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Biomedical subjects

W Stenzinger

Publications and source records attributed to W Stenzinger.

28 records · Page 2Linked to original sources

Analysis of platelet glycoproteins in thrombocytopathias using the lectin-avidin-biotin-peroxidase (LABP) technique.

The application of the lectin-avidin-biotin-peroxidase (LABP) technique for detecting platelet glycoprotein abnormalities in thrombocytopathias is described. Platelet proteins from patients with Glanzmann's thrombasthenia or Bernard-Soulier syndrome were separated by two-dimensional O'Farrell gel electrophoresis, stained with silver or electroblotted onto nitrocellulose sheets. Nitro-cellulose blots were stained utilizing the LABP technique. The absence or severe reduction of glyco-proteins IIb and IIIa and fibrinogen in the platelet protein pattern of patients with thrombasthenia as well as the absence or marked reduction of glycoproteins Ib and V in the platelet protein pattern of a patient with Bernard-Soulier syndrome were clearly demonstrated.

Bernard-Soulier Syndrome↗

Deficiency of intact thrombospondin and membrane glycoprotein Ia in platelets with defective collagen-induced aggregation and spontaneous loss of disorder.

Platelets from a patient with a severe lifelong bleeding tendency, which later spontaneously disappeared, lacked intact thrombospondin and glycoprotein (GP) Ia. Before disappearance of the bleeding disorder, results of coagulation studies and platelet aggregation in response to adenosine diphosphate (ADP), arachidonic acid, thrombin, A23187, epinephrine, and ristocetin were normal. In contrast, aggregation only occurred in the presence of collagen or wheat germ agglutinin at unusually high doses of these agonists. The platelets adhered normally to purified bovine and human type I collagen, and they did not spread in the presence of methylated type I collagen. No collagen-induced clot retraction was observed. Two-dimensional gel electrophoretic analyses of platelet proteins and immunologic studies showed that intact thrombospondin and GP Ia were absent. Aggregation in response to collagen could be restored by adding thrombospondin. Disappearance of the bleeding tendency occurred at the onset of menopause; subsequent analyses revealed that thrombospondin and GP Ia were present in platelets and that collagen-induced platelet aggregation was normal. These results suggest that both thrombospondin and GP Ia are essential in collagen-induced platelet aggregation. The spontaneous disappearance of the bleeding tendency may have been related to hormonal influences.

Bleeding Time↗

Selective staining of platelet glycoproteins using two-dimensional O'Farrell gel electrophoresis and avidin-biotin-conjugated lectins.

A time-saving and sensitive high resolution method for the analysis and identification of platelet glycoproteins using nonradioactive compounds has been developed. Platelet proteins (50 micrograms) of normal subjects were separated by isoelectric focusing and SDS-PAGE. Proteins were either stained with silver or electroblotted onto nitrocellulose. Nitrocellulose blots were treated with the following biotinylated lectins: Abrus precatorius lectin, concanavalin A, Lens culinaris lectin, or wheat germ agglutinin. Staining was achieved by avidin-biotin-coupled peroxidase using 4-chloro-1-naphthol as the substrate. A rapid overview of platelet glycoproteins may be obtained by applying all the lectins to a single blot.

Avidin↗

[Microabscesses of the spleen in patients with acute leukemia].

Eight patients with acute myelogenous leukemia in complete remission after induction chemotherapy developed septic fever. Fever was unresponsive to broad-spectrum antibiotic therapy. Ultrasonography showed multiple 0.5-2 cm in diameter, anechoic densities and some 1-3 cm "target" appearances in spleen and liver. Computed tomography demonstrated multiple, round, 0.5-2 cm areas of diminished attenuation in spleen and liver, which did not enhance like the surrounding parenchyma. These microabscesses increased in size and number without equivalent antifungal therapy and decreased or disappeared after specific treatment. Candida-infection was confirmed by histologically from liver specimens in four patients, fungal organisms were seen microscopically an liver-biopsy in one patient and at autopsy one patient was found to have candida disseminated to the spleen, liver, kidneys, lung and CNS.

Abscess↗

Functional characteristics of murine macrophages responding to migration inhibitory factors.

Mouse bone marrow cells differentiate in culture in the presence of L cell-conditioned medium to macrophages (M phi). Proliferation, release of plasminogen activator, expression of transglutaminase, random motility and response to a standard preparation of purified M phi migration inhibitory factor (MIF) was recorded daily up to 14 days. After an initial phase of proliferation, precursor cells differentiated into M phi. In the course of maturation, plasminogen activator production was transiently expressed between day 4 and 12; beginning on day 5 the cells expressed intracellular transglutaminase. Random motility of cells was high at the beginning of culture but steadily declined thereafter. The response to MIF was only expressed between day 5 and 8. However, it was possible to induce MIF responsiveness in mature, unresponsive M phi by the addition of L cell-conditioned medium. To characterize the MIF-responsive M phi type further, bone marrow-derived M phi at day 6 of culture were separated on a hypotonic Percoll gradient into three distinct cell bands. While all densities of M phi displayed random migration, only cells with a density between 1.060 and 1.065 were responsive to MIF. We conclude that the response of M phi to MIF is a phenotypic trait transiently expressed in the course of maturation.

