[Fibrillary glomerulopathy. Amyloidosis and non-amyloidosis].
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Amyloidosis↗
Biomedical subjects
U Helmchen
Publications and source records attributed to U Helmchen.
Transmyocardial laser revascularization. Histological features in human nonresponder myocardium.
BACKGROUND: The creation of transmyocardial channels from the epicardium to the left ventricular cavity with the use of a CO2 laser is a modern approach in the treatment of patients with chronic ischemic cardiac disease. The histological features of human myocardium at different times after transmyocardial laser therapy have not been previously described. We had the opportunity to examine hearts from patients who died without clinical evidence of a persistent therapeutic effect at 3, 16, and 150 days after transmyocardial laser revascularization (TMR) respectively. METHODS AND RESULTS: We grossly localized the laser-created channels in unfixed and formalin-fixed tissue. Three ventricular levels were defined for cutting the hearts into four segments. Then, transmural blocks were excised and cut crosswise and lengthwise for histological investigation through the use of established staining methods. On day 3, laser-induced channels were filled with abundant granulocytes and thrombocytes, fibrinous network, and detritus and were surrounded by severe myocardial necrosis. Furthermore, the epicardial and endocardial portions were obstructed by fibrinous network and microclots. Granulocytes were mostly absent on day 16; in addition, the channels were filled with erythrocytes or fibrinous network. On day 150, we observed a string of cicatricial tissue admixed with a polymorphous blood-filled capillary network and small veins, which very rarely had a continuous wrinkled link to the left ventricular cavity. CONCLUSIONS: We found different stages of wound healing in human nonresponder myocardium after TMR, resulting in scarred tissue that displayed capillary network and dilated venules without evidence of patent and endothelialized laser-created channels. Experimental studies are necessary to analyze the morphological basis for TMR-mediated effects in human responder myocardium.
Aged↗
[Acute renal failure. Isolated manifestation of a systemic disease].
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Acute Kidney Injury↗
5-Aminosalicylic acid-associated renal tubular acidosis with decreased renal function in Crohn's disease.
The use of 5-aminosalicylic acid (5-ASA, mesalazine) in Crohn's disease is usually well tolerated. Nevertheless, the occasional occurrence of nephrotoxic side effects has been described in several case reports. We present the case of a 34-year-old female in whom chronic use of 5-ASA may have caused renal damage which manifested with tubular acidosis, severe weight loss, shortness of breath and fatigue. For 17 years the patient has suffered from Crohn's disease. She received sulfasalazine (3 g/day) for 12 years and was treated with resin-coated mesalazine (3 g/day) for the last 72 months. Onset of weight loss of 10 kg over a 6-month period, accompanied by progressive shortness of breath and fatigue, lead to a diagnosis of metabolic acidosis and renal bicarbonate loss due to damage to the tubular epithelium. Kidney biopsy demonstrated acute interstitial nephritis which may be related to 5-ASA.
Acidosis, Renal Tubular↗
Dysregulation of carcinoembryonic antigen group members CGM2, CD66a (biliary glycoprotein), and nonspecific cross-reacting antigen in colorectal carcinomas. Comparative analysis by northern blot and in situ hybridization.
Genes coding for CD66a (biliary glycoprotein), carcinoembryonic antigen (CEA) group member 2 (CGM2), and nonspecific cross-reacting antigen (NCA) are members of the human CEA gene subgroup. We investigated a series of 11 colorectal carcinomas by Northern blot and isotopic in situ hybridization (ISH), demonstrating underexpression of CD66a and CGM2 in the majority of the carcinomas as compared with the normal mucosa, whereas NCA was overexpressed. ISH for CD66a and CGM2 mRNA revealed that large areas of the carcinomas remained without or with only faint hybridization signals. However, in every carcinoma, at least some positive foci were observed, indicating remaining cell populations that actively transcribe CD66a and CGM2. In contrast, ISH for NCA displayed strong and extensive autoradiographic signals. By analysis of step sections, foci of CD66a and CGM2 expression were shown to co-localize. Furthermore, these foci contained relatively few nuclei immunohistochemically positive for the proliferation-associated nuclear antigen Ki-67. Our data indicate a dysregulation of the three genes possibly with a common transcriptional control for CD66a and CGM2 and a different control for NCA. The focal expression of CD66a and CGM2 could be interpreted as due to a focal, incomplete, and abortive differentiation or, alternatively, as a consequence of genetic heterogeneity with foci of slow-proliferating subclones.
