CMV infection and vascular rejection in renal transplant patients.
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Biomedical subjects
Publications and source records attributed to R Arndt.
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Cyclosporin A eye drops (4%) were applied to the conjunctival sac of pigmented rabbits for 4 and 6 weeks. Cyclosporin-A was eluted from biopsy specimens of treated eyes and measured by the commercially available radioimmunoassey. Therapeutic Cyclosporin A levels could be demonstrated with chronic application in the rabbit cornea 3 and 10 h after the last eye drop had been administered suggesting a pooling of the substance in corneal tissue. Other ocular compartments (conjunctiva, iris, lens, vitreous, and aqueous humor) gave results below the therapeutic levels. Immunohistological studies with indirect immunofluorescence demonstrated strong binding to corneal and conjunctival epithelial cell membranes.
Our treatment of acute renal cellular rejection in patients on ciclosporin (cyclosporin A) involves the almost complete elimination of T cells (according to individual T cell monitoring in peripheral blood) through antithymocyte globulin (ATG) therapy. We present here the results of treatment of 44 histologically or cytologically proven acute rejection episodes in 33 of 62 consecutive renal transplantation patients. ATG therapy resulted in a 95.5% success rate when duration and dosage were individually adjusted according to T cell elimination in peripheral blood. Only two grafts were lost, both because of vascular occlusions. In neither case could it be clarified whether the loss was due to primary vascular lesions or the result of severe rejection or side effects of ATG. Our data show that the elimination of primed T cells with ATG permits the use of ciclosporin even in the presence of an established immune response.
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The acute-phase proteins CRP, haptoglobin, and sialic acid of 312 surgical patients (159 females and 153 males), aged between 18 and 95 years, were examined with a view to finding parameters for early prediction of perioperative septic complications. Laboratory tests were additionally applied to 39 patients for activated lymphocytes as well as for OKT3-, OKT4-, and OKT8-labelled T-lymphocytes. Straight forward postoperative decline in absolute numbers of OKT3- and OKT4-labelled T-lymphocytes was recordable from patients with septic complications, in contrast to patients with uneventful clinical courses. However, the OKT4 and OKT8 ratio did not yield any correlation with the clinical course. In acute-phase protein testing, a correlation was found to exist between CRP and clinical course. CRP levels in patients without septic complications (Group I) were found to depend clearly on the anatomic site of surgery. Normalisation of CRP levels was recordable from patients with primary septic disease and complete surgical management of the focus (Group II/1). Postoperative decline of CRP values was much less in patients with primary septic disease and incomplete surgical treatment (Group II/2). They had not even reached normality towards the end of observation. On average, unambiguously increased values were recordable as early as three days prior to clinical manifestation from patients with postoperative septic complications (Group III). Septic complications were found to occur along with re-increase or delayed decrease of CRP levels, after the fourth postoperative day. Sensitivity amounted to 78 per cent and specificity to 89 per cent.
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We describe a model for the evaluation of anti-tumour antibody specificity, using a human carcinoma-bearing colon segment. After resection of the human colon tumour, the supplying artery was cannulated and perfused with fresh frozen plasma and heparin. Continuous control of pressure, flow, temperature, pH and various metabolic parameters were performed after administration of 131I-labelled anti-CEA antibody. Highly differentiated adenocarcinomas of the colon showed a much higher antibody uptake than undifferentiated tumours. Between 3 and 7% of the injected antibody was found in the tumour tissue. Autoradiography showed non-homogeneous binding in the tumour tissue. The non-specific antibody perfusion showed no tumour binding. We conclude that the ex vivo perfusion of resected colon carcinomas can be used to measure the kinetics of binding and clearance of MAbs in tumour tissue by direct scintigraphy. The cellular biodistribution of the antibody can be documented by means of autoradiography.
The monoclonal antibody 486P 3-12-1 raised against transitional bladder carcinoma cells was coupled to either the ricin A or B chain. The toxicity of A chain conjugates could be enhanced by addition of either free ricin B chain or by ricin B chain coupled to 486P 3-12-1 or to antibodies conjugated to ricin B and directed against the mouse monoclonal antibody. Using a two-step procedure where the A and B chains of ricin were delivered separately, the appropriate target cells 486P and 647V were killed, while the pancreatic cell line QGP-1 was not affected. The efficiency of killing by immunotoxin was independent whether free or coupled B chain was used, but B chain was essential for mediating the toxicity of the A chain. The two-step procedure enhances the selectivity of immunotoxin treatment by reducing nonspecific toxicity. Such a procedure could be applicable in vivo by direct administration to the bladder cavity.
Monoclonal antibodies directed against tumor-associated antigens of bladder carcinoma were used to identify tumor cells in bladder washout specimens of 40 patients with bladder carcinoma (group 1), 41 with no bladder disease or with urinary tract infections (group 2), 41 who received long-term mitomycin C instillation therapy after excision of the tumors (group 3) and 39 who received no prophylaxis after excision of the tumors (group 4). In all groups the same bladder washout specimen was used for standard urinary cytological and immunocytological tests. True positive results were obtained in 90 per cent of the patients in group 1 according to our immunocytological criteria and in 43 per cent according to standard cytology studies. No urine specimens in group 2 (controls) were immunocytologically positive, while 16 of 41 in group 3 and 17 of 39 in group 4 were positive immunocytologically but only 4 and 5, respectively, were positive according to standard cytology studies. Further followup of these patients will show whether cells positive for monoclonal antibody 486 P 3/12 will permit early detection of recurrent bladder cancer and whether one can identify patients who require prophylaxis after removal of the superficial bladder tumors.
We present two monoclonal antibodies (mab), Mano 4/4 and 486 P3/12, directed against tumor-associated antigens of different subpopulations of transitional cell bladder carcinoma tumors. A detailed description is given concerning their reactivity patterns in an ELISA assay against different cell lines. Using immunohistochemical staining against normal bladder mucosa, mab Mano 4/4 reacts with distinct cells in the basal layer and mab 486 P 3/12 recognizes single cells in the superficial layer. Analysing different transitional-cell carcinomas, mab Mano 4/4 reacts with 17 of 20 and mab 486 P 3/12 with 17 of 19 bladder tumors. It is emphasized that both mabs may add new information in respect to a better characterization of the heterogeneity of bladder carcinoma. A biochemical characterization of the mabs and their corresponding antigens is given. Mab Mano 4/4 is directed against a 28 kD glycoprotein and mab 486 P 3/12 is reacting with a 200 kD glycoprotein belonging to the family of CEA-like proteins.
This paper discusses the potential roles of work pace and work pressure as risk factors in the development of cumulative trauma disorders. Specifically, electromyographic (EMG) data were collected from the forearm flexor muscles of workers performing a highly repetitive task. This task had previously been identified as one that involved a high incidence of cumulative trauma disorders. Workers were asked to increase and decrease their work pace for short periods of time. The EMG data indicated that faster work paces were accompanied by higher forces. However, it was also noted that unsuccessful attempts to speedup or slowdown produced similar increases and decreases in EMG activity, indicating that speed of movement was not the only factor contributing to the changes in muscular activity. The results are discussed in relation to the stress and tension associated with work pressure caused by machine pacing, production standards, and incentive systems.
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