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Biomedical subjects

R Robins-Browne

Publications and source records attributed to R Robins-Browne.

At least 19 recordsLinked to original sources
PubMed2006

Assessing immune function in adult bronchiectasis.

Bronchiectasis is characterized by chronic airway infection and damage and remains an important health problem. Recent literature has emphasized the role of host defence and immune deficiency in the pathogenesis of bronchiectasis, but there have been few studies of immune function in adult bronchiectasis. A comprehensive screen of immune function was conducted in 103 adult patients with bronchiectasis, encompassing full blood examinations, immunoglobulins and IgG isotypes, complement levels, lymphocyte subsets and neutrophil function. Full blood examinations were normal in this cohort, as were complement levels. Statistical analysis confirmed that a significant number of subjects had low levels of IgG3 (13 patients), B cell lymphocytes (six patients) and T helper cell lymphocytes (seven patients) when compared with controls (P<0.05). The most common abnormality was found with testing of the neutrophil oxidative burst. All subjects had a normal neutrophil phagocytic function but 33 of the subjects had an oxidative burst that was below the normal range (P<0001). Almost half the group (45 subjects) had abnormally low levels of one of these four parameters. The findings of low B cells, Th cells and oxidative burst in bronchiectasis are novel. The results emphasize the importance of immune function assessment for adult bronchiectasis.

Adult↗
PubMed2001

Genetic organization of the she pathogenicity island in Shigella flexneri 2a.

In this study we report the complete nucleotide sequence and genetic organization of the she pathogenicity island (PAI) of Shigella flexneri 2a strain YSH6000T. The 46 603 bp she PAI is situated adjacent to the 3' terminus of the pheV tRNA gene and includes an imperfect direct repeat of the 3'-terminal 22 bp of the pheV gene at the right boundary of the PAI. The she PAI carries a bacteriophage P4-like integrase gene within the pheV -proximal boundary of the PAI, intact and truncated mobile genetic elements, plasmid-related sequences, open reading frames exhibiting high sequence similarity to those found on the locus of enterocyte effacement (LEE) PAI of enterohemorrhagic Escherichia coli (EHEC), and the SHI-2 PAI of S. flexneri and several other open reading frames of unknown function. The she PAI also encodes two autotransporter proteins, including SigA, a cytopathic protease that contributes to intestinal fluid accumulation and Pic, a protease with mucinase, and hemagglutinin activities. In addition, an open reading frame (orf) termed sap, has high sequence similarity to the gene encoding Antigen 43, a surface-located autotransporter protein of E. coli. The ShET1 enterotoxin genes, associated predominantly with S. flexneri 2a strains, are also located on the she PAI.

Bacterial Proteins↗
PubMed2000

The sigA gene which is borne on the she pathogenicity island of Shigella flexneri 2a encodes an exported cytopathic protease involved in intestinal fluid accumulation.

In this study, the sigA gene situated on the she pathogenicity island of Shigella flexneri 2a was cloned and characterized. Sequence analysis showed that sigA encodes a 139.6-kDa protein which belongs to the SPATE (serine protease autotransporters of Enterobacteriaceae) subfamily of autotransporter proteins. The demonstration that SigA is autonomously secreted from the cell to yield a 103-kDa processed form and possesses a conserved C-terminal domain for export from the cell were consistent with the autotransporter pathway of secretion. Functional analysis showed that SigA is a secreted temperature-regulated serine protease capable of degrading casein. SigA was cytopathic for HEp-2 cells, suggesting that it may be a cell-altering toxin with a role in the pathogenesis of Shigella infections. SigA was at least partly responsible for the ability of S. flexneri to stimulate fluid accumulation in ligated rabbit ileal loops.

Animals↗
PubMed1996

Analysis of clinical and environment Yersinia isolates in the Republic of Georgia.

The Center for Infectious Diseases Control, Georgian Ministry of Health, isolated 2,493 Yersinia enterocolitica and Y. enterocolitica-like strains, 22 Y. pestis strains, and 21 Y. pseudotuberculosis strains from 130,574 clinical and environmental samples. Analysis of 100 Y. enterocolitica and Y. enterocolitica-like strains showed none to be within traditional pathogenic biogroups or serogroups, and none carried genetic markers for virulence. However, some strains were enterotoxigenic in infant mice, while others were associated with prolonged carriage in adult mice.

Adult↗
PubMed1995

Increasing severity of invasive group A streptococcal disease in Australia: clinical and molecular epidemiological features and identification of a new virulent M-nontypeable clone.