Antigens, CD↗
Prostaglandin E1 inhibits collagen expression in anti-thymocyte antibody-induced glomerulonephritis: possible role of TGF beta.
To test whether or not prostaglandins mediate extracellular matrix formation in immune-mediated glomerular disease, rats with anti-thymocyte antibody-induced glomerulonephritis were treated with prostaglandin E1 (PGE1) (250 micrograms/twice daily/s.c.). Glomerular expression of collagen types III and IV was assessed by Northern blotting, immunohistology and Western blotting. Proliferation of glomerular cells was evaluated by staining for the proliferating cell nuclear antigen (PCNA) and consecutive cell counting. At day five after induction of the disease, glomerular mRNA levels of collagen types III and IV were three- to fivefold higher compared with non-nephritic controls. Similarly glomerular deposition of these collagens was markedly increased when assessed by immunohistology. The treatment of nephritic rats with PGE1 reduced the increased glomerular mRNA levels as well as the protein concentration and the deposition of extracellular collagens. The number of PCNA positive cells which was significantly higher in nephritic rats when compared with control animals (24 hr, nephritis 2.53 +/- 0.33 and Control 0.26 +/- 0.06, P = 0.011; 5 days, nephritis 5.10 +/- 1.13 and Control 0.75 +/- 0.08, cells per glomerular cross section, P = 0.03) was reduced by PGE1 (24 hr, nephritis+PGE1 0.44 +/- 0.30, P = 0.0001; 5 days, nephritis +/- PGE1 1.91 +/- 1.84 cells per glomerular cross section, P = 0.001). Prostaglandin E1 also ameliorated the glomerular infiltration of monocytes at 24 hours (nephritis 4.36 +/- 2.82, nephritis + PGE1 2.20 +/- 1.82, cells per glomerular cross section) and five days (nephritis 1.51 +/- 0.58, nephritis+PGE1 1.12 +/- 0.61, cells per glomerular cross section). To further characterize possible mechanisms by which PGE1 reduces extracellular matrix deposition, the glomerular expression of transforming growth factor (TGF-beta), and interleukin 1 beta (IL-1 beta) was assessed by Northern blotting. Nephritic glomeruli showed increased mRNA levels of TGF-beta at day 5 and IL-1 beta at 24 hours when compared with control kidneys. Treatment of the animals with PGE1 inhibited the mRNA expression of TGF-beta and IL-1 beta. These data demonstrate that PGE1 reduces the glomerular expression of extracellular matrix proteins in anti-thymocyte antibody-induced glomerulonephritis, suggesting a beneficial role of prostaglandins in this proliferative glomerular immune injury. The effects of PGE1 might be mediated by inhibition of TGF-beta and IL-1 beta production.
Alprostadil↗
Isoproterenol stimulates tubular DNA replication in mice.
The beta-adrenergic stimulant isoproterenol is a mitogen for cultured murine proximal tubular cells. The present study was undertaken to test whether isoproterenol has a similar effect on tubular replication in vivo. BALB/c mice were intraperitoneally injected with two different doses of isoproterenol in the presence or absence of beta 1 + 2-receptor antagonist propranolol. Proliferation of renal cells was evaluated by staining of tissue sections for proliferating cell nuclear antigen (PCNA). In addition, cDNA amplification for PCNA was performed in reverse-transcribed RNA isolated from renal cortex. Treatment of mice with 0.1 mg/g body weight isoproterenol for 24 h significantly increased PCNA staining of nuclei compared to controls. This response was completely blocked by propranolol. There was no light-microscopic evidence that the proliferative response was subsequent to ischaemia with tubular necrosis. Semiquantitative cDNA amplification revealed that isoproterenol also stimulated the RNA expression of the PCNA gene. This study shows for the first time that isoproterenol directly stimulates proliferation of mainly proximal tubular cells in vivo as detected by PCNA expression. Since proliferation and differentiation of tubular cells is pivotal for the recovery of renal function in many pathophysiological situations, beta-adrenergic-mediated mitogenesis may be important in the reparative processes surrounding tubular epithelium regeneration.
