Pemphigus research: new directions. An editorial review.
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Adrenal Cortex Hormones↗
Biomedical subjects
R M Lewis
Publications and source records attributed to R M Lewis.
24-Hour urine protein/creatinine ratio in dogs with protein-losing nephropathies.
The 24-hour urine protein/creatinine (U[P/C]) ratio was examined in 19 healthy dogs and in 38 dogs with protein-losing nephropathies. A positive correlation existed between the U(P/C) ratio and the 24-hour urine protein output per kilogram of body weight. The U(P/C) ratio in 18 of 19 healthy dogs was less than 0.2; one dog had a ratio of 0.38. The median U(P/C) ratio in dogs with glomerulonephritis (n = 26) and amyloidosis (n = 6) was 5.73 and 22.50, respectively. The median U(P/C) ratio in dogs with chronic interstitial nephritis (n = 6) was 2.89. In the presence of hypoalbuminemia (albumin less than or equal to 1.5 g/dl), a U/(P/C) ratio greater than 1 indicated a nephrotic syndrome. Severe protein-losing nephropathies (ie, severe glomerulonephritis and amyloidosis) were characterized by U(P/C) ratios greater than 10 and urine protein values exceeding 159 mg/kg/day. The 24-hour U/(P/C) may be more sensitive than the 24-hour urine protein output per kilogram of body weight in the detection of mild glomerular disease. Abnormal U(P/C) ratios were present in 5 dogs, 2 with glomerulonephritis and 3 with chronic interstitial nephritis; that had normal or mildly increased 24-hour urine protein output.
Amyloidosis↗
The electrophysiologic effects of nisoldipine in the conscious dog.
The electrophysiologic effects of nisoldipine, 10 to 100 micrograms/kg, were studied in eight conscious nonsedated chronically instrumented dogs. No change in blood pressure or electrophysiologic measurements followed 10 micrograms/kg nisoldipine. Following 30 micrograms/kg, the mean arterial pressure was decreased from 116 +/- 9 to 105 +/- 10 mm Hg (means +/- SD) and the sinus cycle length decreased from 536 +/- 101 to 428 +/- 75 (msec) without changes in PR, AH, HV intervals, atrioventricular (AV) nodal conduction, or sinus node recovery times. After 100 micrograms/kg, the mean blood pressure was further reduced (87 +/- 17 mm Hg), the sinus cycle length further decreased (378 +/- 71 msec), and the AV nodal effective and functional refractory periods shortened (178 +/- 59 to 148 +/- 43 and 178 +/- 59 to 148 +/- 43 msec, respectively), as did the sinus node recovery time (corrected and uncorrected) and the QT and QTc intervals. No significant changes in atrial or ventricular pacing thresholds, atrial or ventricular refractory periods, or in the HV interval were observed. Nisoldipine, a nifedipine derivative, did not significantly change electrophysiologic parameters in intact conscious animals when given in doses which did not alter blood pressure. When nisoldipine produced significant vasodilatation, the enhancement of AV nodal conduction observed probably reflects a balance of the direct effect of nisoldipine and opposing autonomic activity.
Animals↗
Use of the flexible fiberoptic nephroscope in the preoperative evaluation and delayed repair of traumatic urethral strictures.
A flexible, fiberoptic nephroscope was used in the preoperative evaluation and subsequent repair of obliterative, post-traumatic urethral strictures in 2 men. Antegrade passage of the flexible nephroscope through a previously established suprapubic cystostomy tract afforded direct visualization of the bladder neck and uninvolved urethra proximal to the strictures. Thereby, precise definition of involvement of the membranous urethra and striated external sphincter was established. This facilitated selection between transperineal and transpubic operative approaches as well as intraoperative localization of the proximal margins of the strictures.
Adult↗
Creatine kinase and phosphorylase in cardiac lymph: coronary occlusion and reperfusion.
Cardiac lymph, collected from conscious dogs, was monitored for glycogen phosphorylase and creatine kinase (CK) enzymatic activity during control state, circumflex coronary artery (CFX) occlusion, and reperfusion. CFX occlusions, lasting for intervals as short as 10 min, initiated a release of phosphorylase and CK into the cardiac lymph, which was immediately observed during reperfusion of the ischemic tissue. Blood plasma levels did not appear for several hours. In the absence of reperfusion, the appearance of enzymes in cardiac lymph was delayed and peaked later. Glycogen phosphorylase and CK entered the lymph in greater quantities with reperfusion as the length of occlusion was increased. Histological examination of multiple sections of the reperfused hearts showed infarcts in hearts where CFX occlusions lasted 20 min or longer; occlusions of 10-15 min showed evidence of cell injury and death in two hearts and no definable infarct in the majority. Ischemic intervals of short duration release functionally active glycogen phosphorylase and CK, which reflect changes in myocardial cell egress of macromolecules and/or cell death.
