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Biomedical subjects

S Baron

Publications and source records attributed to S Baron.

At least 55 records · Page 3Linked to original sources
PubMed1999

Why is HIV rarely transmitted by oral secretions? Saliva can disrupt orally shed, infected leukocytes.

BACKGROUND: Oral transmission of human immunodeficiency virus (HIV) by the millions of HIV-infected individuals is a rare event, even when infected blood and exudate is present. Saliva of viremic individuals usually contains only noninfectious components of HIV indicating virus breakdown. OBJECTIVE: To determine whether unknown HIV inhibitory mechanisms may explain the almost complete absence of infectious HIV in the saliva. METHODS: Since most of the infectious HIV that is shed mucosally by asymptomatic individuals is found in, produced by, and transmitted by infected mononuclear leukocytes, we determined whether saliva, which is hypotonic, may disrupt these infected cells, thereby preventing virus multiplication and cell-to-cell transmission of HIV. Specifically, we measured (1) whether mononuclear leukocytes were lysed by saliva and (2) whether the lysis by saliva inhibits the multiplication of HIV and other viruses in infected leukocytes and other cells. RESULTS: Saliva rapidly disrupted 90% or more of blood mononuclear leukocytes and other cultured cells. Concomitantly, there was a 10000-fold or higher inhibition of the multiplication of HIV and surrogate viruses. Further experiments indicated that the cell disruption is due to the hypotonicity of saliva: CONCLUSIONS: Hypotonic disruption may be a major mechanism by which saliva kills infected mononuclear leukocytes and prevents their attachment to mucosal epithelial cells and production of infectious HIV, thereby preventing transmission. Implications for the known oral HIV transmission by milk and seminal fluid, as well as potential oral transmission to contacts and health care workers, are considered. This effective salivary defense may be applicable medically to interdict vaginal, rectal, and oral transmission of HIV by infected cells in seminal fluid or milk by the use of anticellular substances.

Adult↗
PubMed1999

Lipoproteins account for part of the broad non-specific antiviral activity of human serum.

Several antiviral substances have been detected in human serum but few have been shown to possess broad antiviral activity. These broadly active antiviral molecules could be of significance as innate defense mechanisms. We have previously identified and characterized a broadly antiviral glycoprotein, UTI3, which accounts for 50 antiviral units/ml of human and mammalian sera. In addition there are reports of antiviral activity of human serum apolipoprotein A-1 (apo A-1), an important constituent of high density lipoprotein (HDL), against human immunodeficiency virus (HIV) and herpesvirus. Therefore we investigated (1) whether HDL is broadly antiviral, (2) how much of the broad antiviral activity of serum is due to HDL, and (3) the mechanism(s) of HDL's antiviral action. In this paper we report that (1) HDL does have broad antiviral activity, (2) HDL accounts for a modest but significant portion of the antiviral activity of serum, and (3) HDL acts by preventing virus penetration. Overall, HDL may be one of the broadly antiviral defences in the bloodstream.

Animals↗
PubMed1999

L-selectin expression enhances clonogenesis of CD34+ cord blood progenitors.

L-selectin, a surface adhesion glycoprotein expressed on leukocytes, has a well-established role in mediating inflammation and lymphocyte recirculation. Recent evidence suggests that L-selectin may also influence hematopoiesis. We observed that a greater proportion of CD34+ cells express L-selectin in cord blood compared with adult bone marrow, and we hypothesized that L-selectin expression is associated with enhanced clonogenic properties. To test this, we compared CD34+/L-selectin+ cells with CD34+/L-selectin- cells in hematopoietic clonogenic assays. From CD34+/L-selectin+ cell cultures, we observed a 3-fold increase of d 12-14 colony-forming unit-granulocyte/macrophage and multipotent progenitor cells, and a 5-fold enhancement of primitive d 21 high proliferative potential colony-forming cells compared with the progeny of CD34+/L-selectin- cells. We conclude that CD34+ cord blood cells expressing L-selectin are enriched in their clonogenic activity compared with cell fractions lacking L-selectin expression.

