Lupus Nephritis: Glomerulonephritis associated with autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Lupus nephritis is histologically classified into 6 classes: class I - normal glomeruli, class II - pure mesangial alterations, class III - focal segmental glomerulonephritis, class IV - diffuse glomerulonephritis, class V - diffuse membranous glomerulonephritis, and class VI - advanced sclerosing glomerulonephritis (The World Health Organization classification 1982).Nephritis: Inflammation of any part of the KIDNEY.Lung Diseases, Interstitial: A diverse group of lung diseases that affect the lung parenchyma. They are characterized by an initial inflammation of PULMONARY ALVEOLI that extends to the interstitium and beyond leading to diffuse PULMONARY FIBROSIS. Interstitial lung diseases are classified by their etiology (known or unknown causes), and radiological-pathological features.Glomerulonephritis: Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.Kidney Glomerulus: A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.Cystitis, Interstitial: A condition with recurring discomfort or pain in the URINARY BLADDER and the surrounding pelvic region without an identifiable disease. Severity of pain in interstitial cystitis varies greatly and often is accompanied by increased urination frequency and urgency.Heymann Nephritis Antigenic Complex: A complex of antigenic proteins obtained from the brush border of kidney tubules. It contains two principal components LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN-2 and LDL-RECEPTOR RELATED PROTEIN-ASSOCIATED PROTEIN. The name of this complex is derived from researcher, Dr. Walter Heymann, who developed an experimental model of membranous glomerulonephritis (GLOMERULONEPHRITIS) by injecting this antigenic complex into rats to induce an autoimmune response.Proteinuria: The presence of proteins in the urine, an indicator of KIDNEY DISEASES.Interstitial Cells of Cajal: c-Kit positive cells related to SMOOTH MUSCLE CELLS that are intercalated between the autonomic nerves and the effector smooth muscle cells of the GASTROINTESTINAL TRACT. Different phenotypic classes play roles as pacemakers, mediators of neural inputs, and mechanosensors.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Antibodies, Antinuclear: Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.Lupus Erythematosus, Systemic: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.Extracellular Fluid: The fluid of the body that is outside of CELLS. It is the external environment for the cells.Purpura, Schoenlein-Henoch: A systemic non-thrombocytopenic purpura caused by HYPERSENSITIVITY VASCULITIS and deposition of IGA-containing IMMUNE COMPLEXES within the blood vessels throughout the body, including those in the kidney (KIDNEY GLOMERULUS). Clinical symptoms include URTICARIA; ERYTHEMA; ARTHRITIS; GASTROINTESTINAL HEMORRHAGE; and renal involvement. Most cases are seen in children after acute upper respiratory infections.Mice, Inbred NZBKidney Tubules: Long convoluted tubules in the nephrons. They collect filtrate from blood passing through the KIDNEY GLOMERULUS and process this filtrate into URINE. Each renal tubule consists of a BOWMAN CAPSULE; PROXIMAL KIDNEY TUBULE; LOOP OF HENLE; DISTAL KIDNEY TUBULE; and KIDNEY COLLECTING DUCT leading to the central cavity of the kidney (KIDNEY PELVIS) that connects to the URETER.Nephritis, Hereditary: A group of inherited conditions characterized initially by HEMATURIA and slowly progressing to RENAL INSUFFICIENCY. The most common form is the Alport syndrome (hereditary nephritis with HEARING LOSS) which is caused by mutations in genes for TYPE IV COLLAGEN and defective GLOMERULAR BASEMENT MEMBRANE.Mice, Inbred MRL lpr: A mouse substrain that is genetically predisposed to the development of systemic lupus erythematosus-like syndrome, which has been found to be clinically similar to the human disease. It has been determined that this mouse strain carries a mutation in the fas gene. Also, the MRL/lpr is a useful model to study behavioral and cognitive deficits found in autoimmune diseases and the efficacy of immunosuppressive agents.Glomerulonephritis, Membranoproliferative: Chronic glomerulonephritis characterized histologically by proliferation of MESANGIAL CELLS, increase in the MESANGIAL EXTRACELLULAR MATRIX, and a thickening of the glomerular capillary walls. This may appear as a primary disorder or secondary to other diseases including infections and autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Various subtypes are classified by their abnormal ultrastructures and immune deposits. Hypocomplementemia is a characteristic feature of all types of MPGN.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Basement Membrane: A darkly stained mat-like EXTRACELLULAR MATRIX (ECM) that separates cell layers, such as EPITHELIUM from ENDOTHELIUM or a layer of CONNECTIVE TISSUE. The ECM layer that supports an overlying EPITHELIUM or ENDOTHELIUM is called basal lamina. Basement membrane (BM) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. BM, composed mainly of TYPE IV COLLAGEN; glycoprotein LAMININ; and PROTEOGLYCAN, provides barriers as well as channels between interacting cell layers.Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body.Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Glomerulonephritis, Membranous: A type of glomerulonephritis that is characterized by the accumulation of immune deposits (COMPLEMENT MEMBRANE ATTACK COMPLEX) on the outer aspect of the GLOMERULAR BASEMENT MEMBRANE. It progresses from subepithelial dense deposits, to basement membrane reaction and eventual thickening of the basement membrane.Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.Idiopathic Interstitial Pneumonias: A group of interstitial lung diseases with no known etiology. There are several entities with varying patterns of inflammation and fibrosis. They are classified by their distinct clinical-radiological-pathological features and prognosis. They include IDIOPATHIC PULMONARY FIBROSIS; CRYPTOGENIC ORGANIZING PNEUMONIA; and others.Pulmonary Fibrosis: A process in which normal lung tissues are progressively replaced by FIBROBLASTS and COLLAGEN causing an irreversible loss of the ability to transfer oxygen into the bloodstream via PULMONARY ALVEOLI. Patients show progressive DYSPNEA finally resulting in death.Immune Complex Diseases: Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides SERUM SICKNESS and the ARTHUS REACTION, evidence supports a pathogenic role for immune complexes in many other IMMUNE SYSTEM DISEASES including GLOMERULONEPHRITIS, systemic lupus erythematosus (LUPUS ERYTHEMATOSUS, SYSTEMIC) and POLYARTERITIS NODOSA.Extracellular Space: Interstitial space between cells, occupied by INTERSTITIAL FLUID as well as amorphous and fibrous substances. For organisms with a CELL WALL, the extracellular space includes everything outside of the CELL MEMBRANE including the PERIPLASM and the cell wall.Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Glomerulonephritis, IGA: A chronic form of glomerulonephritis characterized by deposits of predominantly IMMUNOGLOBULIN A in the mesangial area (GLOMERULAR MESANGIUM). Deposits of COMPLEMENT C3 and IMMUNOGLOBULIN G are also often found. Clinical features may progress from asymptomatic HEMATURIA to END-STAGE KIDNEY DISEASE.Anti-Glomerular Basement Membrane Disease: An autoimmune disease of the KIDNEY and the LUNG. It is characterized by the presence of circulating autoantibodies targeting the epitopes in the non-collagenous domains of COLLAGEN TYPE IV in the basement membranes of kidney glomeruli (KIDNEY GLOMERULUS) and lung alveoli (PULMONARY ALVEOLI), and the subsequent destruction of these basement membranes. Clinical features include pulmonary alveolar hemorrhage and glomerulonephritis.Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states.Kidney Diseases: Pathological processes of the KIDNEY or its component tissues.Complement C3: A glycoprotein that is central in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C3 can be cleaved into COMPLEMENT C3A and COMPLEMENT C3B, spontaneously at low level or by C3 CONVERTASE at high level. The smaller fragment C3a is an ANAPHYLATOXIN and mediator of local inflammatory process. The larger fragment C3b binds with C3 convertase to form C5 convertase.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Mycophenolic Acid: An antibiotic substance derived from Penicillium stoloniferum, and related species. It blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase. Mycophenolic acid is important because of its selective effects on the immune system. It prevents the proliferation of T-cells, lymphocytes, and the formation of antibodies from B-cells. It also may inhibit recruitment of leukocytes to inflammatory sites. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1301)Complement C1q: A subcomponent of complement C1, composed of six copies of three polypeptide chains (A, B, and C), each encoded by a separate gene (C1QA; C1QB; C1QC). This complex is arranged in nine subunits (six disulfide-linked dimers of A and B, and three disulfide-linked homodimers of C). C1q has binding sites for antibodies (the heavy chain of IMMUNOGLOBULIN G or IMMUNOGLOBULIN M). The interaction of C1q and immunoglobulin activates the two proenzymes COMPLEMENT C1R and COMPLEMENT C1S, thus initiating the cascade of COMPLEMENT ACTIVATION via the CLASSICAL COMPLEMENT PATHWAY.Serum Sickness: Immune complex disease caused by the administration of foreign serum or serum proteins and characterized by fever, lymphadenopathy, arthralgia, and urticaria. When they are complexed to protein carriers, some drugs can also cause serum sickness when they act as haptens inducing antibody responses.Azathioprine: An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance has been listed as a known carcinogen. (Merck Index, 11th ed)Autoimmune Diseases: Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane.Glomerular Mesangium: The thin membranous structure supporting the adjoining glomerular capillaries. It is composed of GLOMERULAR MESANGIAL CELLS and their EXTRACELLULAR MATRIX.Glomerular Basement Membrane: The layer of EXTRACELLULAR MATRIX that lies between the ENDOTHELIUM of the glomerular capillaries and the PODOCYTES of the inner or visceral layer of the BOWMAN CAPSULE. It is the product of these two cell types. It acts as a physical barrier and an ion-selective filter.CreatinineAutoantigens: Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.Ureteral Obstruction: Blockage in any part of the URETER causing obstruction of urine flow from the kidney to the URINARY BLADDER. The obstruction may be congenital, acquired, unilateral, bilateral, complete, partial, acute, or chronic. Depending on the degree and duration of the obstruction, clinical features vary greatly such as HYDRONEPHROSIS and obstructive nephropathy.Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).Rats, Inbred LewNephrotic Syndrome: A condition characterized by severe PROTEINURIA, greater than 3.5 g/day in an average adult. The substantial loss of protein in the urine results in complications such as HYPOPROTEINEMIA; generalized EDEMA; HYPERTENSION; and HYPERLIPIDEMIAS. Diseases associated with nephrotic syndrome generally cause chronic kidney dysfunction.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.Methylprednisolone: A PREDNISOLONE derivative with similar anti-inflammatory action.Idiopathic Pulmonary Fibrosis: A common interstitial lung disease of unknown etiology, usually occurring between 50-70 years of age. Clinically, it is characterized by an insidious onset of breathlessness with exertion and a nonproductive cough, leading to progressive DYSPNEA. Pathological features show scant interstitial inflammation, patchy collagen fibrosis, prominent fibroblast proliferation foci, and microscopic honeycomb change.Kidney Cortex: The outer zone of the KIDNEY, beneath the capsule, consisting of KIDNEY GLOMERULUS; KIDNEY TUBULES, DISTAL; and KIDNEY TUBULES, PROXIMAL.Complement System Proteins: Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Glomerulosclerosis, Focal Segmental: A clinicopathological syndrome or diagnostic term for a type of glomerular injury that has multiple causes, primary or secondary. Clinical features include PROTEINURIA, reduced GLOMERULAR FILTRATION RATE, and EDEMA. Kidney biopsy initially indicates focal segmental glomerular consolidation (hyalinosis) or scarring which can progress to globally sclerotic glomeruli leading to eventual KIDNEY FAILURE.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Acute Disease: Disease having a short and relatively severe course.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Hematuria: Presence of blood in the urine.Antigens, Thy-1: A group of differentiation surface antigens, among the first to be discovered on thymocytes and T-lymphocytes. Originally identified in the mouse, they are also found in other species including humans, and are expressed on brain neurons and other cells.Mice, Inbred C57BLKidney Tubules, Proximal: The renal tubule portion that extends from the BOWMAN CAPSULE in the KIDNEY CORTEX into the KIDNEY MEDULLA. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the U-shaped LOOP OF HENLE.Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.Kidney Function Tests: Laboratory tests used to evaluate how well the kidneys are working through examination of blood and urine.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Severity of Illness Index: Levels within a diagnostic group which are established by various measurement criteria applied to the seriousness of a patient's disorder.Nephrosis: Pathological processes of the KIDNEY without inflammatory or neoplastic components. Nephrosis may be a primary disorder or secondary complication of other diseases. It is characterized by the NEPHROTIC SYNDROME indicating the presence of PROTEINURIA and HYPOALBUMINEMIA with accompanying EDEMA.Hydrostatic Pressure: The pressure due to the weight of fluid.