Search PubMed⌕ Search

Biomedical subjects

K D Gardner

Publications and source records attributed to K D Gardner.

At least 37 records · Page 2Linked to original sources
PubMed1990

Nephrotic syndrome and rapid renal failure in autosomal dominant polycystic kidney disease.

A 44-year-old man, with autosomal dominant polycystic kidney disease and hypertension under satisfactory control, developed nephrotic syndrome with negative serology. Open renal biopsy revealed focal glomerular sclerosis. Prior to the appearance of heavy proteinuria, serum creatinine was 1.7 mg/dl. After the nephrotic syndrome had been established, renal function deteriorated rapidly and hemodialysis was started within 2.6 years. In patients with autosomal dominant polycystic kidney disease, the appearance of nephrotic range proteinuria along with a rapid decline in renal function indicates the presence of a glomerular lesion, which needs to be investigated by renal biopsy.

Adult↗
PubMed1988

Cystic kidneys.

Explore the source record for details and available documents.

Adolescent↗
PubMed1988

Pathogenesis of human cystic renal disease.

Cystic diseases of the kidney are common, often progressive disorders. The best of several alternative hypotheses to explain their development cites tubular dilation and compression of adjacent tissue. The initiating event may involve focal proliferation of epithelial cells and a consequent increase in the resistance to flow along affected tubules. Decompression of cysts has re-emerged as a potentially beneficial approach to therapy in selected cases of renal cystic disease.

Humans↗
PubMed1988

Release of interleukin 1 inhibitory activity (contra-IL-1) by human monocyte-derived macrophages infected with human immunodeficiency virus in vitro and in vivo.

Infection of monocyte-macrophages with human immunodeficiency virus may be central to the pathogenesis of the acquired immunodeficiency syndrome. The ability of infected macrophages to prime T cells through IL-1 production was investigated in vitro. Purified human monocytes maintained in suspension culture were infected with strain HIV-DV. Intracellular expression of virus p24 antigen increased from undetectable levels immediately after infection to 13-59% of cells by 10-14 d; infected macrophages remained viable for up to 60 d. Supernatants collected between 14 and 20 d after infection were examined in the murine thymocyte co-mitogenesis assay and demonstrated to contain a potent IL-1 inhibitor, designated contra-IL-1. Contra-IL-1 activity was present in all supernatants examined after 4 d of infection, and peaked coincident with peak p24 antigen expression. Inhibitory activity was not present in uninfected cells. Contra-IL-1 activity eluted after gel filtration with an approximate molecular weight of 9 kD. Inhibitory activity was removed by exposure to heat or acid pH, or by incubation with chymotrypsin or staphylococcal V8 protease. Contra-IL-1 did not inhibit IL-2- or IL-4-dependent proliferation of murine T cell lines. Despite its ability to inhibit IL-1 activity, contra-IL-1 did not interfere with the binding of recombinant IL-1 beta to a fibroblast cell line. Contra-IL-1 inhibited the proliferation of normal peripheral blood mononuclear cells to both concanavalin A and tetanus toxoid; inhibition could be attenuated by the addition of exogenous IL-1. Messenger RNA extracted from infected macrophages was examined by Northern analysis for the presence of message to IL-1 beta. No message was apparent, suggesting that the presence of contra-IL-1 was not obscuring the concomitant release of IL-1. Infected macrophages stimulated with endotoxin generated readily detectable message for IL-1 beta. Spleen macrophages purified from two patients with AIDS complicated by immune thrombocytopenia spontaneously expressed p24 antigen in vitro and released contra-IL-1 activity into the media. Contra-IL-1 may contribute to the immune dysfunction of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Polarized epithelial cysts in vitro: a review of cell and explant culture systems that exhibit epithelial cyst formation.

