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J Schubert

Publications and source records attributed to J Schubert.

At least 181 records · Page 10Linked to original sources

[Cyto- and molecular genetic studies of renal cell carcinoma with special reference to multifocal carcinoma lesions].

In 86 consecutive radical nephrectomies we found in 12 kidneys (13.8%) a total of 17 multicentric foci of carcinoma. Beside the usual histopathological investigations we performed in seven secondary tumors further cyto-and molecular genetic analyses. The structural and/or numerical chromosome aberrations in the small secondary tumors were similar to the changes in the main tumors. We conclude that these foci have malignant potential. In eight of these results and the multicentricity that was found, we continue to recommend elective radical nephrectomy in renal cell carcinoma.

Aged↗

[Possibilities of therapy and rehabilitation of patients with urinary incontinence].

Rehabilitation of incontinent patients is an interdisciplinary challenge. Many therapeutical options in gynecological urology reveal an optimal rehabilitation of these patients. In the last years, a great scientific progress in the area of neurourology offers patients with severe dysfunction of the lower urinary tract (e.g. spinal cord injury) new concepts to improve their urological problems.

Combined Modality Therapy↗

Combined transplantation of allogeneic bone marrow and CD34+ blood cells.

Allogeneic peripheral blood progenitor cells (PBPCs) were transplanted after immunoselection of CD34+ cells. Two patient groups were studied: group I patients received immunoselected blood CD34+ cells and unmanipulated marrow cells from the same donor. Group II patients were given immunoselected blood and bone marrow (BM) CD34+ cells. One to 6 weeks before bone marrow transplantation (BMT), PBPCs from HLA-identical and MLC- sibling donors were mobilized with granulocyte colony-stimulating factor (G-CSF) (5 micrograms/kg twice daily subcutaneously) for 5 days. Aphereses were performed at days 4 and 5 of G-CSF application. CD34+ cells were separated from the pooled PBPC concentrates by immunoadsorption onto avidin with the biotinylated anti-CD34 monoclonal antibody 12.8 and then stored in liquid nitrogen. BM was procured on the day of transplantation. Patients were conditioned with either busulfan (16 mg/kg) or total body irradiation (12 Gy) followed by cyclophosphamide (120 mg/kg). Cyclosporin A and short methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. After transplantation, all patients received 5 micrograms G-CSF/kg/d from day 1 until greater than 500 neutrophils/microL were reached and 150 U erythropoietin/kg/d from day 7 until erythrocyte transfusion independence for 7 days. Group I consisted of patients with acute myeloid leukemia (AML) (n = 2), chronic myeloid leukemia (CML) (n = 2), and T-gamma-lymphoproliferative syndrome and BM aplasia (n = 1). The patients received a mean of 3.3 x 10(6) CD34+ and 3.7 x 10(5) CD3+ cells/kg body weight of PBPC origin and 4.5 x 10(6) CD34+ and 172 x 10(5) cells/kg body weight of BM origin. Group II consisted of five patients (two AML, two CML, one non-Hodgkin's lymphoma). They received a mean of 3.3 x 10(6) CD34+ and 3.2 x 10(5) CD3+ cells/kg from PBPC and 1.4 x 10(6) CD34+ and 0.6 x 10(5) CD3+ cells from BM. A matched historical control group (n = 12) transplanted with a mean of 5.2 x 10(6) CD34+ and 156 x 10(5) CD3+ cells/kg from BM alone was assembled for comparison. In group I, the median time to neutrophil recovery to > 100, > 500, and > 1,000/microL was 12, 15, and 17 days, respectively. Patients from group II reached these neutrophil levels at days 13, 15 and 17 post BMT. Neutrophil recovery in the control patient group occurred at days 17, 18, and 20 respectively. Group I patients were given platelet transfusions within 18 days and red blood cells within 10 days, whereas for group II patients, these time points were 26 and 17 days, respectively. These same transfusions could be ceased within 38 and 24 days, respectively, in control patients. The addition of about 2% more peripheral blood CD3+ cells (group I patients) did not result in higher grades of acute GVHD (median grade II) as compared with the controls (median grade II). Four of five group II patients showed no signs of acute GVHD. These data suggest that the addition of immunoselected allogeneic CD34+ progenitor cells to BM cells may accelerate hematopoietic recovery.

