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V Hirsch

Publications and source records attributed to V Hirsch.

16 recordsLinked to original sources
PubMed2002

ALVAC-SIV-gag-pol-env-based vaccination and macaque major histocompatibility complex class I (A*01) delay simian immunodeficiency virus SIVmac-induced immunodeficiency.

T-cell-mediated immune effector mechanisms play an important role in the containment of human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) replication after infection. Both vaccination- and infection-induced T-cell responses are dependent on the host major histocompatibility complex classes I and II (MHC-I and MHC-II) antigens. Here we report that both inherent, host-dependent immune responses to SIVmac251 infection and vaccination-induced immune responses to viral antigens were able to reduce virus replication and/or CD4+ T-cell loss. Both the presence of the MHC-I Mamu-A*01 genotype and vaccination of rhesus macaques with ALVAC-SIV-gag-pol-env (ALVAC-SIV-gpe) contributed to the restriction of SIVmac251 replication during primary infection, preservation of CD4+ T cells, and delayed disease progression following intrarectal challenge exposure of the animals to SIV(mac251 (561)). ALVAC-SIV-gpe immunization induced cytotoxic T-lymphocyte (CTL) responses cumulatively in 67% of the immunized animals. Following viral challenge, a significant secondary virus-specific CD8+ T-cell response was observed in the vaccinated macaques. In the same immunized macaques, a decrease in virus load during primary infection (P = 0.0078) and protection from CD4 loss during both acute and chronic phases of infection (P = 0.0099 and P = 0.03, respectively) were observed. A trend for enhanced survival of the vaccinated macaques was also observed. Neither boosting the ALVAC-SIV-gpe with gp120 immunizations nor administering the vaccine by the combination of mucosal and systemic immunization routes increased significantly the protective effect of the ALVAC-SIV-gpe vaccine. While assessing the role of MHC-I Mamu-A*01 alone in the restriction of viremia following challenge of nonvaccinated animals with other SIV isolates, we observed that the virus load was not significantly lower in Mamu-A*01-positive macaques following intravenous challenge with either SIV(mac251 (561)) or SIV(SME660). However, a significant delay in CD4+ T-cell loss was observed in Mamu-A*01-positive macaques in each group. Of interest, in the case of intravenous or intrarectal challenge with the chimeric SIV/HIV strains SHIV(89.6P) or SHIV(KU2), respectively, MHC-I Mamu-A*01-positive macaques did not significantly restrict primary viremia. The finding of the protective effect of the Mamu-A*01 molecule parallels the protective effect of the B*5701 HLA allele in HIV-1-infected humans and needs to be accounted for in the evaluation of vaccine efficacy against SIV challenge models.

Animals↗
PubMed2001

Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4+ T cells by a highly pathogenic simian immunodeficiency virus/HIV type 1 chimera (SHIV): Implications for HIV-1 infections of humans.

The highly pathogenic simian immunodeficiency virus/HIV type 1 (SHIV) chimeric virus SHIV(DH12R) induces a systemic depletion of CD4(+) T lymphocytes in rhesus monkeys during the initial 3-4 weeks of infection. Nonetheless, high levels of viral RNA production continue unabated for an additional 2-5 months. In situ hybridization and immunohistochemical analyses revealed that tissue macrophage in the lymph nodes, spleen, gastrointestinal tract, liver, and kidney sustain high plasma virus loads in the absence of CD4(+) T cells. Quantitative confocal immunofluorescence analysis indicated that greater than 95% of the virus-producing cells in these tissues are macrophage and less than 2% are T lymphocytes. Interestingly, the administration of a potent reverse transcriptase inhibitor blocked virus production during the early T cell phase but not during the later macrophage phase of the SHIV(DH12R) infection. When interpreted in the context of HIV-1 infections, these results implicate tissue macrophage as an important reservoir of virus in vivo. They become infected during the acute infection, gradually increase in number over time, and can be a major contributor to total body virus burden during the symptomatic phase of the human infection.

Adenine↗
PubMed2000

Replication of simian immunodeficiency virus (SIV) in ex vivo lymph nodes as a means to assess susceptibility of macaques in vivo.