We conducted a 12-year review of all cases of group A streptococcal (GAS) bacteremia that were seen at Royal Children's Hospital in Melbourne, Australia, from 1982 through 1993. Forty-two cases were identified. There was a trend towards increased incidence of infections, as well as a clear increase in their severity, during the study period; more previously healthy children were affected during the last 6 years of the study (80% of cases) than during the first 6 years (47% of cases), and more complications occurred during the latter period than during the former (40% vs. 20%, respectively, with an 88% complication rate over the last 12 months). Seventy-four GAS isolates (41 invasive, 23 noninvasive, and 10 indeterminate) were analyzed. An M type 1 clone that was positive for the pyrogenic exotoxin A gene (speA) and that has been found to cause invasive disease in the Northern Hemisphere was most frequent among invasive isolates. Molecular typing also identified a genetically distinct strain that was virulent, mucoid, and M nontypable. Invasive GAS disease in Melbourne has become increasingly aggressive. Newer typing methods should be used in conjunction with traditional serotyping in order to maintain epidemiological surveillance of virulent strains.

Adolescent↗
PubMed1994

Hemagglutinating properties of enteroaggregative Escherichia coli.

Many intestinal bacterial pathogens possess hemagglutinating properties, which are indicative of their adhesive properties to the intestinal mucosal surface. To understand the bacteria-mucosa interaction, 41 strains of enteroaggregative Escherichia coli (EAggEC), a recently described category of diarrheagenic E. coli, isolated mostly from children with diarrhea in Bangladesh, India, Thailand, Central America, and South America were screened for mannose-sensitive hemagglutination and mannose-resistant hemagglutination of erythrocytes from humans, rats, mice, sheep, cattle, and rabbits. Some strains demonstrated mannose-sensitive hemagglutination of erythrocytes. Most isolates showed mannose-resistant hemagglutination of erythrocytes from all species except rabbits. The hemagglutination patterns could be classified into 18 groups. Studies with three selected isolates suggested that hemagglutinins are cell bound and are protein in nature. On the basis of the pattern of inhibition of hemagglutination by various chemicals, 39 isolates were classified into 19 groups. Hemagglutinations of many isolates were inhibited by sialic acid-containing compounds, suggesting that these compounds may be the receptors for these organisms on erythrocytes and possibly on the intestinal mucosa. These data indicate that strains of EAggEC are a heterogeneous group of organisms with different types of hemagglutinins or adhesins for the intestinal mucosal surface. Also, the adhesion characteristics of EAggEC strains may be too complex to be assessed by simple hemagglutination tests.

Adhesins, Escherichia coli↗
PubMed1994

Fibronectin-like immunoreactivity of the basilar membrane of celloidin-embedded human temporal bone sections.

Dysfunction of the mechanical properties of the basilar membrane is a potential cause of presbycusis. In cases of minimal sensorineural or strial degeneration it is believed to play a major role. The membrane has been shown to be partly composed of fibronectin. Fibronectin immunoreactivity is diminished in aged rats. Mesothelial cell line the perilymphatic surface of the membrane and are reduced in number in the aged rat cochlea. Fibronectin immunoreactivity was examined in human temporal bone sections (6 months to 92 years old). Hematoxylin and eosin stained section (17 to 97 years) were immunoreactivity was demonstrable in the human cochlea, but was not reduced, even in the eldest cases examined The number of mesothelial cells was reduced, however, and was related to the age of the individual, but not to the clinical diagnosis or audiogram shape. These two factors do not, therefore, appear to give rise to hearing losses associated with presbycusis.

Adolescent↗
PubMed1994

Cochlear implantation in children: labyrinthitis following pneumococcal otitis media in unimplanted and implanted cat cochleas.

Pneumococcal otitis media is frequent in young children and could lead to labyrinthitis post-implantation. To assess the risk, and methods of minimizing it by a graft to the round window around the electrode entry point, we have used a cat animal model of pneumococcal otitis media. Twenty-one kittens were used in the study. Thirty-two cochleas were implanted when the kittens were 2 months of age. Fourteen cochleas were implanted without using a graft (12 were available for study); 9 had a fascial graft, and 9 a Gelfoam graft (7 were available for study). The implanted kittens had their bullae inoculated with Streptococcus pneumoniae 2 months after implantation and were sacrificed 1 week later. There were also 9 unimplanted control ears which were inoculated when the animals were 4 months of age. Labyrinthitis occurred in 44% of unimplanted control, 50% of implanted ungrafted, and 6% of implanted grafted (fascia and Gelfoam) cochleas. There was no statistically significant difference between the unimplanted control and the implanted cochleas (p < 0.05). There was, however, a difference between the implanted-ungrafted and implanted grafted cochleas, but not between the use of fascia and Gelfoam to graft the round window entry point. As a result, the data indicates that cochlear implantation does not increase the risk of labyrinthitis following pneumococcal otitis media, but it is desirable to use fascia as a graft to the round window around the electrode entry point.

