Biomedical subjects

J R Fitzgerald

Publications and source records attributed to J R Fitzgerald.

11 recordsLinked to original sources

PubMed2001

Evolutionary genomics of Staphylococcus aureus: insights into the origin of methicillin-resistant strains and the toxic shock syndrome epidemic.

An emerging theme in medical microbiology is that extensive variation exists in gene content among strains of many pathogenic bacterial species. However, this topic has not been investigated on a genome scale with strains recovered from patients with well-defined clinical conditions. Staphylococcus aureus is a major human pathogen and also causes economically important infections in cows and sheep. A DNA microarray representing >90% of the S. aureus genome was used to characterize genomic diversity, evolutionary relationships, and virulence gene distribution among 36 strains of divergent clonal lineages, including methicillin-resistant strains and organisms causing toxic shock syndrome. Genetic variation in S. aureus is very extensive, with approximately 22% of the genome comprised of dispensable genetic material. Eighteen large regions of difference were identified, and 10 of these regions have genes that encode putative virulence factors or proteins mediating antibiotic resistance. We find that lateral gene transfer has played a fundamental role in the evolution of S. aureus. The mec gene has been horizontally transferred into distinct S. aureus chromosomal backgrounds at least five times, demonstrating that methicillin-resistant strains have evolved multiple independent times, rather than from a single ancestral strain. This finding resolves a long-standing controversy in S. aureus research. The epidemic of toxic shock syndrome that occurred in the 1970s was caused by a change in the host environment, rather than rapid geographic dissemination of a new hypervirulent strain. DNA microarray analysis of large samples of clinically characterized strains provides broad insights into evolution, pathogenesis, and disease emergence.

Animals↗

PubMed2001

Evolutionary genomics of pathogenic bacteria.

Complete genome sequences are now available for multiple strains of several bacterial pathogens and comparative analysis of these sequences is providing important insights into the evolution of bacterial virulence. Recently, DNA microarray analysis of many strains of several pathogenic species has contributed to our understanding of bacterial diversity, evolution and pathogenesis. Comparative genomics has shown that pathogens such as Escherichia coli, Helicobacter pylori and Staphylococcus aureus contain extensive variation in gene content whereas Mycobacterium tuberculosis nucleotide divergence is very limited. Overall, these approaches are proving to be a powerful means of exploring bacterial diversity, and are providing an important framework for the analysis of the evolution of pathogenesis and the development of novel antimicrobial agents.

Bacteria↗

PubMed2001

Characterization of a putative pathogenicity island from bovine Staphylococcus aureus encoding multiple superantigens.

Previous studies have demonstrated that a proportion of Staphylococcus aureus isolates from bovine mastitis coproduce toxic shock syndrome toxin (TSST) and staphylococcal enterotoxin C (SEC). In this study, molecular genetic analysis of one such strain, RF122, revealed the presence of a 15,891-bp putative pathogenicity island (SaPIbov) encoding the genes for TSST (tst), the SEC bovine variant (sec-bovine), and a gene (sel) which encodes an enterotoxin-like protein. The island contains 21 open reading frames specifying hypothetical proteins longer than 60 amino acids including an integrase-like gene. The element is bordered by 74-bp direct repeats at the left and right junctions, and the integration site lies adjacent to the 3' end of the GMP synthase gene (gmps) in the S. aureus chromosome. SaPIbov contains a central region of sequence identity with the previously characterized tst pathogenicity island SaPI1 (J. A. Lindsay et al., Mol. Microbiol. 29:527-543, 1998). A closely related strain, RF120, of the same multilocus enzyme electrophoretic type, random amplified polymorphic DNA type, and ribotype, does not contain the island, implying that the element is mobile and that a recent insertion/deletion event has taken place. TSST and TSST/SEC-deficient mutants of S. aureus strain RF122 were constructed by allele replacement. In vitro bovine Vbeta-specific lymphocyte expansion analysis by culture supernatants of wild-type strains and of tst and sec-bovine allele replacement mutants revealed that TSST stimulates BTB13-specific T cells whereas SEC-bovine stimulates BTB93-specific T cells. This suggests that the presence of SaPIbov may contribute to modulation of the bovine immune response.

