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Biomedical subjects

C Cannon

Publications and source records attributed to C Cannon.

12 recordsLinked to original sources

Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin.

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory condition of the central nervous system with similarities to multiple sclerosis. In both diseases, circulating leukocytes penetrate the blood-brain barrier and damage myelin, resulting in impaired nerve conduction and paralysis. We sought to identify the adhesion receptors that mediate the attachment of circulating leukocytes to inflamed brain endothelium in EAE, because this interaction is the first step in leukocyte entry into the central nervous system. Using an in vitro adhesion assay on tissue sections, we found that lymphocytes and monocytes bound selectively to inflamed EAE brain vessels. Binding was inhibited by antibodies against the integrin molecule alpha 4 beta 1, but not by antibodies against numerous other adhesion receptors. When tested in vivo, anti-alpha 4 integrin effectively prevented the accumulation of leukocytes in the central nervous system and the development of EAE. Thus, therapies designed to interfere with alpha 4 beta 1 integrin may be useful in treating inflammatory diseases of the central nervous system, such as multiple sclerosis.

Animals

A cell culture model of the blood-brain barrier.

Endothelial cells that make up brain capillaries and constitute the blood-brain barrier become different from peripheral endothelial cells in response to inductive factors found in the nervous system. We have established a cell culture model of the blood-brain barrier by treating brain endothelial cells with a combination of astrocyte-conditioned medium and agents that elevate intracellular cAMP. These cells form high resistance tight junctions and exhibit low rates of paracellular leakage and fluid-phase endocytosis. They also undergo a dramatic structural reorganization as they form tight junctions. Results from these studies suggest modes of manipulating the permeability of the blood-brain barrier, potentially providing the basis for increasing the penetration of drugs into the central nervous system.

Animals

Effect of educational programs, rigid sharps containers, and universal precautions on reported needlestick injuries in healthcare workers.

OBJECTIVE: To evaluate the effect of infection control programs on reported needlestick injuries in a general hospital. DESIGN: Surveillance of all reported needlestick injuries at the University of Cincinnati Hospital was maintained by the infection control department for five years, from 1985 through 1989. Data on individual workers were collected, tabulated on a monthly basis, and reviewed continually to monitor trends in injuries. During this time, the effects of each of three new infection control programs on reported injuries were evaluated sequentially. SETTING: A 700-bed general hospital that serves as the main teaching hospital of the University of Cincinnati. PARTICIPANTS: All employees of University Hospital who reported to personnel health for management of needlestick injuries. INTERVENTIONS: In 1986, an educational program to prevent injuries was initiated and continued throughout the surveillance period. In 1987, rigid sharps disposal containers were placed in all hospital rooms. In 1988, universal precautions were introduced with an intensive inservice. RESULTS: Surveillance identified 1,602 needlestick injuries (320/year) or 104/1,000/year. After the educational program began, reported injuries increased rather than decreased, and this was attributed to increased reporting. Subsequently, after installation of the new disposal containers, reported injuries returned to the levels seen prior to the educational program, but recapping injuries showed a significant decrease from 63/year to 30, or 20/1,000/year to 10. This decrease was observed in nurses but not in other healthcare workers. After universal precautions were instituted, total injuries increased slightly, but recapping injuries remained at 50% of the levels reported prior to the use of rigid sharps disposal containers. CONCLUSIONS: The three infection control programs failed to produce a major reduction in reported needlestick injuries, except for a decrease in recapping injuries associated with the placement of rigid sharps disposal containers in all patient rooms. These observations indicate that new approaches are needed to reduce needlestick injuries.

Accidents, Occupational

The failed appointment.

OBJECTIVE: To determine reasons for failed internal medicine clinic appointments. DESIGN: A retrospective telephone survey of patients within one month of a failed appointment. SETTING: An ambulatory teaching clinic for indigent patients staffed by 30 internal medicine residents where patients have scheduled visits every 30 minutes. PATIENTS/PARTICIPANTS: From the 1,622 scheduled patient visits, the names of 405 patients who failed their appointments were selected for further contact. Successful contact was established with 100 patients. MEASUREMENTS AND MAIN RESULTS: The patients completed a telephone survey administered by residents and students regarding demographics, general health, reasons for failed appointment, and satisfaction with the clinic. Transportation problems accounted for 13% of missed visits, forgetfulness accounted for 11%, personal or family illness and rescheduling problems accounted for 8% each. Miscellaneous reasons accounted for the remainder. Seventeen percent of patients who missed their appointments feared the encounter, but none volunteered this as a reason for their no-show. Fifty-one percent of patients felt that the failed appointments could not have been prevented. Ninety percent of those surveyed were satisfied with their clinic physician, and 82% were seen on-time when appointments were kept. CONCLUSIONS: Lack of transportation appeared to be the most prohibitive factor in continuity of care among this indigent population. Patients are generally seen on-time and are satisfied with their care. Financial pressure does not appear to keep people away. Fear of the physician encounter and forgetfulness may be areas for improved patient education.

