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Biomedical subjects

B D Jones

Publications and source records attributed to B D Jones.

At least 37 records · Page 2Linked to original sources

Preparing and retaining rural physicians through medical education.

PURPOSE: To identify educational approaches that best prepare physicians for rural work and small-town living, and that promote longer rural practice retention. METHOD: In two mail surveys (1991 and 1996-97), the authors collected data from primary care physicians who had moved to rural practices nationwide from 1987 through 1990. A total of 456 eligible physicians responded to both surveys (response rate of 69.0%). The authors identified those features of the physicians' training that correlated with their self-reported preparedness for rural practice and small-town living, and with how long they stayed in their rural practices. Analyses controlled for six features of the physicians and their communities. RESULTS: The physicians' sense of preparedness for small-town living predicted their retention duration (hazard ratio, 0.74, p < .0001), whereas their preparedness for rural medical practice did not predict their retention duration after controlling for preparedness for small-town living (hazard ratio, 0.92; p = .27). For the physicians who had just finished their training, only a few features of their training predicted either rural preparedness or retention. Residency rural rotations predicted greater preparedness for rural practice (p = .004) and small-town living (p = .03) and longer retention (hazard ratio, 0.43, p = .003). Extended medical school rural rotations predicted only greater preparedness for rural practice (p = .03). For the physicians who had prior practice experience, nothing about their medical training was positively associated with preparedness or retention. CONCLUSION: Physicians who are prepared to be rural physicians, particularly those who are prepared for small-town living, stay longer in their rural practices. Residency rotations in rural areas are the best educational experiences both to prepare physicians for rural practice and to lengthen the time they stay there.

Adult↗

Inhibition of Salmonella typhimurium invasion by host cell expression of secreted bacterial invasion proteins.

Pathogenic Salmonella species initiate infection of a host by inducing their own uptake into intestinal epithelial cells. An invasive phenotype is conferred to this pathogen by a number of proteins that are components of a type III secretion system. During the invasion process, the bacteria utilize this secretion system to release proteins that enter the host cell and apparently interact with unknown host cell components that induce alterations in the actin cytoskeleton. To investigate the role of secreted proteins as direct modulators of invasion, we have evaluated the ability of Salmonella typhimurium to enter mammalian cells that express portions of the Salmonella invasion proteins SipB and SipC. Plasma membrane localization of SipB and SipC was achieved by fusing carboxyl- and amino-terminal portions of each invasion protein to the intracellular carboxyl-terminal tail of a membrane-bound eukaryotic receptor. Expression of receptor chimeras possessing the carboxyl terminus of SipB or the amino terminus of SipC blocked Salmonella invasion, whereas expression of their chimeric counterparts had no effect on invasion. The effect on invasion was specific for Salmonella since the perturbation of uptake was not extended to other invasive bacterial species. These results suggest that Salmonella invasion can be competitively inhibited by preventing the intracellular effects of SipB or SipC. In addition, these experiments provide a model for examining interactions between bacterial invasion proteins and their host cell targets.

Amino Acid Sequence↗

Interactions of the invasive pathogens Salmonella typhimurium, Listeria monocytogenes, and Shigella flexneri with M cells and murine Peyer's patches.

Invasive enteric bacteria must pass through the intestinal epithelium in order to establish infection. It is becoming clear that a common target for intestinal mucosa penetration is the specialized epithelial cell of Peyer's patches, the M cell. In order to gain a better understanding of how bacteria interact with M cells, we have compared the interactions of Salmonella typhimurium, Listeria monocytogenes, and Shigella flexneri with M cells by using a murine ligated-loop model. Our results indicate that S. typhimurium possesses a highly efficient mechanism for M cell entry that targets and destroys these cells, while L. monocytogenes and S. flexneri appear to be internalized into M cells in a less disruptive fashion. Early uptake of Listeria or Shigella into M cells appeared to lead to the death of some cells, as evidenced by the appearance of holes in the intestinal epithelium. At later time points, the follicle-associated epithelium of animals infected with these bacteria displayed extensive destruction. These data indicate that enteric pathogens use different strategies to interact with M cells and initiate infection of a host.

Animals↗

Cardiopulmonary effects of bilateral hemithorax ventilation and diagnostic thoracoscopy in dogs.

