vivo model for examining the role of immunomodulatory therapy in modifying HIV infection. Furthermore, our demonstration of the vivo inhibitory effect of IL-10 on acute HIV infection suggests that further studies may be warranted to evaluate whether there is a role for IL-10 therapy in preventing HIV infection in individuals soon after exposure to HIV such as for children born to HIV-infected mothers.