Adult↗

Heterogeneous PIG-A mutations in different cell lineages in paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal defect of hematopoietic stem cells in which affected cells are characterized by the lack of glycosylphosphatidylinositol (GPI)-anchored proteins. The lesion in PNH lies in the defective synthesis of N-acetyl-D-glucosaminyl-phosphatidylinositol (GlcNAc-Pl), the first intermediate in GPI biosynthesis. Reintroduction of the PIG-A gene into GPI(-) patient cells reportedly complements this defect. We have analyzed here PIG-A transcripts of six PNH patients. GPI+ and GPI- cell lines from each individual were used, ie, Epstein-Barr virus-transformed B-lymphoblastoid cell lines, T-cell lines, and natural killer cell clones. Reverse transcriptase polymerase chain reaction and sequencing showed three different PIG-A splicing variants in GPI+ cell lines, in which the largest transcript contained the wild-type PIG-A coding region sequence. GPI-deficient cell lines showed abnormal splicing variants. Sequencing of PIG-A complementary DNA and genomic DNA showed heterogeneous mutations ranging from different point mutations to small deletions. Two lymphocyte cell lines (T- and B-cell lines) of one patient presented with the same mutation. For another patient, two different mutations were detected in one natural killer cell line. Therefore, different cell lineages have somatic mutations in PIG-A that lead to PNH.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Peyronie's disease. Investigation of staging, erectile failure and operative management.

There are still diverse management options in Peyronie's disease, due to its unknown aetiology, progression or remission. Types, extent and duration of operative management in this disease are subject of controversial discussion. We did complex investigations in 132 patients revealing the following items. Diagnostic tests should include both history and physical examination and comparative X-ray and ultrasound investigations. CT is the best method to differentiate pathological lesions in the tunica albuginea. X-ray (xerography) examination demonstrates calcification of the plaque. Papaverin-hydrochloride injection is a valid method to check the extension of concomitant erectile dysfunction and shows the angulation of the penis. Plaque excision and grafting with various materials were used initially with disappointing results (15 patients, only 20% good results). Modified corporal plication has been used subsequently with good results (54 patients, follow-up 3 years, 90% good results). Implantation of penile prosthesis must be evaluated individually.

Erectile Dysfunction↗

Glycosylphosphatidylinositol (GPI)-anchored surface antigens in the allogeneic activation of T cells.

GPI-linked surface molecules have recently been described as structures with an activation potential for human T lymphocytes. To study the role of these molecules in T cell activation we analysed GPI-deficient or normal T cells from patients with paroxysmal nocturnal haemoglobinuria (PNH). On activation with allogeneic Epstein-Barr virus (EBV)-transformed B cell lines GPI-deficient freshly separated T cells or continuously growing T cell lines exhibited a significantly lower proliferation or cytokine production compared with their normal counterparts. In contrast, stimulation via the T cell receptor-associated CD3 structure resulted in a comparable response. There was no difference in activation of normal T lymphocytes when GPI-deficient B cells were used as stimulators compared with normal B cells obtained from the same PNH patient. We conclude from these data that GPI deficiency in PNH leads to a functional deficiency of GPI-deficient T cells. In contrast, no difference in activation of T lymphocytes for GPI-deficient cells on the stimulator cell level was observed.

Antigens, Surface↗

[Experimental therapy of hypoplastic paroxysmal nocturnal hemoglobinuria].

Paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia are associated either as a PNH-aplasia syndrome or the emergence of glycosylphosphatidylinositol-(GPI)deficient blood cells in patients with severe aplastic anemia (SAA). It could be demonstrated that SAA patients with GPI-deficient cells in comparison to those without have a worse response to classical immunosuppressive therapy. Therefore, we treated a female PNH patient with severe thrombocytopenia, anemia and granulopenia with G-CSF and cyclosporine. Within 8 weeks, a trilineage response of hematopoiesis was observed. In addition, the proportion of normal to GPI-deficient granulocytes and monocytes increased significantly.

Adult↗

[The high risk patient with symptomatic prostatic hyperplasia--a therapeutic dilemma?].

Since a few year, a lot of new methods in therapy of symptomatic benign prostate hyperplasia are available. Until now, none of these methods could reach the outcome of surgical therapy. Therefore, surgery is remaining the golden standard in the therapy of BPH. Alternative methods are of great importance in the treatment of "high risk patients". It may be possible to improve the quality of life. Laser therapy and intraurethral catheters are superseding transurethral and suprapubic catheters. The indication for the several methods has to been proven critically.