OBJECTIVE: To describe alterations in respiratory and cardiovascular variables during diagnostic thoracoscopy, using bilateral hemithorax ventilation with sustained pneumothorax. ANIMALS: 7 adult dogs. PROCEDURE: Each dog was anesthetized and instrumented for 2 episodes of cardiopulmonary monitoring that were performed at an interval of more than 14 days. The first anesthetic episode served as a control procedure for the thoracoscopy treatment performed during the second anesthetic episode. Multiple cardiopulmonary variables were evaluated by comparing changes from baseline values within treatments and between treatments. RESULTS: Arterial oxygen tension decreased significantly from baseline values during thoracoscopy but was unchanged during sham treatment. Arterial carbon dioxide tension, clinical shunt fraction, and systemic mean arterial pressure increased during thoracoscopy. In contrast, these variables were unaffected by the sham treatment. Heart rate and cardiac index increased during sham and thoracoscopy treatments; however, the increase was significantly greater during thoracoscopy. Total peripheral vascular resistance significantly decreased from baseline values for both treatments, but the decrease was greater during thoracoscopy. Significant changes were not observed for oxyhemoglobin saturation or pulmonary vascular resistance during either treatment. Dogs recovered without major clinical complications. CONCLUSIONS: Significant changes were found for several cardiopulmonary variables during bilateral hemithorax ventilation with sustained pneumothorax for diagnostic thoracoscopy of clinically normal dogs. CLINICAL RELEVANCE: Diagnostic thoracoscopy with bilateral hemithorax ventilation and sustained pneumothorax is well tolerated in clinically normal dogs and may provide a diagnostic modality enabling intrathoracic procedures with less morbidity than thoracotomy for dogs with intrathoracic disease.

Animals↗

Evaluation of biopsy specimens obtained during thoracoscopy from lungs of clinically normal dogs.

OBJECTIVE: To determine whether lung biopsy specimens obtained during thoracoscopy, using a commercially available ligature, can provide an adequate amount of tissue for histologic evaluation and to characterize changes in the lungs and thoracic cavity that result from the procedure. ANIMALS: 6 mixed-breed dogs. PROCEDURE: All dogs underwent 2 anesthetic episodes. The first anesthetic episode was a sham procedure. During the second anesthetic episode, each dog underwent a thoracoscopic procedure to obtain a lung biopsy specimen, using a commercially available ligature. Biopsy specimens were assessed subjectively by means of histologic evaluation. Samples for arterial blood gas analysis were obtained, and thoracic radiography was performed after surgery. Dogs were evaluated daily for 14 days after thoracoscopy and then were euthanatized. Tissues were evaluated grossly and histologically. RESULTS: Excellent intraoperative visibility and biopsy specimens adequate for histologic evaluation were obtained from all dogs. Significant differences were not found between arterial blood gas values of sham- and thoracoscopy-treated dogs for samples obtained 0.25, 2, and 24 hours after extubation. Examination of thoracic radiographs obtained 2 and 24 hours after thoracoscopy revealed minimal localized pathologic changes. All dogs were clinically normal 24 hours after thoracoscopy, and major postoperative complications were not detected. Gross and histologic findings of specimens obtained during necropsy revealed changes localized to biopsy and trocar sites. CONCLUSIONS: Thoracoscopic placement of ligatures allowed procurement of lung lobe biopsy specimens from clinically normal dogs without complications. CLINICAL RELEVANCE: This procedure may provide a safe and minimally invasive means of obtaining lung biopsy specimens from clinically affected dogs.

Animals↗

Characteristics of clients with schizophrenia who express certainty or uncertainty about continuing treatment with depot neuroleptic medication.

In this exploratory study, the factors corresponding to clients' certainty or uncertainty in continuing with depot neuroleptic medication for schizophrenia were examined. Ninety-four participants from a tertiary care schizophrenia clinic received an educational intervention aid containing information about treatment risks and benefits and were interviewed to elicit their levels of decisional conflict, self-efficacy, and emotional support, as well as expectations of risks and benefits of treatment. Eighty-seven percent of participants decided to continue treatment. Clients who expressed uncertainty (10%) about continuing with treatment had higher levels of decisional conflict (p = .000), lower levels of decision self-efficacy (p = .037) and decision emotional control (p = .003), lower expectations of hospitalization if treatment was stopped (p = .04) as well as lower expectations of benefits and higher expectations of side effects (p = .04), if treatment continued. In addition, reasons identified by participants for certainty or uncertainty were reported. The research may be useful in increasing the awareness of clinicians about the factors contributing to treatment decision making by clients diagnosed with schizophrenia and ultimately improve collaborative decision making.

