Biomedical subjects

P C O'Brien

Publications and source records attributed to P C O'Brien.

At least 307 records · Page 17Linked to original sources

PubMed1981

Role of chemotaxis in the association of motile bacteria with intestinal mucosa: chemotactic responses of Vibrio cholerae and description of motile nonchemotactic mutants.

A motile, chemotactic, Ogawa strain of Vibrio cholerae was attracted by all 20 L-amino acids tested, in contrast to Escherichia coli AW 405, which did not react to several of these. The maximum number of vibrios entering a capillary was much lower when the capillary contained carbohydrates rather than amino acids, but the minimum effective concentrations of the carbohydrates and amino acids tested were of the same order of magnitude. L-Fucose, a sugar known to inhibit the adhesion of this vibrio strain to brush border membranes, had no attraction (taxin activity) for it. A pepsin digest of rabbit mucosal scrapings or tryptone attracted vibrios as strongly as the most active amino acids. Several nonchemotactic and one nonmotile mutant were selected from the parent vibrio. The nonchemotactic mutants were indistinguishable from the parent in their ability to attach in vitro to isolated intestinal brush border membranes, whereas the nonmotile mutant had lost this ability. Parent and nonchemotactic mutants had equal growth rates in stirred and still continuous flow cultures that were maintained in an anaerobic environment.

Amino Acids↗

PubMed1981

Role of chemotaxis in the association of motile bacteria with intestinal mucosa: fitness and virulence of nonchemotactic Vibrio cholerae mutants in infant mice.

Contrary to earlier findings with all other in vivo and in vitro models of cholera studied, nonchemotactic vibrio mutants showed a relatively greater fitness in 5-day-old infant mice as compared with chemotactic parent or chemotactic revertant strains. This trend was manifest in the relatively greater number of nonchemotactic mutants recovered from the upper small intestine at 4 and 18 h after intragastric infection. The same trend was also revealed in the significantly greater virulence (in terms of time to death) of nonchemotactic mutants as compared with the chemotactic parent or revertant strains. Histological studies in infant mice of the penetration of chemotactic and nonchemotactic vibrios into the mucus gel of the small intestine yielded the same findings as in all other models studied, i.e., significantly greater penetration by chemotactic vibrios. There was no correlation between the relative fitness of nonchemotactic vibrios in the small intestine of infant mice and the rate of recovery of viable nonchemotactic vibrios from that site. In contrast, excellent correlation was found between the relative fitness of nonchemotactic vibrios and a decrease in the recovery of viable cells of the chemotactic strain from the small intestine. This indicates that the relatively greater fitness of the nonchemotactic vibrios in infant mice was only apparent and that the observed phenomenon was actually due to an antibacterial mechanism which prevented the accumulation of the chemotactic strains in the small intestine rather than to any stimulating effect on the nonchemotactic mutant itself. To study the in vivo fate of the inoculum in infant mice, vibrios were labeled with either 32P, 35S, or [3H]thymidine. Specific activity determinations of the 32P label were compatible with the assumption of an accelerated rate of death of the chemotactic parent strain in the small intestine. Results with the other isotopes, however, were significantly different. Indeed, the amount of radioactivity retained in the small intestine after feeding labeled bacteria correlated more closely with the isotope used than with the strain of vibrio under study. Consequently, considerable doubt must be cast on the general validity of this not uncommon technique for determining the in vivo location and the death or survival of radioactively labeled bacteria.

Animals↗

PubMed1981

Role of chemotaxis in the association of motile bacteria with intestinal mucosa: in vivo studies.

In vivo loops were prepared in the small intestine of rabbits and injected with mixtures of Vibrio cholerae and polystyrene spheres (1.1-micrometers diameter). The loops were removed and frozen after 15 min and then sectioned in a cryostat. The locations of particles and vibrios were determined microscopically. The vibrio/particle ratio was unity in the lumen of the loops, but increased 10-fold in the deep intervillous spaces, indicating active invasion of the mucus gel by the chemotactic parent strain. Motile nonchemotactic mutants and nonmotile mutants of this strain invaded the mucus at the same rate as inert particles. Similar results were obtained with intestinal loops prepared in germfree mice. When germfree mice were disassociated with mixtures of chemotactic (parent or revertant) and nonchemotactic mutant vibrios in equal proportions, the chemotactic strain rapidly outgrew its nonchemotactic counterpart in the intestine. Nonchemotactic mutants introduced as monoassociates into germfree mice were rapidly overgrown by nonmotile mutants which apparently arose spontaneously in the gut. Motility was therefore beneficial to survival only when it was directed by chemotactic stimuli, whereas it was a liability in the absence of such stimuli. Growth of chemotactic vibrios in small intestinal loops of rabbits paralleled that of nonchemotactic mutants for the first 4 to 6 h. Thereafter, the growth rate of the chemotactic vibrios was significantly faster. This was correlated with a significantly higher degree of association with the mucosa on the part of the chemotactic vibrios.

