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Biomedical subjects

M S Artenstein

Publications and source records attributed to M S Artenstein.

At least 19 recordsLinked to original sources

Antibody-dependent cell-mediated antibacterial activity of human mononuclear cells. I. K lymphocytes and monocytes are effective against meningococi in cooperation with human imune sera.

In cooperation with human heat-inactivated antisera from adults immunized with group C meningococcal polysaccharide, normal human peripheral blood mononuclear cells significantly decreased the viability of group C meningococci (Mgc) in vitro. K lymphocytes (Null cells) and monocytes, (but not T or B lymphocytes) were capable of effecting antibody-dependent cell-mediated (ADC) antibacterial activity in this system. The degree to which meningococcal viability was decreased was a function of the length of the test incubation, the concentration of effector cells, and the amount of antiserum used in the assay. When specific antibodies directed against Mgc were adsorbed from the antiserum, cell-mediated antibacterial activity was abolished. ADC antibacterial activity was also abrogated by performing the assay at 4 degrees C or by heating effector cells to 46 degrees C for 15 min before the assay, Similarities between the ADC antibacterial system and previously described ADCC assays are discussed. The data suggest the K cells (as well as monocytes) may play a role in host immune defense against pathogenic bacteria.

Antibodies, Bacterial↗

A prospective study of corticosteroid and catecholamine levels in relation to viral respiratory illness.

Urinary 17-OHCS, epinephrine and norepinephrine levels were studied for one week before and one week after the onset of acute, severe Adenovirus 4 respiratory illness in 12 Army recruits during Basic Combat Training. During the pre-illness period, a tendency was frequently noted for all three hormone levels to show "spiking" elevations two to four days before illness onset. There was also a tendency for 17-OHCS levels to rise on the day before fever onset. The possible relationship of these pre-illness hormonal changes to stressful experiences and, in turn, to altered host resistance to infectious illness is discussed. Following onset of respiratory illness, 17-OHCS, epinephrine and norepinephrine levels all showed about 60 percent increases over the early pre-illness period baseline value. Elevations of these hormones persisted for about four to five days, roughly in correlation with fever duration, with only slight differences in configuration and timing of curves from one hormone to the next. The problem of evaluating which of several independent variables operating concurrently during infectious illness may be responsible for stimulating the final common neuroendocrine pathways is discussed.

17-Hydroxycorticosteroids↗

Immunogenicity of serogroup A and C Neisseria meningitidis polysaccharide vaccines administered together in humans.

Serogroup A and C Neisseria meningitidis polysaccharide vaccines were administered to U.S. Army recruit volunteers, either two weeks apart or at the same time into two different sites on the same arm, to determine what effect, if any, the combined administration would have on the immunogenicity of each individual component. The vaccines were found to be as immunogenic when administered together as when given separately; in fact, the data suggest a possible enhancement of the response, as measured by the radioactive antigen binding test, to both components when the two vaccines are given together.

Antibody Formation↗

Safety and immunogenicity of a Neisseria meningitidis type 2 protein vaccine in animals and humans.

Two Neisseria meningitidis vaccines consisting principally of outer membrane protein (lot 138I-0) or outer membrane protein plus group C polysaccharide (lot 138I-M1) were prepared from the group C type 2 strain 138I. Lipopolysaccharide and lipid were removed by gel filtration in the presence of sodium deoxycholate. The vaccines were found to be nontoxic and nonpyrogenic in animals. They provided active protection in mice against mucin-enhanced killing by group B type 2 meningococci and induced good titers of type-specific bactericidal and hemagglutinating antibodies in rabbits. In five volunteers the vaccines were well tolerated and induced significant increases in serum bactericidal activity against both group C and group B strains. Three of five volunteers had a two- to fourfold increase in antibodies to the outer membrane proteins, but these antibodies did not appear to have bactericidal activity. The bactericidal antibodies to both group B and group C strains were directed against the capsular polysaccharides.

Animals↗

Immunoepidemiology of meningococcal disease in military recruits. I. A model for serogroup independency of epidemic potential as determined by serotyping.