Animals↗
Protection of canine cardiac mitochondrial function by verapamil-cardioplegia during ischemic arrest.
Hemodynamic and mitochondrial function recover following 60 minutes of ischemic arrest and reperfusion in hearts pretreated with verapamil. The present study was carried out to determine whether verapamil prevents the onset of mitochondrial oxidative impairment after 60 minutes of ischemic arrest without reperfusion. Two preparations of mitochondria isolated following Polytron homogenization and subsequent treatment of the myofibrillar pellet with Nagarse were examined for phosphorylating respiration. The Polytron mitochondria were more sensitive to ischemic arrest than were the Nagarse mitochondria with either glutamate-malate (57% vs. 22% inhibition), succinate (+ rotenone) (41% vs. 14% inhibition), or palmitoylcarnitine (57% vs. 27% inhibition) as respiratory substrates. Verapamil pretreatment significantly increased oxidation of all substrates by the subsequently isolated Polytron mitochondria, but only succinate-supported respiration returned to control levels. In contrast, the small amount of respiratory inhibition exhibited by the Nagarse mitochondria after ischemic arrest was insensitive to verapamil pretreatment. We conclude that the Polytron preparation of mitochondria is more susceptible to ischemia than the Nagarse mitochondria, and this susceptibility correlates with a striking sensitivity to verapamil protection. In general, oxidation of NADH-linked substrates, including palmitoylcarnitine, is more affected by ischemic arrest than succinate, and only oxidation of the latter substrate is totally protected by verapamil. The beneficial action of verapamil on mitochondrial function occurs prior to reperfusion. The data suggest that alterations in calcium homeostasis occur during the ischemic period, as well as in the subsequent reperfusion period.
Animals↗
Effect of metabolic clearance rate and hepatic extraction of insulin on hepatic and peripheral contributions to hypoglycemia.
Effects of alterations in metabolic clearance rates, hepatic extraction, and plasma concentrations of insulin on hepatic and peripheral contribution to hypoglycemia and glucose counterregulation were studied in conscious dogs. Since insulin and sulfated insulin had markedly different metabolic clearance rates (34 +/- 1 vs. 16 +/- 1 ml/kg per min, respectively) and fractional hepatic extraction (42 +/- 1% vs. 15 +/- 2%, respectively), biologically equivalent amounts infused intraportally produced twofold higher hepatic vein and artery sulphated insulin concentrations and concentrations that were 30% higher in the portal vein. This significantly larger arterial/portal concentration ratio (0.67 vs. 0.45, respectively) permitted assessment of differential distribution of insulin on glucose turnover using [3-3H]glucose. Insulin and sulfated insulin (1 and 2 mU/kg per min) caused similar hypoglycemia. While insulin transiently suppressed glucose production and increased glucose disappearance, sulfated insulin had significantly greater effects on glucose disappearance and clearance, without suppression of glucose production. Despite similar hypoglycemia, sulfated insulin caused greater increment in glucagon. 3 mU/kg per min insulin caused more rapid and greater hypoglycemia, greater glucose clearance, and greater glucagon increments without suppression of glucose production, which indicates that with larger doses of insulin counterregulation can absolutely mask the suppressive effect of insulin. The effects of insulin and sulfated insulin were evaluated using euglycemic clamp to eliminate interference from stimulated counterregulation. Sequential infusion of 1 and 2 mU/kg per min of both insulins suppressed endogenous glucose production to 0 at 150 min, which indicates that the apparent lack of a hepatic effect of sulfated insulin during hypoglycemia was masked by greater counterregulation. This greater counterregulation may reflect greater peripheral glucose clearance, and prevented greater hypoglycemia than after the same insulin doses. The results indicate that the different rates of removal and the total metabolic clearance rate caused different concentrations and relative distribution between the portal and arterial blood compartments, leading to the significantly different contributions by the liver and peripheral tissues to the same hypoglycemia.
Animals↗
Fibrillary deposits in glomerulonephritis in a horse.
