Labeling of anti-tumor antibodies and antibody fragments with Tc-99m.
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Biomedical subjects
Publications and source records attributed to A Kunz.
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In addition to the well-known common trauma in the practice of rock climbing, free climbing at top level has given rise to a new specific pathology affecting the flexor apparatus of the fingers. The cases of 23 top level climbers (performance level 6a to 8a) have been reviewed. 1/3 of them had severe pain in their fingers caused by traction movements. 1 climber out of 4 were referred to us for the above symptomatology. The diagnosis was either tendinitis or tenosynovitis, and the treatment was always conservative. Understanding the pathogenesis of the conflict between tendon and pulley movements will permit partly to cure these lesions, but our aim should be to prevent them.
An earlier study by our group reported a frequency of about 40% for oral problems associated with cancer therapy for patients with non-head-and-neck malignancies. Since then, we have instituted a variety of preventive and treatment protocols aimed at the aggressive management of the mouth in patients being treated for malignant disease. In the present study we evaluated the frequency and nature of oral problems associated with cancer treatment in 495 patients treated for non-head-and-neck malignancies between 1978 and 1986. Our analysis indicates that the frequency of oral problems in the study population was 10.5%, compared to 38.7% in 1978. The specific nature and distribution of oral problems by diagnosis, by patient's age, and by type were remarkably consistent. Our results suggest that early and aggressive dental intervention in standardized protocols reduces the frequency of oral problems associated with cancer therapy.
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The authors have used SDS-PAGE and lectin overlay analysis in parallel with lectin-gold cytochemistry to identify Helix pomatia lectin (HPL) binding glycoconjugates in rat kidney glomeruli. Previous work revealed HPL binding sites only beneath podocyte foot process bases, where they contact the glomerular basement membrane. It is shown here that after neuraminidase digestion of thin sections of glomeruli before incubation with HPL-gold complexes, the number of HPL binding sites is markedly increased. These new sites are mainly associated with the podocyte free surface (adjacent to the urinary space) and with capillary endothelial cells. By lectin overlays, this neuraminidase-dependent HPL binding was shown to be due to reaction of the lectin with desialylated podocalyxin. In contrast, HPL binding sites detected prior to neuraminidase digestion are associated with a novel glycoconjugate having a lower electrophoretic mobility than podocalyxin. Although any role for this glycoconjugate is at present speculative, it is strategically positioned at the site of interaction between foot process bases and the glomerular basement membrane. Its presence correlates with normal podocyte architecture, as shown by our previous studies on developmental and aminonucleoside nephrosis-associated changes in HPL binding to podocytes.
The lectin-gold technique was used to reveal Helix pomatia lectin (HPL)-binding sites in human kidney glomeruli. HPL-binding sites were associated mainly with podocyte foot process bases, and extended over the lamina rara externa of the glomerular basement membrane. In addition, kidneys from blood group A1 donors showed labeling of capillary endothelial cells and erythrocytes. After neuraminidase digestion of the sections prior to incubation with HPL-gold complexes, HPL-binding sites appeared on previously negative regions of the glomerulus. This increase in labeling was particularly striking at the level of the podocyte-free surface (adjacent to the urinary space) in all kidneys, and on capillary endothelial cells from donors of blood groups other than A1. These results demonstrate the existence of two distinct glycocalyx domains in human kidney podocytes, and show the application of the lectin-gold technique for the high resolution, ultrastructural detection and quantification of lectin-binding sites in human material.
19 patients suffering from posttraumatic acute renal failure were treated by hemodialysis at least three times a week and sometimes daily. In addition to trauma and acute renal failure (arf), all patients had various other posttraumatic complications. The overall mortality within 12 months from trauma was 84%. The high mortality rate was due mainly to the extent of injury and the occurrence of life-threatening complications, above all sepsis. Whether or not these basic problems are aggravated by arf, the overall results of the treatment call for careful establishment of the indications for these laborious and expensive therapeutic measures.
The visceral glomerular epithelial cells (podocytes) of newborn rat kidneys were examined by the lectin-gold technique to determine the distribution of Helix pomatia lectin-binding sites during glomerular development. Previous work has shown that this lectin, which primarily recognizes terminal N-acetyl-D-galactosamine residues of glycoconjugates (but also N-acetyl-D-glucosamine to a lesser extent), specifically labels the plasma membrane glycocalyx of podocyte foot process bases, whereas the plasma membrane of the podocyte cell body that is in contact with the urinary space is unlabeled. In neonatal glomeruli, the labeling was most intense in those podocytes whose pedicel development corresponded to that seen in adult rat kidneys, whereas immature podocytes were poorly labeled. A quantitative evaluation of the labeling showed a highly significant correlation between the degree of podocyte development (as assessed by counting the number of pedicels per micrometer of basal lamina) and the intensity of H. pomatia lectin-gold particle labeling. These results show that the appearance of pedicels on developing podocytes is accompanied by the appearance of a specific cell coat component(s), detectable using H. pomatia lectin-gold complexes.
