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Biomedical subjects

J L Barnes

Publications and source records attributed to J L Barnes.

At least 55 records · Page 3Linked to original sources
PubMed1985

The role of complement in the pathogenesis of postischemic acute renal failure.

One hour occlusion of total renal blood flow results in oliguric acute renal failure as defined by an abrupt and severe diminution in glomerular filtration rate. In rats, after 1-2 h of such ischemia, the acute renal failure which follows is characterized by decreased renal blood flow and by intratubular obstruction with necrotic cellular debris. The present study has examined the possible role of the complement system in the development of this model of acute renal failure. Immunoreactive C3 was extensively localized within necrotic tubular epithelial cells and the walls of small muscular arteries in reperfused kidneys after 1 h of total renal ischemia. Depletion of complement by the administration of cobra venom factor 18 h prior to the induction of ischemia abrogated C3 localization and significantly attenuated the subsequent fall in renal blood flow following reperfusion but did not alter the oliguria or marked fall in glomerular filtration.

Acute Kidney Injury↗
PubMed1984

Enhancement of glomerular immune complex deposition by a circulating polycation.

It is known that polycations bind to and neutralize glomerular polyanions. Here we examine the effect of the polycation polyethyleneimine (PEI) on glomerular deposition of preformed immune complexes. Bovine serum albumin (BSA)-anti-BSA immune complexes made in 40 times antigen excess were administered following intravenous injection of PEI. Glomerular localization of immune deposits was assessed by quantitative immunofluorescence and electron microscopy and compared to controls receiving diluent without PEI followed by the same dose in immune complexes. In rats receiving PEI, deposits were localized within the glomerular basement membrane (GBM) of all peripheral capillary walls and in the mesangium. In controls, deposits localized exclusively within the mesangium in smaller amounts than after PEI. Thus, neutralization of glomerular polyanion by a circulating polycation enhances the deposition and alters the distribution of immune complexes in glomeruli.

Animals↗
PubMed1984

Size and charge selective permeability defects induced in glomerular basement membrane by a polycation.

Polyethyleneimine (PEI) was given intravenously to rats followed by native ferritin or one of three cationic ferritins. After 15 min kidneys were fixed for electron microscopy. Controls (C) received vehicle without PEI, followed by the appropriate ferritin. PEI-induced permeability change was measured as the ratio (PEI/C) of counted ferritin particles within the glomerular basement membrane (GBM) in the corresponding PEI and control groups. The ratio PEI/C for each tracer was: NF (pI = 4.5-4.8)-107; CF (pI = 7.5-8.2)-3.3; CF (pI = 8.0-8.7)-1.7; and CF (pI = 8.7-9.0)-0.9. When ferritin localization in the subendothelial layer of the GBM was examined separately, PEI/C was increased for all ferritins including the most cationic species. After PEI, GFR and RBF decreased proportionately by half; thus, filtration fraction remained constant. Reduction of renal perfusion pressure to 40 mm Hg showed no alteration of ferritin permeation into the GBM. Thus, PEI effects on ferritin localization in the GBM could not be ascribed to renal hemodynamic perturbations. If the effect of PEI on GBM permeability were to be mediated exclusively by neutralization of the charge barrier, the index PEI/C should be increased for NF, but decreased for all CF. The results show a marked effect of PEI on the charge barrier (PEI/C greater than 100 for NF). But, PEI also enhanced total GBM permeation by CF (7.5-8.2) and CF (8.0-8.7), and increased subendothelial GBM permeation for CF (8.7-9.0). An inverse relationship of the effect of PEI to the cationic charge on CF was evident.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Binding of platelet factor four (PF 4) to glomerular polyanion.

Synthetic polycations have been shown to bind to glomerular polyanion (GPA) and increase glomerular permeability. Here, we show that human platelet factor 4 (PF 4), a platelet secretory protein, binds to GPA. The following methods were used to assess PF 4 binding to GPA: (1) Sections of human and rat renal cortex were incubated with PF 4 or PF 4 was injected intravenously into rats followed by immunofluorescence techniques; (2) 125I-PF 4 was added to isolated glomerular basement membrane (GBM) suspensions and binding assessed isotopically; (3) PF 4 was perfused through rat kidneys ex vivo followed by immunoperoxidase methods for electron microscopy (EM). In vitro and in vivo, PF 4 bound to the mesangium and linearly to capillary walls. Isotopic studies showed dose-dependent saturable binding of PF 4 to GBM which was reversed by heparin. By EM, PF 4 binding sites were resolved in the GBM, particularly in the laminae rarae as punctate densities similar in distribution to anionic sites revealed by cationic dyes. Also, endothelial and epithelial cell surfaces stained. An ionic interaction between PF 4 and GPA was indicated by elimination of staining by washing PF 4-treated sections with buffer containing 1.0 and 3.0 M NaCl or with heparin. Pretreatment of rats with polyethyleneimine (a synthetic polycation) blocked PF 4 binding. Heparin administration in vivo removed previously bound PF 4. By virtue of its affinity for GPA and behavior like a polycation, PF 4 may alter glomerular permeability and play a role in glomerular disease.