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Pulse Therapy, Drug: Administration of high doses of pharmaceuticals over short periods of time.Blood Urea Nitrogen: The urea concentration of the blood stated in terms of nitrogen content. Serum (plasma) urea nitrogen is approximately 12% higher than blood urea nitrogen concentration because of the greater protein content of red blood cells. Increases in blood or serum urea nitrogen are referred to as azotemia and may have prerenal, renal, or postrenal causes. (From Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)Mice, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.Isoantibodies: Antibodies from an individual that react with ISOANTIGENS of another individual of the same species.Dermatomyositis: A subacute or chronic inflammatory disease of muscle and skin, marked by proximal muscle weakness and a characteristic skin rash. The illness occurs with approximately equal frequency in children and adults. The skin lesions usually take the form of a purplish rash (or less often an exfoliative dermatitis) involving the nose, cheeks, forehead, upper trunk, and arms. The disease is associated with a complement mediated intramuscular microangiopathy, leading to loss of capillaries, muscle ischemia, muscle-fiber necrosis, and perifascicular atrophy. The childhood form of this disease tends to evolve into a systemic vasculitis. Dermatomyositis may occur in association with malignant neoplasms. (From Adams et al., Principles of Neurology, 6th ed, pp1405-6)Kidney Transplantation: The transference of a kidney from one human or animal to another.Mesangial Cells: Smooth muscle-like cells adhering to the wall of the small blood vessels of the KIDNEY at the glomerulus and along the vascular pole of the glomerulus in the JUXTAGLOMERULAR APPARATUS. They are myofibroblasts with contractile and phagocytic properties. These cells and their MESANGIAL EXTRACELLULAR MATRIX constitute the GLOMERULAR MESANGIUM.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Kidney Medulla: The internal portion of the kidney, consisting of striated conical masses, the renal pyramids, whose bases are adjacent to the cortex and whose apices form prominent papillae projecting into the lumen of the minor calyces.Chemokine CCL2: A chemokine that is a chemoattractant for MONOCYTES and may also cause cellular activation of specific functions related to host defense. It is produced by LEUKOCYTES of both monocyte and lymphocyte lineage and by FIBROBLASTS during tissue injury. It has specificity for CCR2 RECEPTORS.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Kidney Failure, Chronic: The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.Transforming Growth Factor beta1: A subtype of transforming growth factor beta that is synthesized by a wide variety of cells. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta 1 and TGF-beta1 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. Defects in the gene that encodes TGF-beta1 are the cause of CAMURATI-ENGELMANN SYNDROME.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Capillaries: The minute vessels that connect the arterioles and venules.Kidney Tubular Necrosis, Acute: Acute kidney failure resulting from destruction of EPITHELIAL CELLS of the KIDNEY TUBULES. It is commonly attributed to exposure to toxic agents or renal ISCHEMIA following severe TRAUMA.Leydig Cells: Steroid-producing cells in the interstitial tissue of the TESTIS. They are under the regulation of PITUITARY HORMONES; LUTEINIZING HORMONE; or interstitial cell-stimulating hormone. TESTOSTERONE is the major androgen (ANDROGENS) produced.Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.Chronic Disease: Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care. (Dictionary of Health Services Management, 2d ed)Complement C4: A glycoprotein that is important in the activation of CLASSICAL COMPLEMENT PATHWAY. C4 is cleaved by the activated COMPLEMENT C1S into COMPLEMENT C4A and COMPLEMENT C4B.Antigens: Substances that are recognized by the immune system and induce an immune reaction.Connective Tissue Diseases: A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Collagenases: Enzymes that catalyze the degradation of collagen by acting on the peptide bonds.Vasculitis: Inflammation of any one of the blood vessels, including the ARTERIES; VEINS; and rest of the vasculature system in the body.Drug Therapy, Combination: Therapy with two or more separate preparations given for a combined effect.Mice, Inbred BALB CBrachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Pressure: A type of stress exerted uniformly in all directions. Its measure is the force exerted per unit area. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.Alveolitis, Extrinsic Allergic: A common interstitial lung disease caused by hypersensitivity reactions of PULMONARY ALVEOLI after inhalation of and sensitization to environmental antigens of microbial, animal, or chemical sources. The disease is characterized by lymphocytic alveolitis and granulomatous pneumonitis.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Lupus Vulgaris: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the NASAL MUCOSA; BUCCAL MUCOSA; and conjunctival mucosa.Acute Kidney Injury: Abrupt reduction in kidney function. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Uromodulin: A glycosyl-phosphatidyl-inositol (GPI) - anchored membrane protein found on the thick ascending limb of the LOOP OF HENLE. The cleaved form of the protein is found abundantly in URINE.Leptospira interrogans serovar pomona: A serovar of the bacterial species LEPTOSPIRA INTERROGANS, whose primary hosts include CATTLE and SWINE.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Glucocorticoids: A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Collagen Diseases: Historically, a heterogeneous group of acute and chronic diseases, including rheumatoid arthritis, systemic lupus erythematosus, progressive systemic sclerosis, dermatomyositis, etc. This classification was based on the notion that "collagen" was equivalent to "connective tissue", but with the present recognition of the different types of collagen and the aggregates derived from them as distinct entities, the term "collagen diseases" now pertains exclusively to those inherited conditions in which the primary defect is at the gene level and affects collagen biosynthesis, post-translational modification, or extracellular processing directly. (From Cecil Textbook of Medicine, 19th ed, p1494)Anti-Inflammatory Agents: Substances that reduce or suppress INFLAMMATION.Testis: The male gonad containing two functional parts: the SEMINIFEROUS TUBULES for the production and transport of male germ cells (SPERMATOGENESIS) and the interstitial compartment containing LEYDIG CELLS that produce ANDROGENS.Podocytes: Highly differentiated epithelial cells of the visceral layer of BOWMAN CAPSULE of the KIDNEY. They are composed of a cell body with major CELL SURFACE EXTENSIONS and secondary fingerlike extensions called pedicels. They enwrap the KIDNEY GLOMERULUS capillaries with their cell surface extensions forming a filtration structure. The pedicels of neighboring podocytes interdigitate with each other leaving between them filtration slits that are bridged by an extracellular structure impermeable to large macromolecules called the slit diaphragm, and provide the last barrier to protein loss in the KIDNEY.Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.Kidney Papillary Necrosis: A complication of kidney diseases characterized by cell death involving KIDNEY PAPILLA in the KIDNEY MEDULLA. Damages to this area may hinder the kidney to concentrate urine resulting in POLYURIA. Sloughed off necrotic tissue may block KIDNEY PELVIS or URETER. Necrosis of multiple renal papillae can lead to KIDNEY FAILURE.Tripterygium: A plant genus of the family CELASTRACEAE that is a source of triterpenoids and diterpene epoxides such as triptolide.Tomography, X-Ray Computed: Tomography using x-ray transmission and a computer algorithm to reconstruct the image.Lipocalins: A diverse family of extracellular proteins that bind to small hydrophobic molecules. They were originally characterized as transport proteins, however they may have additional roles such as taking part in the formation of macromolecular complexes with other proteins and binding to CELL SURFACE RECEPTORS.Complement Membrane Attack Complex: A product of COMPLEMENT ACTIVATION cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target CELL MEMBRANE and cell lysis. It is formed by the sequential assembly of terminal complement components (COMPLEMENT C5B; COMPLEMENT C6; COMPLEMENT C7; COMPLEMENT C8; and COMPLEMENT C9) into the target membrane. The resultant C5b-8-poly-C9 is the "membrane attack complex" or MAC.Cryoglobulins: Abnormal immunoglobulins, especially IGG or IGM, that precipitate spontaneously when SERUM is cooled below 37 degrees Celsius. It is characteristic of CRYOGLOBULINEMIA.Hydra: A genus of freshwater polyps in the family Hydridae, order Hydroida, class HYDROZOA. They are of special interest because of their complex organization and because their adult organization corresponds roughly to the gastrula of higher animals.Pulmonary Alveoli: Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place.Fatal Outcome: Death resulting from the presence of a disease in an individual, as shown by a single case report or a limited number of patients. This should be differentiated from DEATH, the physiological cessation of life and from MORTALITY, an epidemiological or statistical concept.Mice, Congenic: Mouse strains constructed to possess identical genotypes except for a difference at a single gene locus.Matrix Metalloproteinase 1: A member of the metalloproteinase family of enzymes that is principally responsible for cleaving FIBRILLAR COLLAGEN. It can degrade interstitial collagens, types I, II and III.Renal Insufficiency: Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.Ancrod: An enzyme fraction from the venom of the Malayan pit viper, Agkistrodon rhodostoma. It catalyzes the hydrolysis of a number of amino acid esters and a limited proteolysis of fibrinogen. It is used clinically to produce controlled defibrination in patients requiring anticoagulant therapy. EC 3.4.21.-.Bronchoalveolar Lavage Fluid: Washing liquid obtained from irrigation of the lung, including the BRONCHI and the PULMONARY ALVEOLI. It is generally used to assess biochemical, inflammatory, or infection status of the lung.Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents.Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Syndrome: A characteristic symptom complex.Antibodies, Antineutrophil Cytoplasmic: Autoantibodies directed against cytoplasmic constituents of POLYMORPHONUCLEAR LEUKOCYTES and/or MONOCYTES. They are used as specific markers for GRANULOMATOSIS WITH POLYANGIITIS and other diseases, though their pathophysiological role is not clear. ANCA are routinely detected by indirect immunofluorescence with three different patterns: c-ANCA (cytoplasmic), p-ANCA (perinuclear), and atypical ANCA.Rats, Inbred BNNecrosis: The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.Prognosis: A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.Fluorescent Antibody Technique, Direct: A form of fluorescent antibody technique utilizing a fluorochrome conjugated to an antibody, which is added directly to a tissue or cell suspension for the detection of a specific antigen. (Bennington, Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)Edema: Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE.Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.Albuminuria: The presence of albumin in the urine, an indicator of KIDNEY DISEASES.Histocytochemistry: Study of intracellular distribution of chemicals, reaction sites, enzymes, etc., by means of staining reactions, radioactive isotope uptake, selective metal distribution in electron microscopy, or other methods.Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands.Prednisone: A synthetic anti-inflammatory glucocorticoid derived from CORTISONE. It is biologically inert and converted to PREDNISOLONE in the liver.Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use.Connective Tissue Cells: A group of cells that includes FIBROBLASTS, cartilage cells, ADIPOCYTES, smooth muscle cells, and bone cells.Polymyositis: Diseases characterized by inflammation involving multiple muscles. This may occur as an acute or chronic condition associated with medication toxicity (DRUG TOXICITY); CONNECTIVE TISSUE DISEASES; infections; malignant NEOPLASMS; and other disorders. The term polymyositis is frequently used to refer to a specific clinical entity characterized by subacute or slowly progressing symmetrical weakness primarily affecting the proximal limb and trunk muscles. The illness may occur at any age, but is most frequent in the fourth to sixth decade of life. Weakness of pharyngeal and laryngeal muscles, interstitial lung disease, and inflammation of the myocardium may also occur. Muscle biopsy reveals widespread destruction of segments of muscle fibers and an inflammatory cellular response. (Adams et al., Principles of Neurology, 6th ed, pp1404-9)Cyclosporine: A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).Lymphatic Diseases: Diseases of LYMPH; LYMPH NODES; or LYMPHATIC VESSELS.Capillary Permeability: The property of blood capillary ENDOTHELIUM that allows for the selective exchange of substances between the blood and surrounding tissues and through membranous barriers such as the BLOOD-AIR BARRIER; BLOOD-AQUEOUS BARRIER; BLOOD-BRAIN BARRIER; BLOOD-NERVE BARRIER; BLOOD-RETINAL BARRIER; and BLOOD-TESTIS BARRIER. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (TIGHT JUNCTIONS) which may limit large molecule movement.