Adult↗
PubMed1998

A host defense role for a natural antiviral substance in the nervous system.

The pathogenesis of virus infections of the nervous system (NS) is regulated by host defenses. The defensive role of a major constitutive antiviral substance was studied by determining its distribution in the human nervous system, its concentration and the ability of this viral inhibitor to protect mice against viral infection. The 4000 kDa inhibitor complex in the human nervous system was detected in brain gray and white matter, spinal cord, and sciatic nerve but not in human cerebrospinal fluid. The inhibitor was found in the extracellular medium incubated with minced murine brain. The inhibitory titer ranged from approximately 50 to 200 antiviral units per gram against polio 1, Semliki Forest, Banzi, mengo, Newcastle disease and herpes simplex 1 viruses. The inhibitor is composed of lipid and essential protein and carbohydrate moieties as determined by enzymatic inactivation. Protection of inhibitor-treated mice was demonstrated against both an alphavirus and a picornavirus. Thus a natural defensive role for the broadly antiviral inhibitor is suggested by its constitutively high concentration, wide distribution in nervous system tissues, presence in extracellular fluid and its ability to provide protection in infected mice.

Animals↗
PubMed1998

An Sp1-binding silencer element is a critical negative regulator of the megakaryocyte-specific alphaIIb gene.

The Sp1 family of transcription factors are often involved in the regulated expression of TATA-less genes, frequently enhancing gene transcription. In this paper, we demonstrate that an Sp1-binding element inhibits the expression of the megakaryocyte-specific alphaIIb gene in all cell lines tested and that this inhibition is actively overcome only in megakaryocyte-like cell lines. We had noted previously in primary megakaryocytes that a 50-base pair (bp) deletion from -150 to -101 bp in the rat alphaIIb promoter region resulted in increased expression. We now show that deletion of this region markedly increased expression in both megakaryocytic and non-megakaryocytic cell lines, eliminating the tissue specificity of the alphaIIb promoter. Electrophoretic mobility shift assays (EMSA) defined a single complex, which bound to a -145 to -125 bp subregion. Point mutations within this region, localized the critical point of binding around bases -136/-135, and expression studies showed that introduction of the -136/-135 mutation into the rat alphaIIb promoter had a comparable result to that seen with the 50-bp deletion. EMSA studies with the homologous human alphaIIb promoter region gave an identical migrating band. Southwestern blots of HeLa nuclear proteins with both the rat -145 to -125 DNA and its human homologue bound to a single approximately 110-kDa protein, the known molecular weight of Sp1. Confirmation that this region of the alphaIIb gene promoter bound Sp1 was accomplished using EMSA studies with an Sp1 consensus probe, anti-Sp1 and -Sp3 antibodies, and recombinant Sp1 protein. Further support for the role of Sp1 in the silencing of the alphaIIb promoter was obtained using a Gal4 binding site substitution for the silencer region of alphaIIb and co-expression of near full-length Sp1/Gal4 fusion protein expression vectors. Ectopic reinsertion of the -150 to -101 bp region, back into the -150 to -101 bp deleted promoter, enhanced rather than decreased expression, suggesting that Sp1's inhibitory role at -136/-135 depends on its local interactions. In summary, we believe that we have identified a cross-species, non-consensus Sp1-binding site that binds Sp1 and that acts as a silencer of alphaIIb expression in many cell lines. A model is presented as to how this Sp1-binding silencer element contributes to the megakaryocyte-specific expression of alphaIIb gene.

Animals↗
PubMed1998

Methods for assessing the physical demands of manual lifting: a review and case study from warehousing.