Adrenergic beta-Agonists↗
Antibody and complement reduce renal hemodynamic function in isolated perfused rat kidney.
To evaluate the effect of antibody and complement on renal hemodynamic changes, glomerular injury was induced in isolated perfused kidneys by an anti-thymocyte antibody (ATS) and rat serum (RS). Glomerular filtration rate (GFR), renal vascular resistance (RVR), and renal perfusate flow (RPF) were assessed over an 80-min period. The possible role of thromboxane (Tx) was tested by the application of the Tx synthesis inhibitor UK-38485 and the Tx receptor blocker daltroban. Perfusion of kidneys with ATS and RS significantly reduced GFR at 10 min (control, 501 +/- 111; ATS + RS, 138 +/- 86 ml.g kidney-1.min-1, significance of F = 0.000) after RS. Similarly, RPF (ml.g kidney-1.min-1) fell from 19.2 +/- 1.8 to 6.1 +/- 2.0 (significance of F = 0.000), whereas RVR (mmHg.ml-1.g.min) increased threefold from 5.2 +/- 0.4 to 17.9 +/- 5.0 at 10 min. These changes were ameliorated by the pretreatment of the rats with daltroban and UK-38485. Addition of erythrocytes to the perfusate increased RVR and GFR, whereas RPF decreased compared with cell-free perfused kidneys. ATS and RS in this preparation also decrease GFR and RPF. The hemodynamic alterations appeared without changes in filtration fraction. Compared with untreated, perfused control kidneys, glomerular Tx formation was significantly increased in ATS and RS perfused kidneys. These data demonstrate that antibody and RS induce impairment of renal hemodynamics, which are mediated by increased Tx formation.
Absorption↗
CD66a (BGP), an adhesion molecule of the carcinoembryonic antigen family, is expressed in epithelium, endothelium, and myeloid cells in a wide range of normal human tissues.
CD66a, also called biliary glycoprotein (BGP), is a member of the carcinoembryonic antigen (CEA) family and of the immunoglobulin superfamily. CD66a is the human homologue of Cell-CAM, a well-defined cell adhesion molecule of the rat. In the present study a monoclonal antibody specific for CD66a was used to locate CD66a in human tissues. CD66a is expressed in epithelia, in certain endothelia, and in cells of the myeloid lineage. Hepatocytes were stained along the bile canaliculi. A characteristic apical membranous staining was observed in enterocytes, superficial absorptive cells of the colon, in the epithelia of esophageal and Brunner's glands, bile ducts and gallbladder, pancreatic ducts, proximal tubules of the kidney, prostate, endometrium, and mammary ducts. Selective staining of endothelia was present in glomeruli and vasa recta of the kidney, small placental vessels, adrenal sinusoids, endometrium, the prostate. Among the cells of the myeloid lineage, granulocytes and myelocytes were positive. The expression of CD66a by human cells and tissues is well comparable with the expression reported for Cell-CAM, the rat counterpart of CD66a. The wide tissue distribution of CD66a indicates that CD66a is a prominent human adhesion molecule.
Antigens, CD↗
Prostaglandin E1 reduces the glomerular mRNA expression of monocyte-chemoattractant protein 1 in anti-thymocyte antibody-induced glomerular injury.
To study whether prostaglandins (PG) can regulate the mRNA expression of monocyte-chemoattractant protein 1 (MCP-1) in glomerular immune injury, MCP-1 mRNA levels were evaluated in anti-thymocyte antibody (ATS) -induced glomerular injury by Northern blotting and reverse transcription-polymerase chain reaction. Immune injury was induced in vivo by the intravenous application of ATS to male Wistar rats and in vitro by the perfusion of isolated rat kidneys with ATS and rat serum. In vivo 3 h and 5 days after antibody application, glomerular mRNA expression of MCP-1 was markedly enhanced compared with controls. In the isolated perfused kidney, antibody and complement also induced an increase in MCP-1 expression at 10 min and 60 min after antibody perfusion. When the rats were treated with PGE (250 micrograms, twice daily), the increase in MCP-1 expression was reduced. This was associated with a reduction of intraglomerular recruitment of monocytes/macrophages. In the isolated perfused kidneys, PGE1 (1 mg/L) prevented the antibody- and rat serum-stimulated increase in glomerular MCP-1 mRNA expression. These data demonstrate that PGE1 reduces glomerular MCP-1 mRNA expression in glomerulonephritis and in the isolated perfused rat kidney after induction of immune injury with antibody and complement. The data suggest that prostaglandins might mediate MCP-1 effects in glomerular immune injuries.