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Spleen: An encapsulated lymphatic organ through which venous blood filters.Chromosome Deletion: Actual loss of portion of a chromosome.Adrenal Cortex HormonesProto-Oncogene Proteins c-kit: A protein-tyrosine kinase receptor that is specific for STEM CELL FACTOR. This interaction is crucial for the development of hematopoietic, gonadal, and pigment stem cells. Genetic mutations that disrupt the expression of PROTO-ONCOGENE PROTEINS C-KIT are associated with PIEBALDISM, while overexpression or constitutive activation of the c-kit protein-tyrosine kinase is associated with tumorigenesis.Immunoenzyme Techniques: Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to INULIN clearance.Lung Diseases: Pathological processes involving any part of the LUNG.In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.gamma-Globulins: Serum globulins that migrate to the gamma region (most positively charged) upon ELECTROPHORESIS. At one time, gamma-globulins came to be used as a synonym for immunoglobulins since most immunoglobulins are gamma globulins and conversely most gamma globulins are immunoglobulins. But since some immunoglobulins exhibit an alpha or beta electrophoretic mobility, that usage is in decline.Endomyocardial Fibrosis: A condition characterized by the thickening of the ventricular ENDOCARDIUM and subendocardium (MYOCARDIUM), seen mostly in children and young adults in the TROPICAL CLIMATE. The fibrous tissue extends from the apex toward and often involves the HEART VALVES causing restrictive blood flow into the respective ventricles (CARDIOMYOPATHY, RESTRICTIVE).Puromycin Aminonucleoside: PUROMYCIN derivative that lacks the methoxyphenylalanyl group on the amine of the sugar ring. It is an antibiotic with antineoplastic properties and can cause nephrosis.Reference Values: The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.Mice, Mutant Strains: Mice bearing mutant genes which are phenotypically expressed in the animals.Nephrosis, Lipoid: A kidney disease with no or minimal histological glomerular changes on light microscopy and with no immune deposits. It is characterized by lipid accumulation in the epithelial cells of KIDNEY TUBULES and in the URINE. Patients usually show NEPHROTIC SYNDROME indicating the presence of PROTEINURIA with accompanying EDEMA.Cryptogenic Organizing Pneumonia: An interstitial lung disease of unknown etiology, occurring between 21-80 years of age. It is characterized by a dramatic onset of a "pneumonia-like" illness with cough, fever, malaise, fatigue, and weight loss. Pathological features include prominent interstitial inflammation without collagen fibrosis, diffuse fibroblastic foci, and no microscopic honeycomb change. There is excessive proliferation of granulation tissue within small airways and alveolar ducts.Scleroderma, Systemic: A chronic multi-system disorder of CONNECTIVE TISSUE. It is characterized by SCLEROSIS in the SKIN, the LUNGS, the HEART, the GASTROINTESTINAL TRACT, the KIDNEYS, and the MUSCULOSKELETAL SYSTEM. Other important features include diseased small BLOOD VESSELS and AUTOANTIBODIES. The disorder is named for its most prominent feature (hard skin), and classified into subsets by the extent of skin thickening: LIMITED SCLERODERMA and DIFFUSE SCLERODERMA.Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.Lymphatic System: A system of organs and tissues that process and transport immune cells and LYMPH.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Myenteric Plexus: One of two ganglionated neural networks which together form the ENTERIC NERVOUS SYSTEM. The myenteric (Auerbach's) plexus is located between the longitudinal and circular muscle layers of the gut. Its neurons project to the circular muscle, to other myenteric ganglia, to submucosal ganglia, or directly to the epithelium, and play an important role in regulating and patterning gut motility. (From FASEB J 1989;3:127-38)Muscle, Smooth: Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)Pneumonia, Atypical Interstitial, of Cattle: A cattle disease of uncertain cause, probably an allergic reaction.B-Lymphocytes: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.Drugs, Chinese Herbal: Chinese herbal or plant extracts which are used as drugs to treat diseases or promote general well-being. The concept does not include synthesized compounds manufactured in China.Radiography, Thoracic: X-ray visualization of the chest and organs of the thoracic cavity. It is not restricted to visualization of the lungs.Leptospirosis: Infections with bacteria of the genus LEPTOSPIRA.Collagen Type IV: A non-fibrillar collagen found in the structure of BASEMENT MEMBRANE. Collagen type IV molecules assemble to form a sheet-like network which is involved in maintaining the structural integrity of basement membranes. The predominant form of the protein is comprised of two alpha1(IV) subunits and one alpha2(IV) subunit, however, at least six different alpha subunits can be incorporated into the heterotrimer.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Crosses, Genetic: Deliberate breeding of two different individuals that results in offspring that carry part of the genetic material of each parent. The parent organisms must be genetically compatible and may be from different varieties or closely related species.Pneumonia, Progressive Interstitial, of Sheep: Chronic respiratory disease caused by the VISNA-MAEDI VIRUS. It was formerly believed to be identical with jaagsiekte (PULMONARY ADENOMATOSIS, OVINE) but is now recognized as a separate entity.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Steroids: A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)Pulmonary Surfactant-Associated Protein C: A pulmonary surfactant associated protein that plays a role in alveolar stability by lowering the surface tension at the air-liquid interface. It is a membrane-bound protein that constitutes 1-2% of the pulmonary surfactant mass. Pulmonary surfactant-associated protein C is one of the most hydrophobic peptides yet isolated and contains an alpha-helical domain with a central poly-valine segment that binds to phospholipid bilayers.Leukocytes: White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).Epithelial Cells: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.Organ Size: The measurement of an organ in volume, mass, or heaviness.Antibodies, Anti-Idiotypic: Antibodies which react with the individual structural determinants (idiotopes) on the variable region of other antibodies.Fluorescent Antibody Technique, Indirect: A form of fluorescent antibody technique commonly used to detect serum antibodies and immune complexes in tissues and microorganisms in specimens from patients with infectious diseases. The technique involves formation of an antigen-antibody complex which is labeled with fluorescein-conjugated anti-immunoglobulin antibody. (From Bennington, Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)
Mir-638 microRNA precursor family: In molecular biology mir-638 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.Focal proliferative nephritis: Focal proliferative nephritis is a type of glomerulonephritis seen in 20% to 35% of cases of lupus nephritis, classified as type III. As the name suggests, lesions are seen in less than half of the glomeruli.Non-specific interstitial pneumonia: Non-specific interstitial pneumonia (NSIP) is a form of idiopathic interstitial pneumonia.GlomerulonephritisPodocin: Podocin is a protein component of the filtration slits of podocytes. Glomerular capillary endothelial cells, the glomerular basement membrane and the filtration slits function as the filtration barrier of the kidney glomerulus.Glomerulation: Glomerulation refers to bladder hemorrhages which are thought to be associated with some types of interstitial cystitis (IC).ProteinuriaKidney: The kidneys are bean-shaped organs that serve several essential regulatory roles in vertebrates. They remove excess organic molecules from the blood, and it is by this action that their best-known function is performed: the removal of waste products of metabolism.Anti-dsDNA antibodies: Anti-dsDNA antibodies are a group of anti-nuclear