The purpose of this paper is to review in vitro cell and explant culture systems that exhibit epithelial cyst formation and that are used as models of polarized epithelial function. We examine a number of culture systems derived from a variety of cell and organ types, briefly describe the methodology and conditions used to establish these cultures and discuss aspects of the experimental application of each system. We conclude that the characteristics of epithelial cyst-forming cultures are dependent upon the origin and identity of the cell population, as well as the multiple factors that define the culture environment. Culture systems in which epithelial cyst development occurs provide tools to study fundamental problems in epithelial biology, such as the establishment and maintenance of cell polarity, cell recognition and cell sorting, also cell-specific functions involving solute and water transport and the production and modification of secreted products. In addition, epithelial cyst culture systems offer useful models to better understand cellular behavior in various pathologic conditions of cyst formation in man.

Animals↗
PubMed1988

Explant culture of human polycystic kidney.

Autosomal dominant polycystic kidney disease is characterized by the formation of large fluid-filled epithelial cysts. To obtain renal cyst wall epithelium for in vitro study, we employed an explant culture technique using medium-hydrated collagen gel as the culture substrate. Pieces of excised cyst wall were submerged within collagen gel. Cells of the cyst lining migrated to form a polarized epithelium at the surface of the surrounding collagen gel. Regions of the outgrowth were isolated by microdissection and used as a source of cells for subculture. Cyst-derived epithelium retained the ultrastructural features of the renal cyst of origin. The cells were cuboidal and bore short apical microvilli. Cells often were joined by apical tight junctions. Intercellular channels were narrow and bordered by short microvillus projections at the basolateral membrane. Epithelial cells rested on a densely staining basal lamina. The explants commonly developed small solitary cysts within their wall that were filled with fluid. These mural cysts were lined by a simple epithelium morphologically similar to the cells that lined the explant. Explantation of human renal cyst wall to culture within collagen gel provides a reproducible method to isolate autosomal dominant polycystic kidney disease epithelium for subculture. This method offers an alternative to the use of proteolytic enzymes to establish morphologically stable cultures of cyst lining cells for use in experimental renal cystic disease.

Cell Division↗
PubMed1987

Morphogenetic clonal growth of kidney epithelial cell line MDCK.

MDCK (Madin-Darby canine kidney) cells were cultured either dispersed within hydrated collagen gel (HCG) or seeded atop a collagen substrate and then immediately overlaid with HCG. Individual cells exhibited clonal growth in three dimensions to form spherical cysts made up of a simple epithelium enclosing a fluid-filled lumen. The cells of MDCK cysts were polarized with the basolateral surface in contact with the collagen gel and the apical surface bordering the lumen. The ultrastructure of MDCK cysts showed similarities to distal nephron. The cells bore apical microvilli and solitary cilia and had occluding junctions and a simple basolateral surface. MDCK cysts increased in size (greater than 800 microns diameter) with continued culture. MDCK cysts grown between layers of HCG were stripped free of the overlying collagen to give direct access to basolateral surface membrane. Unlike monolayer culture, morphogenetic clonal growth of cell line MDCK produces a polarized cell population with a true lumenal and basolateral surface. Collagen-gel-cultured MDCK cysts provide an easily manipulable in vitro cell system that may offer unique advantages for the study of renal cell structure and function.

Animals↗
PubMed1987

Human cystic kidney diseases: epithelial hyperplasia in the pathogenesis of cysts and tumors.

Several examples of human renal cystic disease are associated with tubular epithelial hyperplasia. Micropapillary hyperplasia occurs in autosomal dominant polycystic kidney disease, in localized cystic disease, and in acquired cystic disease; neoplastic or severely dysplastic epithelial hyperplasia occurs in von Hippel-Lindau disease; a histopathologically distinctive epithelial hyperplasia occurs in tuberous sclerosis. In all of these conditions the epithelial hyperplasia appears to be responsible for cyst formation by causing tubular or ductal luminal obstruction, and in all of these conditions, save localized cystic disease (a rare condition with very few reported cases), epithelial hyperplasia imposes an increased risk of malignancy. The risk seems to be highest in patients under treatment with long-term hemodialysis for end-stage kidney disease. Some of these diseases may share common features, but it appears likely that the histopathological differences reflect different features converging on a common result.

Epithelium↗
PubMed1987

Viscoelastic properties of tubule basement membranes in experimental renal cystic disease.

