Specificity and affinity of monoclonal antibodies against carcinoembryonic antigen.

The binding specificities of 52 well-characterized monoclonal antibodies (Mabs) against carcinoembryonic antigen (CEA) from 12 different research groups were studied by immunohistochemistry and immuno flow cytometry. In addition, the binding constant for the interaction between Mab and CEA was determined by a solution-phase assay. Cryostat sections of colon carcinoma and normal colon, stomach, liver, pancreas, and spleen were studied by immunohistochemistry. Peripheral blood granulocytes, monocytes, and lymphocytes were assayed by immuno flow cytometry. The Mabs used here have previously been classified into five essentially nonoverlapping epitope groups (GOLD 1-5) (Cancer Res., 49: 4852-4858, 1989). Most Mabs cross-reacted with different normal tissues, ranging from highly cross-reactive Mabs (positive reaction with 8 of 9 discriminating tissues) to relatively specific Mabs (positive reaction with 1 of 9 discriminating tissues). Five Mabs (10%) were specific, reacting only with colon carcinoma, normal colon mucosa, and normal gastric foveola. There was a correlation between epitope group and binding specificity. Mabs with a high degree of CEA specificity almost exclusively belonged to epitope groups 1, 2, and 3, while highly cross-reactive Mabs belonged to epitope groups 4 and 5. There was no correlation between antibody specificity and affinity for CEA. Specific Mabs with high as well as low affinity were found.

A small interventional device to occlude persistently patent ductus arteriosus in neonates: evaluation in piglets.

OBJECTIVES: We attempted to evaluate the efficacy and tissue reaction of a new miniature interventional ductal occlusion device in neonatal pigs. BACKGROUND: A variety of devices are used to close persistent ductus arteriosus (PDA) by interventional measures. Because of the size of these devices, they have not been applied to term or preterm neonates. Newborn piglets are comparable in size and fragility to human term and preterm neonates. METHODS: Memory-shaped double-cone stainless steel coils were mounted on a titanium-nickel core wire. A snap-in mechanism attaches the coil to the delivery wire, allowing intravascular coil retrieval and repositioning. The system was placed through a 3F Teflon catheter. Two piglet models of PDA were used: 1) ductal patency maintained by stents (n = 6), and 2) ductal patency produced by angioplasty (n = 7) to avoid stent-coil interaction. RESULTS: Placement of the coils within the PDA was possible in all piglets. Before final detachment, the coils were retrieved or repositioned, or both, up to eight times. In all but two piglets the ductus was closed within 1 h of the procedure. The coils were never dislocated and caused no infections or relevant aortic and pulmonary artery obstruction (95% confidence interval for missing complications [0 of 13] extends to 23%). Histologic and electron microscopic studies revealed endothelial coverage of the implants and histiocytic reaction but no local or systemic inflammation or erosion of the implant. CONCLUSIONS: The device was effective in experimental models of PDA. The information obtained warrants initial trials of the device in neonates.

Double-helix coil for occlusion of large patent ductus arteriosus: evaluation in a chronic lamb model.

OBJECTIVES: We sought to evaluate the efficacy and tissue reaction of a new miniature interventional device for occlusion of large patent ductus arteriosus (PDA) in a neonatal lamb model. BACKGROUND: A variety of devices are used to close PDAs by interventional measures. Spring coils found to have a high cumulative occlusion rate have thus far been limited to smaller PDAs because of the physical limitation of grip forces. METHODS: Memory-shaped double-cone stainless steel coils with enhanced stiffness of the outer rings by a double-helix configuration were mounted on a titanium/nickel core wire. A snap-in mechanism attaches the coil to the delivery wire, allowing intravascular coil retrieval and repositioning. The system was placed through a 4F or 5F Teflon catheter. A chronic lamb model (n = 8) of PDA (>5 mm) was used in which ductus patency was secured by a protocol of repetitive angioplasty procedures. The animals were killed after 1 to 181 days, and the ductal region was examined by inspection as well as by light and electron microscopy. RESULTS: Placement of the coils within the PDA was possible in all lambs. Before final detachment, the coils were retrieved or repositioned, or both, up to 12 times. In all but one animal the ductus was closed within 6 days after the procedure. The coils caused no infections or aortic and pulmonary artery obstruction. Histologic and electron microscopic studies revealed endothelial coverage of the implants but no foreign body reaction or local or systemic inflammation or erosion of the implant. CONCLUSIONS: The device effectively closed large PDAs in our model and may overcome the previous limitations of coils. Clinical trials are indicated.