Animals↗

PubMed1981

Role of chemotaxis in the association of motile bacteria with intestinal mucosa: in vitro studies.

Various Sephadex G-15 fractions of pepsin-digested mucosal extract inhibited the in vitro association of cholera vibrios with mucosal slices. Inhibitory activity paralleled the taxin activity of the fractions for these bacteria. This supports the theory that inhibition of mucosal association by pepsin-digested mucosal scrapings was due to the blocking of taxin receptors on the bacterial surface. Nonchemotactic mutants were significantly less efficient than the chemotactic parent or revertant strains in associating with mucosal slices in vitro. Control experiments in which filter paper disks replaced the mucosal slices showed a comparable extent of association of chemotactic and nonchemotactic vibrios with this material. Histological studies indicated that vibrios associated predominantly with the mucus gel of the intestinal slices rather than with the mucosal epithelium or the serosal surface. Intestinal slices attracted chemotactic vibrios even after prolonged washing, suggesting continuous production of the taxin by the tissue. Inert polystyrene particles 1.1 micrometers in diameter penetrated the mucus gel of intestinal slices very poorly, but nevertheless could be detected in low numbers in the deep intervillous spaces within 15 min. In contrast, chemotactic vibrios reached the deep intervillous spaces in significantly higher numbers, whereas motile, non-chemotactic vibrios reacted like the inert particles. It is concluded that mucus gel represents a partial barrier to the penetration of particles of bacterial size and that this barrier can be invaded efficiently by motile bacteria, but only when their locomotion is guided by chemotactic stimuli.

Animals↗

PubMed1981

The spectrum of peripheral neuropathy in myeloma.

The records of 20 patients with typical or sclerotic (sclerotic or mixed sclerotic and lytic) multiple myeloma and peripheral neuropathy who were seen during a 13-year period were analyzed to determine the natural history of the neuropathy. In the 10 patients with typical multiple myeloma, the clinical pattern was heterogeneous. Chemotherapy for multiple myeloma did not affect the neuropathy. The 10 patients who had sclerotic myeloma presented in a relatively homogeneous manner, with a predominantly motor neuropathy. Tumoricidal radiation therapy to localized plasmacytomas resulted in pronounced improvement in the neuropathy of two patients, mild improvement in three, and mild improvement in the endocrine abnormalities of one patient.

Amyloidosis↗

PubMed1981

Effect of artificial pancreas treatment on peripheral nerve function in diabetes.

To determine whether the complete correction of hyperglycemia of diabetes can rapidly improve abnormal peripheral nerve function, eight hyperglycemic insulin-requiring diabetics underwent 3 days of glucose control with an artificial endocrine pancreas, the BIOSTATOR Glucose Controller. Comparison of neurologic assessment before and after BIOSTATOR treatment showed improvement only in ulnar sensory conduction velocity (+ 3.2 +/- 1.4 meters per second, p less than 0.032) and no significant changes in 24 other nerve conduction measurements, computer-assisted examination, and scored neurologic assessment. Any significant beneficial effect on nerve function resulting from correction of hyperglycemia probably requires more than 3 days to be manifested.

Adolescent↗

PubMed1981

Prevalence of monoclonal protein in peripheral neuropathy.

We attempted to survey with serum protein electrophoresis all patients with peripheral neuropathy of unknown cause presenting at our institution within 1 year to determine the prevalence of monoclonal serum proteins in this group. Eighty-four percent of these patients were evaluated, and 10% of these had a monoclonal serum protein. This figure was statistically different from that obtained in two community studies in the literature. Because these patients often present difficult diagnostic problems, serum protein electrophoresis is necessary in the evaluation of cryptogenic neuropathies.

Aged↗

PubMed1981