PubMed Health⌕ Search

Biomedical subjects

M G FARQUHAR

Publications and source records attributed to M G FARQUHAR.

At least 19 recordsLinked to original sources
PubMed1963

Junctional complexes in various epithelia.

The epithelia of a number of glands and cavitary organs of the rat and guinea pig have been surveyed, and in all cases investigated, a characteristic tripartite junctional complex has been found between adjacent cells. Although the complex differs in precise arrangement from one organ to another, it has been regularly encountered in the mucosal epithelia of the stomach, intestine, gall bladder, uterus, and oviduct; in the glandular epithelia of the liver, pancreas, parotid, stomach, and thyroid; in the epithelia of pancreatic, hepatic, and salivary ducts; and finally, between the epithelial cells of the nephron (proximal and distal convolution, collecting ducts). The elements of the complex, identified as zonula occludens (tight junction), zonula adhaerens (intermediary junction), and macula adhaerens (desmosome), occupy a juxtaluminal position and succeed each other in the order given in an apical-basal direction. The zonula occludens (tight junction) is characterized by fusion of the adjacent cell membranes resulting in obliteration of the intercellular space over variable distances. Within the obliterated zone, the dense outer leaflets of the adjoining cell membranes converge to form a single intermediate line. A diffuse band of dense cytoplasmic material is often associated with this junction, but its development varies from one epithelium to another. The zonula adhaerens (intermediate junction) is characterized by the presence of an intercellular space ( approximately 200 A) occupied by homogeneous, apparently amorphous material of low density; by strict parallelism of the adjoining cell membranes over distances of 0.2 to 0.5 micro; and by conspicuous bands of dense material located in the subjacent cytoplasmic matrix. The desmosome or macula adhaerens is also characterized by the presence of an intercellular space ( approximately 240 A) which, in this case, contains a central disc of dense material; by discrete cytoplasmic plaques disposed parallel to the inner leaflet of each cell membrane; and by the presence of bundles of cytoplasmic fibrils converging on the plaques. The zonula occludens appears to form a continuous belt-like attachment, whereas the desmosome is a discontinuous, button-like structure. The zomula adhaerens is continuous in most epithelia but discontinuous in some. Observations made during experimental hemoglobinuria in rats showed that the hemoglobin, which undergoes enough concentration in the nephron lumina to act as an electron-opaque mass tracer, does not penetrate the intercellular spaces beyond the zonula occludens. Similar observations were made in pancreatic acini and ducts where discharged zymogen served as a mass tracer. Hence the tight junction is impervious to concentrated protein solutions and appears to function as a diffusion barrier or "seal." The desmosome and probably also the zonula adhaerens may represent intercellular attachment devices.

Animals↗
PubMed1961

Glomerular permeability. II. Ferritin transfer across the glomerular capillary wall in nephrotic rats.

Ferritin was used as a tracer to investigate glomerular permeability in the nephrotic rat. The results were compared with those previously obtained in normal animals. A nephrotic syndrome was induced by 9 daily injections of the aminonucleoside of puromycin. Ferritin was administered intravenously on the 10th day, and kidney tissue was fixed at intervals of 5 minutes to 44 hours after injection of the tracer and examined by electron microscopy. The observations confirmed that at this stage of the experimental nephrotic syndrome the changes affect predominantly the visceral epithelium (loss of foot processes, reduction and modification of urinary slits, and intracellular accumulation of vacuoles and protein absorption droplets). Less extensive changes were found in other layers (reduction of endothelial fenestrae, an increase in the population of "deep" cells, and a thinning and "loosening" of the basement membrane.) At short intervals (5 to 15 minutes) after ferritin administration, the tracer was found at high concentration in the lumen and endothelial fenestrae, and at decreasing concentrations embedded throughout the basement membrane and incorporated into the epithelium (within cytoplasmic vesicles and within invaginations of the plasmalemma facing the basement membrane). After longer intervals (1 to 3 hours) the distribution of the tracer within the capillary wall was similar except that its concentration in the epithelium was higher, and, in addition to plasma membrane invaginations and small vesicles, ferritin also marked larger vacuoles, dense bodies, and intermediate forms. Large accumulations of tracer typically occurred in the spongy areas of the basement membrane, especially in the axial regions. Ferritin also appeared in the endothelium within membrane-limited vacuoles and dense bodies, particularly in the deep cells. After 6 to 44 hours the tracer still occurred in the lumen and throughout the basement membrane. The ferritin deposits in the spongy areas as well as the ferritin-containing vacuoles of the deep endothelium were larger and more numerous. In the epithelium ferritin was found not only within various membrane-limited bodies, but also "free" within the cytoplasmic matrix. These observations indicate that in the nephrotic glomerulus, as in the normal, the basement membrane functions as the main filtration barrier; however, in nephrosis, the basement membrane is defective and allows leakage of increased quantitites of ferritin and presumably plasma proteins. The basement membrane defect appears to be fine and widespread, occurring at or near the molecular level of organization of the filter. The accumulation of unfiltered ferritin in axial regions together with the demonstration of its subsequent phagocytosis by the "deep" endothelial cells suggest that the latter may function in the removal of filtration residues. Finally, the findings indicate that in the nephrotic, as in the normal animal, the epithelium acts as a monitor that recovers, at least in part, the protein which leaks through the filter, and that in nephrosis, the recovering activities of the epithelium are greatly enhanced because of the increased permeability of the basement membrane.

