PubMed Health⌕ Search

Biomedical subjects

J W Dobbie

Publications and source records attributed to J W Dobbie.

At least 37 records · Page 2Linked to original sources
PubMed1992

Pathogenesis of peritoneal fibrosing syndromes (sclerosing peritonitis) in peritoneal dialysis.

Drawing from diverse sources including epidemiological and clinical data, surgical observations, histopathology, serosal healing responses to fibrin and fibrinolysis, tissue reaction to chronic exposure, and to exo- and endotoxins, new information on mesothelial stem cells, autocrine and paracrine influences on their proliferation and collagen synthesis, and the effect of glucose on fibroconnective tissue, we have begun to piece together the pathogenetic jigsaw of fibrosis in continuous ambulatory peritoneal dialysis (CAPD). The reaction of peritoneal mesothelium and stroma to the stress of continual dialysis results in a spectrum of alterations ranging from opacification through a tanned peritoneum syndrome to sclerosing encapsulating peritonitis (SEP). Any agent that causes irritation of the mesothelial layer and induces serositis, or single severe or multiple episodes of peritonitis resulting in mesothelial loss, predisposes the peritoneum to fibroneogenesis. An accurate definition of the histopathological changes of peritoneal thickening is a prerequisite for defining pathogenesis. This paper is the first attempt to create such a framework. It is evident from many areas of study that fibrin deposition and fibrinolysis, hyalinization of the superficial stromal collagen possibly tanned through nonenzymatic glycosylation by dialysate glucose and the proliferative potential of mesothelial stem cells play an important and possibly interdependent role in excessive fibroneogenesis in certain patients on CAPD. Many of the pieces of the jigsaw are obviously still missing, and the picture is most surely incomplete. Nevertheless, the outline of the pathologic and etiologic landscape should now be discernible.

Acetates↗
PubMed1991

In vivo and in vitro characterization of mesothelial lipid inclusions.

The nature of intracytoplasmic lipid inclusions found in cultured rabbit and rat peritoneal mesothelial cells was examined by ultrastructural and biochemical techniques. Transmission electron microscopy also demonstrated extracellular release of these lipid bodies. Differential fixation with tannic acid revealed 2 types of inclusions, lamellated (lamellar bodies) and nonlamellated (homogeneous). The lamellar bodies were found near or in the Golgi apparatus and on the cell surface where occasionally they were observed in exocytotic pouches. The homogeneous inclusions were the predominant species being found primarily intracellularly. Lipid bodies obtained from the culture media over the cells displayed on electron microscopy the same morphological characteristics as those seen intracellularly. Exposure of confluent cultures of mesothelial cells to the vital lipid stain Nile Red caused the appearance of intensely fluorescent droplets in or on the cells at wave lengths consistent with staining for phosphatidylcholine-rich vesicles. Incubation of the cells with (14C)-choline and subsequent analysis of phospholipid formation revealed high rates of (14C)-phosphatidylcholine addition to both intra- and extracellular lipid pools. Taken together, mesothelial cells exhibit lipid bodies similar in ultrastructure to the surfactant containing organelles of Type II pneumocytes.

Animals↗
PubMed1991

Lectins as probes of membrane carbohydrates in mesothelial cells in vitro.

Carbohydrates present on the surface of cells have been implicated in such processes as bacterial adherence, surfactant secretion and reutilization, and cell-cell recognition. In this study, fluorescein isothiocyanate (FITC) conjugated lectins were used to probe for such carbohydrates on the surface and interior regions of rabbit peritoneal mesothelial cells propagated in vitro. A cell permeabilization technique employing treatment with formalin and saponin provided the greatest presentation of surface membrane structure and lectin binding. FITC-lectins derived from C. ensiformis (Concanavalin A; mannose specific), T. vulgaris, A. hypogaea, E. cristagalli, B. simplicifolia, and M. pomifera bound to the cell surface. When two strains of Edwarsiella tarda were exposed to the mesothelial cells, only the mannose-specific strain (ET-4) demonstrated substantial adherence to the cell surface.

Animals↗
PubMed1991

Lectin staining of peritoneal mesothelial cells in vitro.

