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Biomedical subjects

H Geiger

Publications and source records attributed to H Geiger.

At least 19 recordsLinked to original sources
PubMed2000

Induction of RANTES, HLA-DR, and intercellular adhesion molecule-1 on highly purified distal tubular cells from human kidney.

BACKGROUND: Expression of proinflammatory molecules by tubular epithelial cells plays an important role in renal allograft rejection and inflammatory kidney diseases. Different studies from patients with acute rejection point to the involvement of distal tubular segments. At present no in vitro system for the human distal tubule is established. METHODS: Human distal tubular cells were isolated immunomagnetically. Cultured cells were stimulated with cytokines (interferon-gamma, tumor necrosis factor-alpha, interleukin-1beta, or a cytokine mix). Secretion of RANTES (regulated upon activation, normal T-cell expressed and secreted) was evaluated with an enzyme-linked immunoassay. Expression of HLA-DR and intercellular adhesion molecule (ICAM)-1 was assessed by flow cytometric analysis and immunofluorescence studies. RESULTS: Our data clearly indicate that distal tubular cells express RANTES, HLA-DR, and ICAM-1 in response to a mixture of specific cytokines. Dexamethasone inhibited the induced expression of RANTES and HLA-DR significantly, but not that of ICAM-1. CONCLUSIONS: We demonstrate an appropriate in vitro system for the human distal tubule. The present study proves the involvement of the distal tubular segment during inflammatory kidney diseases.

Cells, Cultured↗
PubMed2000

Renal involvement in HIV-infection. Results from the Frankfurt AIDS Cohort Study (FACS) and a review of the literature.

The current report describes the experience from the Frankfurt AIDS Cohort Study with patients suffering from renal failure. The clinical data of 4993 HIV-infected patients between 1983 and 1998 were analyzed retrospectively. Patients were seen at least twice a year and clinical features, routine laboratory results, including CD4+ cell counts, concomittant diseases, and antiretroviral therapy were documented by standardized methods. The incidence of renal failure during 4 observation periods with different antiretroviral treatment strategies are compared and data are discussed. Within the 16 years of observation 47 patients with impairement of their kidney function were identified. A trend to an increase of RF could be documented (chi superset2 -for trend p = 0.0246). The additional review intends to summarize the diverse reasons leading to renal dysfunction in HIV-infected individuals with special emphasis on glomerular disease and renal complications related to HIV therapy.

Adult↗
PubMed2000

Involvement of the platelet-derived growth factor receptor in angiotensin II-induced activation of extracellular regulated kinases 1 and 2 in human mesangial cells.

In mesangial cells angiotensin II (Ang II) has been shown to activate extracellular regulated kinases 1 and 2 (ERK1/2). Here, we studied the role of the epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor (PDGFR) in Ang II-induced ERK1/2 activation in human mesangial cells. Ang II induced activation of ERK1/2 via the AT(1) receptor, and this response was blocked by the PDGFR-selective tyrosine kinase inhibitor AG1295, but not by AG1478, an EGFR-selective tyrosine kinase inhibitor, indicating participation of the PDGFR, but not of the EGFR in Ang II-induced ERK1/2 activation. In agreement with this assumption, Ang II caused tyrosine phosphorylation of the PDGFR and the adapter protein Shc in an AG1295-sensitive fashion. In conclusion, our data show that Ang II-induced activation of mitogenic signalling cascade in human mesangial cells involves ligand-independent activation of the PDGFR, but not of the coexpressed EGFR.

Angiotensin II↗
PubMed2000

Effects of mycophenolic acid on human renal proximal and distal tubular cells in vitro.