Six macaques, apparently uninfected, following low-dose exposure to the pathogenic SIV(mac251) and SIV(SME660) by the mucosal route, were used in a pilot study to investigate whether infectability of ex vivo lymph nodes could predict resistance and/or susceptibility to SIV infection in vivo. Of six macaques exposed to the less-pathogenic virus SIV(MNE), four resisted viral infection. Analysis of the susceptibility of the PBMC of these four animals before SIV(MNE) challenge indicated that all of them were resistant to infection by the SIV(BK28) isolate and, in three of them, this resistance was dependent on CD8+ T cells. Blocks of lymph nodes of these four macaques were resistant to SIV(MNE) infection ex vivo following SIV(MNE) viral challenge exposure. However, the same blocks from the same animals were permissive to the more virulent SIV(251(32H)). Accordingly, three of these macaques were readily infected following challenge exposure with SIV(251(32H)). Lymphoproliferative responses in blood or lymph nodes, local C-C chemokine production in the lymph-node explants, and cytotoxic T-cell activity measured throughout the study did not correlate with ex vivo resistance or susceptibility to in vivo infection. In conclusion, PBMC and lymph-node resistance or susceptibility to infection ex vivo appeared to correlate with in vivo infectivity and, thus, these approaches should be further tested for their predictive value for in vivo infection.

Animals↗
PubMed1998

[What dosage is sufficient in combined inhalation therapy (fenoterol + ipratropium bromide) in patients with exacerbation of chronic obstructive lung disease?].

The authors compared in a prospective study the bronchodilatating and undesirable effects of combined inhalation treatment (phenoterol + ipratropium bromide) in the treatment of patients with exacerbation of chronic obstructive pulmonary disease, using different dosages. The patients were divided at random into two groups--group one inhaled berodual sol 3.5 ml/day (i.e. 1.75 mg phenoteroli + 0.875 mg ipratropii bromidium), the second group had a dose of double size. During the trial the authors monitored the peak expiration rate, the heart and respiration rate, blood gases and the subjective state of dyspnoea, using a 10 cm line. By comparison of bronchodilatating and undesirable effects they reached the conclusion that a daily dose of 3.5 ml berodual sol. is sufficiently effective. Increasing the daily dose to 7 ml did not produce a greater therapeutic effect nor increase the risk of undesirable effects.

Administration, Inhalation↗
PubMed1997

A molecularly cloned, pathogenic, neutralization-resistant simian immunodeficiency virus, SIVsmE543-3.

An infectious molecular clone of simian immunodeficiency virus SIVsm was derived from a biological isolate obtained late in disease from an immunodeficient rhesus macaque (E543) with SIV-induced encephalitis. The molecularly cloned virus, SIVsmE543-3, replicated well in macaque peripheral blood mononuclear cells and monocyte-derived macrophages and resisted neutralization by heterologous sera which broadly neutralized genetically diverse SIV variants in vitro. SIVsmE543-3 was infectious and induced AIDS when inoculated intravenously into pig-tailed macaques (Macaca nemestrina). Two of four infected macaques developed no measurable SIV-specific antibody and succumbed to a wasting syndrome and SIV-induced meningoencephalitis by 14 and 33 weeks postinfection. The other two macaques developed antibodies reactive in Western blot and virus neutralization assays. One macaque was sacrificed at 1 year postinoculation, and the survivor has evidence of immunodeficiency, characterized by persistently low CD4 lymphocyte subsets in the peripheral blood. Plasma samples from these latter animals neutralized SIVsmE543-3 but with much lower efficiency than neutralization of other related SIV strains, confirming the difficulty by which this molecularly cloned virus is neutralized in vitro. SIVsmE543-3 will provide a valuable reagent for studying SIV-induced encephalitis, mapping determinants of neutralization, and determining the in vivo significance of resistance to neutralization in vitro.

Amino Acid Sequence↗
PubMed1997

[Principles of monitoring patients with exacerbation of chronic obstructive pulmonary disease].

