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D Speiser

Publications and source records attributed to D Speiser.

25 records · Page 2Linked to original sources
PubMed1993

The frequency of pretransplant donor cytotoxic T cell precursors with anti-host specificity predicts survival of patients transplanted with bone marrow from donors other than HLA-identical siblings.

Transplantation with bone marrow from other than genotypically HLA-identical donors is associated with an increased incidence and severity of graft-versus-host disease (GvHD). The precise influence of HLA incompatibilities is not easy to analyze as even perfectly matched, HLA-identical unrelated donors might still express HLA differences that remain undetected by conventional typing. To measure T cell activity against serologically detectable and nondetectable HLA antigens, we analyzed the frequencies of CTL precursors (CTLp) between 11 unrelated HLA-matched and five related haploidentical donor/recipient pairs in graft-versus-host direction. Our results show that whenever HLA class I disparities could be identified by serology, high precursor frequencies (1/28,000-1/94,000) were measured. In contrast, in donor/recipient pairs that differed for class II only, no precursors were detected. CTLp were elevated in two out of eight fully matched donor/recipient combinations. These combinations displayed activities as high (1/21,000; 1/52,000) as the combinations that were serologically HLA class I disparate. The incompatibilities detected by the cellular assay were highly significant for the clinical results after transplantation. High CTLp frequencies before transplantation correlated with unfavorable clinical results independent of the incidence of detected HLA differences. Five out of the six patients with high (> 1/100,000) CTLp frequencies died within 120 days after transplantation. GvHD IV was the cause of death for all (3/5) patients who had received an unmanipulated bone marrow. In the group with intermediate or undetectable CTLp frequencies, eight out of 10 patients are alive, seven (CTLp frequency undetectable) without GvHD more severe than grade II, while one patient (CTLp frequency = 1/180,000) suffered from GvHD grade III. One patient rejected the graft and was rescued by an autologous BMT.

Adolescent↗
PubMed1993

Replacement of HLA class II serology by the HLA-DR microtitre plate oligotyping assay: a one-year experience in unrelated bone marrow donor selection.

Because the selection of unrelated bone marrow donors requires a more accurate HLA-typing technique than is used for sibling donors, we have replaced class II serology by a rapid and highly discriminative HLA-DR DNA oligotyping assay on microtitre plates. We present here our 1-year experience with class II typing for 112 potential donors identified for 33 consecutive leukaemic patients. Although the donors were selected to be HLA-A, -B, -DR serologically identical, the microtitre plate oligotyping assay detected DR incompatibilities in 52.7% of the patient/donor pairs. One third was due to incorrect or incomplete typing of DR11 to DR16, the others to mismatches for the serologically indistinguishable subtypes of DR1, 11, 13 and 15, known to be relevant for T cell recognition.

Bone Marrow Transplantation↗
PubMed1993

Characterization of pretransplant CTL activity in "perfectly matched" unrelated bone marrow donor/recipient combinations.

To characterize the pre-transplant cytotoxic T cell precursor (CTLp) activity of unrelated bone marrow donors towards their HLA-ABDR compatible recipients, we have established T cell clones from the primary (positive) CTLp cultures. Two "perfectly matched" oligo-typed DR/DQ identical combinations and two A/B identical, DR subtype incompatible combinations have been studied in detail. Analysis of the clones shows that in the first two combinations the alloreactivity was directed towards a subtype of A2 (A205) and a subtype of Bw60 respectively. In the other two cases, where class II incompatibilities were present, we have not yet defined the exact specificity. However, because the majority of recipient specific clones were of the CD8 phenotype, it is very likely that also in these two cases differences in class I are being recognized.

Bone Marrow Transplantation↗
PubMedDate not supplied

Microangiopathy of cutaneous blood and lymphatic capillaries in chronic venous insufficiency (CVI).

The severity of microangiopathy in patients with chronic venous insufficiency (CVI) determines the extent of the trophic disturbances of the skin. Resulting from valvular incompetence of deep and/or perforating veins and the accompanying venous outflow obstruction caused by deep venous thrombosis (DVT), the increased ambulatory venous pressure heads are transmitted retrograde into the microvasculature of the skin at the ankle region. In the present study, we have assessed the changes in the cutaneous microvasculature by dynamic fluorescence video microscopy, fluorescence microlymphography, and transcutaneous oxygen tension (tcPO2) measurements. In mild forms of CVI, capillary density, morphologic characteristics, and tcPO2 are still normal. Fluorescent light intensity is, however, significantly increased, indicating an increased transcapillary diffusion of sodium fluorescein (NaF) as a marker for enhanced leakage of the capillaries in the early stage of the disease. The pericapillary halo diameters are significantly enlarged, compared to controls (p < 0.01). In the severe stages of CVI and in patients with venous ulcers, capillary thromboses, probably caused by endothelium-blood cell interactions, may lead to a reduced capillary density. In order to enlarge the exchange surface area, the remaining skin capillaries become tortuous (capillary tufts). Parallel to the reduced capillary number, tcPO2 decreases and can be extremely low at the ulcer rim or at white atrophy spots. Fibrin cuffs are not a specific finding for venous ulceration and do not significantly impair oxygen diffusion. Fluorescence microlymphography permits visualization of the lymphatic capillaries of the superficial skin. In severe stages of CVI, the lymphatic capillary network at the medial ankle area is destroyed, and the remaining lymphatic capillary fragments have an increased permeability to FITC-dextran with a molecular weight of 150,000. These findings demonstrate a special lymphatic microangiopathy in CVI, suggesting an additional lymphatic component in the edema formation.

Adult↗