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Biomedical subjects

J C Dunn

Publications and source records attributed to J C Dunn.

At least 37 records · Page 2Linked to original sources
PubMed1996

Management of peritoneal dialysis-induced hydrothorax in children.

Continuous ambulatory peritoneal dialysis (CAPD) is a safe and effective treatment for children with end-stage renal failure. Approximately three per cent of patients develop a large hydrothorax as a result of a dialysate leak from the peritoneal cavity through an occult diaphragmatic eventration or attenuation of the pleuroperitoneal membrane. Previously, such patients often discontinued CAPD and were placed on hemodialysis even though the complications, expense, and limitation of activity with hemodialysis are undesirable in children. During the past 15 years, 6 of the 193 children (3%) undergoing CAPD at UCLA Medical Center developed a hydrothorax. Three patients were male and three were female. Four patients were treated surgically with diaphragmatic plication, one was treated by reducing the dialysate volume, and one was switched to hemodialysis in preparation for a renal transplant. Each of the four surgically-treated children was able to return to full-volume peritoneal dialysis and has not experienced recurrence of the hydrothorax. Therefore, diaphragmatic plication permits children to quickly resume full-volume CAPD and avoid hemodialysis.

Child, Preschool↗
PubMed1993

Neuropsychological sequelae of Wernicke's encephalopathy in a 20-year-old woman: selective impairment of a frontal memory system.

This article reports the neuropsychological sequelae of Wernicke's Encephalopathy in a 20-year-old woman. After amelioration of acute symptoms, the patient showed a range of cognitive impairments the most marked of which was a severe impairment on free recall tasks involving both verbal and nonverbal material. In contrast, recognition memory appeared remarkably well preserved. Some evidence of frontal lobe and general intellectual impairment was also noted. The case is discussed in terms of the pathophysiology of Wernicke-Korsakoff Syndrome, criteria for its diagnosis, and the multicomponent nature of memory deficits.

Adult↗
PubMed1993

Effect of collagen gel configuration on the cytoskeleton in cultured rat hepatocytes.

The cytoskeleton is important in the maintenance of cellular morphology and differentiated function in a number of cell types, including hepatocytes. In this study, adult rat hepatocytes sandwiched between two layers of collagen gel were compared to cells cultured on a single collagen gel for differences in the organization and expression of the cytoskeletal proteins actin and tubulin. Hepatocytes cultured between two layers of hydrated rat tail tendon collagen (sandwich gel) morphologically resembled cells in intact liver for several weeks. Actin filaments (F-actin) in these hepatocytes were concentrated under the plasma membrane in regions of cell-cell contact. In contrast, hepatocytes cultured on a single collagen gel were flattened and motile and had F-actin containing stress fibers. This was accompanied by a severalfold increase in actin mRNA. Microtubules formed an interwoven network in hepatocytes cultured in a sandwich gel, but in single gel cultures they formed long parallel arrays extending out to the cell periphery. Tubulin mRNA was severalfold greater in hepatocytes cultured on a single gel. Fibronectin and laminin staining were greater in single gel cultures, and these proteins were concentrated in fibrils radiating from the cell periphery. Overlaying a second collagen gel onto hepatocytes that had been cultured on a single gel (double gel rescue) reversed cell spreading and reduced stress fibers. Double gel rescue also resulted in a decrease in actin and tubulin mRNA to levels present in sandwich gel cultures and freshly isolated hepatocytes. These results show that the configuration of the external matrix has a dynamic effect on cytoskeletal proteins in cultured rat hepatocytes.

Actins↗
PubMed1992

Hepatocytes in collagen sandwich: evidence for transcriptional and translational regulation.