BACKGROUND: Mycophenolic acid has been shown to be effective for the prevention and treatment of renal allograft rejection. Rejection episodes were found to be associated with an infiltration of lymphocytes and macrophages/monocytes into the diseased kidney. Expression of RANTES, HLA-DR and ICAM-1 may be important for the pathogenesis of this leukocyte infiltration. Therefore the aim of this study was to evaluate the effect of the antiproliferative and immunosuppressive agent mycophenolic acid (MPA) on cell growth and cytokine-induced expression of RANTES, HLA-DR and ICAM-1 of highly purified proximal (PTC) and distal tubular cells (DTC) from human kidney. METHODS: Human PTC and DTC were cultured in the presence of different concentrations of MPA (0.25-50 microM) or MPA plus guanosine (100 microM). Total cell number (DNA content) was determined after 4 days of cell culture by a non-radioactive fluorescence assay. Cells were stimulated by a combination of cytokines (IL1beta+gammaIFN+TNFalpha=cytomix) or cytomix plus MPA. Secretion of RANTES protein was evaluated with an enzyme-linked-immunosorbent assay. Cell surface expression of HLA-DR and ICAM-1 was assessed by flow cytometric analysis. RESULTS: MPA inhibited cell growth of PTC and DTC in a dose-dependent manner. This effect was totally abolished by the addition of guanosine. Cytokine-induced RANTES expression was synergistically increased in the presence of MPA, an effect that was partially prevented by the addition of guanosine. Cytokine stimulation resulted in de novo expression of HLA-DR and a marked increase of ICAM-1 expression, which was partially inhibited by dexamethasone. Addition of MPA did not influence this stimulated expression. CONCLUSIONS: We demonstrate that MPA has an effect on cell growth and chemokine release of tubular epithelial cells, and that these effects are dependent on the inhibition of cellular guanosine production. The clinical consequences of this possible pro-inflammatory effect of MPA on RANTES release may be abolished by a concomitant treatment with steroids.

Cell Division↗
PubMed2000

Management of renal complications in patients with advanced multiple myeloma.

Although the kidney is frequently involved in malignant monoclonal gammopathy, the clinical outcome of the patients varies considerably. We retrospectively assessed the clinical course in seventeen patients with acute and chronic renal failure suffering from multiple myeloma, and analyzed their case history focusing on the therapeutic management, the possible clinical improvement as well as the patients' outcome. Treatment included chemotherapy (n = 17), forced diuresis (n = 3), hemodialysis (n = 11, 7 chronic, 4 intermittent) and plasmapheresis (n = 3). Renal function improved in five patients, and was stabilized compensated in four. Seven patients developed end-stage renal disease, one refused further treatment and was lost for follow up. In addition to renal failure, the most frequent complications included local bone destruction (all), anemia (n = 12), low platelet count (n = 11), and bacterial infections (n = 9). One year survival rate after admission to the nephrology department was 76 percent. Chemotherapy in combination with renal replacement therapy may improve the clinical course even in MM patients with serum creatinine levels above 3.0 mg/dL or end-stage renal disease.

Adult↗
PubMed1999

An unusual case of Aspergillus endocarditis in a kidney transplant recipient.

The incidence of aspergillosis in kidney transplant recipients is low and most commonly occurs in the early posttransplantation period. We report an unusual case of a 52-year-old female patient with Aspergillus endocarditis as a late complication after kidney transplantation, presumably spread from a necrosis in the gut, associated with previous cytomegalovirus colitis. As complications, the patient experienced septic embolization into the coronary and pulmonary arteries, and an infarction of the right parietal cortex and insula. The patient died as a result of global heart failure after a 10-day course of antimycotic therapy with amphotericin B plus 5-flucytosine during surgical valve replacement.

Aspergillosis↗
PubMed1999

[Spontaneous remission of Goodpasture syndrome in a 21-year-old patient].

HISTORY AND CLINICAL FINDINGS: A 21-year-old man was admitted twice within half-a-year because of fatigue and increasing dyspnoea. Both times the chest x-ray showed extensive pulmonary infiltrates. Clinical remission occurred within a few days of starting antibiotic treatment. INVESTIGATIONS: During the second admission an increased titre for antibodies against glomerular basement membrane was discovered (2560 U/ml); renal functions were normal, but there was haematuria. Renal biopsy revealed linear deposits of IgG along the glomerular basement membrane. DIAGNOSIS, TREATMENT AND COURSE: The pattern of findings indicated Goodpasture's syndrome. Immunosuppressive treatment and plasma separation did not have to be performed because spontaneous remission occurred within a few days. CONCLUSION: This case demonstrates that spontaneous remission may occur in Goodpasture's syndrome.

Adult↗
PubMed1999

[An unusual cause of hepatorenal symptoms].