Alprostadil↗
Angiotensin-converting enzyme inhibition in experimental in-situ immune complex glomerulonephritis: influence on renal function, proteinuria, and morphology.
BACKGROUND: Converting enzyme inhibition (CEI) ameliorates progressive loss of function in non-immune-mediated renal diseases and experimental hypertension. Little, however, is known on the potential role of CEI in established experimental chronic glomerular immune injury. We therefore studied the effect of the CEI ramipril on renal function and morphology in a model of immune mediated glomerular injury. METHODS: The immune complex glomerulonephritis was induced in uninephrectomized rats by intrarenal perfusion with the cationized antigen followed by an intravenous application of the antibody. This disease is characterized by the development of progressive albuminuria and a nephrotic syndrome (albuminuria: immune complex glomerulonephritis 342 +/- 58, control 76 +/- 18 mg/24h; P < 0.001). The CEI by ramipril, dissolved in the drinking water, was given 28 weeks after induction of the disease and treatment was continued for 12 weeks. RESULTS: In these experiments ramipril significantly reduced albumin excretion (immune complex glomerulonephritis + CEI 109 +/- 16 mg/24h; P < 0.01) when compared with untreated nephritic rats. Ramipril, however, did not significantly change inulin clearances (immune complex glomerulonephritis 224 +/- 67, immune complex glomerulonephritis + CEI 278 +/- 48 microliters/min/100 g bw). Glomerular structural damage expressed as glomerular damage index was significantly greater in rats with immune complex glomerulonephritis when compared with controls (immune complex glomerulonephritis 0.91 +/- 0.13; control 0.60 +/- 0.08; P < 0.05), but was uneffected by the treatment with the CEI (immune complex) glomerulonephritis + CEI 1.02 +/- 0.26; control + CEI 0.63 +/- 0.11). CONCLUSIONS: These data demonstrate that ramipril reduced albuminuria in a model of immune complex glomerulonephritis; however, it failed to alter GFR and glomerular damage index. The study suggests that ramipril ameliorates proteinuria independently of obvious glomerular histological changes. The reduction of proteinuria is, however, associated with a significant decrease in filtration fraction and therefore is at least partially haemodynamically mediated.
Albuminuria↗
[ANCA-associated forms of vasculitis].
Among the various types of primary systemic vasculitides, which were recently newly classified (Chapel Hill Classification, 1994), in two forms of small vessel vasculitis, i.e. in Wegener's granulomatosis and in microscopic polyangiitis, the diagnostic utility of anti-neutrophil cytoplasmic antibodies (ANCA) is now well established. In most cases of Wegener's granulomatosis and microscopic polyangiitis the target antigens of these autoantibodies are proteinase 3 (c-ANCA) or myeloperoxidase (p-ANCA), respectively. Both of these autoantibodies are probably not only diagnostic tools but also contribute to the pathogenic mechanisms causing the vascular damage. In Wegener's granulomatosis and in microscopic polyangiitis the upper and lower respiratory tract and the kidneys are preferentially affected. The lesions of Wegener's granulomatosis show an extremely wide morphologic spectrum. In the oropharynx, nasal sinuses, trachea, and large bronchi, they appear for the most part as ulcerations in which a granulomatous response may or may not be evident. Thus in the absence of granulomas, especially in small biopsy material, the diagnosis of Wegener's granulomatosis should by no means be excluded. In the kidneys a focal and segmental necrotizing glomerulonephritis, often associated with crescent formation, is the typical lesion in Wegener's granulomatosis and in microscopic polyangiitis, as well. Histologically, this glomerulonephritis does not differ from the forms also seen in Schoenlein-Henoch disease, in Goodpasture's syndrome and in some cases of systemic lupus erythematosus, but in Wegener's granulomatosis and in microscopic polyangiitis immune glomerular deposits are uncommon. In fact, by analysis of our biopsy material, these "pauci immune" type of necrotizing glomerulonephritis account for nearly 70%. In the past, Wegener's granulomatosis was usually fatal within 5 months of diagnosis. After introduction of the combined therapy with steroids and cyclophosphamide the prognosis improved considerably. Nevertheless, a further improvement is necessary. This could be reached, without any doubt, by an earlier detection of the disease.