A survey of lectin-binding specificities present on rodent and human mesothelial cells propagated and maintained in tissue culture was made using fluorescein isothiocynate conjugated (FITC) lectins. Rodent and human cells exhibited cell-associated fluorescence following exposure to the FITC-lectins from C. ensiformis, T. vulgaris, A. hypogaea, E. cristagalli and B. simplicifolia, but not with lectins from G. max and D. biflorus. Rodent cells were also positive for FITC-M. pomifera lectin binding. Human, but not rodent, cells were positive for FITC-T. purpureas lectin binding. Exposure of rabbit mesothelial cells in vitro to FITC-lectins that bound to the cell surface resulted in the appearance of discrete loci of putatively intracellular fluorescence. Exposure of cells to ferritin-labelled T. vulgaris lectin at 37 degrees C for as little as 7.5 minutes resulted in the appearance of ferritin-size particles in intracellular vesicles. These results demonstrate 1. the presence of lectin-binding sites in and on peritoneal mesothelial cells from rodents and humans and 2. a possible role of such sites in mediating the entry of lectin-like endogenous molecules into the vacuolar apparatus of these cells.

Animals↗
PubMed1991

Morphology of peritoneal dialysis catheter tunnel: macroscopy and light microscopy.

There is scanty knowledge of the morphology of peritoneal dialysis catheter tunnels in humans, even though such knowledge may impact on peritoneal catheter design, implantation and postimplantation care. Past descriptions of catheter tunnels are based mainly on data from animal experiments. Based on these data, it has been assumed that epidermal spreading is inhibited by collagen fibers ingrown into the cuff. Our preliminary investigation indicated that this may not be the case in humans and led us to study catheter tunnel morphology in more detail. Eighteen catheter tunnels (2-5mm of tissue around the catheters) were removed in 17 peritoneal dialysis patients. The catheters were inserted 30 to 2013 days prior to removal (median 366 days). The catheters were removed electively or because of infectious or noninfectious complications. Contrary to the observations in animals, in only 1 case did epithelium extend to the cuff with only a minimal amount of granulation tissue present at the end of a 9 mm long sinus tract. In the remaining cases, the leading edge of the epithelium always met granulation tissue 1-14 mm from the exit, and the cuffs were found 8-33 mm from the exit. In tunnels older than 197 days, dense fibrous tissue was ingrown into the cuffs, and a dense fibrous capsule surrounded the cuff. The uninfected intercuff segment formed a pseudosheath, indistinguishable from a tendon sheath or synovial membrane. Infection in the catheter tunnel propagates through the part of the cuff adjacent to the tubing inside the capsule, suggesting that the cuff per se does not constitute a major barrier for spreading infection. This observation, by exclusion, infers that the beneficial role of an external cuff in decreasing exit infections is by providing firm anchorage of the catheter resulting in restriction of its piston like movement and thereby minimizing trauma and inward conveyance of outer sinus tract flora.

Adolescent↗
PubMed1990

New concepts in molecular biology and ultrastructural pathology of the peritoneum: their significance for peritoneal dialysis.

Continuous ambulatory peritoneal dialysis (CAPD) was developed into a life-maintaining therapy using a membrane whose fundamental biological characteristics were largely unknown. Recognition of this deficiency in our knowledge spurred a belated explosion of research that began with an exploration of the fine structure of the mesothelium. The monolayer of lining cells was found to be more sophisticated than previously imagined, being profusely carpeted with microvilli and bearing motile cilia, and in contrast to endothelium, was shown to possess a cytoplasm replete with organelles in which rough endoplasmic reticulum and lipid inclusions are prominent. Because these findings indicated possible secretory function, a link was sought between these observations and the discovery in effluent dialysate of phosphatidylcholine, a lubricant surfactant. Subsequently, comparison of mesothelial ultrastructure with that of type 2 pneumocytes revealed close concordance, while specialized fixation techniques developed for the preservation of lamellar bodies (the known storage vesicles of alveolar surfactant), when applied to mesothelium, for the first time revealed similar cytoplasmic inclusions. In vitro studies have shown that mesothelium, when incubated with radiolabeled precursor, is capable of synthesizing phosphatidylcholine, the principal constituent of pulmonary surfactant, in amounts similar to those produced by lung. The demonstration that the intensively studied type 2 pneumocyte and mesothelium both secrete lamellar bodies has opened up new possibilities in exploring the physiology, pharmacology, and pathology of the peritoneum. Recent work on mesothelial cell culture has shed new light on the factors involved in healing and regeneration. Recognition of the existence of subserosal multipotential cells and their importance in maintaining the integrity of the mesothelial cell layer is dawning. From the study of peritoneal biopsies in CAPD patients, evidence is accumulating that a process of nonenzymatic glycosylation of protein, similar to that which occurs in diabetes, is responsible for changes in stromal texture and the reduplication of basement membranes. Appreciation of stromal vulnerability to dialysate-induced accelerated aging following mesothelial loss may therefore require a new approach to peritoneal dialysis during peritonitis. Now that CAPD approaches clinical maturity there is increasing recognition of the need for strategies to ensure long-term preservation of the peritoneum as a dialyzing organ. Concomitantly there is a realization that these goals can only be attained through a much deeper appreciation of the molecular biology and pathology of the peritoneum itself.

