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Biomedical subjects

J L Carson

Publications and source records attributed to J L Carson.

At least 109 records · Page 6Linked to original sources
PubMed1987

The relative gastrointestinal toxicity of the nonsteroidal anti-inflammatory drugs.

To assess the relative rate or upper gastrointestinal (UGI) tract bleeding associated with nonsteroidal anti-inflammatory drugs (NSAIDs), we performed a retrospective cohort study using 1980 billing data from all Medicaid patients in the states of Michigan and Minnesota. The rate of UGI tract bleeding in the 30 days following each drug exposure was examined in the 88,044 patients dispensed only one of seven NSAIDs. The rate of UGI tract bleeding differed significantly among users of these drugs. Stratification and logistic regression were used to adjust for multiple potential confounding factors, without substantive changes in the results. An alcohol-drug interaction was found. Sulindac users had the highest rate of UGI tract bleeding, and it was the only drug statistically different from ibuprofen. When the average daily dose of sulindac received was divided by the maximum recommended daily dose, it was notably higher than those for other drugs. Repeated analyses using data from 1982 confirmed these results. We conclude that there are significant and consistent differences in the incidence of UGI tract bleeding associated with the use of NSAIDs in this population.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1986

Developmental changes in glycoconjugate secretion by ferret tracheas.

Surface epithelium and submucosal glands of the ferret trachea undergo extensive postnatal development. This study examined developmental changes in rates of release and types of high molecular weight glycoconjugates secreted by explanted ferret tracheas. Digestion with bovine testicular hyaluronidase separated the high molecular weight glycoconjugates into two types, hyaluronidase-resistant mucins and hyaluronidase-susceptible glycosaminoglycans. Release rates were measured under unstimulated conditions and in the presence of known secretagogues. The unstimulated rate of release of total 3H-glycoconjugates was 4-fold higher at birth than after complete maturation. The mucin content varied from 39 to 74% of total 3H-glycoconjugates; however, no age-related pattern was observed for mucin/glycosaminoglycan ratios. The rate of release of 3H-mucins was 6-fold higher at birth than in the adult but rapidly dropped to adult levels by 28 days of age. The secretory cells in the tracheal epithelium of newborn ferrets had more abundant rough endoplasmic reticulum than did mature goblet cells, suggesting increased synthesis of secretory product. Response to methacholine and trypsin, both known stimulators of mucin release, was not observed until 28 and 54 days of age, respectively. Incorporation of 35S-sulfate into mucins relative to that for 3H-glucosamine increased with age, consistent with increasingly acidic histochemical staining properties of secretory cells. These developmental differences in rates of release, modulation of release, and relative sulfation of mucins may represent changes in secretory and synthetic mechanisms of the secretory cells.

Age Factors↗
PubMed1986

Postnatal development of tracheal surface epithelium and submucosal glands in the ferret.

We explored the usefulness of the postnatal ferret as a model for early developmental events in the large airways, using light and scanning electron microscopy. In the first 28 postnatal days, ferret tracheal surface epithelium and glands undergo dramatic growth and development. Tracheal surface area increases 8-fold. At birth, ciliated cells are sparse (9.4 +/- 1.2% of total epithelial cells). A significant increase in ciliated cells is observed at weekly intervals and by day 28 the ciliated cell is the predominant cell type (54.2 +/- 2.8% of total epithelial cells). Secretory cells decrease from 66.4 +/- 1.0% at birth to 22.2 +/- 2.8% of total epithelial cells. Histochemical staining of the granules of the epithelial secretory cells changes from predominantly non-acidic (staining with PAS but not Alcian blue) to predominantly acidic (staining also with Alcian blue). During the same time interval, tracheal glands develop from intraepithelial cellular aggregates devoid of secretory granules at birth into complex, submucosal tubuloacinar structures composed predominantly of cells containing non-acidic secretory granules at 28 days. Therefore, infant ferrets offer an opportunity to examine the structural and functional components of the mucociliary clearance mechanism at developmental stages which occur prenatally in many laboratory animals and in humans.

Alcian Blue↗
PubMed1985

Acquired ciliary defects in nasal epithelium of children with acute viral upper respiratory infections.

Ciliary function and mucociliary clearance are primary mechanisms of defense in the respiratory tract. We found that infections by several common respiratory viruses in children were associated with ciliary abnormalities that could be detected on ultrastructural examination of the nasal epithelium. Dysmorphic ciliary forms involving microtubular aberrations were observed most often in the early stages of illness in focal sites of the nasal mucosa. Normal epithelial organization and ciliary ultrastructure appeared to be reestablished during the convalescent period, from 2 to 10 weeks after infection. These observations suggest that interference with ciliogenic mechanisms leading to transient, compromised mucociliary clearance may represent a fundamental pathophysiologic disturbance in some respiratory viral infections.