Pressure oscillation regulates human mesangial cell growth and collagen synthesis.

Experimental renal disease models establish glomerular hypertension as a crucial determinant in glomerulosclerosis progression and demonstrate that glomerular capillary pressure reduction delays sclerosis development. An oscillating pressure (OP) chamber was constructed as an in vitro model to study human mesangial cells. Cell cultures were grown under atmospheric pressure (AP) and a controlled OP corresponding to intraglomerular capillary pressure. We show that OP significantly decreases mesangial cell proliferation within 24 hours and attenuates DNA synthesis throughout a 7-day period. To explore the effects of OP on cell metabolism, cell-associated and medium-secreted extracellular (CA and EC, respectively) collagen synthesis were measured by [3H]proline incorporation. In subconfluent cultures, total CA and EC collagen synthesis was unaffected by OP, while in confluent cultures total EC collagen [3H]proline incorporation was increased. To determine whether OP influenced mesangial cell growth induction, the effects of increasing glucose in the cell culture media were investigated. Our data show that the high glucose growth stimulatory effect on cell number and DNA synthesis was suppressed by OP. Under high glucose conditions, total CA collagen synthesis was increased in confluent cultures, whereas the EC collagen fraction remained unchanged. In these cultures, OP caused an additional increase in CA collagen synthesis. This study shows that mesangial cell growth and collagen synthesis are influenced by hyperbaric OP, supporting the hypothesis that glomerular capillary pressure plays a role in progressive glomerulosclerosis development.

Platelets and endothelial cells act in concert to delay thrombolysis--evidence from an in vitro model of the human occlusive thrombus.

The molecular and cellular mechanisms that over a period of hours render a human thrombus progressively resistant to fibrinolysis have been probed with a novel in vitro model. The kinetics of clot formation and fibrinolysis were monitored by laser light scattering with platelet-rich model thrombi contained in cylindrical flow chambers. In selected experiments, human umbilical vein endothelial cells were also cultured to confluence on the inner walls of these "glass blood vessels". Following an "aging" period (0.5, 2 or 4 h), each thrombus was gently perfused with a bolus of plasminogen/recombinant tissue plasminogen activator to induce fibrinolysis. Platelets delayed lysis of 2 h-aged thrombi by approximately 70% and (non-stimulated) endothelial cells by approximately 30%, compared to cell-free control clots. However, even greater lytic delays (approximately 260%) resulted when both vascular cells were present in the same 2 h-aged thrombus. In contrast, rapid lysis was consistently achieved with R298E,R299E t-PA, a genetically engineered plasminogen activator that is insensitive to inhibition by plasminogen activator inhibitor type 1. These observations suggest platelets and endothelial cells act in concert to enrich the fibrin scaffold of an aging human thrombus in plasminogen activator inhibitor. We propose that the presence of both platelets and endothelial cells may contribute to progressive thrombolytic resistance.

Modulation of pro- and antifibrinolytic properties of human peritoneal mesothelial cells by transforming growth factor beta1 (TGF-beta1), tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta).

A decreased fibrinolytic activity of serosal surfaces appears to be a major factor in the development of peritoneal fibrous adhesions. Serosal fibrinolysis is regulated by mesothelial release of tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor types 1 and 2 (PAI-1 and PAI-2). We investigated the influence of tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta1) and interleukin 1beta (IL-1beta) on pro- and antifibrinolytic properties of mesothelial cells (HOMC) using a cell/fibrin clot assay. TGF-beta1, TNF-alpha and IL-1beta induced a dose dependent 2.9, 2.3 and 1.9-fold increase of PAI-1 antigen, respectively, whereas t-PA concentrations decreased to one third of the control values. This modified PAI-1/t-PA secretion pattern leads to a significant delay of fibrinolysis. Analysis of m-RNA levels revealed increased PAI-1 m-RNA concentrations after 12 h and decreased m-RNA concentrations for t-PA after 6 h. Serosal hypofibrinolysis during peritonitis may be explained at least in part by cytokine effects which thus may favor adhesion formation.

Benign metastasizing leiomyoma: a cytogenetically balanced but clonal disease.