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Animals↗
Antiepithelial autoantibodies associated with the feline eosinophilic granuloma complex.
A retrospective study of banked sera from 19 cats with the eosinophilic granuloma complex revealed that 68% of affected cats had circulating antibodies to components of normal cat epithelium. Seemingly, the eosinophilic granuloma complex of cats may be an autoimmune disease; however, epidermal damage caused by the eosinophilic granuloma complex may release altered self-antigens to which the cat's immune system responds.
Animals↗
Prevention and treatment of postoperative infection.
Strategies for the prevention, early recognition, and management of postoperative infections in urologic patients are described. It is suggested that clinicians consider the extent of the patient's exposure to hospital pathogens as well as the hospital's unique bacteriology when devising antibiotic strategies for postoperative infections.
Anti-Bacterial Agents↗
Current challenges in etiology and diagnosis of nosocomial sepsis.
Diagnostic tests and monitoring techniques for bacteremic patients are reviewed. It is concluded that a better understanding of the physiologic mechanisms underlying the bacteremic insult would result in more effective methods of intervention and treatment. Clinicians are urged to be scrupulous in the use and maintenance of urinary catheters, IVs, and respirators.
Adult↗
Monoclonal antibodies against human abnormal (des-gamma-carboxy)prothrombin specific for the calcium-free conformer of prothrombin.
A monoclonal antibody JO1 X 1 was prepared against human abnormal prothrombin using the hybridoma technique. The clone secreting this antibody was selected on the basis of the ability of this antibody to bind to abnormal prothrombin, but not to prothrombin, in the presence of calcium ions. The antibodies were purified by affinity chromatography in EDTA on columns of prothrombin-Sepharose. Bound antibodies were eluted with 15 mM CaCl2. The kinetics of dissociation of antibody from the antibody-prothrombin complex with the addition of calcium ions fit a first-order kinetic model. Increasing CaCl2 concentration increased the rate of antibody-prothrombin dissociation. Ca(II) and Mn(II) inhibited antibody-prothrombin interaction; half-maximal binding was observed at 0.9 and 4 mM, respectively. Mg(II) had little effect on antibody-antigen interaction. The JO1 X 1 antibody bound fragment 1, fragment (1-39), abnormal prothrombin, and prothrombin equivalently in the presence of EDTA, but did not bind to des(1-44)prothrombin in the presence of EDTA or prothrombin in the presence of CaCl2. These results indicate that the monoclonal antibody JO1 X 1 is conformation specific for the calcium-free conformer of prothrombin and directed against an antigenic determinant near the NH2 terminus of prothrombin expressed in the 1-39 region of the protein. This analysis provides confirmation of the presence of a metal-free conformer of prothrombin.
Animals↗
Influence of intravenous administration of nucleoside-coupled spleen cells on murine lupus nephritis in female (NZB X NZW)F1 mice.
In this study, we examine the influence of the intravenous administration of nucleoside-coupled spleen cells on the spontaneous development of murine lupus nephritis in young and adult BWF1 mice. In both age groups, this treatment failed to affect the autoimmune disease. Rather, in young mice administration of nucleoside-coupled spleen cells accelerates the appearance of anti-DNA antibody suggesting that BWF1 have a specific defect in the immunoregulation of anti-DNA antibody production. The significance of this finding for the pathogenesis of the disease in BWF1 mice is discussed.
Animals↗
Hepatic extraction of exogenous insulin in depancreatized conscious dogs.
Hepatic and mesenteric extraction of exogenous insulin and glucose appearance and clearance were compared in conscious depancreatized and normal dogs after intraportal or peripheral intravenous insulin infusion. Portal vein insulin levels were higher, whereas arterial insulin levels were lower after intraportal compared with intravenous peripheral infusion of insulin. During the intraportal infusion of 1 and 2 mU X kg-1 X min-1 insulin, 40 +/- 3% of the insulin presented to the liver was extracted by that organ in the diabetic dogs, similar to the value obtained in normal dogs (39 +/- 5%). Hepatic extraction of insulin after intravenous peripheral infusion of that hormone was similar in normal and diabetic dogs and was not significantly different from intraportal infusion. Mesenteric extraction of insulin in the diabetic dogs (13 +/- 2%) was similar to the 19 +/- 3% in the normal animals. The blood sugar changes were similar after both routes of insulin infusion. Suppression of glucose appearance in diabetic dogs was also similar during both routes of infusion. Glucose clearance during the peripheral intravenous infusion of insulin in diabetic dogs was greater than during intraportal insulin. These findings indicate that hepatic extraction of exogenous insulin was similar in normal and depancreatized dogs and was not influenced by the different infusion routes. Suppression of glucose appearance in diabetic dogs was similar after both routes despite different portal vein insulin levels. The peripheral action of intravenous peripheral infused insulin in diabetic dogs was greater than that of intraportal insulin reflecting the higher arterial insulin levels.