Animals↗
PubMed1993

Effectiveness of low-dose intradermal hepatitis B vaccination. Five years' experience of primary vaccination.

OBJECTIVE: To determine whether intradermal hepatitis B vaccination is an effective procedure. DESIGN: A study of antibody responses to hepatitis B vaccine in 753 medical students. SETTING: Routine vaccination of medical students with intradermal doses of hepatitis B vaccines of various origins. OUTCOME MEASURES: Rates of seroconversion and geometric mean levels of antibody achieved. RESULTS: Seroconversion rates, indicated by antibody to hepatitis B surface antigen (anti-HBs) levels of 10 mIU/mL or more, varied between 82% and 94.7% with different preparations of the vaccine. With a four-dose intradermal schedule over two successive cohorts, Engerix-B (SmithKline Beecham) gave better responses, in this context, than H-B-Vax II (Merck Sharp & Dohme). Any reactions to the vaccination were mild and local. CONCLUSION: The intradermal route is a practical method of vaccination against hepatitis B in healthy young adults when the cost of the vaccine is an inhibiting factor.

Adult↗
PubMed1993

The effect of enterohemorrhagic Escherichia coli O157:H7 on intestinal structure and solute transport in rabbits.

BACKGROUND: The effect of enterohemorrhagic Escherichia coli O157:H7 infection on intestinal morphology and solute transport was examined. METHODS: New Zealand white rabbits, aged 10 days, were infected with E. coli strain EDL933 (O157:H7 containing the 60-megadalton plasmid-encoding adhesion factors VT1 and VT2) and compared with controls. Small and large intestinal histology and solute transport were studied 5 days after inoculation. Ion transport in the distal colon was also examined in animals infected with different strains encoding a combination of pathogenic factors. RESULTS: Infection with EDL933 induced diarrhea and mucosal disease in the colon, inhibited colonic Na+ absorption, and stimulated of Cl- secretion, but had no impact on the small intestine. Infection with strains A7785-C3A (O157:H7, plasmid-, VT1+, VT2+) and 85-170 (O157:H7, plasmid+, VT-) induced similar transport changes to EDL933. C600/1 (E. coli K-12, plasmid+, VT1+) decreased Na+ and Cl- absorption only. CONCLUSIONS: Abnormalities of colonic structure and ion transport could account for diarrhea production, but pathogenic factors other than the 60-megadalton plasmid-encoding adhesion factor and verotoxins appear to be involved in enterohemorrhagic E. coli infection.

Animals↗
PubMed1993

Prevalence of verocytotoxigenic Escherichia coli serotype O157:H7 in children with diarrhoea attending a Sydney hospital.

Verotoxin producing Escherichia coli, in particular serotype O157:H7, have been implicated as an important cause of acute gastroenteritis in children. This study was undertaken to determine if E. coli O157:H7 is an important cause of acute gastroenteritis in children in metropolitan Sydney. During the period from October 1990 to September 1991, stools from patients presenting with acute diarrhoea to The Children's Hospital, Camperdown, were examined for the presence of common bacterial pathogens. In addition, stools were grown on sorbitol McConkey agar and sorbitol non-fermenting organisms were serotyped with O157 antiserum by slide agglutination. The isolates were then tested with H7 antisera and investigated for the production of verocytotoxin and other pathogenic markers including plasmid-associated EHEC adhesin and chromosomally encoded attachment-effacement gene. Only two strains (isolated from two different patients, 0.1% of specimens tested) were agglutinated by O157 antiserum and both were non-motile (H-). However, both strains produced verotoxin and expressed other virulence markers, suggesting that they were responsible for the diarrhoea. Both patients experienced mild, self limited gastroenteritis. We conclude that E. coli O157:H7 is an uncommon cause of acute gastroenteritis in Sydney children presenting to a children's hospital.

Acute Disease↗
PubMed1992

Sharing of virulence-associated properties at the phenotypic and genetic levels between enteropathogenic Escherichia coli and Hafnia alvei.

Seven strains of Hafnia alvei isolated from diarrhoeal stools of children resembled enteropathogenic Escherichia coli (EPEC) in that they produced attaching-effacing (AE) lesions in rabbit ileal loops and fluorescent actin staining in infected HEp-2 cells. In addition, a DNA probe from a chromosomal gene required by EPEC to produce AE lesions, hybridised to chromosomal DNA from all seven H. alvei strains. These findings indicate that there is a sharing of virulence-associated properties at the phenotypic and genetic levels by H. alvei and EPEC. H. alvei strains with these properties should be considered diarrhoeagenic.