Benign metastasizing leiomyoma (BML) is a rare condition, characterized by the occurrence of multiple smooth-muscle nodules, most often located in the lung after previous hysterectomy because of histologically benign appearing leiomyoma. Although the condition resembles a metastatic process, case studies provided evidence that it may be the result of an intravenous leiomyomatosis or an independent and multifocal smooth-muscle proliferation. Comparative genomic hybridization and X-chromosome inactivation analysis were used in a case of BML to determine whether pulmonary and uterine tumors are related one to another. A balanced karyotype, previously reported in leiomyomas and an identical X-chromosome inactivation pattern found in all tumorlets, is most consistent with a monoclonal origin of both uterine and pulmonary tumors and the interpretation that pulmonary lesions are metastatic.

Trisomy 8 as sole karyotypic aberration in an ovarian metastasizing Sertoli-Leydig cell tumor.

Sertoli-Leydig cell tumors (SLCTs) represent a rare group of sex-cord stromal tumors of the ovary of unknown pathogenesis. We report a SLCT of intermediate differentiation with peritoneal recurrence and lymph node metastasis 12 months after removal, including cytogenetic analysis by comparative genomic hybridization and fluorescence in situ hybridization, which showed trisomy 8 as sole unbalanced karyotypic aberration. Our results provide evidence that a simple numeric chromosomal abnormality in SLCT may be associated with a malignant phenotype and suggest that the molecular pathogenesis of SLCT may be different from ovarian granulosa-stromal cell tumors.

Enhanced occlusion of vessels combining retrievable, detachable coils as differential electrodes with percutaneous, intravascular radiofrequency electrocoagulation. An experimental study.

RATIONALE AND OBJECTIVES: The authors evaluate the feasibility to accelerate occlusion of high-velocity flow vessels by a combination of transcutaneous coil placement and application of radiofrequency current. METHODS: Piglets (n = 8) were anesthetized and acutely instrumented via cutdowns in both carotid and one brachial arteries. Two identical cylindrically shaped coils (length, 3 mm; outer diameter, 2.4 mm; inner diameter, 1.4 mm) were mounted on titanium-nickel core wire and placed via 3-French Nylon catheters in both iliac arteries. The coils were kept connected to the delivery wire, which is isolated from the surrounding tissue by the catheter. The first-placed system served as control, the contralateral coil was connected to a radiofrequency generator closing electrical circuit via an external indifferent electrode. Angiograms via the brachial artery demonstrated the adequate placement of the coils and the status of the iliac arteries without and with current application. In 6 of the 8 cases, 25 watts of radiofrequency current were applied repeatedly over 10 seconds to the coil on one side at 4-minute intervals until occlusion was demonstrated. In 2 of 8 cases. 25 watts were applied continuously over 30 seconds. The coils were detached from the wire the catheters removed. Additional angiograms were performed after 5, 15, 45, and 60 minutes to show the patency of the control setting. RESULTS: Complete occlusion was achieved in all cases after a maximum of three consecutive applications of current for 10 seconds. The control remained patent for a minimum of 45 minutes. On gross and histologic examination the arteries on both sides remained intact. Disruption and charring occurred only after continuous application of current over 30 seconds. CONCLUSIONS: It is feasible to use detachable coils in conjunction with high-frequency electrocoagulation to promote coil fixation and accelerate occlusion of vessels with high blood flow.

Interventional atrioseptostomy by application of monopolar high-frequency alternating current. In vitro evaluation of a new device.

RATIONALE AND OBJECTIVES: The authors evaluate the use of a new device for interventional creation of atrial septal defects (ASD) working with high-frequency alternating current in an in vitro study with porcine atria. METHODS: The device consists of a symmetrical cage of six superelastic monofile wires, including a microthermistor that is placed via a catheter into a punctured hole in the porcine foramen ovale. The device is used as a differential electrode for monopolar, temperature-controlled application of high-frequency alternating current for thermal modelling of ASD. RESULTS: Application of current for 60 seconds caused temperature-dependent, sized ASDs. CONCLUSION: In vivo animal studies to evaluate possible side effects and long term patency of the ASDs are justified and warranted.

Retrievable patent ductus arteriosus plug for interventional, transvenous occlusion of the patent ductus arteriosus. Evaluation in lambs and preliminary clinical results.

