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Biomedical subjects

M Pollack

Publications and source records attributed to M Pollack.

At least 73 records · Page 4Linked to original sources
PubMed1982

Pseudomonas aeruginosa exotoxin A inhibits proliferation of human bone marrow progenitor cells in vitro.

Pseudomonas aeruginosa exotoxin A, a potent inhibitor of eukaryotic protein synthesis, is produced in vivo during human infection. We tested the hypothesis that exotoxin A may be responsible for the leukopenia which sometimes accompanies pseudomonas disease by examining the in vitro toxicity of exotoxin A for human bone marrow granulocyte-macrophage progenitor cells (colony-forming units in culture [CFU-c] in the soft agar cloning system. Colony formation by freshly obtained marrow cells from five normal subjects was inhibited by exotoxin A in a concentration-dependent manner. The mean 50 and 100% inhibitory concentrations of toxin were 1.4 x 10(-10) and 1.4 x 10(-8) M, respectively, and significant inhibition was observed at a toxin concentration as low as 1.4 x 10(-13) M in two subjects. The inhibitory effect of exotoxin A on colony formation was specifically neutralized by antiserum to exotoxin A. Although mouse CFU-c were somewhat less sensitive to exotoxin A in vitro compared with human CFU-c, exotoxin A produced significant leukopenia in vivo in mice. These data suggest a possible mechanism for the leukopenia which sometimes occurs in human pseudomonas disease.

ADP Ribose Transferases↗
PubMed1981

Genetic and hormonal characterization of cryptic 21-hydroxylase deficiency.

Cryptic 21-hydroxylase deficiency has been previously described in asymptomatic family members of patients with classical congenital adrenal hyperplasia (CAH). These family members were detected by high baseline 17-hydroxyprogesterone levels found in the course of family studies. The hormonal responses to ACTH of the family members with cryptic 21-hydroxylase deficiency were determined and compared to the responses of patients with CAH, patients with acquired adrenal hyperplasia, family members predicted to be heterozygous for CAH, family members predicted to be unaffected, and the general population. The ACTH-stimulated levels of 17-hydroxyprogesterone and delta 4-androstenedione in the cryptic family members were elevated above the level of the general population or family members heterozygous for classical CAH, but below that of patients with CAH. The hormonal profile of patients with cryptic 21-hydroxylase deficiency is similar to that of patients with acquired adrenal hyperplasia. The response of family members heterozygous for the cryptic gene (21-OH CRYPTIC/21-OH NORMAL) was indistinguishable from that of family members heterozygous for the classical CAH gene (21-OH CAH/21-OH NORMAL). These studies support our previous proposal that patients with cryptic 21-hydroxylase deficiency are genetic compounds, having one gene for a severe enzyme deficiency and one gene for a mild 21-hydroxylase deficiency. Thus, the 21-hydroxylase genotype in cryptic 21-hydroxylase deficiency is 21-OH CAH/21-OH CRYPTIC.

Adolescent↗
PubMed1980

Histoplasma capsulatum endocarditis.

Endocarditis is a rare manifestation of disseminated Histoplasma capsulatum infection. A 22-year-old man presented with a seven month history of fever, weight loss, and progressive aortic insufficiency. The diagnosis of H. capsulatum was suggested by a diagnostic rise in complement fixation titers and positive echocardiographic findings. The diagnosis was confirmed prior to surgery by positive bone marrow culture. Progressive congestive heart failure necessitated replacement of the aortic valve which subsequently grew H. capsulatum. In this case, a combination of amphotericin B therapy and valve replacement was curative.

Adult↗
PubMed1980

A prospective double-blind study of side effects associated with the administration of amantadine for influenza A virus prophylaxis.

During a study of efficacy of amantadine prophylaxis of influenza A virus infection in young adults, gross and subtle side effects were monitored. Eighty-eight students were randomly selected to receive either amantadine or placebo for four weeks or both in a sequential crossover design of two weeks each. Side effects (i.e., dizziness, nervousness, and insomnia) occurred in 33% of those receiving amantadine and in 10% of those receiving placebo (P less than 0.005). Although side effects were well tolerated by most subjects, six volunteers discontinued amantadine because of marked complaints. Cessation of side effects occurred in more than half of those continuing amantadine. Sixteen students receiving amantadine had decreased performance on sustained attention tasks as compared with ones receiving placebo (P less than 0.05). Gross and subtle side effects of amantadine observed in this study on currently recommended dosage are higher than previously reported, which may be an important factor in consideration of mass prophylaxis.

Adolescent↗
PubMed1980

Circulating immune complexes in cystic fibrosis.