In patient treated on account of exacerbations of chronic obstructive pulmonary disease the authors monitor the peak expiration frequency (PEF) or spirometry, blood gases, pulse and respiration rate, grade of dyspnoea, ECG, blood count, blood sugar level, serum lactate concentration theophyllinaemia. It is necessary also to make an X-ray examination of the chest and bacteriological examination of sputum. The authors describe the method of different examinations and the relationship of the monitored parameters to the pathophysiology of the disease.

Humans↗
PubMed1995

Antibodies to the putative SIV infection-enhancing domain diminish beneficial effects of an SIV gp160 vaccine in rhesus macaques.

OBJECTIVE: To demonstrate that antibodies against amino acids (aa) 603-622 of the SIV gp41 transmembrane glycoprotein enhance infection of SIV in vivo. DESIGN: A synthetic peptide derived from aa 603-622 of SIVmac251 gp41 was synthesized and tested for immunogenicity in rabbits and SIV-infected rhesus macaques. Next, SIV-naive animals were immunized with either a recombinant vaccinia virus expressing the SIV gp160 envelope glycoprotein (VVrgp160) and boosted three times with aa 603-622 (group 1, four animals), wild-type vaccinia virus and boosted with aa 603-622 (group 2, two animals), or VVrgp160 followed by three doses of an irrelevant peptide (group 3, two animals). Animals were challenged with SIVmac251. RESULTS: Peptide aa 603-622 was immunogenic in rabbits. SIV-infected rhesus monkeys immunized with the peptide developed two-three log increases in antibodies to this peptide and antibodies that could enhance SIV infection in vitro. SIV-naive rhesus macaques in group 1 had higher levels of antibody to the peptide by enzyme-linked immunosorbent assay and higher levels of enhancing antibodies at the time of SIV challenge than the animals in groups 2 or 3. Following challenge with SIVmac251 the group 1 animals had detectable p27 antigen longer than animals in group 2 and 3 and died of simian AIDS before the respective animals in the two control groups (P < 0.05 by log-rank test). CONCLUSIONS: aa 603-622 of SIV gp41, like aa 579-613 of HIV gp41, can stimulate production of antibodies that enhance SIV and HIV infection in vitro. Furthermore, immunization with this peptide suppressed beneficial effects of a gp160 vaccine and appeared to enhance SIV infection in vivo.

Animals↗
PubMed1994

An analysis of birth weight by gestational age using a computerized perinatal data base, 1975-1992.

OBJECTIVE: To develop birth weight-for-gestational age nomograms based on a computerized perinatal data base collected prospectively from 1975-1992. METHODS: Using information from over 60,000 singleton deliveries (January 1975 through October 1992) at the MetroHealth Medical Center in Cleveland, Ohio, standard curves for normal birth weights were computed. Nomograms were developed for the overall population and for subgroups determined by factors known to affect fetal growth, including sex, race, smoking status, and gestational diabetes. The nomograms included the tenth, 50th, and 90th percentiles of birth weights for 24-44 weeks' gestation. Gestational age was based on clinical obstetric estimates confirmed by Dubowitz assessment of the neonate. In addition, third-order regression models were developed to predict median birth weight using gestational age. These models were validated using delivery data for the months of November and December, 1992, which were not included in model development. RESULTS: The most significant predictors of median birth weight were the first-, second-, and third-order gestational ages, which explained over 80% of the total variation in birth weight. Other significant factors influencing birth weight included infant gender, maternal race, parity, smoking, and diabetes status. Among the marginally significant factors influencing birth weight were pay status and maternal age. In general, before 33 weeks' gestation, there were few differences in the birth weight percentiles of various groups except for those with diabetes; infants of diabetic women exhibited greater birth weights as early as 26 weeks' gestation. CONCLUSIONS: Considering the large size of the data base and the diverse background of the study population, we believe that these nomograms provide useful norms of birth weight for an indigent urban population. These norms enhance the obstetrician's and neonatologist's ability to identify true cases of retardation or acceleration of intrauterine growth. Simple mathematical models provide easy calculation of the median birth weights for 24-44 weeks while adjusting for many confounding factors.

Adult↗
PubMed1989

Structure, origin, and transforming activity of feline leukemia virus-myc recombinant provirus FTT.