Animals↗
PubMed1990

Categorization of ultrastructural changes in peritoneal mesothelium, stroma and blood vessels in uremia and CAPD patients.

This paper presents an interim report on the findings of the International Peritoneal Biopsy Registry (IPBR). The registry was set up for the collection and morphological examination of specimens of peritoneal tissue obtained at surgical implantation or removal of the catheter before, during or after treatment with continuous ambulatory peritoneal dialysis (CAPD). The key objective of the Registry is the accumulation of information on the effect of peritoneal dialysis, peritonitis and any other complication of the therapy, on the structural integrity of peritoneal mesothelium, stroma and blood vessels.

Basement Membrane↗
PubMed1989

Morphology of the peritoneum in CAPD.

Stimulated by the development of continuous ambulatory peritoneal dialysis (CAPD), it was only in the last decade that normal and dialysate-exposed peritoneum were examined by electron microscopy. Biopsies of parietal peritoneum from patients on CAPD show ultrastructural alterations in the mesothelium consisting of an increased development of the rough endoplasmic reticulum but a decrease in surface microvilli and micropinocytotic vesicles as compared to tissue from normal controls or uremic individuals. Alterations in amount and consistency of submesothelial ground substance, and number and disposition of collagen fibers combined with mesothelial changes together constitute the 'reactive' peritoneum of peritoneal dialysis.

Fibrosis↗
PubMed1989

Mesothelium secretes lamellar bodies in a similar manner to type II pneumocyte secretion of surfactant.

In the early 1970s it was found that a specific lipid-fixing technique of tissue preparation for electron microscopy (tannic acid-glutaraldehyde) preserved and thus unmasked distinctive inclusions in Type II pneumocytes which were called lamellar bodies. This discovery was the first crucial step in demonstrating that lamellar bodies were the storage granules from which alveolar surfactant was secreted. In a previous study a comparison between mesothelium and Type II pneumocytes showed close ultrastructural similarities. In the present investigation of normal peritoneal tissue from man, monkey, rabbit and mouse, following primary tannic acid-glutaraldehyde fixation and modified embedding procedures similar to those used for lung, examination by transmission electron microscopy demonstrated in all mesothelial cells examined, characteristic lamellar structures similar to those described in Type II pneumocytes. Exocytotic extrusion of lamellar bodies from the apical portion of the mesothelial cell, and the presence of lamellar bodies on the cell surface in a manner identical to that found in Type II pneumocytes was also observed. These findings provide compelling evidence that a process of specialized biosynthesis and secretion of phospholipids similar to that established for Type II pneumocytes also occurs in mesothelial cells.

Animals↗
PubMed1989

Isolation and propagation in vitro of peritoneal mesothelial cells.

Mesothelial cells lining the peritoneal cavity are the primary site of molecular exchange during peritoneal dialysis, a life support system for over 50,000 patients worldwide. In this study, techniques are described for the isolation and propagation in culture of peritoneal mesothelial cells from rats and rabbits. For comparison, mesothelial cells were also obtained from the serosal surface of human colonic tissue. By electron microscopy the cultured cells were found to exhibit microvilli, a well-developed endoplasmic reticulum and golgi apparatus, micropinocytotic vesicles, and lipid-filled intracellular vesicles. Immunochemical probes revealed the expression by these cells in vitro of cytokeratin, fibronectin, vimentin, and keratin, but not von Willebrand factor. Mesothelial cells from rat, rabbit, and human exhibited contact inhibition, but differences in growth rates and dependence on supplements to the growth media. This work provides a multispecies comparison of the behavior of mesothelial cells in vitro for the purpose of developing an experimental system for the study of mesothelial cell biology and the role of these cells in peritoneal dialysis.

Animals↗
PubMed1988

Phosphatidylcholine synthesis by peritoneal mesothelium: its implications for peritoneal dialysis.