antibodies and their target antigen is double stranded DNA. Blood tests such as enzyme-linked immunosorbent assay (ELISA) and immunofluorescence are routinely performed to detect anti-dsDNA antibodies in diagnostic laboratories.Systemic lupus erythematosus and pregnancy: For women with systemic lupus erythematosus (SLE), pregnancy can present some particular challenges for both mother and child.ImmunofluorescenceAlport syndromeAutoantibody: An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases, (notably lupus erythematosus), are caused by such autoantibodies.Glomerular basement membrane: The glomerular basement membrane (GBM) of the kidney is the basal lamina layer of the glomerulus. The glomerular capillary endothelial cells, the GBM and the filtration slits between the podocytes perform the filtration function of the glomerulus, separating the blood in the capillaries from the filtrate that forms in Bowman's capsule.Brain biopsyRaji cell: Raji cell line is the first continuous human cell line from hematopoietic origin. The cell lines produce an unusual strain of Epstein-Barr virus which will both transform cord blood lymphocytes and induce early antigens in Raji cells.Combined pulmonary fibrosis and emphysema: Combined pulmonary fibrosis and emphysema describes a medical syndrome involving both pulmonary fibrosis and emphysema. The combination is most commonly found in male smokers.Autologous immune enhancement therapy: Autologous immune enhancement therapy (AIET) is a treatment method in which immune cells are taken out from the patient's body which are cultured and processed to activate them until their resistance to cancer is strengthened and then the cells are put back in the body. The cells, antibodies, and organs of the immune system work to protect and defend the body against not only tumor cells but also bacteria or viruses.Immunosuppressive drug: Immunosuppressive drugs or immunosuppressive agents or antirejection medications are drugs that inhibit or prevent activity of the immune system. They are used in immunosuppressive therapy to:Gross pathology: Gross pathology refers to macroscopic manifestations of disease in organs, tissues, and body cavities. The term is commonly used by anatomical pathologists to refer to diagnostically useful findings made during the gross examination portion of surgical specimen processing or an autopsy.CD4 immunoadhesin: CD4 immunoadhesin is a recombinant fusion protein consisting of a combination of CD4 and the fragment crystallizable region.Anti-glomerular basement membrane antibody: Anti-glomerular basement membrane antibody (anti-GBM Ab) is an antibody which is found in Goodpasture's syndrome but not found in microscopic polyangiitis.PrednisoloneComplement component 4: Complement component 4 is a protein involved in the complement system.Mycophenolic acidC1q domain: In molecular biology, the C1q domain is a conserved protein domain. C1q is a subunit of the C1 enzyme complex that activates the serum complement system.Serum sickness-like reaction: Serum sickness-like reactions refer to adverse reactions that have similar symptoms to serum sickness, but in which immune complexes are not found.James, William; Berger, Timothy; Elston, Dirk (2005).AzathioprineAutoimmune diseaseLung receptor: Lung receptors sense irritation or inflammation in the bronchi and alveoli.Intraglomerular mesangial cellCreatinineBiomarkers of aging: Biomarkers of aging are biomarkers that better predict functional capacity at a later age than chronological age. Stated another way, biomarkers of aging would give the true "biological age", which may be different from the chronological age.CollagenCongenital nephrotic syndromeTemporal analysis of products: Temporal Analysis of Products (TAP), (TAP-2), (TAP-3) is an experimental technique for studyingTumor progression: Tumor progression is the third and last phase in tumor development. This phase is characterised by increased growth speed and invasiveness of the tumor cells.MethylprednisoloneNintedanibRenal cortexComplement deficiencyLow-voltage electron microscope: Low-voltage electron microscope (LVEM) is an electron microscope which operates at accelerating voltages of a few kiloelectronvolts or less. While the low voltage electron microscopy technique will never replace conventional high voltage electron microscopes, it is quickly becoming appreciated for many different disciplines.FresolimumabMature messenger RNA: Mature messenger RNA, often abbreviated as mature mRNA is a eukaryotic RNA transcript that has been spliced and processed and is ready for translation in the course of protein synthesis. Unlike the eukaryotic RNA immediately after transcription known as precursor messenger RNA, it consists exclusively of exons, with all introns removed.Primary and secondary antibodies: Primary and secondary antibodies are two groups of antibodies that are classified based on whether they bind to antigens or proteins directly or target another (primary) antibody that, in turn, is bound to an antigen or protein.Thin basement membrane diseaseProximal convoluted tubule: The proximal tubule is the portion of the duct system of the nephron of the kidney which leads from Bowman's capsule to the loop of Henle.Tingible body macrophage: A tingible body macrophage is a type of macrophage predominantly found in germinal centers, containing many phagocytized, apoptotic cells in various states of degradation, referred to as tingible bodies (tingible meaning stainable).Horst Ibelgaufts' COPE: Cytokines & Cells Online Pathfinder Encyclopaedia > tingible body macrophages Retrieved on June 27, 2010 Tingible body macrophages contain condensed chromatin fragments.New Zealand rabbitNephrosis: Nephrosis refers to a non-inflammatory nephropathy.EdemaRenal functionIsoantibodiesDermatomyositis: - (ILDS M33.910)Chronic allograft nephropathy: Chronic allograft nephropathy, abbreviated CAN and also known as sclerosing/chronic allograft nephropathy, is the leading cause of kidney transplant failure and happens month to years after the transplant.Renal medullaCCL8: Chemokine (C-C motif) ligand 8, also known as monocyte chemoattractant protein 2 (MCP-2), is a protein that in humans is encoded by the CCL8 gene.DNA condensation: DNA condensation refers to the process of compacting DNA molecules in vitro or in vivo. Mechanistic details of DNA packing are essential for its functioning in the process of gene regulation in living systems.Nathan W. LevinCapillaryLeydig cell: Leydig cells, also known as interstitial cells of Leydig, are found adjacent to the seminiferous tubules in the testicle. They produce testosterone in the presence of luteinizing hormone (LH).Extracellular matrixNon-communicable disease: Non-communicable disease (NCD) is a medical condition or disease that is non-infectious or non-transmissible. NCDs can refer to chronic diseases which last for long periods of time and progress slowly.Fire (Rodgers novel): Fire is an apocalyptic science fiction/horror novel by Alan Rodgers, published in 1990 as an original paperback from Bantam Books. It was reprinted by specialty publisher Wildside Press in 2000.
(1/503) Eotaxin contributes to renal interstitial eosinophilia.