A myc-containing recombinant feline leukemia provirus, designated FTT, was molecularly cloned from the cat T-cell lymphoma line F422. Its transforming activity, as well as the nucleotide sequence of the 3' 2.7 kilobases of FTT, including v-myc, was determined. The predicted v-myc protein differs from feline c-myc by three amino acid changes and is truncated by two amino acids at the carboxyl terminus. Comparison with feline leukemia virus (FeLV), feline c-myc, and other FeLV proviruses indicates that recombination junctions involved in the generation of FeLV-onc viruses occur at preferred locations within the virus. They usually follow or occur within the sequence ACCCC at 5' junctions and may result from homologous recombination between sequences of marked purine-pyrimidine strand bias, especially at 3' junctions. Some recombination sites also resemble recombinase recognition sequences utilized in immunoglobulin and T-cell receptor variable-region joining. Transfection of primary rat embryo fibroblasts and subsequent in vivo analysis revealed that morphologic and tumorigenic transformation require cotransfection of FTT with human EJ-ras DNA; neither gene alone is sufficient. FTT v-myc is expressed in these transformed rat cells as a 3.0-kilobase subgenomic RNA; however, in contrast to the depressed level of c-myc expression in v-myc-involved feline tumors, steady-state levels of rat c-myc RNA and protein are apparently unaltered.

Amino Acid Sequence↗
PubMed1987

The genome organization of STLV-3 is similar to that of the AIDS virus except for a truncated transmembrane protein.

Nucleotide sequence analysis of the 3' portion of the genome of simian T-lymphotropic virus type 3 from African green monkeys (STLV-3agm) reveals that it has the same general genome structure as the human immunodeficiency virus (HIV-1), the etiologic agent of AIDS. Short segments of strong amino acid homology and similar predicted protein structure characterize the tat and art/trs open reading frames (orf) of both viruses. Strong conservation of 3' orf and of another, cs-orf, for which no protein product has been identified suggests that they both encode proteins important to the life cycle of these viruses. The extracellular glycoproteins of STLV-3 and HIV-1 share a similar backbone structure and 50%-55% amino acid homology in constant domains of the HIV-1 protein. The most evident departure in structural organization is truncation of the transmembrane glycoproteins in two STLV-3agm clones and a biologically active, noncytopathic clone of HTLV-4.

Amino Acid Sequence↗
PubMed1987

Monoarthritis as the presenting manifestation of localized Ewing's sarcoma in an older patient.

Monoarthritis, infrequently recognized as a manifestation of primary malignant disease of the bone, is rarely associated with Ewing's sarcoma. Our patient presented with knee monoarthritis, and histology established the diagnosis of Ewing's sarcoma. His disease apparently remitted with chemotherapy but recurred in multiple sites one year later, and repeat chemotherapy failed to produce a remission.

Adult↗
PubMed1986

Cross-reactivity to human T-lymphotropic virus type III/lymphadenopathy-associated virus and molecular cloning of simian T-cell lymphotropic virus type III from African green monkeys.

Simian T-lymphotropic retroviruses with structural, antigenic, and cytopathic features similar to the etiologic agent of human acquired immunodeficiency syndrome, human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV), have been isolated from a variety of primate species including African green monkeys (STLV-IIIAGM). This report describes nucleic acid cross-reactivity between STLV-IIIAGM and HTLV-III/LAV, molecular cloning of the STLV-IIIAGM genome, and evaluation of its structure and genetic relationship to other retroviruses. Overlapping clones from a cell line infected with virus from a single animal were found to encompass the entire STLV-IIIAGM genome and exhibit a limited degree of restriction-site variability. Specific hybridizing fragments were detected in DNA from this and other STLV-IIIAGM-infected cell lines. A fraction of viral DNA present in at least two STLV-IIIAGM lines persists as unintegrated viral DNA, a characteristic of infection with cytopathic retroviruses. Strongest cross-reactivity was detected between HTLV-III/LAV pol- and gag- genes and STLV-IIIAGM, whereas no cross-reactivity was detected between STLV-IIIAGM and molecular clones of human T-lymphotropic virus types I and II (HTLV-I and -II), visna virus, bovine leukemia virus, or feline leukemia virus.