Hereditary and acquired renal cysts develop from tubule segments that enlarge progressively. We measured the deformability of basement membranes surrounding individual normal tubules and cysts to determine if cysts might develop by simple extension of abnormally-deformable basement membrane in response to normal or increased transtubule hydrostatic pressures. Deformability (cm/dyne) was measured in individual tubules and cysts in vitro by a micropipet aspiration technique that related negative pressures within the pipet to the distance the tubule or cyst wall was aspirated into the pipet. Viscoelastic creep was determined from the time-dependent effect of pipet aspiration on membrane deformation. Proximal and collecting tubules, glomerular capsules and cysts were microdissected from controls and animals with acquired (Diphenylthiazole [rats]. Nordihydroguaiaretic acid [rats]), hereditary (C57 BL/6J [cpk/cpk] mice) and spontaneous (CFWw mice) renal cystic diseases. The major resistance to deformation was localized to the basement membrane since collagenase destroyed the elasticity of tubule and cyst walls. Tubule basement membranes adjacent to cysts appeared abnormal by electron microscopy in the animals fed DPT, but measurements of deformability and viscoelastic creep showed no differences between normal and cystic tubules in any animal model. Deformability values of cysts (7.7 +/- 1.1, 10.9 +/- 1.1, 11.2 +/- 0.6, 9.4 +/- 0.8 X 10(-3) cm/dyne in DPT, NDGA, C57 BL/6J and CFWw, respectively) are consistent with the interpretation that high transtubule pressures ranging from 39 to 134 cm H2O would be required if cysts form by simple stretching of the basement membrane secondary to a transepithelial hydrostatic pressure-gradient. Since in vivo measurements of hydrostatic pressures across cyst walls are not high enough we conclude that cysts do not enlarge due to increased deformability of tubule basement membranes.

Animals↗
PubMed1987

Endotoxin provocation of experimental renal cystic disease.

Germ free rats provide a unique model in which to assess biological response to environment. In 48 germ-free male, Sprague-Dawley rats we examined the consequences of oral exposure to nordihydroguaiaretic acid (NDGA), a nephrotoxin; to Staphylococcus epidermidis and bacillus species, non-endotoxin-containing bacteria; to Escherichia coli and Proteus mirabilis, endotoxin-containing bacteria; and injected E. coli endotoxin on peripheral leukocyte counts and renal morphology. Morphological changes were evaluated by light microscopy and scored blindly on a 0 to 4+ scale for 15 parameters of renal structure. Means of these renal "pathology scores" correlated with counts of polymorphonuclear leukocytes and lymphocytes in the peripheral blood. The highest counts and scores were found in rats given NDGA and exposed to endotoxin, either by injection or by oral feeding of endotoxin-containing bacteria. Counts and scores were lower in the absence of endotoxin and with non-endotoxin-containing bacteria, given alone or in combination with either NDGA or endotoxin. Results exclude bacterial colonization and intrarenal accumulation of NDGA as causes of nephropathy. They indicate that endotoxin and NDGA act synergistically to provoke renal damage in the germ free NDGA-fed rat and suggest that leukocytes are involved in the process.

Animals↗
PubMed1987

Epithelial hyperplasia in human polycystic kidney diseases. Its role in pathogenesis and risk of neoplasia.

The importance of tubular epithelial hyperplasia in polycystic kidney diseases has become apparent during the last decade. Micropapillary hyperplasia occurs in autosomal dominant polycystic kidney disease, in localized cystic disease, and in acquired cystic disease. Neoplastic or severely dysplastic epithelial hyperplasia occurs in von Hippel-Lindau disease. A histopathologically distinctive epithelial hyperplasia occurs in tuberous sclerosis. In each of these conditions, epithelial hyperplasia may be related to cyst formation and may also impose an increased risk of malignancy--a risk that seems to be highest in patients under treatment with long-term hemodialysis for end-stage kidney disease. Although hyperplasia in some of these diseases may share a common pathway of development, it is more probable that the histopathologic differences reflect different pathogenetic pathways that converge on a common endpoint.

Epithelium↗