Animals↗
PubMed1984

Ischemic acute renal failure in the rat: protective effect of uninephrectomy.

Experiments were performed to investigate the effect 2-wk prior nephrectomy has on the recovery from a 40-min renal artery occlusion. Two groups were initially examined. Group 1 animals underwent sham nephrectomy and group 2 animals right nephrectomy 14 days prior to a 40-min left renal artery clamp. The percent recovery of inulin clearance in group 2 (33 +/- 6%) was not significantly different from that in the group 1 (36 +/- 8%) when measured 3 h after reflow. At 24 and 48 h of reflow, however, group 2 animals had a significantly higher percent recovery of inulin clearance (24 h: 31 +/- 5%; 48 h: 50 +/- 11%) than group 1 animals (24 h: 1 +/- 1%; 48 h: 8 +/- 4%). Similarly the histology was better preserved at 24 and 48 h in group 2. To further investigate this enhanced recovery, three additional groups were studied. Group 3 underwent right nephrectomy at the time of renal artery occlusion. Group 4 had right uretero-venostomies created immediately prior to the ischemic insult, and group 5 had their aortas rather than left renal arteries clamped. Each group shared with group 2, ischemia to all functioning excretory tissue. The percent recovery of inulin clearance in group 3 (48 +/- 9%), group 4 (54 +/- 5%), and group 5 (42 +/- 6%) were each significantly (P less than 0.005) higher than in group 1 (8 +/- 4%) when measured at 48 h. We conclude that the protection offered by uninephrectomy is not a consequence of hypertrophy but that alterations in the environment which follow ischemia to all functioning excretory renal tissue are responsible for the enhanced recovery seen.

Acute Kidney Injury↗
PubMed1984

Prostaglandin I2 attenuates ischemic acute renal failure in the rat.

We gave prostaglandin I2 (PGI2) (8 ng X kg-1 X min-1 i.v.) for 20 min before, during, and 20 min after clamping of the rat left renal artery for 40 min to evaluate the effect of PGI2 in this model of acute renal failure. Control animals were given glycine buffer (PGI2 diluent). Glomerular filtration rate was estimated by the clearance of inulin 24 h later from each kidney. In group I rats (studied during hydropenia) inulin clearance in the control (right) kidney averaged 1.4 ml/min. Inulin clearance in kidneys exposed to 40 min of ischemia was 0.05 (glycine treated) versus 0.22 (PGI2 treated) ml/min. Although PGI2 offered significant protection in the group I animals, the differences were small and many of the glycine-treated ischemic kidneys were anuric. In the group II studies the same protocol was employed except that 5% body wt volume expansion was done with Ringer solution prior to measurement of inulin clearance. In the group II rats inulin clearance in control (right) kidneys averaged 1.5 ml/min. Inulin clearance after 40 min of renal ischemia was 0.04 ml/min in glycine-treated rats versus 0.90 ml/min in PGI2-treated animals. Histological examination of the group II ischemic kidneys revealed cellular necrosis and cast formation in the S3 segments of the glycine-treated animals and significantly less necrosis and cast formation in the PGI2-treated animals. The degree of necrosis and casts was inversely related to inulin clearance. Accordingly, PGI2 significantly attenuated the fall in inulin clearance measured 24 h after ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1984

Renal ischemic injury in the dog: characterization and effect of various pharmacologic agents.

Renal ischemia has been implicated as a major factor in the pathogenesis of acute renal failure. Despite several differences between the intrarenal norepinephrine infusion and renal artery occlusion models, they have been assumed to be prototypic models of ischemic renal injury. In our previous studies, an intrarenal infusion of norepinephrine caused a marked reduction in inulin clearance 3 hours after infusion. This reduction could be significantly attenuated by the concurrent infusion of mannitol, furosemide, or bradykinin. The effects of these three protective agents were evaluated before and after variable durations of renal artery occlusion to establish the similarities between the models and the magnitude of versatility of these protective agents. In the renal artery occlusion model, capsular fascia was stripped to eliminate collateral flow and ensure maximal renal ischemia. Three hours after 120 minutes of renal artery occlusion (n = 7), inulin clearance returned to 5.7% +/- 2.2% (SEM) of the control values and was not statistically different from that observed in the norepinephrine model. Intrarenal infusion of mannitol, furosemide, or bradykinin prior to and during the occlusion period, however, had no protective effect. Shorter durations of renal artery occlusion were evaluated to ensure an equivalent or decreased severity of acute renal failure compared with the norepinephrine model. After 90 or 60 minutes of renal artery occlusion, the clearance of inulin returned to 10.9% +/- 3.3% (n = 8) and 31.1% +/- 8.2% (n = 4) of control values, respectively. An intrarenal infusion of mannitol, furosemide, or bradykinin still had no significant protective effect, despite the decreased insult in the 60-minute renal artery occlusion studies. In summary, these findings demonstrate fundamental differences between renal artery occlusion and the norepinephrine model of renal functional impairment, and they suggest that the insult associated with norepinephrine infusion may involve factors other than cessation of blood flow.