CASE REPORT: A 65-year-old patient with normal blood pressure had an exclusive elevation of the cholestasis enzymes (alkaline phosphatase 297 U/l, gamma-GT 315 U/l) and elevated bilirubin levels (1.4 mg/dl) since August 1994. A biopsy of the liver in March 1995 showed features of a "subacute viral hepatitis"; DD drug-induced or toxic lesions. Serological tests gave no support for an acute hepatitis. Intra- or extrahepatic cholestasis could not be proved neither by ultrasound nor by an endoscopic retrograde cholangiopancreatography. Since November 1995 serum creatinine increased up to 1.7 mg/dl (March 1995 1.1 mg/dl) and proteinuria (2.1 g/d) developed. Due to worsening of renal function (serum creatinine 2.8 mg/dl) and increasing proteinuria (3.5 g/d) without nephrotic syndrome, a kidney biopsy was performed. Histologically an amyloidosis (type A lambda) was proven, involving glomerula, kidney vessels and tubules. Further biopsies from the stomach and the duodenum showed profound infiltration of the mucosa and submucosa with amyloid. Therefore, staining of the liver biopsy of March 1995 with congo red proved the diagnosis of liver amyloidosis. By a punch biopsy of the iliac crest a low-grade non-Hodgkin's lymphoma could be identified as the cause for this generalized amyloidosis. DISCUSSION: In the present case, the reason for these unusual hepatorenal symptoms with unclear cholestasis over years as the first clinical symptom and a succeeding progressive renal insufficiency with proteinuria could be found by the use of kidney biopsy and extending the analysis of a liver sample taken by biopsy 1 year ago. Immunoglobulin light chains produced by a low-grade non-Hodgkin's lymphoma caused a generalized amyloidosis type A lambda. CONCLUSION: As a consequence, by an occurrence of unusual hepatorenal symptoms with cholestasis and progressive renal failure, amyloidosis should be considered as a pathogenetic factor.

Aged↗
PubMed1999

[Antiphospholipid antibody syndrome].

BACKGROUND: Antiphospholipid antibodies comprise a family of auto-antibodies mainly characterized by the presence of the lupus anticoagulant (LA) and anticardiolipin antibodies (ACA). CLINICAL APPEARANCE: The antiphospholipid antibody syndrome is defined by the appearance of frequent thromboses, repeated fetal losses and thrombocytopenia. Other clinical manifestations associated with APA include migraine, chorea, hemolytic anemia, heart valve disease, Budd-Chiari syndrome, perpetual pancreatitic episodes, intestinal infarctions, malignant hypertension, livedo reticularis, pre-eclampsia, fetal growth retardation or catastrophic antiphospholipid syndrome. LA and ACA occur in a variety of clinical conditions (secondary antiphospholipid antibody syndrome, SAPS), including other autoimmune disorders, infectious diseases, neoplastic disorders, in association with the use of certain drugs or in otherwise healthy individuals (primary antiphospholipid antibody syndrome, PAPS). TREATMENT: Patients with thrombosis associated with APA should receive long-term anticoagulation therapy, whereas treatment of asymptomatic patients seems to be not indicated, because only approximately 10% of patients with APA may develop thrombotic complications. In patients with PAPS there is no evidence that the prophylactic administration of immunosuppressive drugs will prevent thromboembolic events.

Antibodies, Antiphospholipid↗
PubMed1999

The flavonoids of Tanacetum parthenium and T. vulgare and their anti-inflammatory properties.

The lipophilic flavonoids in leaf and flower of Tanacetum parthenium and T. vulgaris have been compared. While those of T. parthenium are methyl ethers of the flavonols 6-hydroxykaempferol and quercetagetin, the surface flavonoids of T. vulgare are methyl ethers of the flavones scutellarein and 6-hydroxyluteolin. Apigenin and two flavone glucuronides are surprisingly present in glandular trichomes on the lower epidermis of the ray florets of T. parthenium. The opportunity has been taken to revise the structures of the four 6-hydroxyflavonol methyl ethers of T. parthenium based on NMR measurements. These are now shown to be uniformly 6- rather than 7-O-methylated. Tanetin, previously thought to be a new structure, is now formulated as the known 6-hydroxykaempferol 3,6,4'-trimethyl ether. The vacuolar flavonoids of both plants are dominated by the presence of apigenin and luteolin 7-glucuronides; nine other glycosides were present, including the uncommon 6-hydroxyluteolin 7-glucoside in T. vulgare. When the major flavonol and flavone methyl ethers of the two plants were tested pharmacologically, they variously inhibited the major pathways of arachidonate metabolism in leukocytes. There were significant differences in potency, with the tansy 6-hydroxyflavones less active than the feverfew 6-hydroxyflavonols as inhibitors of cyclo-oxygenase and 5-lipoxygenase.