Animals↗
An improved method for chronic His bundle recordings in conscious dogs.
Because anesthetics routinely used in cardiovascular experiments significantly alter the physiological state and electrophysiological function of the heart, our goal was to develop a surgically simple, inexpensive, and reliable animal model for chronic conscious electrophysiological studies. Our method differs from prior methods by implantation of bipolar stainless steel electrodes with pin length varied to adapt for the varied thickness of different cardiac chambers, electrode placement at the junction between the right atrium and aortic root posterior to the right coronary artery for recording the His potential, and unipolar His recordings.
Animals↗
Adaptation of canine saphenous veins to grafting. Correlation of contractility and contractile protein content.
Saphenous veins are used extensively to replace stenotic coronary arteries. However, the contractile and biochemical adaptations of grafted veins are unknown. The three purposes of this work were to characterize the contractile properties of grafted veins, to determine whether altered contractile characteristics were associated with quantitative changes in actin, myosin and collagen, and to determine which changes were associated with the surgical procedure and which with placement in the arterial circulation. Canine saphenous veins were removed and returned to their original location (venous autograft), while others were used to replace a segment of femoral artery (arterial graft). The grafts were removed 1, 4, and 8 weeks later and compared with the contralateral saphenous vein. Both graft types exhibited an increase in sensitivity to norepinephrine but not to potassium chloride. The venous autograft exhibited a reversible reduction in myosin content and in maximum contractile response (force/cross-sectional area) to potassium chloride and norepinephrine. In contrast, the arterial graft exhibited increased wall thickness and content of all measured proteins and decreased maximum contractile response. The latter occurred even though there was an increase in the net production of actin and myosin. Expressing the maximum contractile response in terms of the myosin content did not normalize the contractile response. These results suggest that, except for the elevated sensitivity to norepinephrine, the vein is capable of recovering from the effects of surgery within 8 weeks; however, placement of the vein in the arterial circulation delays this recovery and initiates a hypertrophic response that includes an attenuation of contractile function.
Adaptation, Physiological↗
Antitubular basement membrane autoantibody in a dog with chronic tubulointerstitial nephritis.
Linear deposition of immunoglobulin G was seen by direct immunofluorescence along the tubular basement membranes in the kidney of a dog with chronic tubulointerstitial nephritis. Autoantibody eluted from the affected kidney bound to the tubular basement membrane of normal canine kidney, but not to several other normal canine basement membranes. The pathogenic significance of the autoantibody in this dog was not determined.
Animals↗
Effects of portal and peripheral venous insulin infusion on glucose production and utilization in depancreatized, conscious dogs.
The relation between portal vein insulin concentrations and suppression of hepatic glucose production, as well as peripheral venous insulin level and increase of peripheral glucose utilization, was compared in conscious, depancreatized, diabetic dogs after infusion of insulin at 0.25 and 0.5 mU/kg/min into either the portal system or the peripheral circulation. Glucose appearance and clearance was measured using [3-3H]-glucose. Before infusion of insulin, portal vein insulin concentrations were undetectable. The intraportal infusion of insulin at 0.25 mU/kg/min increased portal vein insulin to 16 +/- 1 microU/ml, significantly higher than the arterial concentration (9 +/- 1 microU/ml). Infusion of the same amount of insulin into a peripheral vein raised peripheral insulin levels to 14 +/- 1 microU/ml and portal vein concentrations to 12 +/- 1 microU/ml. When 0.5 mU/kg/min of insulin was infused into the portal system, the portal vein insulin level was 28 +/- 2 microU/ml and significantly greater than the arterial concentration (16 +/- 1 microU/ml). After the same amount of insulin was infused into a peripheral vein, the arterial insulin level was higher than that of the portal vein (25 +/- 1 microU/ml versus 20 +/- 1 microU/ml, respectively). The ensuing hypoglycemia was greater after the 0.5 mU/kg/min infusion compared with the 0.25 mU/kg/min infusion. At each dose there was no significant difference between the peripheral venous or the portal route.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