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Biomedical subjects

K Sack

Publications and source records attributed to K Sack.

At least 37 records · Page 2Linked to original sources

Renin immunochemistry, sodium excretion and relative heart weight in cyclosporine- or alimentary-induced magnesium deficiency in rats.

Rats were given a magnesium-(Mg) depleted (Mgd), or a Mg-standard (Mgst) or a Mg-enriched (Mge) diet, with 20 mg/kg/day cyclosporine (Cy) or olive oil per os for 90 days (6 groups). Anti-renin antibody was applied and the percent of renin-positive glomeruli (RI) was taken. Sodium excretion (NaU), relative heart weight (HW), as a measure of hypertension, and total femur Mg were measured. Compared to dietary controls, femur Mg was reduced under Cy and Mgd or Mgst indicating Mg deficiency. RI was higher in all Cy groups (p < 0.01), and Nau was lower in Mgd + Cy and in Mgst + Cy (p < 0.01). Correspondingly, HW was found to be significantly higher in Mgd + Cy and Mgst + Cy. In animals under Mge + Cy, there were no differences in NaU and HW compared to controls. The results indicate a relation between Cy-related hypertension and Mg status: Mg deficiency seems to enhance the hypertensive effect of Cy via sodium retention.

Animals↗

1,25-dihydroxycholecalciferol enhances the expression of MHC class II antigens and intercellular adhesion molecule-1 by human renal tubular epithelial cells.

PURPOSE: Beside its role in calcium and phosphorus metabolism, 1,25-dihydroxycholecalciferol (1,25-D3) exerts multiple effects on cytokine and major histocompatibility complex (MHC) class II expression in monocytes and lymphocytes. In different renal diseases tubular epithelial cells express MHC class II molecules and cell adhesion molecules,, such as intracellular adhesion molecule-1 (ICAM-1). Therefore, modulation of MHC class II and ICAM-1 expression in renal tubular epithelial cells by 1,25-D3 may be relevant to lymphocyte adhesion to tubular epithelial cells and immune mediated renal injury. However, the expression of MHC class II antigens and cellular adhesion molecules by renal tubular epithelial cells in response to 1,25-D3 has not been investigated. MATERIALS AND METHODS: We generated human renal tubular epithelial cells and SV40 transfected tubular epithelial cells to investigate immune modulation of 1,25 on renal epithelial cells. Major histocompatibility complex class II molecules and ICAM-1 were detected by a specific enzyme linked immunoassay. RESULTS: We found a dose-dependent increase of both constitutive and induced MHC class II and ICAM-1 expression in tubular epithelial cells stimulated with 1,25-D3. Dose-dependent stimulation of MHC class II and ICAM-1 expression was not restricted to primary human renal tubular epithelial cells but was also detected in SV40 transfected cells. CONCLUSIONS: Expression of MHC class II and ICAM-1 is crucial for antigen presentation by and lymphocyte adhesion to renal tubular epithelial cells. Modulatory effects of 1,25-D3 on immune accessory function of renal tubular epithelial cells may be of clinical significance in renal diseases.

Calcitriol↗

Preoperative application of glucocorticosteroids efficaciously reduces the primary immunological response in kidney transplantation.

Early acute rejection episodes have a considerable influence on long-term prognosis of renal transplants. Therefore the aim of primary immunosuppressive therapy must be effective suppression of the immunological response following antigen recognition. Owing to their pharmacological properties, intravenously given glucocorticosteroids are suitable for the alteration of the primary immunological response. However, even after intravenous administration, glucocorticosteroids have a latency of hours prior to reaching maximum activity. In a prospective clinical study, 111 patients undergoing renal transplantation were preoperatively treated with 500 mg methylprednisolone for immunosuppressive induction. A historical group of 40 patients who had received the same dose as intraoperative bolus, was used for comparison. Postoperative immunosuppression did not substantially differ between the two groups. The incidence of acute rejections within 30 d after transplantation was a clinical parameter of the study. The mitogenic cytokine induction was measured in blood samples which were collected intraoperatively and on days 1, 2, and 5 after transplantation. Cytokine release served as an in vitro parameter for the immunological responsiveness of the transplant recipient. In the group under study, the incidence of acute rejections was 21% (23/111) and, in contrast, 43% (17/30) in the historical group (p < 0.05). 89% of the patients in the group being studied showed normal renal function after 1 yr, compared to 78% in the reference group (n.s.). Following preoperative (mean 5.09 h) administration of glucocorticosteroids, mitogenic cytokine induction (IL-1 beta, IL-2, sIL-2R and IFN-gamma) was almost completely blocked at the time of transplantation. A prospective, randomized study has just been started to evaluate the effect of preoperative administered glucocorticosteroids on the incidence of acute rejections and long-term allograft survival.