RATIONALE AND OBJECTIVES: The clinically most widely used devices (Porstmann-plug, Rashkind-umbrella, Botallooccluder) have inherent specific limitations (eg, transarterial approach, residual shunts, limited retrieval). The authors assess practicability, efficacy, and tissue reaction of the new retrievable transvenous plug device for the occlusion of the persistent patent ductus arteriosus (PDA). METHODS: A foam plug (polyvinyl alcohol) is mounted on a titanium core pin where, at both ends, small legs (titanium nickel alloy) with titanium heads are anchored, to ensure safe fixation in the ductus. The device is introduced transvenously through a long sheath (Mullins sheath) and held by a modified biopsy forceps allowing complete retrieval until final release. A common lamb model of large PDAs (n = 11) was used to test for practicability and the histomorphologic outcome. Clinical results were obtained from a consecutive series of 16 patients (aged 13 to 71 years). RESULTS: In all lambs, placement of the plug within the PDA was possible. Histopathology (follow-up 10 to 215 days; mean 112 days) revealed an adequate ingrowing of the device and no pathologic foreign body reaction. The diameter of the human PDAs ranged from 3 to 7 mm (mean 5 mm). The size of the sheath used for introducing the plug (diameter 8 to 16 mm) ranged from 8 to 16 French. Fourteen of 16 PDAs were closed immediately after or on day 1 after implantation, 1 was closed after the 12-month follow-up, and 1 needed an additional plug after 30 months for definitive closure. CONCLUSIONS: The device demonstrated practicability and biocompatibility in our experimental lamb model and effectively closed the PDA in a consecutive series of 16 patients. A greater number of patients and a longer follow-up period are necessary for the definitive clinical assessment of the new device.

Simultaneous appearance of an adenomyoma and pancreatic heterotopia of the stomach.

Adenomyomas of the stomach are rare tumours characterised by duct/gland-like structures embedded within a smooth muscle stroma. Although the histogenesis of adenomyomas remains unclear, the histological appearance has justified the assumption that these are abortive forms of pancreatic heterotopia. We report an unusual case with simultaneous and independent appearance of both adenomyoma and pancreatic heterotopia of the stomach including immunohistochemical characterisation, supporting the concept of a common histiogenetic origin of both lesions.

Pathomorphological aspects of heparin-induced thrombocytopenia II (HIT-II syndrome).

The therapeutic use of heparin results in thrombocytopenia in 5-30% of patients. In 0.1-1% of patients treated with heparin, the platelet count decreases to between 100 x 10(9)/l and 50 x 10(9)/l and leads to severe synchronous central arterial and venous thrombosis with a mortality of 18-36%. This is known as "white-clot syndrome" or heparin-induced thrombocytopenia II (HIT-II syndrome). Whilst the clinical aspects and the central type of thrombosis in HIT-II syndrome are well documented, the histomorphology and differential diagnosis of thrombosis are not. We report three cases of HIT-II syndrome with thrombosis of the central arteries and veins. The HIT-II thrombi could be differentiated from thrombi of other origins, particularly from mural thrombi. Heparin-induced thrombi were seen on microscopical examination to be like onion skin in structure, and immunohistochemistry showed that they had a markedly reduced content of fibrin and clearly enhanced amounts of IgG and IgM. The layered structure thus implied appositional growth. The thrombi in HIT-II syndrome do not seem to be induced by activation of the coagulation cascade, but by platelet aggregation mediated by anti-platelet antibodies.

A large keratan sulfate proteoglycan present in human cervical mucous appears to be involved in the reorganization of the cervical extracellular matrix at term.

OBJECTIVE: To elucidate the function of keratan sulfate proteoglycan (KS-PG) in the human uterine cervix, we analyzed its distribution with respect to physiologic conditions. METHODS: Immunohistochemistry was used to localize KS bearing proteoglycans (mAb 5D4) and decorin (mAb 6B6) in the lower uterine segment. Proteins present in cervical mucous were labeled with biotin, glycosaminoglycan chains were digested enzymatically, and the samples were analyzed by Western blot. RESULTS: Decorin was detected throughout the extracellular matrix, in tissues from menstruating nonpregnant women, in early pregnancy, from women who had cesarean at term, at postpartum hysterectomy, and from postmenopausal women. In menstruating nonpregnant women, in early pregnancy (first trimester), and in postmenopausal women, KS-PG was detectable only in epithelial, mucous-producing cells. Interestingly, in samples obtained either at the time of cesarean at term (lower uterine segment) or after postpartal hysterectomy, KS-PG was detectable throughout the extracellular matrix, indicating that the expression of KS-PG is associated with reorganization of the tissue. Biochemical analysis of the KS present in mucous revealed a core protein in the range of 220 kDa, suggesting an identity with the large KS-PG described previously. CONCLUSION: At parturition, a large KS-PG, which is virtually exclusively present in the cervical mucous of either early or nonpregnant women, was detected in the extracellular matrix. This finding indicates that cervical ripening is accompanied not only by quantitative but also by qualitative changes in the composition of the extracellular matrix.