Acute Disease↗
PubMed1985

Diagnostic accuracy of four assays of prostatic acid phosphatase. Comparison using receiver operating characteristic curve analysis.

We compared the diagnostic characteristics of four assays of prostatic acid phosphatase by two methods. In the first analysis, receiver operating characteristic (ROC) curves were developed and the areas under the curves were calculated. In the second analysis, the sensitivity of each assay was compared with the sensitivities of the other assays with specificities set at equal levels. One or more assays were performed in 1,298 patients; 141 underwent all four assays. Pairwise comparisons of the areas under the ROC curves showed no significant differences. No differences were found in the sensitivities of the four assays when the upper limits of normal were selected to provide equal specificities. We conclude that there is little difference in diagnostic accuracy among the prostatic acid phosphatase assays. Our findings contrast with previous studies that used only one upper limit of normal and that found some assays to be superior to others. Receiver operating characteristic curve analysis corrects for the bias introduced by the choice of an upper limit of normal.

Acid Phosphatase↗
PubMed1985

Response of human ciliated respiratory epithelium to brief in vivo ozone exposure: an ultrastructural study.

Ciliated nasal epithelium obtained from human volunteers exposed under controlled conditions to 0.4 ppm of ozone for 4 hr was examined by transmission electron microscopy. These investigations were initiated to evaluate the utility of human ciliated nasal epithelium as a model for the characterization of possible ultrastructural level cytopathic effects induced by short-term, low-level in vivo exposure to ozone. Particular attention was given to both the qualitative and quantitative evaluation of ciliated cells in the nasal respiratory epithelium in response to ozone exposure. The results of these investigations indicated that cell structure is generally retained and no appreciable manifestation of injury is evident in human nasal mucosa in response to the regimen of ozone exposure employed during these studies. Although these investigations were completed under highly controlled circumstances and with the constraints attendant to research on humans subjects, they may provide a fundamental base for future examinations of the potential injurious effects of ozone on human respiratory epithelium under conditions more relevant to habitual environmental exposure.

Cilia↗
PubMed1985

Effects of a teratogen on [3H]uridine nucleotide transfer between human embryonal cells and on gap junctions.

Intercellular communication (IC) mediated by gap junctions (gj) occurs during embryonal development and appears to be important for normal differentiation through the exchange of morphogenetic signalling substances. Disruption of IC by chemicals may induce abnormal development resulting from failed cell-cell interactions. It was established in the present study that genotypically normal human embryonal palate mesenchyme (HEPM) cells displayed IC in cell culture and that the transfer of [3H]uridine nucleotides was inhibited by the potent embryotoxin and teratogen 12-O-tetradecanoyl-phorbol-13-acetate (TPA). IC was mediated by gj which were revealed by freeze-fracture and electron microscopy. Quantitative morphometric analysis showed that inhibition of IC by TPA coincided with a significant reduction in the number of gj. The observations suggest that inhibition of IC by the teratogen TPA may be one among the many mechanisms believed to be responsible for the induction of abnormal development by chemical teratogens.

Cell Communication↗
PubMed1985

Rotary-shadowed freeze-fracture replicas: a simple method for the analysis of fracture faces.

In rotary-shadowed freeze-fracture replicas, intramembrane particles on the periphery of a membrane fracture face are not uniformly shadowed from all sides. Those eccentrically positioned intramembrane particles with a net centripetally directed shadowing are on a convex fracture face. In contrast, those eccentrically positioned intramembrane particles with a net centrifugally directed shadowing are on a concave fracture face. Centrally positioned intramembrane particles on convex faces are uniformly shadowed from all sides; however, central depressions of concave faces are often unshadowed.

Animals↗
PubMed1984

New observations on the ultrastructure of mammalian conducting airway epithelium: application of liquid propane freezing, deep etching, and rotary shadowing techniques to freeze-fracture.

Freshly isolated, viable hamster tracheal epithelium was rapidly frozen in a jet of liquid nitrogen-cooled propane followed by freeze-fracture, deep etching, and rotary shadowing. Examination of the replicas by transmission electron microscopy revealed characteristic features of both ciliated and nonciliated cells, profiles of tight junctional complexes, and two distinct types of membrane particle complexes. The findings of this study suggest that rapid freezing of viable biological specimens coupled with freeze-fracture, deep etching, and rotary shadowing may provide a useful approach to achieving some additional perspectives of cell structure and function. Since the experimental protocol avoided any use of chemical fixation and processing procedures generally employed in electron microscopy, this study also validates for airway epithelium the details of fine structure observed using more conventional ultrastructural methods.

Animals↗
PubMed1981

Morphometric aspects of ciliary distribution and ciliogenesis in human nasal epithelium.