Animals↗
PubMed1984

Premature delivery and subsequent reproduction.

To examine the relationship between premature delivery and subsequent reproductive behavior, we attempted to trace 100 mothers four years after the birth of a surviving preterm or term infant. Seventy mothers were successfully traced. Maternal age, ethnicity, gravidity, parity, religion, and socioeconomic status, and the sex, birthweight, gestational age, mode of delivery, and hospital days of the index infant were jointly related to three outcome measures: occurrence of subsequent pregnancy, and, among those who again became pregnant, pregnancy interval and number of subsequent children. Among women who had one or more subsequent births during the follow-up period, those whose index infants were of lower gestational age had fewer subsequent births (r = 0.602, df = 32, p less than 0.011). No other variables, including cesarean birth, were significantly related to later reproductive behavior. These findings indicate that the birth of a premature infant may have a significant effect of decreasing or delaying subsequent reproduction. Through confirmatory studies are needed, awareness of this relationship may help obstetric perinatologists and neonatologists sensitively discuss plans for contraception and further childbearing with women who have experienced the stress of the birth of a premature infant.

Black or African American↗
PubMed1981

Amniotic fluid phosphatidylglycerol: a potentially useful predictor of intrauterine growth retardation.

Intrauterine growth retardation, a major complication of pregnancy, remains difficult to detect reliability prior to birth. In this retrospective study of 82 pregnancies which resulted in birth of small infants, preceding clinical factors and amniotic fluid (AF) maturity tests were examined for their ability to differentiate small for gestational age (SGA) from appropriate for gestational age (AGA) infants of comparable weight. AF maturity tests included phosphatidylglycerol (PG), phosphatidylinositol (PI), lecithin to sphingomyelin ratio (L/S), PG/PI, PG/S, PI/S, foam tests, and fat cell count. Discriminant analysis revealed that AF PG was potentially the most useful parameter for predicting the birth of an SGA infant. The predictive value of PG was related to the strong correlation of AF PG with term gestation. High AF PG could potentially predict SGA infants with a true positive rate of 60%; 64% of all SGA infants could be correctly identified by means of only AF PG. The results of this study suggest that, in selected high-risk pregnancies, amniocentesis late in gestation with determination of PG may be helpful in classifying small infants as either growth retarded or preterm.

Amniotic Fluid↗
PubMedDate not supplied

Cloning of HTLV-4 and its relation to simian and human immunodeficiency viruses.

Although much is now known of the strain variation among the type-1 human immunodeficiency virus (HIV-1), which is the cause of AIDS (acquired immune deficiency syndrome) in the United States, Europe, and Central Africa, much less is yet known about a second group of viruses that have been found in West Africans. One member of this group, named human T-cell lymphotropic virus type 4 (HTLV-4), has been isolated from healthy Senegalese. Another is the virus isolated from West Africans with AIDS-like illness and originally called LAV-2 but now renamed HIV-2. Both these viruses seem to be less closely related to HIV-1 than they are to a virus of healthy African green monkeys, known variously as simian T-cell lymphotropic virus type 3 (STLV-3) or simian immunodeficiency virus (SIV), which in turn is related to viruses isolated from healthy sooty mangabeys and captive macaques with a form of immunodeficiency (to distinguish these viruses they are referred to as STLV-3 (or SIV)agm, STLV-3mac, or STLV-3smm). To clarify the relationship between the various HIVs, STLV-3s and HTLV-4 we are determining and comparing the molecular and biological characteristics of several of them. Following our recent publication of a restriction-site map of STLV-3agm, we now report that the equivalent map of three isolates of HTLV-4 is remarkably similar to it. In addition we present comparative sequence data on the long terminal repeats (LTR) of HTLV-4, STLV-3agm, HIV-1 and HIV-2, together with evidence that cloned HTLV-4 uses the same receptor as HIV-1 and induces some, but not all, of the cytopathic effects attributed to most isolates of HIV-1 and HIV-2.

Animals↗