scholarly journals EXPERIMENTAL GLOMERULONEPHRITIS

1965 ◽  
Vol 122 (3) ◽  
pp. 565-578 ◽  
Author(s):  
Emil R. Unanue ◽  
Sun Lee ◽  
Frank J. Dixon ◽  
Joseph D. Feldman

Rats with nephrotoxic serum nephritis were studied for the presence of a possible autoimmune response to renal antigens formed and/or liberated during the immunologic reactions taking place in the glomeruli. The experiments consisted of transplantation of a normal isologous kidney to a nephritic rat and parabiosis of a normal rat to a nephritic rat. Neither functional nor morphologic abnormalities were noted in the normal kidneys in either situation. Transfer of the rabbit nephrotoxic antibody to the normal kidneys was noted in both experiments, indicating a continual dissociation and reassociation of nephrotoxic antibody with the tissue antigens of the host. Some of the nephritic rats showed a decrease in proteinuria and a slowing in the progression of the nephritis during the period in which the normal kidney was transplanted or a normal rat was united in parabiosis.

2017 ◽  
Vol 44 (1) ◽  
pp. 11-16
Author(s):  
V. Dielievska ◽  
P. Kravchun

Abstract Patients with chronic obstructive pulmonary disease (COPD) have high risk of cardiovascular events due to the remodeling of the heart and vessels. We investigated whether in COPD cardiac remodeling is associated with immune response to the inflammation by studying activated T-lymphocytes, CD3+, CD4+, CD8+ subsets of T-lymphocytes autoimmune lymphocytotoxic and granulocytotoxic antibodies, circulating immune complexes, bacterial sensibilization and hypersensitivity by the delayed type to the host heart tissue antigens. It turned out that progression of COPD is characterized by the decrease of cell immunity with formation of bacterial sensibilization and autosensibilization to the heart tissue antigens, strongly associated with cardiac remodeling. Thus, the presence of autoimmune response significantly contributes to the changes of heart geometry in patients with COPD.


1965 ◽  
Vol 121 (5) ◽  
pp. 697-714 ◽  
Author(s):  
Emil R. Unanue ◽  
Frank J. Dixon

A direct correlation between the amount of kidney-fixing antibody and the degree of associated renal injury was demonstrated for rabbit and duck nephrotoxic antibodies. No evidence for a qualitative difference among nephrotoxic antibodies of a given type was obtained. It appeared that duck nephrotoxic antibody was directed against a wider spectrum of rat renal antigens than was rabbit nephrotoxic antibody. In order to produce immediate proteinuria an amount of rabbit or duck gamma-2 kidney-fixing antibody capable of occupying approximately 45 per cent or more of the capillary filtration surface was needed. For immediate proteinuria an amount of rabbit gamma-2 kidney-fixing antibody capable of reacting with more than one-half of the available antigenic sites was needed. Less than twice that amount of rabbit antibody completely saturated available antigenic sites in the kidney. Virtually all nephrotoxic antibodies in hyperimmune rabbit nephrotoxic sera were of the gamma-2 variety while nephrotoxic antibodies in comparable duck nephrotoxic sera were found in gamma-2 (with 5.8 and 7.4S sedimentation coefficients) and gamma-1M fractions. Gamma-1M duck nephrotoxic antibody was 60 times more potent a nephritogen than gamma-2 duck nephrotoxic antibody on a molecular basis. Mercaptoethanol abolished the nephrotoxicity of gamma-1M duck antibody and reduced that of gamma-2 duck antibodies but had no effect on rabbit gamma-2. In no case did mercaptoethanol treatment have an effect on the kidney-fixing properties of the antibodies involved. After injection of nephrotoxic antibodies there appeared to be a prompt fixation of a majority of the antibody to tissue antigens primarily in the kidney. However, a small amount of potentially kidney-fixing antibody remained in the circulation for a considerable period apparently reflecting a dissociation of less avid antibodies with an equilibrium between fixed and free antibody. The role of this more easily dissociable antibody in the progression of nephrotoxic nephritis is not certain but it is possible that it could play a role in the early progression of the disease.


2001 ◽  
Vol 200 (2) ◽  
pp. 77-92 ◽  
Author(s):  
Ryuko Matsuda ◽  
Noboru Kaneko ◽  
Yoshifumi Horikawa ◽  
Fumiko Chiwaki ◽  
Makoto Shinozaki ◽  
...  

1975 ◽  
Vol 53 (8) ◽  
pp. 930-933 ◽  
Author(s):  
P. Wadoux ◽  
T. C. Welbourne

The contribution of D-glutamyltransferase (D-GT) (EC 2.3.2.1) to total renal ammonia production was determined by employing DL-methionine-DL-sulfoximine (MSO) as an inhibitor of D-GT. Rat kidney homogenates were assayed for NH3-liberating activity under optimal D-GT or γ-glutamyltranspeptidase (γ-GTP) (EC 2.3.2.2) conditions. MSO inhibits only D-GT activity. The contribution of D-GT to total renal ammonia production was then evaluated in the isolated perfused rat kidney employing identical substrate (5 mML-glutamine) and inhibitor (15 mM MSO) concentrations as employed in the homogenate study. Under these conditions, MSO inhibits 70% of the total ammonia production by the normal kidney; in addition, the ratio of ammonia produced per glutamine taken up rose from 1.0 to 1.8. In kidneys from chronically acidotic rats, MSO reduced total ammonia production only 35% while the NH3/glutamine ratio rose from 1.0 to 1.8. D-GT appears to be the predominant source of NH3 production in the normal rat kidney; γ-GTP does not contribute significantly. The rise in the NH3/glutamine ratio after D-GT inhibition is consistent with glutamine utilization via the activated mitochondrial glutaminase (EC 3.5.1.2) – glutamate dehydrogenase (EC 1.4.1.2) pathway.