Acute Kidney Injury↗
PubMed1983

Host-parasite interactions in the pathogenesis of experimental renal candidiasis.

To study the pathogenesis of renal candidiasis, viable Candida albicans blastospores were injected directly into the left renal artery of New Zealand white rabbits. The progression of the disease was followed by light and electron microscopy over a 6-day period. Within 5 minutes after injection of the yeasts, the organisms localized within glomerular and peritubular capillaries of the cortex. Localization of yeasts within the capillaries occurred through adherence, demonstrated by the presence of surface fibrils originating from the yeast cells. Two to 10 hours later, inflammatory nodules comprised of polymorphonuclear leukocytes formed within capillary lumina. Many of the entrapped yeasts remained viable and extended through adjacent endothelium and epithelium by the formation of germ tubes which penetrated between or directly through intact host cells. After 24 hours, numerous hyphal forms were observed within tubules of the cortex, and some necrotic host cells were noted at sites of penetration. Abscesses replaced renal parenchyma in focal areas during subsequent time intervals. These studies indicate that attachment of Candida albicans to endothelium within capillaries of the cortex is a key event in the disease process. Also, growth of germ tubes into renal tubules provides a temporal advantage for amplification of Candida organisms.

Adhesiveness↗
PubMed1983

Low plasma 25-hydroxyvitamin D and serum calcium levels in institutionalized epileptic subjects: associated risk factors, consequences and response to treatment with vitamin D.

In a survey of 108 subjects with a history of epilepsy in a hospital for the mentally handicapped, administration of both phenobarbitone and phenytoin was associated with low serum calcium and plasma 25-hydroxyvitamin D (25-(OH)D) levels in female subjects only. Intake of phenytoin (as mg/kg body weight) in female subjects exceeded that in males by 22 per cent, whilst the intake of phenobarbitone was 37 per cent higher. The doses of phenobarbitone and phenytoin were each inversely related to plasma 25-(OH)D concentration, but anticonvulsant drug dosage did not correlate with the magnitude of the decline of plasma 25-(OH)D concentration in winter (November-February). No influence of sodium valproate was detected on serum calcium or on plasma 25-(OH)D levels. Limited exposure to ultraviolet irradiation (UVR) or oral administration of vitamin D restored plasma 25-(OH)D to normal levels and healed osteomalacia in a subject with tuberous sclerosis. In this subject, fit frequency declined in response to UVR and to a lesser extent in response to oral vitamin D, despite the attainment of similar levels of serum calcium and of plasma 25-(OH)D. Serum calcium levels in the other 108 subjects were lower in those experiencing the most frequent fits, but serum calcium could not be restored to levels found in subjects not receiving anticonvulsant drugs unless supraphysiological doses of vitamin D were given. Vitamin D deficiency in the epileptic population receiving drugs was assessed by the response of alkaline phosphatase to vitamin D administration. A consistent fall of serum alkaline phosphatase was found only if the initial level exceeded 175 per cent of the normal value established by reference to a population not receiving phenobarbitone or phenytoin. By this criterion five out of 45 subjects (11 per cent), aged nine to 36 years were vitamin D deficient.

25-Hydroxyvitamin D 2↗
PubMed1982

Vitamin D from skin: contribution to vitamin D status compared with oral vitamin D in normal and anticonvulsant-treated subjects.

1. The plasma 25-hydroxycholecalciferol [25-(OH)D3] response to measured u.v. irradiation applied thrice weekly for 10 weeks was investigated in normal and in anticonvulsant-treated subjects. 2. Levels of plasma 25-(OH)D3 achieved after u.v. irradiation were similar in both normal and anticonvulsant-treated subjects, suggesting that hepatic microsomal enzyme induction does not lead to low plasma 25-(OH)D3 concentrations. 3. Cholecalciferol was present in plasma of normal subjects in a very low concentrations (less than 5.0 nmol/l) and did not increase until plasma 25-(OH)D3 levels exceeded 62.5 nmol/l. 4. Cholecalciferol occurred in significant concentrations in plasma during whole body u.v. irradiation or during oral dosage of 62.5 nmol (100 i.u) or more daily. 5. Plasma 25-(OH)D3 concentrations reached a steady state after 5-6 weeks of u.v. irradiation or of oral intake within the usual intake range. 6. Cholecalciferol synthesis in skin calculated from the steady-state equation was 0.0015 +/- 0.0008 nmol/mJ. 7. Cholecalciferol synthesis in skin was also calculated from the oral dosage required to yield the same plasma 25-(OH)D3 concentration as u.v. irradiation and was 0.0024 +/- 0.0018 nmol/mJ. 8. Rates of cholecalciferol synthesis calculated from these data suggest that many of the population of England receive insufficient u.v. irradiation to maintain vitamin D status throughout the year.

Adolescent↗