Adult↗

S fimbriae of uropathogenic Escherichia coli bind to primary human renal proximal tubular epithelial cells but do not induce expression of intercellular adhesion molecule 1.

We have recently reported an increase of expression of the intercellular adhesion molecule 1 by renal carcinoma cells in response to S fimbriae of Escherichia coli. Now we demonstrate that E. coli expressing S and P fimbriae strongly binds to human proximal tubular epithelial cells. However, in primary and simian virus 40-transfected renal tubular epithelial cells S fimbriae do not enhance the expression of intercellular adhesion molecule 1.

Bacterial Adhesion↗

[Intestinal vasculitis and glomerulonephritis in hepatitis C- associated cryoglobulinemia].

In a 53-year-old female patient with recurrent, sometimes bloody diarrhea, the long standing diagnosis of an ANA-negative lupus erythematosus with membranoproliferative glomerulonephritis, leucocytoclastic vasculitis and chronic hepatitis was ruled out and the diagnosis of a hepatitis C associated cryoglobulinaemia was established. The origin of the diarrhea was due to intestinal vasculitis as a result of cold food or beverages.

Cryoglobulinemia↗

[Polycythemia in the late metastasis of an erythropoietin-producing renal-cell carcinoma].

An 85-year-old woman had a right-sided renal cell carcinoma removed 20 years ago. At haemoglobin concentration. Two years ago she had a syncope, at which time the haemoglobin concentration was 16.9 g/dl. Ultrasound and computed tomography (CT) revealed an extensive retroperitoneal space-occupying lesion, which however was not investigated further, and no therapeutic consequences were drawn. An erythrocytosis (7.5 x 10(6)/microliters) and elevated haemoglobin concentration (> 20 g/dl) were found when she was examined after a fall in which she had sustained only minimal injury. The retroperitoneal mass had slightly increased in size. Histological examination of a CT-guided fine-needle biopsy revealed metastases of the hypernephroid carcinoma. The serum erythropoietin concentration was increased (42.4 U/l) and failed to increase even after repeated venesections, indicating erythropoietin production by the late metastases of the renal cell carcinoma. There was no evidence for any systemic haematological disease. Six months after the diagnosis of metastases the patient died at home, presumably of a cerebrovascular accident.

Aged↗

[alpha 2-macroglobulin in urine. Significance for differential diagnosis of rejection and infections after kidney transplantation].

The value of measuring the urinary concentration of alpha 2-macroglobulin in addition to that of C-reactive protein (CRP) was assessed in a prospective study of 78 consecutive patients (29 women, 49 men; mean age 48.7 [19-75] years) after renal transplantation. alpha 2-Macroglobulin was never demonstrated in urine when the course was normal (n = 38), cytomegalovirus infection had occurred (n = 26) or acute cyclosporin nephrotoxicity (n = 5) or glomerular disease in the transplant (n = 10). CRP was present in only a few such cases. Interstitial rejections (n = 26) always led to urinary alpha 2-macroglobulin and CRP excretion without haematuria, while in vascular rejection (n = 3) the haemoglobin test was also positive. Urinary infection (n = 20) and urosepticaemia (n = 6) always brought about the urinary excretion of alpha 2-macroglobulin and CRP, as well as a usually highly positive haemoglobin test. alpha 2-Macroglobulin was absent but CRP always present in extrarenal bacterial infections (n = 30). Postrenal blood admixture was always characterized by a positive haemoglobin test and alpha 2-macroglobulin in urine, while in most cases (83%) CRP was absent. --These results indicate that the constellation "alpha 2-macroglobulin negative/CRP positive" is a pathognomonic for extrarenal bacterial infection (sensitivity 100%, specificity 98.9%). The presence of alpha 2-macroglobulin alone makes postrenal blood admixture probable. If both proteins are present in the urine, rejection and urogenital bacterial infection must be excluded by further tests.

