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Biomedical subjects

J W Dobbie

Publications and source records attributed to J W Dobbie.

At least 55 records · Page 3Linked to original sources

Silicate nephrotoxicity in the experimental animal: the missing factor in analgesic nephropathy.

Three silicon-containing compounds (magnesium trisilicate BP, crushed quartz and crushed Arran granite) were added to the drinking water (250 mg/l) of three groups of male guinea pigs for four months. At autopsy all animals receiving magnesium trisilicate showed a focal tubulo-interstitial nephritis mainly affecting the distal nephron. Similar but less intense lesions were encountered in two animals receiving crushed quartz. No renal lesions were found in the control group or in animals receiving crushed Arran granite. The concentration of soluble silicates in drinking water, measured as elemental silicon (Si) by atomic absorption spectroscopy (AAS) was determined for twenty-eight locations in different regions of Britain. Following ingestion of magnesium trisilicate, significant increases in urinary excretion of Si were demonstrated in two healthy adults using atomic absorption spectroscopy.

Animals↗

Prolactin status in chronic nephropathy in the rat.

Decreased specific prolactin binding to kidney membrane preparations, and an upward trend in serum prolactin levels were observed concomitantly with the onset of chronic progressive nephropathy im male rats of the OFA Sandoz SPF strain. Females of the same strain developed a less severe form of the disease at a later age, but failed to show the changes in prolactin status seen in male rats. Nephropathy in both male and female animals was associated with morphological abnormalities of a predominantly tubular nature, but was not associated with development of renal failure as indicated by serum urea and creatinine levels. Possible mechanisms for the observed alterations in prolactin status are discussed.

Aging↗

Prolactin status in experimentally induced acute renal failure in the rat.

Serum prolactin levels were elevated in male Sprague-Dawley rats with acute renal failure induced by glycerol administration. Specific prolactin binding to kidney membrane preparations was reduced in glycerol and antirat glomerular basement membrane serum-treated rats, after morphological and biochemical acute renal failure was evident. Extensive tubular damage after glycerol administration may account for loss of renal binding, since prolactin receptors are mainly tubular in localization. However, the predominant glomerulopathy, with less severe tubular lesions, after antirat glomerular basement membrane serum suggests that reduced renal prolactin binding in these animals is unlikely to be due to tubular destruction alone. Thus, alterations in prolactin status occur with development of experimentally induced acute renal failure and suggest altered renal responsiveness to prolactin in uraemia.

Acute Kidney Injury↗

Ultrastructural studies on the peritoneum with special reference to chronic ambulatory peritoneal dialysis.

Specimens of peritoneum from normal rat, mouse, man, uraemic patients and patients on chronic ambulatory peritoneal dialysis (C.A.P.D.) were examined by en face silver stained preparations and by electron microscopy. The ultrastructural features of the mesothelium and subjacent tissues in normal man, animal and uraemic patients were closely similar. Cellular degeneration and oedema were observed in the mesothelium of patients on C.A.P.D.

Animals↗

Prolactin receptors in the rat kidney.

Specific binding of 125I-labelled ovine prolactin iodinated by a lactoperoxidase method was demonstrated in crude membrane preparations of kidneys and adrenals of male Sprague-Dawley rats and livers from female rats. Membrane preparations derived from the 100,000 g fractions of tissue homogenates contained most of the specific prolactin binding. Kinetic and affinity characteristics of prolactin binding to kidney membranes were examined in detail. Maximal specific binding occurred after incubation for 30 h at room temperature. Scatchard analysis indicated that prolactin binding to kidney membranes was of high affinity (dissociation constant = 1.4 x 10(-10) mol/l) and similar to that for liver membranes, although kidney membranes from male rats bound approximately sixfold less prolactin/mg membrane protein than did liver membranes from female rats. Specific prolactin binding was demonstrated in both renal medulla and cortex. Autoradiography showed maximal prolactin binding activity in the epithelial cells of the proximal tubule and faint activity in the tubular cells throughout the nephron. Specificity of uptake by proximal tubular cells was indicated by the gross reduction in prolactin activity when excess ovine prolactin was administered simultaneously. The demonstration of specific binding sites for prolactin localized primarily in the proximal tubules was consistent with renal action of prolactin, predominantly on sodium metabolism.

Adrenal Glands↗

Hyperprolactinaemia in renal disease.

Basal prolactin concentrations in 357 patients with renal disease of defined pathology have been compared with those in 210 control subjects. Elevated prolactin concentrations were found in 113 renal patients (32%) including 53 patients in whom elevated concentrations were possibly attributable to drug therapy. In the remaining 60 patients who had hyperprolactinaemia not attributable to drugs, elevated concentrations (P less than 0.005) were found exclusively in patients with impaired renal function. A significant correlation was observed between prolactin and creatinine concentrations in these patients (r = 0.45 P less than 0.005) and prolactin reverted towards normal after successful renal transplantation. A significant arteriovenous prolactin concentration difference across the kidney (mean 16% range 8-29% P less than 0.02) was found in seven patients with non-renal non-endocrine disease. It is concluded that the hyperprolactinaemia found commonly in patients with impaired renal function is only partly attributable to drug therapy. The positive correlation between prolactin and creatinine reversion of prolactin towards normal after successful transplantation and arteriovenous hormone concentration differences across the normal kidney suggests that the kidney has a important role in prolactin metabolism. Abnormal regulation of prolactin secretion in renal failure may also be involved.

Adolescent↗

Ultrastructure, distribution, and density of lamellar bodies in human peritoneum.

OBJECTIVE: To determine the ultrastructure, relative density, and location of lamellar bodies in the various regions, structures, cells, and intercellular matrix in normal human peritoneum; to carry out engineering analysis of the role of lamellar structures in serosal lubricancy and deduce what effect this system may have on the process of peritoneal dialysis. DESIGN: Five samples of normal human parietal peritoneum obtained at elective operation were fixed in a tannic acid-glutaraldehyde mixture and submitted to examination by transmission electron microscopy. Detailed analysis using reconstruction of serial electron micrographs and tracings of montages were employed in determining location, disposition, density, and geometric patterns of lamellar bodies in all levels of the peritoneal membrane. RESULTS: Lamellar profiles were found in greatest density enmeshed in surface microvilli and in mesothelial cytoplasm. Lamellar bodies were frequently observed capping the external portion of mesothelial junctional complexes, and within intercellular junctions. Lamellar bodies were also encountered in macrophages, both in the peritoneal cavity and submesothelial tissue, and also in fibroblasts. Lamellar bodies were present in low density in the matrix ground substance of submesothelial connective tissue, in blood vessel walls between smooth muscle, in endothelial cell cytoplasm, and in vascular lumina. CONCLUSION: Three-dimensional analysis of lamellae on mesothelial surfaces indicates that an arrangement of constantly changing microscopic spheres and cylinders would act as "ball and roller bearings" among the microvilli for the lubrication of opposing surfaces. The entrapment of fluid in lamellar bubbles, which in normal peritoneum fill the microvillous layer, would, if maintained in peritoneal dialysis, constitute a stagnant layer of considerable stability and inertia.

Biomechanical Phenomena↗