Aged↗

[Erysipelas and elephantiasis of the scrotum. Surgical and drug therapy].

Elephantiasis is the outcome of persistent lymphedema. It is refractory to different therapy modalities. The social approachability of patients with this disease is impaired by severe functional and cosmetic disturbances. The causal relationship between etiology and recurrent disease is demonstrated by two cases. Treatment options are discussed. Radical surgery is decisive for primary success since chronic inflammation and chronic edema support each other. Metabolic equilibrium, disinfecting skin areas and antibiotic prophylaxis are urgent steps in the successful treatment of Erysipelas disease.

Adult↗

[Injuries to the external male genitals].

Genital injuries are rare in comparison to other traumatologic injuries. Diagnostic and therapy demand a detailed urological knowledge and high abilities in the surgical and the microsurgical field. The emergency doctor/urologist, who firstly treats the patient, decides about the therapeutic outcome. Delays in the diagnostic procedures and false therapeutic indications may be followed by impairments in cosmetic and function of the genitale for the patient. Therefore, we demand an early consultation of an urologist.

Adolescent↗

The loss of Fc gamma RIIIb in paroxysmal nocturnal hemoglobinuria is functionally replaced by Fc gamma RII.

Neutrophils from patients with paroxysmal nocturnal hemoglobinuria (PNH) show a deficiency for the glycosylphosphatidylinositol- (GPI) linked Fc gamma receptor IIIb (Fc gamma RIIIb, CD16). The functional consequences of this defect are not clear. Here, we examined Fc gamma RIIIb-deficient neutrophils for their activation via Fc gamma receptors. Hydrogen peroxide (H2O2) production and change of intracellular free calcium [Ca2+]i were used as parameters for cell activation. Fc gamma RII and Fc gamma RIIIb stimulation was reached by cross-linking using fragments of monoclonal antibodies or incubation with monoclonal IgG cryoglobulin complexes. In parallel to the deficiency of Fc gamma RIIIb expression, H2O2 production and [Ca2+]i influx were decreased after cross-linking of Fc gamma RIIIb in PNH neutrophils compared with that for normal neutrophils. Stimulation via Fc gamma RII was not affected. Cryoglobulin complexes previously shown to activate normal neutrophils predominantly via Fc gamma RIIIb stimulated PNH neutrophils at a level not significantly weaker than controls. But this activation was mediated only via Fc gamma RII as shown by blocking studies. The results suggest that the loss of GPI-anchored Fc gamma RIIIb is functionally replaced by Fc gamma RII during the immune complex stimulation of PNH neutrophils. Therefore, the equipment of neutrophils with pleomorphic Fc gamma receptors prevents an immunodeficiency in PNH.

Calcium↗

Development of the glycosylphosphatitylinositol-anchoring defect characteristic for paroxysmal nocturnal hemoglobinuria in patients with aplastic anemia.

The introduction of immunosuppressive therapy for treatment of aplastic anemia has led to a considerable improvement in the prognosis of this disease. However, long-term follow-up of these patients showed a high incidence of "late" hematologic complications such as myelodysplasia and paroxysmal nocturnal hemoglobinuria (PNH). The detection of the glycosylphosphatitylinositol (GPI)-anchoring defect on peripheral blood cells of patients with aplastic anemia is now available as a new tool for early specific detection of PNH and is more sensitive than the Ham-test. Granulocytes appear to be the first cells affected in 11 patients with a GPI-anchoring defect of 29 suffering from aplastic anemia investigated in the present study. The later involvement of erythrocytes and a positive Ham test was observed in 1 patient. From our data it can be concluded that the rate of PNH resulting from aplastic anemia might be higher than reported in the literature when the Ham test alone was used for follow-up. Furthermore, our results suggest the clinical response to immunosuppressive therapy appears to be worse in the group developing the GPI-anchoring defect than in the group without this deficiency.

Adolescent↗

The value of prognostic factors in prostatic cancer.

Several prognostic parameters of prostatic carcinoma needed to help guide treatment in individual patients are discussed. Tumour volume, nodal and bone metastases, grading, prostate-specific antigen and DNA ploidy have been correlated with prognosis. Recent studies have analysed tumour volume in detail. However, currently there is no single prognostic factor which can predict tumour aggressiveness on an individual patient basis to rationalize decisions. Multivariate analyses are therefore in progress to determine independent prognostic variables.

Humans↗