Expression of glucose transporter 1 (Glut-1) in cell lines and clinical specimens from human prostate adenocarcinoma.

BACKGROUND: Increased uptake and metabolism of glucose is a characteristic of malignant transformation. Overexpression of glucose transporters, especially Glut-1, is a common event in human malignancies. To date, little is known about the role of Glut-1 in human prostate cancer (PC). The aim of this study was to investigate the expression of Glut-1 both in PC cell lines and clinical specimens of primary PC. MATERIALS AND METHODS: The PC cell lines DU145, PC3 and LNCaP were assessed for Glut-1 mRNA expression by Northern blot analysis. In a total of 45 primary PC specimens, radioactive (35S) in situ hybridizations (RISH) for Glut-1 mRNA expression were performed on frozen sections. Quantification of Glut-1 expression was obtained by use of an image analysis system. RESULTS: Glut-1 expression was detected in all 3 cell lines. Expression in the more poorly-differentiated cell lines DU145 and PC3 was even higher than in the hormone-responsive LNCaP cell line. In situ hybridizations in primary PC revealed Glut-1 expression just above the detection limit in well-differentiated tumors. Significantly increased Glut-1 expression was detected in moderately- to poorly-differentiated PC. CONCLUSION: Glut-1 is expressed in PC cell lines and primary PC. The level of expression increases with advancing grade of malignancy. These findings support a role for Glut-1 in PC proliferation.

Simultaneous immunohistochemical and biochemical hormone receptor assessment in breast cancer provides complementary prognostic information.

The prognostic value of the biochemical and the immunohistochemical assessment of estrogen- and progesterone receptor (ER, PR) status was tested in 111 breast cancer patients, mostly focusing on whether the results reveal complementary prognostic information. The biochemical receptor analysis was performed on snap-frozen tumor tissue using a standard protocol (ER-DCC, PR-DCC). The immunohistochemical staining was done on 4 microns thick paraffin sections and was evaluated semiquantitatively (ER-IHC, PR-IHC) and immunohistometrically by means of image analysis (ERMEAN, PRMEAN). 74% of the ER-DCC and 50% of the PR-DCC assays were interpreted as positive. The positivity rates of the immunohistochemical reactions ranged between 78% and 81% for ER and between 66% and 82% for PR, depending on the interpretation mode. The concordance rate for the DCC method was 68%, and ranged between 77% and 85% for the immunohistochemical results on paraffin sections. ER-DCC and PR-DCC showed a better survival for receptor-positive patients; however, this tendency was only statistically significant for the PR-DCC (p = 0.0294). Patients with immunohistochemically determined ER- or PR-positivity revealed a significantly better survival than receptor-negative patients, the effect being stronger for the progesterone receptor (ER: p = 0.0253, PR: p = 0.0005). Combining the different methods and receptors in a multivariate analysis, we observed that a) ER and PR reveal complementary prognostic information to each other after immunohistochemical determination (p < or = 0.0018) and that, b) complementary prognostic information was also obtainable by comparing the biochemical and the immunohistochemical PR-analysis (p < or = 0.0084); slightly more significant results were obtained for ERMEAN and PRMEAN compared to ER-IHC and PR-IHC. Considering the lymph node status and a combined receptor analysis (PR-DCC, ERMEAN, PRMEAN) as the two strongest prognosticators in multivariate Cox models, the combined receptor analysis was able to discover for each of the three groups of NO- and N1-patients different survival probabilities (p < 0.0001). In conclusion, the ER-DCC appears to be dispensable in all patients. In lymph node-negative patients, the PR-DCC has no outstanding merit, indicating that the neccessity of this method is also controversial. In priamry tumors of lymph node-positive patients, however, all three remaining types of receptor analysis should be evaluated for their therapeutic implications.

Infectious agents in coronary lesions obtained by endatherectomy: pattern of distribution, coinfection, and clinical findings.