BACKGROUND: A potent eosinophil chemotactic cytokine, human eotaxin, is directly chemotactic for eosinophils. Therefore, the specific expression of eotaxin in tissue might play a crucial role in tissue eosinophilia. However, the precise molecular mechanism of the recruitment and activation of eosinophils in human renal diseases remains to be investigated. We evaluated the role of eotaxin in the pathogenesis of human diffuse interstitial nephritis with marked infiltration of eosinophils. METHODS: In this study, we examined 20 healthy volunteers. 56 patients with primary or secondary glomerular diseases and two hypereosinophilic syndrome patients without renal involvement. Urinary and serum eotaxin levels were determined by an enzyme-linked immunosorbent assay. We also detected the presence of eotaxin protein immunohistochemically. RESULTS: On the one hand, urinary levels of eotaxin were significantly higher before the initiation of glucocorticoid administration in the patient with interstitial nephritis with marked infiltration of eosinophils. On the other hand, urinary eotaxin levels were not detected in any patients with nephrotic syndrome, interstitial nephritis without eosinophils, hypereosinophilic syndrome without renal involvement or other renal diseases. Serum eotaxin levels were not detected in any of the patients. Therefore, the detection of eotaxin in the urine was specific for renal interstitial eosinophilia. Moreover, endothelial cells, infiltrating mononuclear cells and renal epithelial cells in the tubulointerstitial lesions were immunostained with specific anti-eotaxin antibodies. Furthermore, the elevated urinary levels of eotaxin decreased dramatically during glucocorticoid-induced convalescence. HYPOTHESIS: We hypothesize that in situ expression of eotaxin may provide a new mechanism to explain the renal interstitial eosinophil infiltration. (+info)
(2/503) Glomerular, tubular and interstitial nephritis associated with non-steroidal antiinflammatory drugs. Evidence of a common mechanism.
AIMS: To study the mechanisms behind NSAID-associated nephropathy. METHODS: Analysis of published case reports satisfying strict criteria for NSAID nephropathy. RESULTS: Ninety-seven cases with acute nephritis (AN; 19 patients), minimal change nephropathy (MC; 38 patients), membranous glomerulonephritis (MGN; 19 patients), focal sclerosis (FS; 13 patients) and other glomerulonephritis subgroups (8 patients) were identified. Hypersensitivity reactions were seen in all groups, most often in AN. Proteinuria was more severe in MC and FS than in MGN and unrelated to amount of glomerular deposits. The mean NSAID treatment time was 1.7 months in AN, 8.2 months in MC and 39 months in MGN and associated with amount of glomerular deposits, fusion of podocytes and proteinuria, and inversely associated with hypersensitivity, interstitial damage and renal failure. Rheumatic diseases were common in MGN. At follow-up 68 of 72 patients who had discontinued NSAID treatment had improved, 57 with normal renal function. CONCLUSIONS: NSAID nephropathy may be caused by hypersensitivity. The reaction is milder than in drug-induced acute tubulointerstitial nephritis, probably because the offending drug inhibits the inflammatory reaction it has started itself. Heavy proteinuria is probably due to lymphokines produced as a result of the immunological response. If the allergic reaction is strong, AN is produced rapidly with severe renal failure but little proteinuria; if it is less violent, immunocompetent cells may develop to produce lymphokines and proteinuria. Immune complexes may be formed eventually, secondary to the increased glomerular permeability, more easily in patients with a hyperactive immune system and with little consequence for renal function. (+info)
(3/503) Antiproteinuric therapy while preventing the abnormal protein traffic in proximal tubule abrogates protein- and complement-dependent interstitial inflammation in experimental renal disease.
In proteinuric glomerulopathies, the excess traffic of proteins into the renal tubule is a candidate trigger of interstitial inflammatory and immune events leading to progressive injury, and a key target for the renoprotective action of antiproteinuric drugs. Among proteins trafficked to the proximal tubule, the third component of complement (C3) can be activated locally and contribute to inflammation at sites of protein reabsorption. Experiments were performed in rats with renal mass reduction (RMR, 5/6 nephrectomy) with the following aims: (1) to study Ig (IgG) and complement deposition in proximal tubules, and interstitial macrophage infiltration and MHC class II expression at intervals after surgery by double immunofluorescence analysis; (2) to assess whether lisinopril (angiotensin-converting enzyme inhibitor [ACEi], 25 mg/L in the drinking water, from either day 1 or day 7) limited IgG and C3 accumulation and interstitial inflammation at day 30. In 7-d remnant kidneys, intracellular staining for both IgG and C3 was detectable in proximal tubules in focal areas; C3 was restricted to IgG-positive tubular cells, and there were no interstitial ED-1 macrophage and MHC II-positive cellular infiltrates. In 14-d and 30-d remnant kidneys, proximal tubular IgG and C3 staining was associated with the appearance of interstitial infiltrates that preferentially localized to areas of tubules positive for both proteins. RMR rats given ACEi had no or limited increases in levels of urinary protein excretion, tubular IgG, and C3 reactivity, and interstitial cellular infiltrates in kidneys at 30 d, even when ACEi was started from day 7 after surgery. These findings document that (1) in RMR, IgG and C3 accumulation in proximal tubular cells is followed by leukocyte infiltration and MHC II overexpression in the adjacent interstitium; (2) ACEi while preventing proteinuria limits both tubular accumulation of IgG and C3 and interstitial inflammation. The data suggest that ACE inhibition can be renoprotective by limiting the early abnormal protein traffic in proximal tubule and consequent deleterious effects of excess protein reabsorption, including the accumulation and local activation of complement as well as the induction of chemokines and endothelin genes known to promote interstitial inflammation and fibrosis. (+info)
(4/503) Binding of human neutrophils to cell-surface anchored Tamm-Horsfall glycoprotein in tubulointerstitial nephritis.
BACKGROUND: Human Tamm-Horsfall glycoprotein (T-H) is a glycosylphosphatidylinositol-anchored protein exposed at the surface of distal nephron cells, and urinary T-H is the released soluble counterpart. The latter has been implicated in tubulointerstitial nephritis, and the proinflammatory potential has been related to its ability to bind in vitro human neutrophils (PMNs). We have examined the conditions required for the binding of neutrophils to cell-surface anchored T-H and the consequent effects. METHODS: A HeLa cell-line derivative permanently transformed with human T-H cDNA and expressing T-H at the cell surface was used throughout the study. The adhesion of PMNs to cells expressing T-H was analyzed by immunofluorescence microscopy before and after the opsonization of cells with anti-T-H antibodies. The oxidative burst induced by adhesion of PMNs to the cells was determined by the activation of myeloperoxidase. Quantitative and qualitative changes in the release of T-H under the adhesion of activated PMNs were determined by dot-blot and Western blot analysis. RESULTS: No binding of neutrophils to cell-surface-anchored T-H was observed. On the contrary, the opsonization of cells with anti-T-H antibodies resulted in a dramatic adhesion of neutrophils. Such an adhesion induced the oxidative burst of PMNs and a large increment in the release of T-H, as well as the release of the slightly faster migrating T-H form, which is normally retained intracellularly. CONCLUSIONS: These results support the notion that, after the autoimmune response, the adhesion of neutrophils to cell-surface T-H contributes to the pathogenesis of tubulointerstitial nephritis, favoring a further accumulation of T-H in the interstitium and inducing the loss of cell integrity via reactive oxygen metabolites generated by activated neutrophils. (+info)
(5/503) High water intake ameliorates tubulointerstitial injury in rats with subtotal nephrectomy: possible role of TGF-beta.