1963 ◽  
Vol 117 (6) ◽  
pp. 1019-1034 ◽  
Author(s):  
Dietrich K. Hammer ◽  
Frank J. Dixon

The primary phase of nephrotoxic serum nephritis produced by rabbit nephrotoxic serum appears to be dependent to a great extent, but not completely, upon the participation of serum complement. On the other hand, duck nephrotoxic serum produces its primary renal injury without detectable utilization of or dependence upon serum complement. The secondary phase of nephrotoxic serum nephritis appears to be largely or entirely dependent upon the host's antibody response to the heterologous gamma globulin fixed in the glomeruli. No evidence could be obtained for the existence of an autoimmune antikidney response by the host in this experimental model.


1974 ◽  
Vol 139 (4) ◽  
pp. 793-800 ◽  
Author(s):  
Chue Shue Lee ◽  
S. Michael Mauer ◽  
David M. Brown ◽  
David E. R. Sutherland ◽  
Alfred F. Michael ◽  
...  

Immunoglobulins and complement are deposited in the glomerular mesangium of rats with progressive glomerulosclerosis secondary to chemically induced diabetes mellitus. Isotransplantation of a kidney from a rat diabetic for 6 mo into a normal recipient results within 2 mo in the disappearance of IgG, IgM, and ß1C from the mesangium and arrest or reversal of the light microscopic glomerular lesions. Kidneys isotransplanted from normal donors into diabetic rats developed mesangial matrix thickening and deposition of IgG, IgM) and ß1C in the mesangium. No glomerular changes occur upon transplantation of a normal kidney into a normal rat. These findings indicate that diabetic glomerular changes in the rat are reversible and are secondary to the diabetic state rather than to the inducing agent.


2021 ◽  
Vol 28 (4) ◽  
pp. 513-543
Author(s):  
Aristo Vojdani ◽  
Elroy Vojdani

Autoimmune diseases affect 5–9% of the world’s population. It is now known that genetics play a relatively small part in the pathophysiology of autoimmune disorders in general, and that environmental factors have a greater role. In this review, we examine the role of the exposome, an individual’s lifetime exposure to external and internal factors, in the pathophysiology of autoimmune diseases. The most common of these environmental factors are toxic chemicals, food/diet, and infections. Toxic chemicals are in our food, drink, common products, the air, and even the land we walk on. Toxic chemicals can directly damage self-tissue and cause the release of autoantigens, or can bind to human tissue antigens and form neoantigens, which can provoke autoimmune response leading to autoimmunity. Other types of autoimmune responses can also be induced by toxic chemicals through various effects at the cellular and biochemical levels. The food we eat every day commonly has colorants, preservatives, or packaging-related chemical contamination. The food itself may be antigenic for susceptible individuals. The most common mechanism for food-related autoimmunity is molecular mimicry, in which the food’s molecular structure bears a similarity with the structure of one or more self-tissues. The solution is to detect the trigger, remove it from the environment or diet, then repair the damage to the individual’s body and health.


Author(s):  
S.S. Spicer ◽  
B.A. Schulte

Generation of monoclonal antibodies (MAbs) against tissue antigens has yielded several (VC1.1, HNK- 1, L2, 4F4 and anti-leu 7) which recognize the unique sugar epitope, glucuronyl 3-sulfate (Glc A3- SO4). In the central nervous system, these MAbs have demonstrated Glc A3-SO4 at the surface of neurons in the cerebral cortex, the cerebellum, the retina and other widespread regions of the brain.Here we describe the distribution of Glc A3-SO4 in the peripheral nervous system as determined by immunostaining with a MAb (VC 1.1) developed against antigen in the cat visual cortex. Outside the central nervous system, immunoreactivity was observed only in peripheral terminals of selected sensory nerves conducting transduction signals for touch, hearing, balance and taste. On the glassy membrane of the sinus hair in murine nasal skin, just deep to the ringwurt, VC 1.1 delineated an intensely stained, plaque-like area (Fig. 1). This previously unrecognized structure of the nasal vibrissae presumably serves as a tactile end organ and to our knowledge is not demonstrable by means other than its selective immunopositivity with VC1.1 and its appearance as a densely fibrillar area in H&E stained sections.


Author(s):  
John M. Basgen ◽  
Eileen N. Ellis ◽  
S. Michael Mauer ◽  
Michael W. Steffes

To determine the efficiency of methods of quantitation of the volume density of components within kidney biopsies, techniques involving a semi-automatic digitizing tablet and stereological point counting were compared.Volume density (Vv) is a parameter reflecting the volume of a component to the volume that contains the component, e.g., the fraction of cell volume that is made up of mitochondrial volume. The units of Vv are μm3 /μm3.Kidney biopsies from 15 patients were used. Five were donor biopsies performed at the time of kidney transplantation (patients 1-5, TABLE 1) and were considered normal kidney tissue. The remaining biopsies were obtained from diabetic patients with a spectrum of diabetic kidney lesions. The biopsy specimens were fixed and embedded according to routine electron microscogy protocols. Three glomeruli from each patient were selected randomly for electron microscopy. An average of 12 unbiased and systematic micrographs were obtained from each glomerulus and printed at a final magnification of x18,000.


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