Assessment of the physical demands of potentially hazardous manual material handling (MMH) activities is fundamental to the prevention of disabilities from occupationally related low back pain, a problem costing the nation billions of dollars annually. Although there is a variety of ergonomic assessment methods available for assessing MMH activities, there is a lack of practical information to assist users in choosing the most appropriate assessment methods of a particular job. This article reviews currently available assessment methods and presents case study results of a physically demanding repetitive manual lifting job in two grocery warehouses. The case study will provide a framework for a comparison of the methods and a discussion of relevant application issues designed to assist users in selecting appropriate methods for assessing MMH jobs. Based on the results of the study, it is concluded that all of the ergonomic methods were in agreement that the job of grocery selector has a high level of risk for low back pain. Differences between the methods were noted, however, that should be considered when choosing a specific method for a specific application.

Anthropometry↗
PubMed1998

Epidemiology of pertussis in French hospitals in 1993 and 1994: thirty years after a routine use of vaccination.

BACKGROUND: Despite widespread vaccination during 30 years, the hypothesis of a resurgence of pertussis in France has been raised by outbreaks and sporadic case reports. No surveillance data were available after 1985. METHODS: A survey was undertaken in 1993 and 1994 in a pediatric hospital network able to confirm cases; the network (22 hospitals) represents 19.6% of pediatric admissions in France. Case definition included clinical (> or = 21 days of paroxysmal cough), laboratory-confirmed (culture or serology by immunoblot) or epidemiologically confirmed pertussis (documented contact with a laboratory-confirmed case). The pattern of transmission was studied in the household. Vaccine status was obtained from health records. RESULTS: during a 15-month period 560 cases (316 index cases, 244 household contact cases) were reported; 49% of index cases and 20% of contact cases were confirmed by culture and/or serology. Sixty-five percent of index cases were younger than 1 year of age (the incidence in this age group could be estimated to be 95/100000) and 66% were hospitalized for a mean duration of 2 weeks. Infection was acquired from parents (34%) and siblings (46%). Seventy-three percent of index cases were unvaccinated. CONCLUSIONS: Although pertussis vaccination coverage is very high in France, the organism is still circulating, affecting, within the pediatric population, mostly non- or incompletely vaccinated infants. These results strongly support the importance of adhering to the immunization schedule and suggest introducing booster dose(s) to prolong vaccine immunity and reduce the exposure to Bordetella pertussis of infants too young to be immunized.

Adolescent↗
PubMed1997

[Epidemiological estimation of the effectiveness of the pertussis vaccination during outbreaks in a community. Les pédiatres et bactériologistes du réseau RENACOQ].

BACKGROUND: With the recent pertussis vaccine trials, the efficacy of acellular vaccines is now well known, estimated at 85% for multicomponent vaccines. On the other hand, the estimates of whole cell vaccines efficacy varies from 36% to 98% with the different vaccines used. We evaluated the field effectiveness of the French whole cell pertussis vaccine during outbreaks in schools and centers for disabled children. METHODS: Four limited outbreaks between 1993 and 1995 were investigated using a retrospective cohort study design. Vaccine effectiveness (VE) was assessed for the following case definition: clinical pertussis, laboratory-confirmed pertussis, epidemiologically confirmed pertussis (documented contact with a laboratory confirmed case). Immunization history was obtained by reviewing the child health record book. Effectiveness of a whole vaccination (four injections) and of a partial vaccination (one to three injections) were estimated as 1-(attack rate among vaccinated/attack rate among non-vaccinated). RESULTS: A whole immunization conferred good protection against pertussis with an estimated VE higher than 92% in three surveys, lower in the fourth survey (84%) in which antibiotic prophylaxis was set up very rapidly. A partial immunization conferred a mild protection (median: 60%). CONCLUSIONS: These results are consistent with a previous report about the effectiveness of this whole cell vaccine using the screening method in a hospital network survey in France. In the same way, a large efficacy trial in Senegal comparing it with an acellular bivalent vaccine estimated its efficacy at 96%. This high efficacy together with a satisfactory vaccine coverage leads to the current epidemiological profile of pertussis in childhood in France: majority of cases occurring before 6 months of age, limited outbreaks in school children, many of whom being unvaccinated or partially vaccinated.

