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Biomedical subjects

J C Olson

Publications and source records attributed to J C Olson.

At least 55 records · Page 3Linked to original sources

Regions of toxin A involved in toxin A excretion in Pseudomonas aeruginosa.

Toxin A is excreted by Pseudomonas aeruginosa as a mature 66,583-dalton protein. In this study, we used molecular cloning and deletion analysis to define specific regions of the toxin molecule involved in its excretion. Subclones that express either the amino terminus, the carboxy terminus, or toxin A molecules with internal deletions were constructed. The hypotoxigenic mutant PAO-T1 was used as a host for the expression of the toxin constructs. When overexpressed (by the presence of extra copies of the toxin A-positive regulatory gene, regA, in trans), toxin A-cross-reactive materials produced by most of these constructs were detected in the supernatant of PAO-T1. The supernatant of P. aeruginosa PAO-T1 contained proteolytic activity that degraded toxin A-derived products but not the intact toxin molecule. A single SalI intragenic deletion (coding for the leader peptide, the first 30 amino acids, and the last 305 amino acids of the toxin) resulted in a relatively stable product in the supernatant of PAO-T1. The product of the carboxy terminus construct (which codes for the last 305 amino acids of the toxin) was detected in the lysate of PAO-T1 only. The data suggest that the amino terminus region of toxin A (the leader peptide plus the first 30 amino acid of the mature protein) is sufficient for its excretion, and that a second region, amino acids 309 through 413, protects an internally truncated toxin A molecule from the proteolytic activity in the supernatant of P. aeruginosa PAO-T1.

Adenosine Diphosphate Ribose↗

Influence of paternal immunity on idiotype expression of offspring.

The immune response of the rat to group A streptococcal carbohydrate (SACHO) and an associated idiotype, Id-1, was used to examine the effect of paternal immunity on Id-1 and SACHO-specific antibody expression by the offspring. First litters, conceived before immunization of the father, had significantly higher Id-1 levels than litters conceived by the same parental pairs after hyperimmunization of the father (P greater than 0.01). Total anti-SACHO levels were not affected. The effect appeared to be independent of the level of Id-1 expressed by the father or grandfather. No significant difference in Id-1 production was found between offspring of actively immune, neonatally Id-1 suppressed fathers and fathers expressing high levels of Id-1. We suggest that the paternal immunoregulatory influence acts via the maternal immune system to modify the idiotype repertoire expressed in the immune response of the offspring, and is not the result of genetic transmission of a trait acquired by the father. Some possible mechanisms of transmission are discussed.

Animals↗

Regulation of the expression of a mammalian idiotype in chickens.

Id-1, an idiotype associated with rat anti-Group A streptococcal carbohydrate (anti-SACHO) antibodies has not been detected in any other tested species immunized with Group A streptococcal vaccine (GASV). The immunization of chickens with rat Id-1 prior to challenge with GASV, however, induced the production of Id-1 and anti-Id-1 in some chickens. The concentrations of both idiotype and anti-idiotype were regulated by challenges with GASV. Thus, it appears that this non-mammalian species has the genetic potential to express the mammalian Id-1 network but such a potential is normally masked by regulatory pressures.

Animals↗

Results in the treatment of postoperative endophthalmitis.

A retrospective study of 40 cases of postoperative endophthalmitis was conducted between July 1979 and May 1981. Treatment consisted of topical, periocular, and systemic antibiotics, as well as the use of intraocular antibiotic injection in all cases. In addition, 22 cases had a diagnostic and therapeutic vitrectomy. The cases selected for vitrectomy included cases with worse presenting visual acuity, higher percentage of positive culture results, and more virulent organisms. Because of a poor clinical response to initial therapy, 13 cases had repeat intraocular cultures performed between 24 and 72 hours at the time of repeat intraocular antibiotic injection. All 13 repeat intraocular cultures were negative. Complications of the treatment included four retinal detachments (three in the vitrectomy group). In the culture-positive cases, a final visual acuity of 20/400 or better was achieved in 13 of 29 cases (45%), and complete loss of vision (NLP) resulted in 10 of the 29 cases (34%).

Administration, Topical↗

The assessment of anti-idiopathic antibodies as effective immunoregulatory probes in vivo.

In order to increase our understanding of the potential to use anti-idiotypic antibodies as immune modulators in vivo, we extensively analysed influences induced by one such antibody (anti-Id-l) following its administration to animals of different ages, genetic backgrounds, and immunological histories. Id-l is an inter-strain idiotype associated with rat anti-Group A streptococcal carbohydrate antibodies. The intraperitoneal (i.p.) injection of anti-Id-l antibodies, prepared against Id-l+ antibodies from an HPR rat could effectively induce long-term idiotype suppression in all tested strains of rats, regardless of the age at the time of treatment, the RTl haplotype or IgG2c or k-chain allotype. Total anti-streptococcal antibodies were not suppressed by this treatment. Although long-term suppression could be induced at any age, the percentage of animals suppressed following neonatal injections was consistently less than that following adult injections of anti-idiotypic antibodies. In addition, neonatal injections of anti-Id-l or Id-l with anti-Id-l appeared to enhance Id-l production in a minority of the animals. Similar treatment of adult animals never increased Id-l synthesis, suggesting that cells associated with enhanced Id-l production in older animals are either refractory to activation-differentiation signals and/or are sequestered and no longer accessible by i.v. or i.p. routes of administration of the probe. Auto-anti-Id-l immunity induced by immunizing adult rats with heavy, light, F(ab')2 fragments or whole IgG molecules could also induce an Id-l suppressed state. We were not able to induce significant Id-l suppression if animals were immunized with antigen prior to the injection of anti-Id-l. There was evidence, however, that such treatment might lead in time to the development of some idiotype specific suppression.