Recurrent respiratory infections associated with "mucoid" Pseudomonas aeruginosa characterize the advanced stages of cystic fibrosis. To determine if chronic antigenic stimulation is associated with circulating immune complexes (CIC), we assayed the sera of 20 hospitalized patients using the technique of precipitation with 4% polyethylene glycol. Elevated CIC levels, defined by > 310 micrograms IgG per ml, were found in 18 of 20 patients, (range, 350 to 3200 micrograms/ml). Serum, supernatant, and resuspended precipitates were assayed for hemagglutinating antibodies against pseudomonas lipopolysaccharide (LPS or endotoxin) and exotoxin A antigens. Both serum anti-LPS (range, 1:64 to 1:2048) and antitoxin titers (range, 1:64 to 1:16, 384) were markedly elevated and higher than titers in supernatants and resuspended precipitates, indicating antibody excess. "Enrichment" ratios for antibodies present in CIC were calculated by proportion of titer to immunoglobulin in the precipitated complex relative to these values in serum. Mean enrichment ratios of 13.1 and 13.9 were obtained for LPS antibody before and after 2 mercaptoethanol reduction, but the mean enrichment ratio for antitoxin was only 2.07. Serially diluted supernatants and precipitates were boiled for 1 hr and tested for endotoxin-like activity by the limulus test. At > 1:8 dilutions, precipitates were positive, and supernatants were negative. These findings indicate that CIC's are common in advanced cystic fibrosis, and analysis of the precipitated complexes demonstrates significant (> 13-fold) enrichment of antibodies against LPS but not exotoxin antigens, as well as endotoxin-like activity in boiled precipitates.

Antibodies↗
PubMed1980

Cryptic 21-hydroxylase deficiency in families of patients with classical congenital adrenal hyperplasia.

Serum androgens and 17-hydroxyprogesterone concentrations and HLA genotypes were determined in 124 families of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH). In 8 pedigrees, we discovered 16 pubertal or postpubertal family members of either sex who had biochemical evidence of 21-hydroxylase deficiency but were without clinical symptoms of excess virilism, amenorrhea, or infertility. We designated these family members as individuals with cryptic 21-hydroxylase deficiency. Within each generation, the family members with cryptic 21-hydroxylase deficiency were HLA identical. It is proposed that these family members are genetic compounds, having 21-hydroxylase deficiency as a result of two recessive gene defects: 1) a severe 21-hydroxylase gene defect present in the index case with classical CAH (21-OHCAH) and 2) a mild 21-hydroxylase gene defect (21-OHCRYPTIC). Thus, the CAH genotype in the family members with cryptic 21-hydroxylase deficiency is 21-OHCAH/21-OHCRYPTIC. Lod score analysis for linkage between the cryptogenic 21-OH trait and HLA gave a combined Lod score for males and females of theta = 0.00 of 3.409. Close genetic linkage between HLA and 21-OHCRYPTIC was thus established. This study provides support for the previously reported heterogeneity of 21-hydroxylase deficiency which may result from allelic variability at the locus for steroid 21-hydroxylase.

17-alpha-Hydroxypregnenolone↗
PubMed1979

Enzyme-linked immunosorbent assay for Pseudomonas aeruginosa exotoxin A.

An enzyme-linked immunosorbent assay (ELISA) is described for Pseudomonas aeruginosa exotoxin A. A double antibody sandwich method was used, employing polyvinyl microtiter plates as the solid phase, a primary coat of monospecific rabbit antitoxin serum, an outer layer composed of a horseradish peroxidase-sheep antitoxin immunoglobulin G conjugate, and an ortho-phenylene-diamine substrate. Absorbance (optical density) of hydrolyzed end product was read spectrophotometrically at 492 nm. ELISA detected as little as 30 pg (0.3 ng/ml) of purified toxin, and absorbance was linear over a 20-fold or greater concentration range. Toxin was demonstrated in culture filtrates from 42 of 48 (88%) consecutive clinical P. aeruginosa isolates compared with 37 of 48 (77%) positive by hemagglutination inhibition. Results of the two assays correlated closely (r = 0.82, P less than 0.001). Specificity was confirmed by neutralizability of ELISA activity with monospecific antitoxin. ELISA was thus a sensitive, specific, and quantifiable technique for the assay of P. aeruginosa exotoxin A in both purified and crude culture materials.

Enzyme-Linked Immunosorbent Assay↗
PubMed1979

Protective activity of antibodies to exotoxin A and lipopolysaccharide at the onset of Pseudomonas aeruginosa septicemia in man.