Acyltransferases↗

DNA aneuploidy in congenital melanocytic nevi: suggestive evidence for premalignant changes.

Nuclei with abnormal (aneuploid) DNA content were detected by flow cytometric analysis in 4 of 39 congenital melanocytic nevi and in 0 of 62 acquired nevi. Three of the 4 nevi with DNA-aneuploidy were greater than 20 cm in their largest diameter. We suggest that DNA aneuploidy is an indicator of a premalignant condition in congenital nevi in cases where histologic examination does not reveal any evidence for malignant melanoma. Cells with abnormal DNA content (aneuploid cells) are not uniformly distributed in giant congenital nevi: in one lesion we observed an area with a high percentage of cells with DNA aneuploidy, areas with a low percentage of aneuploid cells, and parts that were found to be normal by flow cytometric analysis. Nuclear pleomorphism was found histologically in the area with the high percentage of aneuploid cells while the areas with the low percentage of aneuploid cells were histologically normal. Thus, flow cytometry seems to be an additional sensitive method for the detection of nuclear abnormalities that are not always apparent by conventional histology. Increase in the relative amount of growth phase (S-phase cells), indicating elevated proliferative activity, was detected in 6 of 39 congenital pigmented nevi and in 6 of 62 acquired nevi.

Adult↗

[Combined therapy with AMSA and etoposide (VP 16-213) in refractory acute myeloid leukemia. A phase I study].

In a phase I study the combination of AMSA and etoposide was applied to 12 patients with intensively pretreated, refractory AML to evaluate the basis for a subsequent phase II study in terms of drug dosage and timing. Each treatment cycle consisted in a 5-day regimen of AMSA 210 mg/m2/d days 2, 3 and 4. Etoposide was administered on days 1 and 5 with a constant loading dose of 100 mg/m2 by an 1-h infusion followed by a 23-h infusion, the dose of which was escalated in 3 steps from 110 mg/m2 to 200 mg/m2 and 230 mg/m2. In 18 treatment cycles the recommended dosage for a subsequent phase II study was found to be 660 mg/m2 etoposide per cycle together with 630 mg/m2 AMSA per course. Main side effects were nausea and vomiting as well as mucositis; 1 patient developed a severe intrahepatic cholestasis. In 11 from 16 evaluable treatment cycles a significant reduction of bone marrow blasts was observed with a mean cytoreduction rate of 0,26 log10/d. 4 patients, 3 of whom were primarily resistent to 2 TAD induction courses, achieved a partial remission.

Aminoacridines↗

Tumor angiogenic activity (TAA) production in vitro and growth in the nude mouse by human malignant melanoma.

The production of angiogenic activity by eleven human melanoma lines in vitro was compared with the extent of tumor growth in the nude mouse. Angiogenic activity was assayed by measuring the vascular response of the chick chorioallantoic membrane to serum-free supernatants. Growth in the nude mouse was determined after subcutaneous injection of cells 60 days later. Angiogenic activities ranged from negative to highly positive. In five lines angiogenic activity in vitro correlates with the extent of tumor growth in the nude mouse. In contrast, two lines did not show such a correlation, e.g. they produced large tumours without any detectable angiogenic activity. Histological examination of these two tumors revealed moderate degrees of vascularization and only low degrees of necrosis. It is concluded that the extent of tumor growth in the nude mouse is partly independent of the production of angiogenic activity by the tumor cells themselves.

Angiogenesis Inducing Agents↗

Treatment of refractory multiple myeloma with the vincristine-adriamycin-dexamethasone (VAD) regimen.

Seventeen patients with advanced refractory multiple myeloma were treated with a 4-day continuous infusion of vincristine and adriamycin in combination with 4-day intermittent high-dose dexamethasone (VAD). Ten patients entered a partial remission (59%). Complete remission was not achieved in any patients. The median response duration was 11 months and the median survival of the responding patients was 18 months versus 5 months for non-responders. Major complications during VAD treatment were infections probably due to a combination of myelosuppression and intensive corticosteroid therapy. The VAD regimen offers a useful chemotherapy that produces an overall high response rate even in intensively pretreated patients resistant to first line therapy. The treatment results in a clear tendency to longer survival in responding patients.

Adult↗