This study investigated the possibility that the peritoneum is capable of synthesizing phosphatidylcholine (PC), a lubricant surfactant, in an amount similar to that produced by pulmonary alveoli. The synthesis of PC by rat lung (positive control), liver (negative control), and transparent mesentery (test tissue) was determined by in vitro incubation of these tissues in the presence of (methyl-14C) choline chloride for three hours at 37 degrees C in Warburg flasks. All lipid material present in tissue and incubation media was extracted by the Folch technique. Carrier egg PC was added to each sample and total PC was isolated using high performance thin-layer chromatography. The PC fractions were counted for total radioactivity. No statistically significant difference was observed between the mean radioactive value for mesenteric tissue compared with lung tissue. The mean radioactive value for liver when compared with mesenteric and lung tissue was significantly lower (P less than 0.001). Thus, under the conditions of the experiment, we have demonstrated for the first time that peritoneal tissue is capable of synthesizing PC in amounts similar to that produced by the lung. Electron microscopy of transparent mesentery (test tissue) showed that mesothelium constituted the bulk of the cell population. Therefore, it is most likely that the PC that has been detected in peritoneal fluid is produced by the mesothelial cell. These findings are of significant relevance to developing concepts on the role of surfactant phospholipids in the physiology of peritoneal dialysis.

Animals↗
PubMed1986

Urinary and serum silicon in normal and uraemic individuals.

The urinary excretion of silicon (Si) in humans was studied in normal subjects on a low Si diet, a normal diet, and after ingestion of silicate antacid. Measurements of 24-hour urinary excretion of Si showed that urinary Si was derived mainly from dietary intake. The serum concentration of Si was determined in normal individuals and in patients with chronic renal failure. In health, serum Si is maintained within a narrow range, but a significant hypersilicaemia occurs in uraemia. The concentration of Si was measured in the water supply, dialysate and pre-dialysis and post-dialysis serum in patients on regular haemo-dialysis in three areas with low, intermediate and high concentrations of Si in the water supply. Si was removed during dialysis in the region where it was naturally low in the water or where reverse osmosis was used, but it was dialysed into patients in regions with intermediate and high concentrations in the water. Serum Si levels returned to normal after renal transplantation. Preliminary analysis of the geographical variation in the Si content of tap water suggests that uraemic hypersilicaemia may protect haemodialysed patients from the development of aluminium dementia. The kidney would appear from these studies to be the major organ for elimination of absorbed Si.

Adult↗
PubMed1986

TNO-6 has no effect in gastrointestinal cancer: N-acetyl-glucosaminidase shows renal damage.

Twenty-five patients, 16 with gastric cancer and nine with colonic cancer, received TNO-6 30 mg m-2 every four weeks. No objective tumour response was recorded. Nausea and vomiting occurred in 21 patients and was severe in 17. Severe marrow suppression developed in five patients. Renal function was unaffected in all but one patient who developed renal failure, probably as a result of septicaemia. However, the renal tubular enzyme N-acetyl-beta-D-glucosaminidase was measured in six patients and showed a rise in all. In this study TNO-6 had no anti-tumour activity in gastrointestinal malignancy, but produced significant renal tubular damage.

Acetylglucosaminidase↗
PubMed1985

Phenylbutazone-induced systemic vasculitis with crescentic glomerulonephritis.

Two patients had phenylbutazone-induced systemic vasculitis syndrome. Both presented with acute oliguric renal failure, and renal biopsies showed severe crescentic glomerulonephritis with marked interstitial inflammatory cell infiltration. Withdrawal of phenylbutazone and treatment with immunosuppressives and plasma exchange led to recovery of renal function in one case.

Acute Kidney Injury↗
PubMed1984

Acute infectious disease presenting as acute renal failure.

A diverse range of infectious diseases has presented with acute renal failure (ARF) in the West of Scotland in the past five years. Full recovery is possible provided the specific diagnosis is made early and treatment with temporary renal support is combined with effective antimicrobial therapy.

Acute Kidney Injury↗
PubMed1983

Aluminium hydroxide versus sucralfate as a phosphate binder in uraemia.

In an attempt to discover a phosphate binding agent for use in uraemia that would not lead to appreciable systemic absorption of aluminium the effect of sucralfate was evaluated after three weeks and compared with that of the existing standard agent aluminium hydroxide. Sucralfate caused a decrease in serum phosphate concentration comparable with that obtained with aluminium hydroxide, but similar absorption of aluminium resulted. Sucralfate may be the phosphate binder of choice in patients with uraemia and peptic ulceration; care should be taken in using large doses of the drug in patients with normal renal function.

Adolescent↗