Alterations in the ultrastructural organization of podocyte plasma membrane domains were quantitatively assessed in puromycin aminonucleoside-treated rats by the use of 1) Helix pomatia lectin-gold complexes for detection of a specific glycocalyx component(s) normally associated with foot process bases and 2) freeze-fracture for detection of intramembrane particles and endocytotic invaginations on the plasma membrane. Lectin-binding sites were significantly reduced on podocyte foot process bases during the 7-day treatment period; and in freeze-fracture, the plasma membrane of the foot process base showed an increase in intramembrane particle number and size and an increased number of endocytotic invaginations, compared with the numbers in control animals. The cell body of nephrotic animals also had a significantly increased intramembrane particle density, compared with the control animals. These results provide direct evidence that the normal structure of specific plasma membrane regions is perturbed in podocytes that have lost their characteristic array of foot processes and support a role for these domains in the maintenance of normal podocyte architecture.
In two hospitals an identical diabetes teaching and treatment programme (in-patient, Monday to Friday, group teaching) was set up. Seventy-eight consecutive, conventionally treated Type 1 diabetic patients (duration of diabetes 10 +/- 6 years), referred during a certain period, were reinvestigated after 1 year, and again (for assessment of metabolic control only) 22 months after the teaching and treatment programme. Initially, mean glycosylated haemoglobin was 2.6%, after one year 1.0%, and after 22 months 1.5% above the upper limit of the normal range (p less than 0.001). Hospital admissions were reduced from a mean of 10 to a median of 1 day per patient per year (p less than 0.001). The long-term quality of diabetes care achieved by the diabetes teaching and treatment programme was unrelated to intelligence quotient, diabetes duration, or diabetes-related knowledge. Patients with normal levels of glycosylated haemoglobin on follow-up (33% of all patients) had particularly good compliance rates, and significantly lower initial values of glycosylated haemoglobin than patients with glycosylated haemoglobin levels greater than or equal to 10%. The data indicate that the diabetes teaching and treatment programme resulted in a substantial long-term improvement of metabolic control and a striking reduction of hospital admissions. The study substantiates the feasibility of applying this teaching and treatment programme on a large scale to other hospitals, so as to improve the quality of diabetes care and decrease health care costs.
A new histochemical technique in which lectin-gold complexes are applied directly to thin and semi-thin sections of tissue was used to determine the distribution of Helix pomatia lectin binding sites in the proximal tubule of Rat kidney. Whereas a strong labeling was seen on the brush border and baso-lateral plasma membranes of convoluted tubules, the plasma membrane of cells from the medullary straight segment was unlabeled. Some profiles at the frontier between cortex and medulla had a mosaic of positive and negative cells. These results show, therefore, considerable segmental variation in the glycocalyx composition of Rat proximal tubules.
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An immunoassay utilizing chemiluminescence and paramagnetic particles has been developed for the new fully automated random access LIAISON immunoanalyzer. The LIAISON Ferritin assay is a two-site immunoluminometric one-step assay using two highly specific monoclonal antibodies. A specially designed unique Reagent Integral contains all specific reagents. The cooled reagent compartment guarantees an on-board stability of at least 4 weeks. The assay works with a 2-point calibrated master curve. To perform, the assay, 10 microliters sample is added to 300 microliters tracer and 20 microliters antibody-coated magnetic particles. After 10 min incubation the particles are separated, washed and the chemiluminescent signal is generated. The time to first result is only 15 min. The assay with a unique extended standard range up to 3,000 ng/ml shows no high dose hook effect up to 150,000 ng/ml (spiked sera). The cross-reactivity to human liver ferritin is 100%, to human spleen ferritin 66% and to human heart ferritin 8%. Precision (within-run < 3%; between-run < 5%), linearity, recovery and sensitivity (< 0.2 ng/ml) are excellent. The assay shows a very good correlation to LlA-mat Ferritin (r = 0.994). In summary the LIAISON Ferritin run on the new LIAISON immunoanalyzer and is a very rapid and accurate method rapidly providing reliable results.
BACKGROUND AND PURPOSE: Transcranial color-coded duplex sonography (TCCD) is a diagnostic technique for evaluation of intracranial arteries in patients with acute stroke. Echo-enhancing contrast agents (EEAs) are necessary to visualize intracranial vessels in up to 30% of patients because of limited acoustic bone windows. In this study, we assessed the diagnostic efficacy of echo-enhanced TCCD (eTCCD) in correlation with the gold standard, digital subtraction angiography (DSA). METHODS: We prospectively evaluated all patients with eTCCD who subsequently underwent DSA for evaluation of cerebrovascular symptoms over a 24-month period. We administered Levovist as an EEA. Two blinded reviewers analyzed all eTCCD findings and correlated them with DSA. RESULTS: We included 132 consecutive patients (40 women, 92 men; mean age, 58 +/- 14 years) with 164 datasets: 24/164 had normal findings, 98/164 had abnormalities of extracranial carotid arteries, 32/164 had abnormalities of intracranial arteries, and 21/164 had abnormalities in vertebrobasilar circulation as determined by DSA. For eTCCD, we found a sensitivity of 82% (95% confidence interval [CI]: 75%-90%), a specificity of 98% (95% CI: 90%-100%), a positive predictive value of 99% (95% CI: 94%-100%), and a negative predictive value of 75% (95% CI: 64%-85%); 7/164 (4%) examinations were inconclusive because of insufficient bone windows. The interobserver agreement was almost perfect (kappa value, 0.92; 95% CI: 0.87-0.97). CONCLUSION: eTCCD provides high diagnostic validity for the status of the major intracranial arteries. In particular, a normal vessel status reliably assessed by an experienced sonographer could supersede further imaging procedures. In patients with acute ischemic stroke not eligible for established angiographic techniques, eTCCD may be useful as an alternative imaging technique.