Aging↗

Inheritance patterns of idiotype expression: maternal-fetal immune regulatory networks.

The production of Id-1, a cross-reactive idiotype associated with rat anti-group. A streptococcal carbohydrate antibodies, by 11 strains of rats indicates that genes coding for Id-1 are in the germline. Its expression, however, follows a complex inheritance pattern. It was our intent in these studies to determine if immune responsiveness of streptococcus (GASV) immunized females could alter Id-1 expression of GASV-immunized progeny, and, in turn, introduce complications in Id-1 inheritance patterns. - We observed that Id-1-specific immune reactivity of GASV-immunized females could induce significant alterations in Id-1 production by progeny. The relationship between maternal and progeny Id-1 was complex, reflecting the complexity of autologous regulation of Id-1 production, and could be the opposite of what one would predict based upon parental transfer of Id-1 regulatory genes. The nongenetic nature of the maternal regulatory influence was confirmed by foster-mother studies. - We conclude that antigen-induced maternal immune responsiveness can exert a permanent regulatory influence on idiotype expression by progeny and consequently introduce error in to the interpretations of idiotype inheritance patterns. The recognition of this maternal regulatory influence also lends further support to Jerne's hypothesis that idiotype-specific immune networks play a significant role in the regulation of immune responsiveness in vivo.

Animals↗

Lymphoid thyroiditis following immunization with group A streptococcal vaccine.

Severe lymphoid thyroiditis and associated hypothyroidism occurred in all of 7 male and 4 female F(7) derivatives (seventh generation) of rats immunized in each generation against Group A streptococci. This evidence of thyroiditis produced by immunization against a nonthyroidal antigen suggests that some cases of Hashimoto's thyroiditis in humans may result from nonspecific immune responses.

Animals↗

Pathogenicity of Escherichia coli recovered from food.

In Western nations, pathogenic biotypes are sporadically encountered in foodborne gastroentetis. Cholera, dysentery, and chronic ulcerative colitis syndromes are recognized. E. coli has been associated on the average with 2% of annual food outbreaks and 5% of total cases. In developing nations, the incidence may be greater. In contrast with Salmonella and Shigella, significance can be assessed only by fulfillment of Koch's postulates. Preliminary studies using vascular permeability reaction for the detection of heart-labile toxin and the Sereny keratoconjunctivities test for demonstration of invasiveness indicate limited incidence of these pathogenicity markers in cultures from foods. Two per cent of isolates from cheeses involved in recent outbreaks were toxigenic; 14% were invasive. Corresponding values for food isolates not associated with illness were 10 and 0, respectively. To facilitate examination of multiple isolates, 10 may be pooled for the detection of heat-labile toxin, and 5 for invasiveness. Present model pathogenicity systems require standardization, estimation of specificity and sensitivity limits, examination by collaborative study, and ascertainment of human equivalence. Supplemental tests include capacity for colonization of intestinal epithelium and intracellular growth. Stereotypes based upon serology, host range, and recognized toxic factors may require modification.

Developing Countries↗

Microbiological methods. Methodology for enteropathogenic Escherichia coli.

Pathogenic biotypes of Escherichia coli grow poorly at temperatures greatly different from that of the host. Percentages quantitatively recovered at 42.0, 44.0, 44.5, and 45.5 degrees C in lauryl tryptose broth were 100, 76, 76, and 42, respectively. Corresponding values for 175 strains of varied origin were 98, 89, 82, and 65%. Maximal growth temperature is dependent upon medium. Lauryl tryptose and elevated coliform broths were equivalent in the recovery of small inocula (100 cells/ml) at 41.5-44.5 degrees. MacConkey, enteric enrichment, and Gram-negative broths were inhibitory at corresponding values. Growth at elevated temperature in nutrient broth is enhanced by carbohydrate. Standard lactose enrichment media fail to recover slow lactose fermenters. An acidified glutamic acid medium was unsuitable for recovery of E. coli. The data suggest modification of standard temperatures for the recovery of pathogenic biotypes. Previously recommended analytical methods have been simplified and supplemented. The enhancement of motility in indole-nitrite broth at 35 degrees C is recommended. A 4-tube semiquantitative test is offered for tentative identification of somatic and capsular antigens. Inclusion of Alkalescens-Dispar strains is warranted by their pathogenic behavior. Examination in Shigella and Alkalescens-Dispar sera is required to cover the dysentery-like biotypes. Pathogenic potential cannot be inferred from serotype.

Bacteriological Techniques↗

Enterotoxigenicity of Staphylococcus aureus cultures isolated from acute cases of bovine mastitis.

To determine whether staphylococci causing bovine mastitis are potential causes of human intoxications, 142 cultures identified as etiological agents of acute cases and 18 cultures causing chronic cases of staphylococcal mastitis were obtained from investigators in the United States and Canada, examined microscopically, and tested for carbohydrate utilization, terminal pH, catalase, coagulase, egg yolk hydrolysis, gelatin hydrolysis, cytochrome oxidase, urease production, nitrate reduction, micrococcal nuclease, phage type, and enterotoxin production. Three cultures were not confirmed as Staphylococcus aureus. Of the 157 S. aureus cultures, 23 produced staphylococcal enterotoxins. Although a direct relationship between staphylococcal mastitis and outbreaks of staphylococcal food poisoning was not proved, results indicated that staphylococcal infections of the bovine mammary gland represent a significant reservoir of enterotoxigenic strains of S. aureus.

Animals↗