Animals↗

PubMed2000

Molecular population and virulence factor analysis of Staphylococcus aureus from bovine intramammary infection.

Staphylococcus aureus isolates from cows in Ireland (n = 102) and the USA (n = 42) were characterized by RAPD-PCR and analysed for the production of a number of putative virulence factors. Of these strains 63 representative isolates were screened for the corresponding virulence factor genes by PCR or Southern hybridization or both. The isolates were divided into 12 distinct clonal types on the basis of their RAPD fingerprint profiles. Of the isolates, 107 (74.3%) tested positive for clumping factor in a slide agglutination test, all 24 RAPD type 7 isolates being negative for clumping factor. PCR analysis of region R, a repeat region of the clfA gene, revealed eight region-R sizes. There was a strong association between RAPD type and the clfA region-R genotype among Irish isolates. Of the RAPD type 7 isolates, 21 (87.5%) coproduced toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin C (SEC). Over 90% of isolates demonstrated haemolytic activity on sheep or rabbit red blood cells and all isolates harboured the gamma-haemolysin (hlg) locus. Of the Irish isolates, all those of RAPD type 7 were sensitive to penicillin G, whereas 86% of RAPD types 4 and 5 strains were resistant. Furthermore, RAPD types 5 and 7 were more likely to be associated with clinical mastitis whereas RAPD type 4 isolates were more often associated with a latent infection. The current study identifies some of the putative virulence factors produced by the predominant clonal types of bovine Staph. aureus that may be considered as components of a vaccine.

Animals↗

PubMed1997

Fine-structure molecular epidemiological analysis of Staphylococcus aureus recovered from cows.

Sixty-three Staphylococcus aureus isolates recovered from bovine sources in the USA and the Republic of Ireland were characterized by multilocus enzyme electrophoresis (MLEE), ribotyping, and random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) typing at two separate laboratories. The S. aureus isolates were assigned by MLEE to 10 electrophoretic types (ETs) (Index of Discrimination, D = 0.779). In contrast, the same isolates were assigned to 13 ribotypes (D = 0.888), and to 12 RAPD types (D = 0.898). A common clone, ET3, of worldwide distribution, was represented by six distinct combinations of ribotypes and RAPD types. S. aureus clones recovered from cows in Ireland were also associated with mastitis in dairy cows in the USA. These findings are consistent with the hypothesis that only a few specialized clones of S. aureus are responsible for the majority of cases of bovine mastitis, and that these clones have a broad geographic distribution.

Animals↗

PubMed1987

Group instruction with profoundly retarded persons: acquisition, generalization, and maintenance of a remunerative work skill.

We evaluated a group instruction program for teaching a vocational skill to profoundly retarded adults. The program involved designated trainer roles and both individual student-directed and total group-directed procedures. Results indicated that, following the program, participants acquired the skill of stamping addresses on envelopes, the skill generalized across an untrained type of envelope, and the skill maintained over time. The group activity was incorporated into the regular classroom without increased disruption and the participants earned a wage for their productivity. Implications for the development of a group instruction technology for severely handicapped persons are discussed.

Adult↗

PubMed1984

A rapid training procedure for teaching manual sign language skills to multidisciplinary institutional staff.

The benefits of teaching manual sign language skills to severely and profoundly mentally retarded persons are becoming well documented. However, if these individuals are to use manual signing for functional communication, then their daily caregivers must also be skilled in the use of signs. In this study, a program for teaching signing skills to institutional personnel was evaluated. The generality of the program's effectiveness was investigated in three studies involving different groups of staff: paraprofessional direct care staff, specialty habilitation persons, and nurses. Results showed that the training program, consisting of written and verbal instructions, modeling, practice, and verbal feedback, was effective in rapidly teaching signs to all participating staff members. Also, the acquired signing skills maintained over time, the program was well received by staff, and staff used the signs in their routine interactions with institutionalized residents. Results are discussed with respect to the need to insure that handicapped individuals have a manual signing community with which to use their signing skills and to important components of effective staff training programs.