Bacterial Adhesion↗
PubMed1988

Characterization of enteroadherent-aggregative Escherichia coli, a putative agent of diarrheal disease.

Escherichia coli that exhibit the aggregative pattern of adherence to HEp-2 cells (enteroadherent-aggregative E. coli [EA-AggEC]) have been epidemiologically incriminated as a cause of diarrhea. We undertook a preliminary microbiological and pathogenetic characterization of 42 isolates of this putative pathogen. The strains were negative by tests with DNA probes for enteropathogenic, enterotoxigenic, enteroinvasive, and enterohemorrhagic E. coli and, by serotype, did not fit these categories. Thirty-nine of 42 strains had a 55-65-megadalton plasmid; many shared DNA homology. With one representative strain, plasmid transfer was accompanied by transfer of smooth lipopolysaccharide, fimbriae expression, and the aggregative property. EA-AggEC caused characteristic lesions in rabbit and rat ileal loops. The intestinal lesions and (Shiga-like) limb paralysis and death in rabbits inoculated with live organisms suggest toxin involvement; assays for Shiga-like toxins were negative. These preliminary results support the contention that EA-AggEC may represent a distinct category of diarrheagenic E. coli.

Animals↗
PubMed1987

Patterns of adherence of diarrheagenic Escherichia coli to HEp-2 cells.

A total of 516 Escherichia coli strains randomly isolated from coprocultures of 154 Chilean children with diarrhea and 66 controls were examined with DNA probes and tested for adherence to HEp-2 cells. Three adherence patterns were distinguished, localized, true diffuse and "aggregative." Enteropathogenic E. coli (EPEC) were detected by EPEC adherence factor probe among 86 of the 372 isolates (23%) from patients with diarrhea vs. 14 of 144 (10%) strains from controls (P less than 0.0002). Of 95 strains that manifested localized adherence, 97% were EPEC adherence factor probe-positive; thus the HEp-2 assay may serve as an alternative to the probe in identifying EPEC adherence factor-positive EPEC. True diffuse adherence was not associated with diarrhea. In contrast the aggregative pattern appears to signify a new, distinct class of diarrheagenic E. coli (enteroadherent-aggregative E. coli). The aggregative pattern was found in only 3 of 27 enterotoxigenic, 0 of 4 enteroinvasive, 0 of 2 enterohemorrhagic and 2 of 86 EPEC strains but in 84 of 253 probe-negative strains (P less than 0.00001) from patients with diarrhea; in comparison only 20 of 134 probe-negative strains from controls were aggregative E. coli (P less than 0.00001 vs. probe-negative strains from diarrhea patients).

Bacterial Adhesion↗
PubMed1986

Thyrotrophin (TSH) binding sites on Yersinia enterocolitica recognized by immunoglobulins from humans with Graves' disease.

Antibodies against the gram negative enteric bacterium Yersinia enterocolitica have been found in a high proportion of persons with autoimmune thyroid disorders, especially in those with Graves' disease or hyperthyroidism (Shenkman & Bottone, 1981). There is strong evidence that Graves' disease is caused by receptor autoantibodies which mimic the bioeffects of thyroid stimulating hormone (TSH) on the thyroid (Manley, Knight & Adams, 1982). Recently, saturable binding sites for TSH were demonstrated in Y. enterocolitica under non-physiological conditions (Weiss et al., 1983). We have characterized TSH binding sites on Y. enterocolitica under physiological conditions and studied their interaction with Graves' immunoglobulins (Ig's). Saturable and specific binding of receptor-purified 125I-TSH to lysozyme/EDTA-treated Y. enterocolitica (serotype 03) was demonstrated under both non-physiological and physiological conditions. Scatchard binding plots were linear indicating a single class of binding site (Kd 1 X 10(-7) M, maximum of 30,000 binding sites per cell). In the presence of Graves' Ig's the binding of 125I-TSH to Y. enterocolitica was significantly inhibited. Graves' Ig's also precipitated a protein of relative molecular mass (Mr) 64,000 from Triton-solubilized, 125I-labelled Y. enterocolitica, similar in size to one of the proteins precipitated by Graves' Ig's from human thyroid membranes. These findings are consistent with the hypothesis that thyroid autoimmunity may be triggered by bacterial infection via a mechanism involving crossreactivity at the level of the TSH receptor. They also suggest that elements of mammalian endocrine systems are highly conserved and have a function in prokaryotes.

Antibodies, Bacterial↗