Animals↗
PubMed1961

Glomerular permeability. I. Ferritin transfer across the normal glomerular capillary wall.

Ferritin was used as a tracer to investigate pathways and mechanisms for transfer across the various layers of the glomerular capillary wall. Kidney tissue, fixed at intervals of 2 minutes to 2 hours following an intravenous injection of ferritin, was examined by electron microscopy. The observations confirmed the existence of three distinct and successive layers in the glomerular capillary wall (the endothelium, the basement membrane, and the visceral epithelium). In addition, they demonstrated a number of new structural features: namely (a) discrete fibrils in the subendothelial spaces; (b) a characteristic, highly elaborate, cytoplasmic organization in the visceral epithelium; and (c) special structures resembling "desmosomes" in the slits between foot processes. In animals sacrificed at short time intervals (2 to 15 minutes) following ferritin administration, ferritin molecules were found at high concentration in the lumen and endothelial fenestrae, at low concentration in the basement membrane, and in very small numbers within the epithelium. Later (1 to 2 hours), the tracer particles were still present in the lumen and within endothelial fenestrae, and, in addition, had accumulated on the luminal side of the basement membrane, especially in the axial regions of the vessels. Larger numbers of ferritin molecules were also found in the epithelium-in invaginations of the cell membrane at the base of the foot processes, and in various membrane-limited bodies (vesicles, multivesicular bodies, vacuoles, and dense bodies) present within the cytoplasm. These observations suggest that the endothelial fenestrae are patent and that the basement membrane is the main filtration barrier. Since the basement membrane has no demonstrable pores, it is probably not a simple sieve but presumably is a gel-like structure with two fine fibrillar components embedded in an amorphous matrix. Both the epithelium and endothelium may be concerned with building and maintaining this structure. Finally, the intracellular accumulation of particles in the epithelium suggests that the latter acts as a monitor that recovers, at least in part, the small amounts of protein which normally leak through the filter.

Animals↗
PubMed1960

Segregation of ferritin in glomerular protein absorption droplets.

Ferritin was used as a tracer to study the mechanism by which proteins are segregated into droplets by the visceral epithelium of glomerular capillaries. In glomeruli from both normal and aminonucleoside-nephrotic rats ferritin molecules introduced into the general circulation penetrated the endothelial openings and were seen at various levels in the basement membrane. Striking differences between nephrotic and controls were seen only in the amount of ferritin incorporated into the epithelium. In normal animals, a few ferritin molecules were seen in small invaginations of the cell membrane limiting the foot processes, within minute vesicles in the epithelium, or within occasional large vacuoles and dense bodies. In nephrotics, epithelial pinocytosis was marked, and numerous ferritin molecules were seen within membrane invaginations and in small cytoplasmic vesicles at all time points. After longer intervals, the concentration of ferritin increased in vacuoles and particularly within the dense bodies or within structures with a morphology intermediate between that of vacuoles and dense bodies. In nephrotic animals cleft-like cavities or sinuses were frequently encountered along the epithelial cell surface facing the urinary spaces. Some of these sinuses contained material resembling that filling the dense bodies except that it appeared less compact. The findings suggest that ferritin molecules-and presumably other proteins which penetrate the basement membrane-are picked up by the epithelium in pinocytotic vesicles and transported via the small vesicles to larger vacuoles which are subsequently transformed into dense bodies by progressive condensation. The content of the dense bodies may then undergo partial digestion and be extruded into the urinary spaces where it disperses. The activity of the glomerular epithelium in the incorporation and segregation of protein is similar in normal and nephrotic animals, except that the rate is considerably higher in nephrosis where the permeability of the glomerular basement membrane is greatly increased.

Animals↗
PubMed1957

An electron microscope study of the glomerulus in nephrosis, glomerulonephritis, and lupus erythematosus.

Renal biopsies from 16 patients with nephrosis, 7 patients with glomerulonephritis, and 3 patients with disseminated lupus erythematosus were studied with the electron microscope. The observations presented indicate that early in the course of each of these diseases alterations occur in the fine structure of the glomeruli which serve to distinguish one disease process from another. In nephrosis, some distortion of the organization of the epithelial foot processes was seen in all patients. These epithelial changes constituted the early, consistent lesion of the disease. There was frequently also a swelling of the endothelium. In glomerulonephritis, pronounced proliferative changes involving the endothelium and to a lesser extent the epithelium, together with the laying down of a basement membrane-like material, represented the predominate pathologic processes. There was also a swelling of both endothelial and epithelial cytoplasm. The epithelial foot processes generally appeared normal. In patients with a clinically "mixed" picture of nephrosis and nephritis, the glomerular changes were likewise "mixed," for various combinations of epithelial, endothelial, and basement membrane abnormalities were present. In disseminated lupus erythematosus, a more or less generalized thickening of the basement membrane proper associated with a variable degree of endothelial proliferation was seen. It is suggested that an accentuation of the process of basement membrane thickening results in the "wire loop" appearance sometimes seen by light microscopy. Although the earliest alterations in glomerular fine structure were characteristic for each of the disease processes, at later stages the changes were not always distinctive. The resulting scarred or "hyalinized" glomeruli, composed of relatively homogeneous, basement membrane-like material, and a few atrophic cells, appeared quite similar. Although the functional implications of the structural changes observed remain obscure at this time, it is believed that insight into mechanisms may stem from such observations.

Basement Membrane↗