Animals↗
PubMed1999

A radiation hybrid map of the zebrafish genome.

Recent large-scale mutagenesis screens have made the zebrafish the first vertebrate organism to allow a forward genetic approach to the discovery of developmental control genes. Mutations can be cloned positionally, or placed on a simple sequence length polymorphism (SSLP) map to match them with mapped candidate genes and expressed sequence tags (ESTs). To facilitate the mapping of candidate genes and to increase the density of markers available for positional cloning, we have created a radiation hybrid (RH) map of the zebrafish genome. This technique is based on somatic cell hybrid lines produced by fusion of lethally irradiated cells of the species of interest with a rodent cell line. Random fragments of the donor chromosomes are integrated into recipient chromosomes or retained as separate minichromosomes. The radiation-induced breakpoints can be used for mapping in a manner analogous to genetic mapping, but at higher resolution and without a need for polymorphism. Genome-wide maps exist for the human, based on three RH panels of different resolutions, as well as for the dog, rat and mouse. For our map of the zebrafish genome, we used an existing RH panel and 1,451 sequence tagged site (STS) markers, including SSLPs, cloned candidate genes and ESTs. Of these, 1,275 (87.9%) have significant linkage to at least one other marker. The fraction of ESTs with significant linkage, which can be used as an estimate of map coverage, is 81.9%. We found the average marker retention frequency to be 18.4%. One cR3000 is equivalent to 61 kb, resulting in a potential resolution of approximately 350 kb.

Animals↗
PubMed1999

Cross-talk between group IIA-phospholipase A2 and inducible NO-synthase in rat renal mesangial cells.

Features of glomerulonephritis are expression of the inducible form of NO synthase (iNOS) as well as expression of the secretory group IIA-phospholipase A2 (sPLA2) in mesangial cells. Interleukin 1beta (IL-1beta) induces both enzymes with a similar time course resulting in an increase in nitrite production and sPLA2-IIA activity. In this study we investigated the relationship between the formation of NO and sPLA2-IIA induction in rat renal mesangial cells. Incubation of mesangial cells with the NO-donor, spermine-NONOate, for 24 h induced sPLA2-IIA mRNA expression and activity, whereas S-nitroso glutathione alone had only a small stimulatory effect. Stimulation of cells with IL-1beta caused a marked increase in sPLA2-IIA mRNA and activity that were potentiated 3 fold by both NO donors. Coincubation of cells with IL-1beta and the NOS inhibitor, L-N(G) monomethylarginine (L-NMMA), caused a dose-dependent inhibition of cytokine-induced sPLA2-IIA mRNA expression and activity. sPLA2-IIA activity was not stimulated by 8-bromo-cyclic GMP indicating that NO-induced sPLA2-IIA induction is independent of cyclic GMP-mediated signal transduction. These data show that NO contributes to the expression by cytokines of sPLA2-IIA and establishes a novel type of interaction between iNOS and sPLA2-IIA in mesangial cells. This cross-talk between inflammatory mediators may help to promote and sustain an inflammatory state in the kidney.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

Captopril test: time over?

OBJECTIVE: The role of non-invasive tests for the detection of renovascular hypertension is still a matter of controversy. The 'captopril test' is widely used; its clinical usefulness, however, remains questionable. The aim of the current study was therefore to report our own experience and to review the published data on the diagnostic significance of the test. PATIENTS AND METHODS: Data from 485 hypertensive patients who underwent a captopril test in consecutive order at our institution were analysed retrospectively. After a 30-min resting period in the supine position 50 mg of captopril was given orally. Blood was collected before and 90 min after dosage for the determination of plasma renin concentration (normal range 3.5-8.0 ng/ml/h). An increase by 100% or more of the baseline value was considered a positive response. Blood pressure was recorded at baseline and at 90 min. RESULTS: A positive response was present in 62 patients; further diagnostic work-up revealed significant renal artery stenosis in 11 of these patients. In the 423 patients with a negative response renal artery stenosis was found in three cases. With some limitations of retrospective analyses in mind, sensitivity and specificity of the test were calculated as 79% and 89%, respectively. No severe complication occurred during the test. CONCLUSION: Our data on the diagnostic indices and the safety of the captopril test are in good agreement with most published series. Altogether, available data suggest that the captopril test has a limited diagnostic accuracy as a screening test for the detection of renovascular hypertension. New radiologic non-invasive techniques with greater diagnostic value are therefore likely to challenge the clinical role of the test in the future.