Adult↗

MR imaging of the arthritic knee: improved discrimination of cartilage, synovium, and effusion with pulsed saturation transfer and fat-suppressed T1-weighted sequences.

PURPOSE: To assess the applicability of three-dimensional (3D) magnetic resonance (MR) imaging with pulsed saturation transfer (ST) or fat saturation in depicting articular structures in arthritic knees. MATERIALS AND METHODS: Eleven patients underwent MR imaging with T1-weighted spin-echo (SE); unenhanced and contrast material-enhanced T2*-weighted 3D gradient-echo with and without on-resonance pulsed ST; and T1-weighted, fat-presaturated 3D gradient-echo techniques. Images with ST were subtracted from those without ST. RESULTS: Both fat-suppressed imaging and ST-subtraction (STS) techniques generated a high contrast-to-noise ratio among cartilage, synovium, effusion, bone, and adipose tissue. Both techniques depicted hypertrophic synovial tissue on unenhanced images; contrast material was necessary to differentiate between synovium and cartilage on STS images. CONCLUSION: 3D MR imaging with fat-suppressed or STS techniques provides good discrimination among articular structures in arthritic knees. Fat-suppressed imaging is faster than STS imaging and offers better contrast between cartilage and synovium. These techniques may improve monitoring of arthritic disease progression and therapeutic response.

Arthritis, Rheumatoid↗

The long persistence of CMV DNA in the blood of renal transplant patients after recovery from CMV infection.

A total of 30-50% of all renal transplant recipients undergo infections caused by human cytomegalovirus. With the introduction of ganciclovir and foscarnet for specific antiviral therapy there is an increasing demand for diagnostic tools that allow the early and rapid identification of CMV as the causative agent of the observed disease. We and others previously showed the direct detection of pp65 antigen in peripheral blood leukocytes to be an excellent marker for active cytomegalovirus infection. In order to establish whether the detection of CMV DNA by the polymerase chain reaction (PCR) supplies further information in this regard, we compared both methods. In 41 renal transplant patients the PCR assay yielded a sensitivity of 100% compared with 87.5% of the antigenemia assay. Specificities reached 67% and 92.5%, respectively. In 5 patients without both serological signs of infection and antigenemia, CMV DNA was also found. The duration of CMV DNA detection in PBL during active infection was significantly longer than antigenemia. Even after successful treatment of symptomatic CMV disease, DNA was present for a period of weeks without any relapse of disease. In contrast, antigenemia disappeared after antiviral therapy and reappeared only in one patient with relapse of CMV disease. We conclude that PCR offers no advantages over antigen detection in monitoring for CMV infections after renal transplantation.

Base Sequence↗

[C-reactive protein in the urine. The differential diagnosis of renal functional disorders following kidney transplantation].

A prospective study was undertaken in 73 patients (24 women, 49 men; mean age 47.9 [21-64] years) after renal transplantation to discover whether the presence of C-reactive protein in urine (CRPu) and its serum concentration (CRPs) are of value in the differential diagnosis of abnormal function in the transplanted kidney. CRPu concentration was measured with a highly sensitive immunoluminometric assay (minimal threshold value 6 micrograms/l). CRPu was demonstrated in 36 histologically proven rejection episodes and 21 bacterial infections proven by culture. In contrast, no CRPu was demonstrated when the course was normal and in individual cases of cyclosporin renal toxicity, as well as in 27 of 34 cases of cytomegalovirus infection. In addition, the CRPs to CRPu ratio was a sensitive means of distinguishing between rejection (CRPs/CRPu less than 1) and bacterial infection (CRPs/CRPu greater than 1). Determining CRPu concentration thus proved to be useful in the initial monitoring of renal transplantation before starting any specific urinary protein diagnosis, as well as (together with CRPs) in the diagnosis of severe posttransplantation complications.

Adult↗