BACKGROUND: It has been shown that tubulointerstitial injury correlates well with a decline of renal function. In this study, we investigated the effect of high water intake (HWI) on functional and structural parameters in rats with subtotal nephrectomy. METHODS: Two weeks after the ablative procedure, rats were divided into two groups. One group received the treatment with HWI (3% sucrose added to drinking water) for eight weeks. Functional parameters were compared with sham-operated control (CONT) or nephrectomized rats without treatment (NX). Remnant kidneys were then assessed histologically for evidence of interstitial fibrosis and glomerulosclerosis. RESULTS: Creatinine clearance was significantly improved in HWI rats compared with NX rats. Simultaneously, urinary protein was also significantly reduced in HWI rats. HWI predominantly ameliorated interstitial lesions and, to a lesser extent, glomerular lesions. Northern blot analysis demonstrated that transforming growth factor-beta (TGF-beta) mRNA expression was significantly suppressed in HWI rats. In situ hybridization revealed that HWI suppressed TGF-beta mRNA expression mainly in the outer medulla. Fibronectin mRNA was also reduced by the HWI treatment. The changes in TGF-beta and fibronectin mRNA were in parallel with Na+/myo-inositol cotransporter (SMIT) mRNA, which is regulated by extracellular osmolarity. Immunohistochemistry demonstrated that protein expression of TGF-beta and fibronectin coincided with the mRNA expression. CONCLUSION: These results suggest that HWI reduces TGF-beta mRNA expression in medullary interstitium and ameliorates tubulointerstitial injury in rats with reduced renal mass. (+info)
(6/503) Cynomolgus polyoma virus infection: a new member of the polyoma virus family causes interstitial nephritis, ureteritis, and enteritis in immunosuppressed cynomolgus monkeys.
Polyoma virus infection causes acute interstitial nephritis and ureteral stenosis in humans but has rarely been noted in other species. In the present study, a hitherto unknown polyoma virus was detected in 12 of 57 cynomolgus monkeys after 3 to 11 weeks of immunosuppression given to promote acceptance of renal allografts or xenografts. This virus, termed cynomolgus polyoma virus (CPV), is antigenically and genomically related to simian virus 40 (SV40). The tubular epithelial nuclei of the collecting ducts in the medulla and cortex reacted with an antibody for the SV40 large T antigen and by electron microscopy contained densely packed paracrystalline arrays of 30- to 32-nm diameter viral particles. A polymerase chain reaction analysis of DNA extracted from affected kidneys detected polyoma virus sequences using primers for a highly conserved region of the large T antigen of polyoma virus. Sequence analysis showed 7 base substitutions and 3 to 5 deletions in the 129-nucleotide segment of amplified products, compared with the corresponding portion of SV40, yielding 84% homology at the amino acid level. CPV caused interstitial nephritis in six renal allografts, a xenograft kidney, and six native kidneys. Infected animals showed renal dysfunction and had tubulointerstitial nephritis with nuclear inclusions, apoptosis, and progressive destruction of collecting ducts. CPV was detected in the urothelium of graft ureters, associated with ureteritis and renal infection. Viral infection was demonstrable in smooth muscle cells of the ureteric wall, which showed apoptosis. One animal had diarrhea and polyoma virus infection in the smooth muscle cells of the muscularis propria of the intestine. Spontaneous resolution occurred in one case; no animal had virus detected in tissues more than 3 months after transplantation. Thus, immunosuppression predisposes cynomolgus monkeys to a polyoma virus infection with clinical consequences quite similar to BK virus infection in humans, including renal dysfunction. We also suggest that this may be the pathogenetic basis for the significant incidence of late onset, isolated ureteral stenosis observed in these recipients. (+info)
(7/503) Renal changes associated with naproxen sodium administration in cynomolgus monkeys.
Naproxen sodium was administered to cynomolgus monkeys (Macaca fascicularis) by oral gavage at daily doses of 44, 88, or 176 mg/kg for 2 wk (2 monkeys/gender) or of 44 mg/kg for 13 wk (4 monkeys/gender). Body weight loss occurred in at least one monkey in all naproxen sodium-dosed groups in the 2-wk (up to 16% loss) and 13-wk (up to 22% loss) studies. Increases in plasma naproxen concentrations were dose proportional between 44 and 88 mg/kg but were less than dose proportional between 88 and 176 mg/kg. Up to 2-fold increases in creatinine and/or serum urea nitrogen values as well as higher renal weights occurred in monkeys receiving 176 mg/kg for 2 wk or 44 mg/kg for 13 wk. Microscopically, renal changes were observed in all naproxen sodium-dosed groups. Renal findings after 2 wk of exposure included increased interstitial ground substance, tubular dilatation, and tubulointerstitial nephritis; in the 13-wk study, cortical tubular atrophy and interstitial fibrosis were also observed. These studies identify the kidney as the target organ of naproxen sodium in cynomolgus monkeys. (+info)
(8/503) Crescentic glomerulonephritis: a clinicopathologic analysis of 17 cases with emphasis on glomerular and interstitial neutrophil infiltration.
In order to determine the extent to which specific forms of glomerulonephritis (GN) contribute to the pool of crescentic GN, renal tissues from 17 crescentic GN patients were examined with special attention to glomerular and interstitial neutrophil infiltration. Renal tissues from five normal kidneys served as normal controls. Renal biopsy tissues from five patients with postinfectious GN in which crescent formation was not observed were also examined as disease controls. The patients were put into both three groups according to immunofluorescence findings and two groups according to the active or inactive phase of the crescents: group 1 with anti-glomerular basement membrane crescentic GN, one case; group 2 with immune complex crescentic GN, ten cases; and group 3 with pauci-immune crescentic GN, six cases. Four of the nine individuals tested were positive for anti-neutrophil cytoplasmic antibody (44.4%). Glomerular and interstitial neutrophil infiltrations were prominent in both the active and inactive phase groups, compared to normal controls (p<.05). Glomerular neutrophil infiltration was significantly prominent in the active phase group, compared to the inactive phase group (p<.001). In both the active and inactive phase groups, interstitial neutrophil infiltration was prominent, compared to disease control groups (p<.05). These results support the concept of the participation of periglomerular leukocytes in the renal tissue damage of crescentic GN, although the role of neutrophils was not examined. (+info)
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