Adolescent↗
PubMed1996

IFN-alpha therapy is effective in suppressing the clinical experimental myasthenia gravis.

To study the therapeutic efficacy of IFN-alpha after the onset of clinical signs of experimental autoimmune myasthenia gravis (EAMG), we treated mice with clinical EAMG with recombinant human IFN-alpha or mouse IFN-alpha. In the first experiment, 7 of 16 (44%) mice had a complete clinical remission in the recombinant human IFN-alpha-treated group, in contrast to none in the placebo group (0/14) (p = 0.006). There was a higher incidence of death and severe disease in the placebo group (7/14) relative to the IFN-alpha group (4/16). In the second experiment, 6 of 18 (33%) mice in the mouse IFN-alpha-treated group had a complete clinical remission, while none of 17 (0%) mice in the placebo-treated group had remission (p = 0.011). Again, more mice died or worsened in the placebo group (11/17) compared with the IFN-alpha group (7/18). IFN-alpha treatment significantly reduced the anti-acetylcholine receptor (AChR) Ab levels, especially the IgG1 and IgG2b isotypes, and the amount of anti-AChR Abs bound to muscle AChR. IFN-alpha treatment also lowered CD4 cells in the lymph nodes and spleen, and suppressed the in vitro lymphocyte proliferative response to AChR and its dominant peptide in a dose-dependent manner.

Animals↗
PubMed1996

Respiratory syncytial virus infection of human respiratory epithelial cells up-regulates class I MHC expression through the induction of IFN-beta and IL-1 alpha.

CD8+ T cells mediate some of the damage to the lung epithelium following respiratory syncytial virus (RSV) infection. Since CD8+ T cells recognize antigen-laden class I MHC molecules on the target cells, we examined in this study the expression of class I MHC by RSV-infected respiratory epithelial cells. Respiratory epithelial cell lines and bronchial epithelial cells from normal human tissue responded to RSV infection with an increased expression of class I MHC as determined by flow cytometry and immunoprecipitation of class I MHC from metabolically radiolabeled cells. The increase in class I MHC expression was dependent on infectious, replicating virus. UV-irradiated culture supernatants from RSV-infected A549 cells, when added to fresh A549 cell cultures, induced an increase in class I MHC expression by those cells. The class I MHC increasing activity within supernatants from A549 cells was due, in large part, to IFN-beta, and to a lesser extent to IL-1 alpha. The addition of neutralizing Abs to both cytokines completely blocked the increase in class I MHC expression by cells treated with the above-mentioned supernatants. These results demonstrate that RSV infection elicits IFN-beta production by respiratory epithelial cells, which in turn leads to an increase in their synthesis of class I MHC, which would facilitate their recognition and lysis by RSV-specific CD8+ T cells.

Adjuvants, Immunologic↗
PubMed1996

Evaluation of symptom surveys for occupational musculoskeletal disorders.

Symptom surveys have been used extensively as part of workplace ergonomic screening programs and epidemiologic assessments of musculoskeletal disorders in groups of workers. This paper examines the reliability and validity of two musculoskeletal symptom surveys, the Nordic Musculoskeletal Questionnaire (NMQ) and a survey used in conjunction with epidemiologic assessments by the National Institute for Occupational Safety and Health (NIOSH). Journal articles assessing the validity and reliability of the NMQ were reviewed. A retrospective assessment combining two NIOSH cohorts with a total of 852 workers assessed the reliability and validity of that survey. Reliability was assessed through test-retest methods and interitem correlations between similar questions. Validity was assessed by comparison with results from physical examination assessments of workers and self-reports of workers seeking medical care. Both reliability and validity were found to be acceptable for the purposes of workplace ergonomics programs. Implications for use of these surveys for prevention and treatment outcomes research are discussed.

