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Biomedical subjects

D P Stevens

Publications and source records attributed to D P Stevens.

At least 37 records · Page 2Linked to original sources

A strategy for coping with change: an affiliation between a medical school and a managed care health system.

Case Western Reserve University School of Medicine (CWRU), a private research-focused medical school, and Henry Ford Health System (HFHS), an integrated health system with a preponderance of managed care, have established a formal, broad affiliation that includes substantial commitments that bind the two organizations. Among them are formal full-time faculty appointments at CWRU for qualified professional staff of HFHS, designation of an associate dean for CWRU at HFHS, election of HFHS faculty to key medical school committees such as admission, curriculum, and promotions and tenure, and the commitment of funds to the affiliation by both organizations: a grant from HFHS to CWRU for curriculum development, and investment from CWRU to HFHS. The alliance of two such organizations is made complex by a number of issues. They include differences of institutional cultures as well as traditional issues in academic health centers such as departmental authority over curriculum and faculty appointments, competition for academic preeminence, and competition among hospitals for patients. The affiliation was facilitated by shared commitments to education, agreement on the need to adapt student education to the emerging managed care environment, a shared commitment to health services research, investment in the concept that learners add value to a health care delivery setting, and the desire to develop graduates with knowledge of practice in managed care. The authors conclude that medical schools and integrated managed care health systems gain sufficiently from such an affiliation that the investment of time, effort, and resources is readily justified.

Academic Medical Centers↗

Continuous quality improvement and the education of the generalist physician.

The new health care environment--centered on patients, focused on health, and managed by generalists--requires new competencies for the generalist physician. Among these are knowledge and skills for the continuous improvement of health care. In many areas, generalist physicians already use quality improvement methods and principles to improve the health and health care of their communities. Efforts to teach medical students and residents to improve quality continuously in health care are beginning. Early lessons are: (1) quality improvement is most effectively learned in the context of real work; (2) initial emphasis must be on the basics; (3) the focus is on the needs of those we serve; (4) interdisciplinary skills are essential and best learned during clinical training; and (5) the best learning environment for future generalist physicians, one which results in optimism about the future and the ability to make things better, is an environment that is continuously improving.

Arizona↗

Generation and purification of recombinant fimbrillin from Porphyromonas (Bacteroides) gingivalis 381.

Fimbrillin is the major subunit protein of fimbriae from the human periodontal pathogen Porphyromonas (Bacteroides) gingivalis. We describe here the generation and initial characterization of recombinant fimbrillin (r-fimbrillin) isolated from P. gingivalis 381. A fragment of DNA encoding the gene for fimbrillin was generated by polymerase chain reaction and cloned into the expression vector pET11b. Plasmids containing the recombinant gene were transfected into Escherichia coli. Clones were selected on plates for ampicillin resistance and individually screened by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) for protein production after activation with IPTG (isopropyl-beta-D- thiogalactopyranoside). One clone, OW0.2, produced significant amounts of a 42-kDa protein after induction with IPTG. This clone contained the pET11b plasmid with a 1-kb insert that had sequence homology to the gene encoding fimbrillin. The majority of recombinant protein from clone OW0.2 was found in the cytoplasm within inclusion bodies. Protein aggregates were solubilized in 8 M urea, and SDS-PAGE analysis showed two major protein bands, one at 42 kDa and the other at 17 kDa. These two proteins coeluted from a DEAE-Sepharose column at 0.15 M NaCl and were reactive to rabbit antiserum to fimbrillin in a Western blot (immunoblot). A preparation giving a single protein band at 42 kDa in SDS-PAGE was obtained by size fractionation by using continuous-elution electrophoresis. Lymph node cells from animals immunized with either fimbrillin from P. gingivalis or r-fimbrillin showed antigen-specific proliferation to both P. gingivalis fimbrillin and r-fimbrillin in an in vitro recall assay. Therefore, it appears that r-fimbrillin is chemically, antigenically, and serologically identical to fimbrillin isolated from P. gingivalis 381.

Animals↗

Immunological signals which control T cell responses.

A number of identifiable immunological parameters can influence the elicitation and regulation of antigen-specific inflammatory responses to immunogenic epitopes. Injection of antigen in vivo can lead to the activation of type IV hypersensitivity responses, or to the induction of immunological tolerance to that antigen. We have used the hapten trinitrophenol as a model system for studying the factors which influence the generation and regulation of hypersensitivity responses to immunogenic epitopes in vivo. The generation of hypersensitivity or tolerance to trinitrophenyl depends on a number of immunological factors, including the form of the antigen, the route of immunization, and the presence of immune complexes of antibody and antigen on the surface of the antigen-presenting cell. Immunization with trinitrophenyl resulting in unresponsiveness can be the result of either the inability to prime inflammatory cells in vivo or the induction of suppressor T cells.

Animals↗

Elastase is a constituent product of T cells.

Proteases produced by immune cells have been found to be important components of the immune response to antigen. A protease previously unrecognized as a specific T cell product has been identified which has the gene sequence, serologic crossreactivity, and enzymatic specificity of elastase. T cell elastase, found in combination with the natural elastase inhibitor alpha 1-antitrypsin (alpha 1-protease inhibitor, alpha 1-PI), is produced by both CD4+ and CD8+ T lymphocytes, and is found both in a membrane-bound and in a soluble form in murine T cell lines.