Adult↗

Non-invasive Salmonella typhimurium mutants are avirulent because of an inability to enter and destroy M cells of ileal Peyer's patches.

Salmonella typhimurium initiates infection of a host by invading M cells of Peyer's patches within the small intestine. The ability of the bacteria to invade mammalian cells has been shown to be regulated by environmental conditions, including oxygen concentrations, osmolarity, and growth phase. We have previously created oxygen-regulated Tn5lacZY S. typhimurium mutants that are defective in invasion. We have now identified the invasion genes disrupted by eight of the transposon insertions. These genes encode transcriptional regulators (hilA and invF), type III secretory components (orgA, invG and spaR) and secreted proteins (invC and invD). Examination of the protein-secretion profiles of the non-invasive mutants indicated that each of the mutants was defective in secretion of between one and six proteins. We have also demonstrated that the loss of tissue culture cell invasiveness corresponds to an inability to invade and destroy M cells of Peyer's patches in a murine ligated loop model. Virulence studies, performed in mice, demonstrated that these defects significantly reduced the ability of the mutants to cause murine typhoid fever by an oral route of infection. Virulence by an intraperitoneal route of infection was unaffected. The data indicate that in vitro invasiveness, invasion-protein secretion, and M-cell invasion are critical indicators of S. typhimurium virulence.

Amino Acid Sequence↗

Study of the role of the htrB gene in Salmonella typhimurium virulence.

We have undertaken a study to investigate the contribution of the htrB gene to the virulence of pathogenic Salmonella typhimurium. An htrB::mini-Tn10 mutation from Escherichia coli was transferred by transduction to the mouse-virulent strain S. typhimurium SL1344 to create an htrB mutant. The S. typhimurium htrB mutant was inoculated into mice and found to be severely limited in its ability to colonize organs of the lymphatic system and to cause systemic disease in mice. A variety of experiments were performed to determine the possible reasons for this loss of virulence. Serum killing assays revealed that the S. typhimurium htrB mutant was as resistant to killing by complement as the wild-type strain. However, macrophage survival assays revealed that the S. typhimurium htrB mutant was more sensitive to the intracellular environment of murine macrophages than the wild-type strain. In addition, the bioactivity of the lipopolysaccharide (LPS) of the htrB mutant was reduced compared to that of the LPS from the parent strain as measured by both a Limulus amoebocyte lysate endotoxin quantitation assay and a tumor necrosis factor alpha bioassay. These results indicate that the htrB gene plays a role in the virulence of S. typhimurium.

Animals↗

Mutation of the htrB gene in a virulent Salmonella typhimurium strain by intergeneric transduction: strain construction and phenotypic characterization.

The htrB gene product of Haemophilus influenzae contributes to the toxicity of the lipooligosaccharide. The htrB gene encodes a 2-keto-3-deoxyoctulosonic acid-dependent acyltransferase which is responsible for myristic acid substitutions at the hydroxy moiety of lipid A beta-hydroxymyristic acid. Mass spectroscopic analysis has demonstrated that lipid A from an H. influenzae htrB mutant is predominantly tetraacyl and similar in structure to lipid IV(A), which has been shown to be nontoxic in animal models. We sought to construct a Salmonella typhimurium htrB mutant in order to investigate the contribution of htrB to virulence in a well-defined murine typhoid model of animal pathogenesis. To this end, an r- m+ galE mutS recD strain of S. typhimurium was constructed (MGS-7) and used in inter- and intrastrain transduction experiments with both coliphage P1 and Salmonella phage P22. The Escherichia coli htrB gene containing a mini-Tn10 insertion was transduced from E. coli MLK217 into S. typhimurium MGS-7 via phage P1 and subsequently via phage P22 into the virulent Salmonella strain SL1344. All S. typhimurium transductants showed phenotypes similar to those described for the E. coli htrB mutant. Mass spectrometric analysis of the crude lipid A fraction from the lipopolysaccharide of the S. typhimurium htrB mutant strain showed that for the dominant hexaacyl form, a lauric acid moiety was lost at one position on the lipid A and a palmitic acid moiety was added at another position; for the less abundant heptaacyl species, the lauric acid was replaced with palmitoleic acid.