One hundred twenty strains of Neisseria meningitidis were serotyped with use of cross-absorbed rabbit antisera in a bactericidal test. Fifty-eight epidemic strains of serogroup B, C, and Y that occurred simultaneously among military recruits at two basic training centers during a period of epidemic meningococcal disease were compared with 62 strains of serogroups A, B, C, and Y isolated worldwide. Antisera to the six original antigenic factors of the Gold serotyping schema were adequate for typing 94% of strains, including all of the epidemic strains. The array of serotyping factors in the epidemic strains differed from those in the nonepidemic strains. Epidemic strains were almost exclusively of two serotypes, with type CII predominant among strains of groups B and C. Concurrent strains of groups B and C were invariably of the same serotype. A model for the epidemic potential of meningococcal strains, which is based on their serotype and serogroup antigens, and a modification of the original Gold typing schema are presented.

Adult↗

Clinical correlation of strain differentiation of Neisseria gonorrhoeae.

An in vitro bactericidal assay that utilized a set of 20 typing antisera to Neisseria meningitidis was developed to distinguish differences in strains of Neisseria gonorrhoeae based on patterns of killing. When test conditions were rigidly standardized, the method was sensitive and reproducible. Strains of gonococci from 20 unrelated patients had 20 different patterns of killing. Sets of strains of N. gonorrhoeae that were likely to be identical on the basis of clinical histories were examined. Organisms isolated from consorts reacted in an identical fashion in seven of nine instances. The two nonidentical sets of strains from consorts were also different in their antibiotic sensitivity patterns. The case history of one patient suggested that one of these strains was obtained from a source of infection other than the named consort, and a second patient was reinfected with a strain from her partner four months later. Four sets of strains were cultured at different intervals after appropriate therapy. On the basis of bactericidal patterns, the strains from one patient were the same, a finding that suggested treatment failure; the strains from other patients were not identical, a fact that suggested that patients were reinfected.

Antigens, Bacterial↗

Analysis of parameters affecting the solid phase radioimmunoassay quantitation of antibody to meningococcal antigens.

An indirect solid phase radioimmunassay (SPRIA) performed in flexible polyvinyl microtiter plates was modified for quantitative determination of antibodies to various bacterial antigens. Parameters affecting quantitation of the assay were investigated by using meningococcal serotype antigens and rabbit antisera plate was essentially complete after 1 hr at 37 degrees C, and only 4 to 8% of the bound antigen was released during the course of the assay. About 90% of the specific primary antibody (PAb) added to the antigen-coated wells was bound after overnight incubation at room temperature, whereas, 10 to 25% of the bound PAb was released before completion of the assay. Under conditions of limiting PAb the time required for saturation binding of 125I-anti-immunoglobulin (secondary antibody = SAb) to the PAb was dependent on the concentration of SAb. At a concentration of 20 ng SAb/25 mul, maximum binding occurred in 12 to 16 hr at 22 degrees C. Uncer conditions of extreme SAb excess the cpm of 125I-SAb bound was directly proportional to the amount of PAb bound. Under these conditions the cpm of 125I-SAb bound per well can be related to the amount of PAb added per well by a time-dependent calibration coefficient K(t) which is the product of three parameters: 1) the specific activity of the 125I-SAb, 2) the ratio of PAb bound to SAb bound and, 3) the fraction of added PAb remaining bound to the plate. Experimentally determined values for these parameters were used to calculate K(t) and quantitate the specific antibody in nine rabbit antisera with the SPRIA. A close correlation (r=0.985) was found between these results and the results of quantitative precipitin tests performed by using the same antisera and antigens. Although the SPRIA results were an average of 33% lower, a more accurate value for K(t) can easily be determined by performing the SPRIA on several sera calibrated by the quantitative test. Reproducibility of the SPRIA for 10 replicate determinations was +/- 6.7%. The assay described is capable of measuring a minimum of about 0.5 mug antibody/ml of serum and appears to be applicable to many different antigens.

Animals↗

Coxsackievirus B5 infection and aseptic meningitis in neonates and children.