Chi-Square Distribution↗
PubMed1996

Cluster of cases of haemolytic uraemic syndrome due to unpasteurised cheese.

A cluster of four patients (1 girl, 3 boys) from a French village (2,000 inhabitants) had acute haemolytic uraemic syndrome (HUS) between March 1992 and May 1993. All had prodromes with fever and diarrhoea, then acute renal failure, anaemia, schistocytosis and thrombocytopenia. Peritoneal dialysis was carried out in three children (duration 3-12 days). The verotoxin VT2 gene was identified by polymerase chain reaction in the stools of two children. Some days prior to the diarrhoea, all children had eaten a cheese made with unpasteurised mixed cows' and goats' milk from the same farm. A case control study showed that the occurrence of HUS was linked to the consumption of this milk product (P = 0.006). The VT 2 gene was isolated from the cheese and from the stools of goats and cows from the farm, but not from the stools of farm employees.

Acute Disease↗
PubMed1996

Biological effects of the interferons and other cytokines.

There were seven workshops that primarily concerned the biological effects of the interferons and the other cytokines. These were: Workshop 6, The refractory state in the response to interferons (IFNs) and antibodies in treated patients; Workshop 7, IFNs, multiple sclerosis, and the nervous system; Workshop 9, Viral inhibition of the response to IFNs and other cytokines; Workshop 10, Cell growth inhibition by IFNs and other cytokines; Workshop 12, Cytokines and cell death; Workshop 13, Interactions between cytokines; and, Workshop 14, Cytokine gene therapy. Summaries of each of these sessions follow.

Animals↗
PubMed1996

Decrease of intracellular fluorescein fluorescence polarization (IFFP) in human peripheral blood lymphocytes undergoing stimulation with phytohaemagglutinin (PHA), concanavalin A (ConA), pokeweed mitogen (PWM) and anti-CD3 antibody.

In the present study we describe the induction of changes in intracellular fluorescein fluorescence polarization (IFFP) in lymphocytes undergoing activation with a variety of stimulants. These stimulants included the lectins phytohaemagglutinin (PHA), concanavalin (ConA), pokeweed mitogen (PWM) and anti-CD3 antibody. Changes in IFFP were detected in individual cells using the Cellscan apparatus. Our results show that by employing mitogenic concentrations of PHA, as revealed in a [3H]-thymidine incorporation assay, a decrease in the IFFP in human peripheral blood lymphocytes (PBL) occurred within 40 min. ConA and anti-CD3 affected similarly IFFP, whereas PWM, a B lymphocyte lectin, had no effect on IFFP at the concentrations employed. Kinetic analysis revealed that changes in IFFP occurred within 20-40 min after exposure to the stimulants and lasted for 24 h. Our results show that stimulants which activate CD3+ lymphocytes caused immediate changes in IFFP, in an enriched population of human PBL. The possible mechanisms involved in IFFP modulation following exposure to selected stimulants are discussed.

Antibody Specificity↗
PubMed1996

The intracellular domain of the second chain of the interferon-gamma receptor is interchangeable between species.

In this report we show that the mouse interferon (IFN)-gamma R1 and IFN-gamma R2 subunits expressed in hamster cells are capable of rendering the cells sensitive to mouse IFN-gamma as measured by induction of class I MHC antigens and the activation of the transcription factor Stat1 alpha. However, these cells showed no antiviral protection in response to IFN-gamma when challenged with vesicular stomatitis virus (VSV) but limited protection when challenged with encephalomyocarditis virus (EMCV). Furthermore, the cytoplasmic domains of the IFN-gamma R2 subunits, like the cytoplasmic domains of the IFN-gamma R1 chains, can be interchanged between species with no loss of biologic activity, demonstrating that the species-specific interaction of the IFN-gamma R1 and IFN-gamma R2 chains involves only the extracellular domains of the two proteins.

Amino Acid Sequence↗