Acyltransferases↗

Tumor necrosis factor alpha (rhTNF) fails to stimulate angiogenesis in the rabbit cornea.

BACKGROUND: The objective of this study was to thoroughly examine the in vivo angiogenesis activity of human recombinant tumor necrosis factor alpha (rhTNF). METHODS: rhTNF (0.5 ng to 1.0 microgram) was incorporated into the slow release polymers Hydron or HYPAN and implanted into the rabbit cornea. Release of biologically active rhTNF from the polymers was determined with the L929 cytotoxicity assay. RESULTS: All concentrations tested failed to elicit capillary formation beyond that observed for controls. Less than 2% of the rhTNF was released from the Hydron over 7 days. HYPAN released five times the amount of rhTNF in vitro, but even at doses of 500 ng (104.3 ng suggested release) no angiogenesis was stimulated. CONCLUSIONS: Under the circumstances tested, rhTNF is not angiogenic in vivo.

Acrylic Resins↗

Salmonellosis: host immune responses and bacterial virulence determinants.

The lifestyle of bacterial pathogens requires them to establish infection in the face of host immunity. Upon entering a potential host, a variety of interactions are initiated, the outcome of which depends upon a myriad of attributes of each of the participants. In this review we discuss the interactions that occur between pathogenic Salmonella species and the host immune systems, but when appropriate to broaden perspective, we have provided a general overview of the interactions between bacterial pathogens and animal hosts. Pathogenic Salmonella species possess an array of invasion genes that produce proteins secreted by a specialized type III secretion apparatus. These proteins are used by the bacteria to penetrate the intestinal mucosa by invading and destroying specialized epithelial M cells of the Peyer's patches. This maneuver deposits the bacteria directly within the confines of the reticuloendothelial system. The host responds to these actions with nonspecific phagocytic cells and an inflammatory response as well as by activating specific cellular and humoral immune responses. Salmonella responds to this show of force directly. It appears that the bacteria invade and establish a niche within the very cells that have been sent to destroy them. Efforts are underway to characterize the factors that allow these intracellular bacteria to customize intracellular vacuoles for their own purposes. It is the constant play between these interactions that determines the outcome of the host infection, and clearly they will also shape the evolution of new survival strategies for both the bacterium and the host.

Animals↗

Clozapine: current status and role in the pharmacotherapy of schizophrenia.

OBJECTIVE: This study evaluates clozapine and its present role in the pharmacotherapy of schizophrenia. METHOD: Clozapine's current clinical status is reviewed, as is its position with respect to other treatment options. RESULTS: Clozapine represents the prototype of "atypical" neuroleptics, with evidence of clinical efficacy in both positive and negative symptoms, as well as a diminished risk of extrapyramidal side effects. It is the only neuroleptic to date that has established itself as having little, if any, risk of tardive dyskinesia. More recent research has focused on its potential for overall savings in health care costs, as well as possible benefits in the area of neuropsychological functioning. CONCLUSION: Evidence suggesting that the course of schizophrenia can be altered by effective treatment favours a systematic approach that optimizes treatment options. While clozapine does not represent a 1st-line agent because of its risk of agranulocytosis, it has an integral role to play in treatment-resistant schizophrenia or in individuals experiencing intolerable side effects with conventional neuroleptics.

Agranulocytosis↗

Endoscopic and surgical retrieval of fishhooks from the stomach and esophagus in dogs and cats: 75 cases (1977-1993)

Medical records of 3 cats and 72 dogs that had a fishhook endoscopically or surgically retrieved from the stomach or esophagus were reviewed. Endoscopic retrieval was successful in 41 of 62 (66%) animals, and retrieval time and hospitalization time for endoscopic retrieval were significantly shorter than times for surgical retrieval. Rate of failure of endoscopic retrieval was higher for animals with treble-barb, rather than single-barb, fishhooks. Whether a fishhook could be successfully retrieved endoscopically was independent of body weight, amount of time the fishhook had been present, location of the hook, and orientation within the esophagus.

Animals↗