Amino Acid Sequence↗

Regulation of oxygen concentration delivered to infants via nasal cannulas.

The administration of oxygen to infants via nasal cannulas is now a common practice in neonatal units although the inspired oxygen concentration reaching the patient's airway is unknown. We measured the hypopharyngeal oxygen concentration in 10 infants who were receiving oxygen via nasal cannulas and assessed the impact of changes in the flow rate and inspired oxygen concentration. Weaning these infants by reducing the flow rate, even if changes are slight, produces clinically important changes in the oxygen concentration reaching the airway. Such changes are poorly tolerated by infants with chronic lung disease. Changing the flow rate and inspired oxygen concentration, rather than the flow rate alone, provides greater precision and is likely to avoid excessive and abrupt changes in the oxygen concentration reaching the airway.

Administration, Intranasal↗

Cypermethrin pour-on for the control of ticks (Ixodes ricinus) on sheep.

Trials were carried out on 11 farms to assess the effectiveness of 2.5 per cent w/v cypermethrin pour-on for the control of ticks on sheep. Treatment at the rate of 5 ml/10 kg bodyweight gave 92 per cent control of ticks on ewes for up to nine weeks and 88 per cent control on lambs for up to eight weeks.

Administration, Topical↗

Phagocytosis of Giardia muris by macrophages in Peyer's patch epithelium in mice.

No mechanism for the initiation of immunological clearance of Giardia from the mammalian intestinal tract has been identified. In normal and nude mice experimentally infected with G. muris, we examined antigen-sampling epithelium over Peyer's patch follicles by electron microscopy for evidence of interaction between G. muris and lymphoid cells. Invading G. muris were found in the epithelium near dying or desquamating columnar cells. Macrophages beneath the basal lamina extended pseudopods into the epithelium, trapping invading G. muris and enclosing them in phagolysosomes. In normal mice, which clear G. muris in 4 to 6 weeks, macrophages containing digested G. muris were surrounded by rosettes of lymphoblasts in the epithelium. In nude mice deficient in lymphocytes, there was apparent hyperplasia of macrophages, which filled the follicle domes, resulting in more frequent entrapment of G. muris but no contact between macrophages and lymphoblasts in the epithelium. In nude mice, which require 6 months to control G. muris infection, lymphoblast contact with macrophages containing distinctive microtubular remnants of G. muris was only identified in the follicle dome. This close physical association of lymphoblasts and macrophages containing G. muris remnants suggests that this macrophage activity represents intraepithelial antigen processing as well as a defense against the effects of the uncontrolled entrance of microorganisms and other antigenic particles into Peyer's patch lymphoid follicles.

Animals↗

Purification of Giardia muris trophozoites by using nylon fiber columns.

A method is described for purification of large quantities of Giardia muris trophozoites from the small intestine of the mouse by using density layer centrifugation and nylon fiber columns. Centrifugation of trophozoites obtained from the small intestine on Metrizamide, specific gravity 1.10, followed by incubation on a nylon fiber column at 37 degrees C for 120 min, yielded up to 15 X 10(6) viable purified trophozoites per infected mouse.

Animals↗

Ultrastructural observations on giardiasis in a mouse model. II. Endosymbiosis and organelle distribution in Giardia muris and Giardia lamblia.

Ultrastructural observations of Giardia muris in a mouse model revealed endosymbiotic microbes not previously reported in Giardia. Endosymbionts 240--360 nm wide, 600--1,400 nm long, and with an internal structure similar to that of bacilli were not seen entering Giardia but were found and appeared to divide within Giardia. No evidence was found of digestion of the endosymbionts by the giardia host in either the trophozoite or the cyst form. Endosymbionts were concentrated centrally around the nuclear area and were uncommon in peripheral feeding regions. The same cellular organelles seen in G. muris were found in Giardia lamblia from human jejunal biopsy material, but no endosymbionts were identified in G. lamblia trophozoites from the seven patients examined. Endosymbionts within Giardia may be found to alter trophozoite pathogenicity, metabolism, range of infectivity, antigenic surface characteristics, and host specificity, as they do in other protozoa.

Animals↗

Ultrastructural observations on giardiasis in a murine model. I. Intestinal distribution, attachment, and relationship to the immune system of Giardia muris.

Infected immunocompetent mice were studied prospectively in a well-described murine model system with the use of ultrastructural techniques to establish normal distribution of Giardia muris trophozoites, their relationships to intestinal mucosa, particularly Peyer's patches, and structural indications of the normal reaction of intestine and intestinal immune organs. Trophozoites colonized the proximal 25% of the intestine, adhered to microvilli of columnar cells near the bases of villi, wedged into furrows in the epithelial surface, or lodged in mucus within the unstirred layer. Density of trophozoite colonization of the jejunal epithelium correlated with stool cyst excretion. Over Peyer's patches, Giardia adhered to columnar cells and not to M-cells, which transport soluble antigens and particulate material from the lumen into the lymphoid system. Giardia entered intestinal lymphoid structures by incursions through defects in the lymphoid follicle epithelial barrier. During clearance of parasites, lymphocytes crossed the epithelium and attached to Giardia in the lumen. Giardia produced no apparent ultrastructural damage in normal mice but elicited a previously undescribed intraluminal cellular immune response during clearance by the host.

Animals↗