Anti-Glomerular Basement Membrane Disease↗
Intramural hemorrhage of the thoracic aorta. Diagnostic and therapeutic implications.
BACKGROUND: Intramural hemorrhage (IMH) was recently identified at necropsy and anecdotally in vivo as a unique aortic syndrome (without entry and with no flap-like intraluminal component, such as overt aortic dissection). However, little is known about diagnosis, prognosis, and outcome of IMH. METHODS AND RESULTS: Between 1983 and 1993, 360 patients from two medical centers with clinical indications of aortic dissection were prospectively evaluated; they presented to the emergency department a median of 3.5 hours after onset of back or chest pain or other suggestive symptoms. Among 195 patients with aortic syndromes, 25 patients (12.8%) were diagnosed to have IMH of the thoracic aorta with no evidence of a primary intimal tear, flap, or overt dissection by multiple noninvasive imaging modalities, including magnetic resonance imaging (n = 12), contrast-enhanced computed tomography (n = 14), and transesophageal echocardiography (n = 3) in random order. There were 16 men and 9 women with a median age of 56 +/- 13 years (range, 15 to 80 years). Arterial hypertension was present in the majority (84%), and Marfan's syndrome was present in 3 patients (12%). IMH was diagnosed within 4 days of hospital admission (median, 2.5 hours). IMH involved the ascending aorta (type A) in 12 cases (48%), the aortic arch in 2 (8%), and the descending aorta (type B) in 11 cases (44%); imaging results were validated by crossmatching with intraoperative, pathomorphological, and/or angiographic findings. IMH was 8.5 +/- 5 cm in length and 2.0 +/- 1.2 cm in aortic wall thickness. Aortic regurgitation and pericardial and mediastinal effusion were present in 5 of 12 patients (42%) with type A IMH and 2 of 11 patients (18%) with type B IMH. IMH progression to overt dissection, rupture, and/or acute tamponade occurred in 8 of 25 patients (32%) within 24 to 72 hours, indicating the need for urgent intervention. The 30-day mortality rate of IMH afflicting the ascending aorta was 80% (4 of 5 cases) with medical treatment (sedation and blood pressure control) versus no mortality in 7 cases with early surgical repair (P < .01); after 1 year, 71.4% of surgically treated patients were alive versus 20% in the medical group (P < .05). IMH of the aortic arch resulted in an early mortality of 50% (1 of 2 patients) with medical treatment. In IMH confined to the descending thoracic aorta, survival with medical treatment was not different from surgical therapy; there was 1 early death among 6 patients with medical therapy and none out of 5 patients with surgery (P = NS). At 1-year follow-up, medical and surgical therapy groups had survival rates of 80% and 83%, respectively (P = NS). CONCLUSIONS: IMH is associated with a clinical profile and prognosis similar to classic dissection and may be considered an ominous precursor of overt aortic dissection. Tomographic noninvasive imaging ensures rapid, nontraumatic diagnosis of IMH. The outcome of IMH of the ascending aorta appears favorable only with immediate surgical repair.
Adolescent↗
[Type I cryoglobulinemia].