The influence of extracellular matrix configuration on the tissue-specific function of cultured hepatocytes was investigated. Adult rat hepatocytes sandwiched between two layers of collagen gel were compared to cells cultured on a single layer of collagen gel for differences in the total RNA content, the level of albumin-specific mRNA, the rate of albumin gene transcription, and the rate of albumin mRNA translation. Adult hepatocytes in the sandwich system maintained the level of albumin mRNA similar to that found in the normal liver for at least six weeks, whereas the level of albumin mRNA declined rapidly in the single gel system. After one week of culture, hepatocytes in the single gel system could be induced to recover the high level of albumin mRNA and albumin production when a second layer of collagen gel was overlaid at that time. Furthermore, sandwiched hepatocytes maintained significantly higher transcriptional activity compared to cells in the single gel system. In addition to transcriptional control, the ultimate rate of albumin production was shown to depend on the rate of translation, which increased with culture time and reached a plateau in one to two weeks. This increase in translational activity over time in culture was observed in both the sandwich and the single gel systems and, thus, appeared to be independent of the configuration of extracellular matrix.

Albumins↗
PubMed1992

Assessment of artificial liver support technology.

Despite more than 30 yr of research and development, an artificial liver has still not yet become clinical reality. Although previous attempts using a multiplicity of techniques including hemodialysis, hemoperfusion, plasma exchange, extracorporeal perfusion, and crosshemodialysis have shown minor improvement in patients with acute hepatic failure, limited clinical trials have failed to demonstrate any survival benefit. Encouraged by the progress on techniques that maintain long-term cultures of hepatocytes, more recent efforts have been directed at the use of hepatocytes as the basis of liver support. This review takes a critical look at past and present concepts in the development of artificial liver supports and both qualitatively and quantitatively evaluates the advantages and disadvantages of the available methodology.

Animals↗
PubMed1990

A new approach to the cryopreservation of hepatocytes in a sandwich culture configuration.

Current methods of cryopreservation of hepatocytes in single cell suspensions result in low overall yields of hepatocytes, demonstrating long-term preservation of hepatocellular functions. A novel culture method has recently been developed to culture liver cells in a sandwich configuration of collagen layers in order to stabilize the phenotypic expression of these cells in vitro (J. C. Y. Dunn, M. L. Yarmush, H. G. Koebe, and R. G. Tompkins, FASEB J. 3, 174, 1989). Using this culture system, rat hepatocytes were frozen with 15% (v/v) Me2SO to -70 degrees C, and stored at approximately -100 degrees C. Following rapid thawing, long-term function was assessed by measuring albumin secretion in culture for 7-14 days postfreezing. Comparison was made with cryopreservation of liver cells in single cell suspensions. Cryopreservation of liver cells in suspension resulted in only a 2% yield of cells which could be successfully cultured; albumin secretion rates in these cultured cells over 48 hr were 26-30% of secretion rates for nonfrozen hepatocytes. Freezing cultured liver cells in the sandwich configuration after 3, 7, and 11 days in culture maintained 0, 26, and 19% of the secretion rates of nonfrozen hepatocytes, respectively. Morphology of the cryopreserved cells appeared grossly similar to cells without freezing; however, this morphological result was patchy and represented approximately 30% of the cells in culture. These results represent the first demonstration of any quantitative long-term preservation of hepatocellular function by cryopreservation, suggesting that cultured hepatocytes can survive freezing and maintain function.

Animals↗
PubMed1989

Hepatocyte function and extracellular matrix geometry: long-term culture in a sandwich configuration.

Adult rat hepatocytes cultured in a collagen sandwich system maintained normal morphology and a physiological rate of albumin secretion for at least 42 days. Hepatocytes cultured on a single layer of collagen gel essentially ceased albumin secretion within 1 wk but could recover function with the overlay of a second layer of collagen gel. This culture configuration more closely mimics the hepatocytes' in vivo environment and provides a simple method for their long-term maintenance.

Albumins↗
PubMed1983

Spatial metrics of integral and separable dimensions.

Two experiments were conducted to investigate the relationship between dimensional integrality and the form of the combination rule or spatial metric used in a similarity judgment task. In Experiment 1, two groups of eight subjects judged the dissimilarity of all pairwise combinations of 12 rectangles differing in height and width (integral dimensions) or 12 circles differing in size and diameter orientation (separable dimensions). The dimensional organization and spatial metric of both sets of dimensions were determined. The results showed that differences in height and width contributed independently to judgments of the overall dissimilarity of rectangles and that these dimensions were combined using a Euclidean metric. In contrast, substantial interactions between circle size and diameter orientation were found. Combinations of these dimensions also appeared to violate the triangle inequality implying that no spatial metric was appropriate. In Experiment 2, parallelogram size and tilt were similarly analyzed. Although some degree of dimensional interaction was observed, it was found that on the average these dimensions were combined using a city-block metric. In a subsequent speeded classification task, orthogonal interference was observed, which suggested that size and tilt are integral dimensions. The implications of both experiments for the supposed association between the Euclidean metric and dimensional integrality are discussed.