Adolescent↗
PubMed1999

Lipoprotein(a) stimulates growth of human mesangial cells and induces activation of phospholipase C via pertussis toxin-sensitive G proteins.

BACKGROUND: Renal disease is commonly associated with hyperlipidemia and correlates with glomerular accumulation of atherogenic lipoproteins, for example, lipoprotein(a) [Lp(a)], and mesangial hypercellularity. Specific binding of Lp(a) to mesangial cells and induction of c-myc and c-fos expression has been demonstrated. Therefore, in this study, we investigated a possible growth stimulatory effect and mode of action of Lp(a) in human mesangial cells. METHODS: Lp(a) was purified from the regenerate fluid of a dextran sulfate column-based low-density lipoprotein apheresis system. Human mesangial cells were isolated by a sequential sieving technique from patients undergoing tumor nephrectomy. DNA synthesis was measured by [3H]-thymidine incorporation. The intracellular calcium concentration ([Ca2+]i) was determined by Fura 2-fluorescence, and inositol 1,4,5-trisphosphate (1,4,5-IP3) concentration was measured by a radioreceptor assay. RESULTS: The data show that Lp(a) bound to the cells with a Kd of 17.0 micrograms/ml and increased DNA synthesis and cell proliferation. Lp(a) caused a rapid increase in 1,4,5-IP3 and [Ca2+]i via a pertussis toxin-sensitive mechanism. The phospholipase C (PLC) inhibitor U73122 abolished Lp(a)-induced cell proliferation. In contrast, vasopressin-induced increase in 1,4,5-IP3 and [Ca2+]i was pertussis toxin insensitive. CONCLUSION: This study revealed that Lp(a) stimulates growth of human mesangial cells. Lp(a)-induced signaling involves binding to a receptor and stimulation of PLC via Gi proteins. Stimulation of PLC appears to be essential for the growth stimulatory effect of Lp(a). Whether these effects of Lp(a) contribute to the pathophysiology of renal disease needs to be determined.

Blood Proteins↗
PubMed1999

Hypertension is associated with hyperlipidemia, coronary heart disease and chronic graft failure in kidney transplant recipients.

BACKGROUND: Hypertension is a common concomitant condition in renal transplant recipients. There is accumulating evidence that this disorder is an important risk factor for chronic renal graft failure and other cardiovascular complications in these patients. SUBJECTS AND METHODS: The current retrospective study in 330 patients treated with cyclosporin or azathioprin covered 5 years and aimed to further characterize the interrelation between hypertension and renal graft failure. Furthermore, the association of hypertension with hyperlipidemia and the prevalence of coronary heart disease was evaluated. RESULTS: Altogether, before transplantation 182 patients were normotensive (no antihypertensive medication except diuretics) and 105 were hypertensive (blood pressure > 160/95 mmHg or patients requiring antihypertensive medication); for the remaining 43 patients no data were available. After transplantation the prevalence of hypertension in the cyclosporin group was 71, 76 and 70% after 1, 3 and 5 years, respectively. The respective numbers for the azathioprin group were 60, 59 and 58%. Hypertension was associated with graft dysfunction both in cyclosporin- and azathioprin-treated patients. Hyperlipidemia (cholesterol, triglycerides) was more severe in hypertensive than in normotensive patients. The prevalence for hypertension was higher in patients with coronary artery disease than in patients without the disease. CONCLUSION: The results further support the view that hypertension may be a risk factor for the development of chronic renal graft failure and coronary artery disease in this population. Furthermore, the association of hypertension with hyperlipidemia hints to an unfavorable accumulation of renal and cardiovascular risk factors in a large number of renal allograft recipients.

Azathioprine↗