In metropolitan Washington, DC, an outbreak of aseptic meningitis in children was recognized in the summer and fall of 1972. Age-specific attack rates were highest in children less than 1 year of age. The incidence of cases showed two peaks: one in July and another in October. Coxsackievirus B5 was associated with cases occurring in July, August, and September, but was not implicated in the October cases. Seventy-six percent of the confirmed coxsackievirus B5 infections in aseptic meningitis patients occurred in infants less than 2 months old. Specific meningeal symptoms were less frequently observed in these young infants, although viral isolations were more common (13 of 15) compared to patients over 2 months of age (four of 19). Analysis of reported coxsackievirus B5 infections in Washington, DC, and the United States as a whole suggests a five- or six-year periodicity.

Adolescent↗

Duration of antibody responses after vaccination with group C Neisseria meningitidis polysaccharide.

Persistence of serum antibodies after vaccination with group C Neisseria meningitidis polysaccharide was followed in 23 volunteers. Each subject had received a single 50-mug dose of vaccine subcutaneously or intradermally one to five years earlier. Three individuals received a second inoculation eight months after the primary one with no evidence of booster antibody response. Hemagglutination antibody titers rose significantly in 22 of 23 volunteers within two to four weeks of injection; mean titers fell two- to threefold within the first year and then remained stable for four years. Bactericidal tests showed antibody response in 86% of subjects and antibody persistence comparable to that found in the hemagglutination tests. Titers of radioactive antigen-binding antibodies increased significantly in all 22 subjects tested, and after two to four years titers remained at 30% or more of peak concentration. The prolonged duration of antibody responses to polysaccharides in humans suggests that immunity will also persist.

Adult↗

Problems and progress towards vaccination against bacterial infections of the respiratory tract.

A large number of bacterial species are causative agents of respiratory tract disease. The discussion will center on three infections selected because they represent different problems in control on the basis of epidemiologic and immunochemical factors. Group A hemolytic streptococci are common upper respiratory tract pathogens which may initiate severe non-suppurative sequelae such as rheumatic fever and glomerulonephritis. Recent progress concerning M protein vaccines will be reviewed. Pneumococci are still the most frequent cause of pneumonia at all ages. Pneumococcal vaccines are the prototype for purified polysaccharide vaccines since their effectiveness was demonstrated 30 years ago. The major problem in vaccination is the very large number of capsular serotypes. Pseudomonas aeruginosa represents the relatively new problem of gram-negative bacterial infections in the immunodepressed host. Demonstration of seven immunotypes as the cause of 90% of human infections has led to preparation of a multivalent vaccine composed of lipopolysaccharide antigens. Current knowledge of this vaccine will be discussed.

Antigens, Bacterial↗

Immunologic hyporesponsiveness in man to group C meningococcal polysaccharide.

By using a hemagglutination-inhibition assay, certain lots of purified group A meningococcal polysaccharide vaccines were found to contain trace amounts of group C polysaccharide (0.032 to 0.128%). Young adult human volunteers inoculated with these vaccines showed a very poor group C serum anti-polysaccharide antibody response as determined by a radioactive antigen-binding assay. Two weeks later volunteers were given a 50-mug subcutaneous injection of purified group C polysaccharide. Serum specimens obtained 1 month later showed a significant suppression of group C antibody response in comparison with subjects who had initially received group A vaccines which were free of group C antigen. The observed hyporesponsiveness may represent an example of immunologic tolerance in man.

Antigen-Antibody Reactions↗

Control of meningococcal meningitis with meningococcal vaccines.

The development of effective meinigococcal vaccines was based upon the finding that immunity to the meningococcus was directly correlated with serum bactericidal antibodies. Purified high molecular weight capsular polysaccharides of serogroups A and C meningococci stimulated the production of humoral antibodies which had group specific bactericidal activity. In controlled field trials in Army recruits, group C polysaccharide vaccines were highly effective in preventing group C disease. Following its use as a routine immunization in recruits in October 1971 group C meningococcal disease has been almost completely eliminated from Army training centers. Group A vaccine has been field tested in Egyptian school children with great success. Group B polysaccharide has failed to induce bactericidal antibodies in humans and, therefore, new research is underway to attempt to develop a cell wall protein antigen as a vaccine against group B disease.

Adult↗