Education of Persons with Intellectual Disabilitie↗

PubMed1983

Acute peptic ulcer in childhood. Emergency surgical therapy in 39 cases.

Acute peptic ulcers occurred in 39 infants and children, 22 girls and 17 boys. Eleven patients were less than one year of age. Peptic ulcers were secondary to systemic disease or ulcerogenic medications in 34 cases. Hemorrhage occurred in 27 patients, perforation in 12. Endoscopy was the most useful diagnostic procedure for hemorrhage. Free air was seen on abdominal roentgenogram in all perforated patients. Ligation of the ulcer bed, vagotomy, and pyloroplasty were performed in 25 patients with bleeding. One patient required total gastrectomy. Simple plication was performed in nine patients with perforation. Plication was combined with pyloroplasty and tube duodenostomy in one patient each, and vagotomy and antrectomy were required in one patient. Operative mortality was 5.2%. There were two late deaths (Reye's syndrome and burn sepsis). No ulcer has recurred.

Acute Disease↗

PubMed1982

A program for increasing manual signing by autistic and profoundly retarded youth within the daily environment.

A program was implemented to increase the manual signing of five profoundly retarded and four autistic youth within their daily environment. Each participant was nonvocal or minimally vocal. The program was based on modified incidental teaching strategies and was implemented by direct care personnel under supervision in an institutional setting. Specific components included rearranging the physical environment to prompt signing, altering routine staff-resident interactions to prompt, manually guide and/or reinforce signing; and conducting mini-training sessions. Additionally, staff modeled signs intermittently throughout the day. The program was sequentially implemented during two staff work shifts on each of two resident living modules. Observations conducted at four separate time periods during the day indicated that significant increases in signing occurred for all participating youth and that the increases generally maintained during follow-up checks at 5 and 17 weeks. Differential effects of the increased signing on frequency of vocalizations were noted across residents. A staff acceptability survey indicated favorable staff reports on the usefulness of signing to communicate with the youth. Results are discussed regarding the significance of manual signing for seriously developmentally disabled persons and the importance of ensuring that signing skills are used in the daily environment and not exclusively in formal training sessions. Also, areas for continued research are noted in terms of more refined analyses of client skills and subsequent progress in manual communication programs.

Adolescent↗

PubMed1981

Involving institutional staff in the development and maintenance of sign language skills with profoundly retarded persons.

A program to involve institutional staff in developing manual sign language skills with profoundly retarded persons was evaluated. In Experiment 1, six direct care staff, with close supervision, taught a small repertoire of signs to six profoundly retarded residents who had not benefited from previous training in vocal language. Training was conducted in a group format using instructions, modeling, manual guidance, contingent reinforcers, and feedback. During training, all residents learned to identify pictures of objects with manual signs. Generalization observations during unstructured times on the residents' living unit indicated that staff used their signing skills with the residents in addition to their vocal interactions but the residents did not increase their signing or vocalizing. In Experiment 2, the residents' skills in signing with real objects on their living unit as opposed to pictures of objects were evaluated and provided with additional training where necessary. Results indicated that all participating residents learned to communicate with signing during structured interactions on their living unit, and the skills maintained during follow-up assessments ranging from 39 to 49 weeks. Results are discussed regarding the variable generalization effects noted as well as the general benefits and disadvantages of teaching manual signing skills to profoundly retarded persons.

Adolescent↗

PubMed1978

Osseous choristoma of the choroid.

A case is presented in which the diagnosis was made clinically of an osseous lesion of the choroid in an otherwise normal eye. The clinical diagnosis of an osseous choristoma was confirmed by the use of ultrasonography, orbital roentgenograms, and computerized axial tomography. Enlargement of the lesion was documented photographically during a four-month period. The causes of intraocular ossification are discussed, and the typical clinical features of osseous choristoma of the choroid are suggested.

Adolescent↗