BACKGROUND: Cytomegalovirus (CMV), Chlamydia pneumoniae (C. pneumoniae), and Helicobacter pylori (H. pylori) have been implicated in atherosclerosis and restenosis after angioplasty. The patterns of distribution within coronary lesions and possible coinfections of these pathogens in the coronary vasculature had not previously been evaluated. DESIGN: A prospective, observational clinical study. METHODS: Large coronary specimens (9-105 mm long) were obtained by endatherectomy of 53 patients undergoing aortocoronary bypass surgery. Samples were taken from two different sites of every lesion, resulting in a total of 106 probes. Presence of each pathogen was determined by polymerase chain reaction, subsequent hybridization, and DNA sequencing. RESULTS: Cytomegalovirus and C. pneumoniae were detected in 30 and 32% of the samples, respectively; H. pylori was not detectable. The pathogens were not homogeneously distributed. A concurrent infection with both pathogens was observed in five of 106 (5%) lesions and five of 53 (9%) patients. Restenotic lesions were more often found in specimens in which cytomegalovirus was detected (five of 16 versus two of 37). Patients with C. pneumoniae-positive coronary lesions more commonly presented with unstable angina. CONCLUSIONS: Inhomogeneous infections with cytomegalovirus and C. pneumoniae of coronary atherosclerotic lesions are found to be prevalent when serial analysis is performed. Concurrent infection with both pathogens occurs coincidentally; however, possible clinical implications of this new observation and the pathogenic impact on atherosclerosis need further investigation.

Further evidence that acanthosis nigricans maligna is linked to enhanced secretion by the tumour of transforming growth factor alpha.

The pathogenesis of cutaneous paraneoplastic syndromes is still under discussion. Since many of these syndromes, including acanthosis nigricans, are proliferative skin disorders it is believed that products secreted by the tumour stimulate the keratinocytes to proliferate. Growth factors like transforming growth factor alpha (TGF-alpha) are known to be highly mitogenic for keratinocytes in vitro. Here we report on a patient with a poorly differentiated gastric cancer and a full clinical picture of acanthosis nigricans characterized by diffuse hyperkeratosis and multiple papillomatous lesions of the skin with involvement of the conjunctivae. In Southern blot analysis of the tumour tissue from this patient amplification of the epidermal growth factor (EGF) receptor, the common ligand for TGF-alpha and EGF, was shown. Immunohistochemically, prominent staining was found throughout the tumour using anti-TGF-alpha antibodies. In a series of 25 investigated gastric tumour biopsies, four tumours showed amplification of the EGF receptor and one additional biopsy was positive for TGF-alpha. Since there is no other report describing the link between TGF-alpha and acanthosis nigricans, except that of Ellis et al. 1987, we present a new case suggesting a possible link between growth factors and acanthosis nigricans maligna.

Coronary vasculopathy in polycythemia vera.

Thrombosis is a common complication in polycythemia often causing death. In coronary artery occlusion, thrombosis due to hyperviscosity and thrombocytosis is mostly discussed as the origin of the infarction. We discuss the case of a 30-year-old male patient, with polycythemia, who died of myocardial infarction. On autopsy the vessels showed neither ateriosclerotic changes nor thrombotic occlusions. Instead, a marked intima proliferation was found leading to multiple occlusions whereas media and adventitia were unchanged. This pattern of a coronary vasculopathy has not been described before, and can be interpreted as an alternative mechanism for vascular occlusion in polycythemia. Similar histopathological changes have already been found in skin lesions in erythromelalgia, a common symptom in polycythemia.

Remission of IgA nephropathy following treatment of cytomegalovirus infection with ganciclovir.

Following the detection of cytomegalovirus antigen in mesangial cells of some patients with IgA nephropathy, an important role of human cytomegalovirus in the pathogenesis of IgA nephropathy has been discussed. We studied a case of IgA nephropathy with rapid deterioration of renal function associated with cytomegalovirus infection. Following an infection of the upper respiratory tract, a 57-year-old woman developed with hematuria and acute renal failure. The histological diagnosis of IgA nephropathy was established and renal function transiently improved during immunosuppressive therapy. However, the ensuing clinical course was complicated by severe bleeding from intestinal ulcera, thrombocytopenia, pneumonia and relapse of renal failure. The histological investigation of colonic mucosa showed characteristic "owl's eye" cells leading to the diagnosis of cytomegalovirus disease as the cause of intestinal bleeding. Immunosuppression was stopped and treatment with ganciclovir started. Pneumonia as well as intestinal bleeding disappeared and, of particular note, renal function improved considerably. Following discontinuation of antiviral therapy CMV-disease reoccurred and renal function deteriorated again. The patient was restarted on ganciclovir therapy and, again, serum creatinine fell quickly. This impressive and reproducible clinical improvement of renal insufficiency under antiviral therapy with ganciclovir provides some evidence for an important role of cytomegalovirus in the pathogenesis of this case of IgA nephropathy.