Serum antibodies to exotoxin A and type-specific lipopolysaccharide were measured by passive hemagglutination in 52 patients with Pseudomonas aeruginosa septicemia. Their comparative protective activities were evaluated by relating the titers of each at the onset of bacteremia to subsequent outcome. High acute serum antitoxin and antilipopolysaccharide titers (log2 reciprocal mean titers greater than 5) were associated with survival (76% of 17 with high vs. 46% of 24 with low antitoxin titers, P = 0.05; 85% of 13 with high vs. 48% of 29 with low antilipopolysaccharide titers, P = 0.03). In contrast, neither antibody titer was significantly associated (P less than or equal to 0.05) with patients' age or sex, severity of underlying disease, presence of leukopenia, steroid or immunosuppressive therapy. Despite a correlation between acute titers of the two antibodies (r = 0.33, P = 0.06), they appeared to protect independently and additively. Whereas 75% of 8 patients with high antitoxin titers and only 38% of 16 with low titers survived with low antilipopolysaccharide titers (P = 0.10), 100% (6/6), 73% (8/11), and 38% (6/16) survived, respectively, when both, one, or neither antibody was present in high titer (P = 0.01). Furthermore, the association between high acute serum antitoxin titers and survival was more pronounced in patients with rapidly fatal underlying disease (P = 0.06) and leukopenia (P = 0.12) than in more favorable prognostic and immune categories. These data indicate that serum antibodies to exotoxin A and lipopolysaccharide are found in most patients with P. aeruginosa septicemia and both are protective. Both antibodies may have therapeutic or prophylactic potential, whereas serum antiexotoxin A antibodies may be particularly beneficial in compromised hosts.

Adolescent↗
PubMed1979

Hormonal phenotype and HLA-genotype in families of patients with congenital adrenal hyperplasia (21-hydroxylase deficiency).

The response of 17-hydroxyprogesterone (17-OHP) and cortisol (F) to a 6-hr ACTH stimulation in families of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency was studied. These studies demonstrated that siblings who should be heterozygous carriers of the 21-hydroxylase deficiency gene based on HLA genotyping are hormonally different from the general population. In pre- and early pubertal children predicted to be heterozygous carriers of the gene based on HLA genotyping, the 17-OHP level (13.1 +/- 4.5 ng/ml), the rate of increase of 17-OHP (0.03 +/- 0.01), and the ratio of 17-OHP/F at 6 hr (0.27 +/- 0.07) were significantly higher (P less than 0.001) than in the control population, (3.9 +/- 1.9, 0.009 +/- 0.005, and 0.08 +/- 0.04 ng/ml, respectively). In late and postpubertal males, these hormonal parameters in the heterozygotes (17 +/- 9.7, 0.04 +/- 0.026, 0.42 +/- 0.33 ng/ml, respectively) were significantly higher (P less than 0.001) than in the general population (5.3 +/- 1.6, 0.009 +/- 0.004, and 0.1 +/- 0.03 ng/ml, respectively). In postmenarchal females, the mean hormone responses in the heterozygotes (12.1 +/- 9.7, 0.03 +/- 0.02, and 0.27 +/- 0.24 ng/ml, respectively) were significantly higher (P less than 0.005, less than 0.01, less than 0.005, respectively) than in the general population (5.2 +/- 2.5, 0.01 +/- 0.007, and 0.1 +/- 0.04 ng/ml, respectively). However, the overlapping values did not permit a clear differentiation of the hormonal responses in these two groups. Another (ACTH) stimulation in one family demonstrated that a father of a patient probably is a previously unrecognized homozygous affected patient and,thus, revision of the congenital adrenal hyperplasia (CAH) genotype for this family was required.

Adrenal Hyperplasia, Congenital↗
PubMed1978

Mechanism of action of Pseudomonas aeruginosa exotoxin A in experimental mouse infections: adenosine diphosphate ribosylation of elongation factor 2.

The data presented indicate that one of the primary actions of Pseudomonas aeruginosa exotoxin during experimental infection is the inactivation of elongation factor 2 (EF-2) in various mouse organs. Organs from mice infected with the toxigenic P. aeruginosa strain PA103 contained considerably less EF-2 activity than did organs from uninfected controls. Whereas EF-2 activity was reduced in all organs examined from PA103-infected animals, the largest decrease was observed in the liver, where the active EF-2 levels were reduced by 70 to 90%. In addition, consistent inhibition of protein synthesis in livers but not in other organs was observed in mice infected with the toxigenic PA103 strain. Treatment of mice with antitoxin before infection with strain PA103 prevented inactivation of EF-2. When mice were infected with lethal doses of the nontoxigenic P. aeruginosa WR5 strain, tissue EF-2 levels were not markedly reduced below those derived from uninfected control animals.

Adenosine Diphosphate↗