Adolescent↗
PubMed1982

Impotence--the team approach to investigation and surgical treatment.

A multidisciplinary study group was established to assess impotent patients. One hundred and forty-eight patients were fully assessed and 25 potent volunteers underwent measurement of nocturnal penile tumescence (NPT). This report describes the selection process and results of surgical implantation of the American Medical Systems (AMS) inflatable and the Jonas silver-silicone prostheses.

Adult↗
PubMedDate not supplied

The presence of androgen-binding protein in the guinea-pig testis, epididymis and epididymal fluid.

Androgen-binding protein (ABP) is present in the guinea-pig testis, epididymis and epididymal fluid. Guinea-pig ABP sediments as an approx. 4.6S species on sucrose gradients containing 0.01 M KCl. Electrophoresis on non-denaturing polyacrylamide gels indicated that specific androgen binding was present in epididymal cytosol, but not in plasma. Time-course studies indicated that binding equilibrium is approached in about 2.5 h; the dissociation half-time of [3H]5 alpha-DHT from guinea-pig ABP is 5.64 +/- 0.62 h (n = 6) at 4 degrees C. The relative affinities of some steroids for guinea-pig ABP in relation to 5 alpha-DHT = 1 are: testosterone = 0.55 +/- 0.13 (n = 4), estradiol = 0.14 +/- 0.03 (n = 4), the anti-androgen cyproterone acetate = 0.0025 +/- 0.0002 (n = 3). Guinea-pig ABP exhibited an equilibrium dissociation constant of 6.34 +/- 0.52 nM (n = 3) at 4 degrees C and there were 3.43 +/- 0.78 (n = 3) pmoles of binding sites per mg of protein when homogenates of the whole epididymis were assayed. The concentration of ABP was lowest in the caput-corpus region of the epididymis, highest in the proximal cauda, and intermediate in the distal cauda. Essentially all of the ABP present in the distal cauda was intraluminal, as evidenced by the fact that flushing of the duct eliminated most of the [3H]5 alpha-DHT binding activity.

Androgen-Binding Protein↗
PubMedDate not supplied

Long-term in vitro function of adult hepatocytes in a collagen sandwich configuration.

In an effort to reconstruct the cellular polarity normally found in the liver, adult rat hepatocytes were sandwiched between two layers of hydrated rat tail tendon collagen matrix. Functionally, sandwiched hepatocytes maintained the secretion of albumin, transferrin, fibrinogen, bile acids, and urea for at least 6 weeks, whereas cells cultured on a single layer of collagen gel ceased such secretion in 1-2 weeks. After 1 week of culture on a single layer of collagen gel, hepatocytes could still recover these lost functions when a second layer of collagen gel was applied. The exact nature of the substrate for constructing the sandwich system appeared to be unimportant as long as it allowed cellular attachment. Hepatocytes cultured in the sandwich system appeared to maintain a distribution of actin filaments similar to the in vivo state, whereas cells cultured on a single layer of collagen gel showed abnormal formation of stress fibers. These studies suggest that simple manipulations of the configuration of extracellular elements can dramatically alter the behavior of cultured hepatocytes.

Actins↗
PubMedDate not supplied

Hepatocytes from rat liver perfusions. Physicochemical effects on polyribosome size.

Hepatocytes have been used extensively both in vitro and in vivo for a wide variety of studies. Although isolated hepatocytes appear similar to their in vivo counterparts, they are different in some respects. One aspect in which they differ is their ability to translate proteins. The isolation process appears to inflict sufficient damage to reduce the average polyribosome size within the isolated hepatocytes and this size reduction correlates with a lower rate of protein production. Two methods of liver perfusion that better maintain the normal distribution of polyribosomes are described in this report. It is clear from these studies that new isolation methods that result in high yields of viable hepatocytes that function maximally are needed.

Animals↗