Observations of freeze-fracture preparations of human nasal epithelium have provided a unique perspective of the spatial distribution of epithelial cell cilia unattainable by more conventional ultrastructural techniques. The initial stages of ciliogenesis were characterized ultrastructurally in these preparations by differentiation of the lumenal aspect of the epithelial cell membrane prior to the emergence and maturation of new cilia. Morphometric analyses of the resultant electron micrographs indicate that the development of an optimal ciliary population during differentiation of ciliated cells may be integral to the adequate functioning of respiratory mucociliary mechanisms. The frequency with which such ciliogenic structures are observed indicates that ciliogenesis is a common feature of the nasal epithelium and suggests that epithelial cell turnover in the nasal cavities is relatively rapid.

Cilia↗
PubMed1981

Measurements of nasal transepithelial electric potential differences in normal human subjects in vivo.

Nasal transepithelial electrical potential difference (PD) was estimated in vivo in normal human subjects. The PD between a bridge perfused with Ringer's solution placed on the nasal mucosal surface and a reference electrode in a subcutaneous space was recorded. The magnitude of the PD depended upon the region of the nasal cavity touched by the exploring bridge. The PD values ranged from -4 mV (lumen negative) on the anterior tip of the inferior turbinate to approximately -30 mV on the inferior surface of the turbinate. Biopsies of the anterior turbinate were characterized by squamous epithelial cells, whereas ciliated cells dominated the epithelium from regions of higher PD. Epithelial abrasion abolished PD. No differences in PD were noted between the left and right nasal cavities, and repetitive measurements of PD at the same site yielded comparable values. No differences in nasal PD were noted between young male or female subjects but PD declined as a function of age. Amiloride (10(-4)M) and lidocaine (10(-1)M) reduced PD (-59% and -30%, respectively), whereas amphotericin B (5 X 10(-5)M) raised PD (+29%). We concluded that nasal PD can be accurately measured in vivo in humans, and that measurements of nasal bioelectric properties may serve as a relatively noninvasive index of respiratory epithelial function.

Action Potentials↗
PubMed1980

Ultrastructural observations on cellular and subcellular aspects of experimental Mycoplasma pneumoniae disease.

The ultrastructural organization of Mycoplasma pneumoniae membranes and spatial relationships of this pathogen to epithelial cells in tracheal organ cultures were examined ultrastructurally by freeze-fracture techniques. Areas of morphologically distinct cell membrane variability characterized by membrane blebs and altered distributions of membrane associated particles were observed in replicas of M. pneumoniae cells. Inspection of the host tracheal epithelium demonstrated the alignment of M. pneumoniae to the epithelium with an accompanying deterioration in the integrity of the lumenal surface membranes and subsequent loss of the epithelial cell cytosol. Ciliary dysfunction was suggested by the observation of ciliary lesions and of disorganized epithelial cell cilia. The methodology used in these studies has permitted a new perspective of host-pathogen interactions at both the cellular and subcellular levels in tracheal organ cultures. These studies may also illustrate ultrastructural correlates of the alteration of host macromolecular synthesis in experimental M. pneumoniae infection.

Animals↗
PubMed1979

Ciliary membrane alterations occurring in experimental Mycoplasma pneumoniae infection.

Experimental infection of hamster ciliated tracheal epithelium in organ culture with virulent Mycoplasma pneumoniae resulted in the deterioration o ciliary necklaces and an altered distribution of membrane-associated particles on the shafts of the affected cilia. To our knowledge that is the first report of an altered disposition of ciliary membrane-associated particles in response to a specific infectious agent.

Animals↗
PubMed1979

An ultrastructural study on a new type of hepatic perisinusoidal cell in fish.

A new type of perisinusoidal cell containing numerous microfilaments is described for the first time. It is found in abundance in the livers of both marine and freshwater fish. These perisinusoidal cells are situated within the space of Disse and adhere firmly through desmosomes both to sinusoidal endothelial cells and to hepatocytes. The cytoplasmic microfilaments are striking and make these cells readily distinguishable from the perisinusoidal fat-storing cells of Ito. Although the function of these cells is not known, the observations presented here suggest that they may provide a supportive framework within the liver.

Animals↗
PubMed1979

New observations on the fine structure of the liver in goldfish (Carassius auratus).

A re-examination of goldfish liver was made through the use of SEM of fractured samples and TEM of ultrathin-sections and freeze-etch replicas. Several new hepatic fine structures described in the present study are morphologically similar to those reported previously in many higher vertebrates including mammals. Hepatic sinusoids of goldfish contain fenestrations which are arranged into sieve plates. Although the hepatic plates are made up of two layers of hepatocytes, the parenchymal cells of gold fish liver are morphologically similar to mammalian hepatocytes, particularly with respect to the sinusoidal surfaces which are studded with numerous microvilli. The intercellular surfaces of hepatocytes have both nexus and demosomal junctions, similar to those found in various epithelial cells of higher vertebrates, between the openings of the intracellular bile canaliculi and the intralobular bile ductules which are situated in the center of the bicellular hepatic plate.

Animals↗