Adult

Identification and cloning of two species of cadherins in bovine endothelial cells.

By taking advantage of the extensive homology found in the cytoplasmic domains of several cloned cadherin molecules, we were able to identify two species of cadherins in bovine aortic endothelial cells using the polymerase chain reaction (PCR). The two species of PCR products were subsequently used as DNA probes to isolate the corresponding cDNA clones from bovine adrenal microvascular endothelial cells. Sequence comparison with other characterized cadherin molecules indicates that the major cDNA species encodes a cadherin molecule highly homologous to chicken and mouse N-cadherins, while the minor species is most homologous to mouse and human P-cadherins. Northern blot analysis with the corresponding cDNA probe showed a wide distribution of bovine N-cadherin among non-neuronal, as well as neuronal tissues, while P-cadherin was most abundant in kidney among all the bovine tissues tested, but was undetectable in placenta.

Amino Acid Sequence

Isolation and culture of HCO3- -secreting intercalated cells.

Intercalated cells of the distal nephron secrete either H+ or HCO3-. We have succeeded in isolating HCO3- -secreting intercalated cells from the rabbit kidney. When seeded onto collagen-coated permeable supports, these cells form monolayers with a resistance of 595 +/- 75 omega.cm2. The monolayers maintain the characteristics of an epithelium, with apical microvillae and tight junctions. They display the same polarity as do HCO3- -secreting intercalated cells in vivo, namely apical peanut lectin binding and apical Cl- -HCO3- exchange. The monolayers are capable of transepithelial HCO3- transport via this exchanger. The rate of Cl- -dependent transepithelial HCO3- transport is 4 +/- 0.4 nmol.min-1.cm-2. Transepithelial HCO3- transport is completely abolished by 50 microM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid applied to the apical side of the monolayer. These cultured HCO3- -secreting intercalated cells should prove useful for defining the cellular regulation of HCO3- secretion.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid

Chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells: evaluations of 108 chemicals.

Results from the testing of 108 coded chemicals in Chinese hamster ovary (CHO) cells for the induction of chromosome aberrations and sister chromatid exchanges (SCEs) are presented. All chemicals were tested with and without exogenous metabolic activation, using protocols designed to allow testing up to toxic doses. Cell harvest times could also be extended if chemical-induced cell cycle delay was seen. Chromosome aberrations were induced by 43 of the chemicals, and 66 induced SCEs; 37 of the chemicals were positive for both endpoints.

Animals

Regulation of proton transport in urinary epithelia.

In urinary epithelia, like the turtle bladder, protons are transported by a H+ translocating ATPase located in the luminal membrane. We have recently discovered that the H+ pump is stored in small vesicles that lie underneath the luminal membrane. CO2, a major regulator of H+ transport causes these vesicles to fuse with the membrane thereby inserting more H+ pumps. We have now isolated these vesicles from the turtle bladder and from beef kidney medulla. Based on inhibitor sensitivity and substrate specificity this proton translocating ATPase is different from the mitochondrial F0-F1 ATPase, yeast plasma membrane and the gastric H+,K+-ATPase. Solubilization and reconstitution of the enzyme into liposomes shows retention of transport activity and inhibitor sensitivity.

Acid-Base Equilibrium

Carbon-dioxide-induced exocytotic insertion of H+ pumps in turtle-bladder luminal membrane: role of cell pH and calcium.

The contents of endocytic vesicles and other intracellular organelles (such as Golgi and microsomes) are acidified by an electrogenic proton-translocating ATPase that is remarkably similar to that found in urinary epithelia. We recently found that the number of H+ ATPases in the apical plasma membrane of these epithelia is regulated by exocytotic insertion of endocytic vesicles whose membranes contain this H+ pump. Carbon dioxide, a major stimulus for urinary acidification, causes rapid fusion of these vesicles with the luminal membrane, thereby inserting these pumps there and increasing the rate of net transepithelial H+ secretion; CO2 also inhibits endocytic retrieval of the pumps from the luminal membrane. Such reciprocal regulation of endocytosis and exocytosis by a physiological modulator makes this system particularly attractive for studying the cellular events regulating membrane fusion. Here we present evidence that CO2 induces exocytosis by a cascade of events, the first step of which is cytoplasmic acidification. Cell acidification then increases calcium activity, which causes the fusion event.

Animals