HISTORY AND CLINICAL FINDINGS: For 2 years a 52-year-old man had repeated bouts of purpura, arthralgia and fever. He was known to have abnormal monoclonal gammaglobulins, type IgG-lambda and vasculitis when he had another bout with acute renal failure and necrotizing ulcers in the legs. TESTS: Several laboratory tests were abnormal: erythrocyte sedimentation rate (122 mm), haemoglobin level (9.1 g/dl), white cell count (32,000/microliters), platelet count (562,000/microliters), creatinine level (4.1 mg/dl) and liver enzyme activities. He also had proteinuria (4.5 g daily) and nephritic urinary sediments. The immunoglobulin was subtype IgG3, and a cryoglobulinaemia was also present. Total complement level (CH 50) was not measurable. Bone marrow aspirate revealed plasmocytoma infiltration, and renal biopsy demonstrated necrotizing arteritis, as well as granular subendothelial deposits of IgG and complement. TREATMENT AND COURSE: After three plasma separations and initiation of the first treatment cycle with a four-day infusion of vincristine, doxorubicin and dexamethasone the creatinine concentration fell to within the normal range and the necroses healed slowly. No cryoglobulin activity has been demonstrable over the past 24 months.
Acute Kidney Injury↗
Colchicine for secondary nephropathic amyloidosis in cystic fibrosis.
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Adult↗
Antineutrophil cytoplasmic autoantibodies, autoantigens, and systemic vasculitis.
Antineutrophil cytoplasmic antibodies (ANCA) encompass a heterogeneous group of autoantibodies targeting antigens in neutrophils (PMN), monocytes, and endothelial cells. ANCA are routinely detected by the indirect immunofluorescence technique (IFT) and at least three different patterns of fluorescence can be distinguished which have been assigned the acronyms cANCA, pANCA and aANCA. cANCA is mostly induced by proteinase 3 (PR3) antibodies (PR3-ANCA), and pANCA by myeloperoxidase (MPO) antibodies (MPO-ANCA), while aANCA has unidentified subspecificity. Over the past decade, ANCA have been the subject of extensive investigation. They have proved to be of significant value both as diagnostic tools and for follow-up in several forms of systemic vasculitis (e.g. Wegener's granulomatosis, WG; microscopic polyarteritis, MPA; Churg-Strauss syndrome, CSS) which are now termed 'ANCA-associated vasculitides'. Furthermore, it is suspected that the presence of ANCA is an important factor in the pathogenesis of these disease groups. Data regarding the detection of ANCA and their diagnostic value and role in the pathogenesis of vasculitic disorders will be discussed in this review. Growing evidence points to a pathophysiological and diagnostic relevance of the distribution of the ANCA target antigens PR3 and MPO (presence in the circulation, on cell membranes, and in tissue extracellularly). An autoimmune process has been implicated in the pathogenesis of ANCA-associated vasculitis, but it is uncertain which mechanism underlies the induction of the ANCA-related immunoresponse. In this paper mechanisms such as antigenic cross-reactivity between human PMN proteins and extrinsic antigens by molecular mimicry, idiotypic immunoglobulin regulation, and T-cell reactivity to PR3 and MPO will be discussed.
Antibodies↗
ANG II is a mitogen for a murine cell line isolated from medullary thick ascending limb of Henle's loop.
A murine SV40-transformed renal epithelial cell line derived from medullary thick ascending limb of Henle's loop (MTAL) was established and characterized by morphology, antigen expression, and biochemical criteria. These MTAL cells express a single class of high-affinity receptors for angiotensin II (ANG II) and transcripts for the AT1 subtype of ANG II receptors. ANG II, in a dose-dependent manner, induced proliferation of MTAL cells. This observation is in striking contrast to syngeneic proximal tubular cells in which it was previously shown that the peptide induced cellular hypertrophy and slightly inhibited proliferation [G. Wolf and E. G. Neilson. Am. J. Physiol. 259 (Renal Fluid Electrolyte Physiol. 28: F768-F777, 1990]. The AT1-receptor antagonist losartan (10(-6) M), but not an AT2-receptor antagonist, blocked the mitogenic effects of ANG II in MTAL cells. Coincubation of quiescent MTAL cells with ANG II and 5% fetal calf serum further increased proliferation compared with cells grown only in serum. In contrast to proximal tubular cells, ANG II failed to induce transforming growth factor-beta 1 mRNA and protein synthesis in MTAL cells. Our data collectively suggest that ANG II is a mitogen for MTAL cells in vitro. Therefore, epithelial cells derived from different parts of the nephron, even when transformed with SV40 virus and while under cell culture conditions, exhibit a distinct pattern of growth behavior after stimulation with ANG II.
Angiotensin II↗
[Lupus nephritis].
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Antibodies, Antinuclear↗