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Biomedical subjects

R Ackermann

Publications and source records attributed to R Ackermann.

At least 55 records · Page 3Linked to original sources
PubMed1999

Urological treatment and clinical course of BK polyomavirus-associated hemorrhagic cystitis in children after bone marrow transplantation.

Hemorrhagic cystitis (HC) is a major complication of bone marrow transplantation (BMT). We describe the clinical course and urological management of BK polyomavirus-associated HC in children after bone marrow transplantation. From 8/88 to 11/95, a total of 117 consecutive pediatric patients received BMT. Nine patients (7. 7%) developed HC after transplantation. HC in all 9 patients was characterized by late onset (day +24 to +50 post-BMT), long duration (1-7 weeks) and the excretion of BK polyomavirus in the urine as confirmed by electron microscopy, DNA hybridization and PCR techniques. Six children developed mild HC (grade 1-2) and were treated successfully by hyperhydration. In 3 patients, severe HC (grade 3-4) over 6 weeks required surgical interventions. In these 3 patients, cystoscopy revealed circumscript papulous tumors as the source of hematuria. Severe and persistent hematuria required blood transfusions, insertion of large suprapubic catheters and permanent bladder irrigation because of recurrent blood clot retention. Attempts to stop the hematuria in 2 of these patients by coagulation and laser vaporization (Nd:YAG) failed to stop the bleeding. Differential diagnosis of hematuria after BMT includes urinary tract infection, cyclophosphamide-induced chemical cystitis and bleeding due to BMT-induced thrombocytopenia. With the increasing number of BMTs in children, urologists may be confronted with BK polyomavirus-associated HC and must consider this in the differential diagnosis of hematuria after BMT.

Adolescent↗
PubMed1998

[Positron emission tomography with [18 F]-2-fluoro-2-deoxy-D-glucose (18FDG-PET) in diagnosis of retroperitoneal lymph node metastases of testicular tumors].

In 1991, this prospectively designed study was started to assess the potentials of positron emission tomography with 18FDG in the diagnostic workup for the detection of lymph node metastases in testicular cancer, since there were no data available concerning this subject at this time. In 54 patients (27 patients with pure seminoma, 27 patients with non-seminomatous tumors) 18FDG-PET results were compared with the findings obtained with abdominal computed tomography, serum level of tumor markers (AFP, beta-HCG), and the histopathological findings after primary or post-chemotherapy retroperitoneal lymph node dissection. In 21 patients with pure seminoma (clinical stage I according to the Lugano classification) 18FDG-PET results were identical with those of the abdominal computed tomography, so PET does not add relevant informations in this group of patients. In 7 patients presenting with non-seminomatous testicular cancer (stage I), PET was not able to detect the existing micrometastases in 4 patients. In 1/7 case PET examination showed a suspicious focal lesion, this lymph node had 2 micrometastases within inflammatory changes. In 1/7 patient 18FDG-PET definitely revealed metastatic lesions, while the CT scans where judged to be unobtrusive and tumor marker levels were within the normal range. In the 4 patients with pure seminomas stage II B and II C (N = 6), that have undergone retroperitoneal lymph node dissection following chemotherapy, 18FDG-PET correctly predicted absence of tumor in 3 out of these 4, and in 1/4 patient the benign nature of a persistent large tumor after two cycles of polychemotherapy was correctly identified which eventually turned out to be a ganglioneuroma. This lesion falsely was classified as malignant tumor with abdominal computed tomography, and in 2/4 patients post-chemotherapy residual retroperitoneal lesions in the CT scans could not be assessed exactly whether or not malignant tumor was present. In 20 patients presenting with non-seminomatous testicular cancer (stage II and III) 18FDG-PET was able to demonstrate therapeutic effects of chemotherapy by showing decreasing tracer activity in those regions, that had hypermetabolic foci prior to chemotherapy. It became evident in testicular cancer that there is a single entity which is not characterized by increased glucose metabolism, the mature teratoma. In lesions detected by abdominal computed tomography which do not present increased 18FDG uptake, mature teratoma as well as scar/necrosis or rare other tumors with normal glucose metabolism can be supposed, but additional characteristics based on different 18FDG uptake were not observed. In 1/20 case post-chemotherapy PET scan detected a hypermetabolic lesion, which was suspicious for metastatic spread, but in the histopathological examination this lesion was identified as inflammatory tissue reaction. Based on the data reported here in 18FDG-PET cannot be considered a standard diagnostic tool in the staging examinations in testicular cancer. It is of clinical relevance in patients who present residual tumor after chemotherapy. In this situation 18FDG-PET is helpful in deciding whether or not a residual mass post-chemotherapy contains active tumor. 18FDG-PET can not replace retroperitoneal lymph node dissection for staging purposes.

Adult↗
PubMed1998

Collagens in the liver extracellular matrix bind hepatocyte growth factor.

BACKGROUND & AIMS: Hepatocyte growth factor (HGF), a potent mitogen for hepatocytes, binds to heparan sulfate. Because immunoreactive HGF can be detected in the interstitial extracellular matrix (ECM), where little heparan sulfate is found, the aim of this study was to investigate binding of HGF to several collagens and noncollagenous ECM proteins in vitro. METHODS: 125I-labeled HGF was incubated with collagens I-VI, single collagen chains and their cyanogen bromide peptides, with fibronectin, fibrinogen, and laminin that were either immobilized on polystyrene or blotted to nitrocellulose after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Biological activity of collagen-bound HGF was investigated in cell culture. RESULTS: HGF displayed binding of moderate affinity (Kd approximately 10(-9) mol/L) to immobilized collagen types I, III, IV, V, and VI. Binding of HGF to all collagens could be inhibited by single chains of either collagens I, III, or VI. Fragmentation with cyanogen bromide indicated unique collagenous peptides mediating the interaction. Collagen-bound HGF induced primary hepatocyte proliferation and MDCK cell scattering in a dose-dependent manner. CONCLUSIONS: Interstitial collagens I, III, V, and VI serve as abundant, low-affinity binding sites for HGF in the ECM. This interaction is mediated by unique collagenous peptides, opening the potential to modulate HGF availability and activity by collagen-derived peptide analogues.

Cells, Cultured↗
PubMed1998

Dual-parameter immunoflow cytometry in diagnosis and follow-up of patients with bladder cancer.

OBJECTIVES: The aim of this study was to evaluate the clinical significance of a dual-parameter immunoflow cytometry (DPI-FCM) assay in the detection of tumor cells in barbotage specimens of bladder cancer patients. METHODS: DPI-FCM is an automated method, based on the utilization of two monoclonal antibodies (mAbs) either used for a preselection of urothelial cells (mAb Due AUT 2) or the analysis of the expression of a differentiation antigen within the preselected urothelial cells (mAb Due ABC 3). The ratio of ABC 3-positive urothelial cells was used to discriminate between the normal and malignant state of the urothelium. At the time of examination 40 patients had endoscopically overt bladder tumors. Another 30 patients without endoscopically visible tumors were examined before routine rebiopsy. Thirty barbotage specimens from patients with diseases not related to bladder cancer were examined as controls. RESULTS: Overall, the sensitivity of DPI-FCM in patients with endoscopically overt and invisible residual tumors was 95 and 83%, respectively, regardless of concomitant urinary tract infection. The sensitivity of DPI-FCM for both patient groups was 86, 95 and 94% for tumor grades 1, 2 and 3, respectively. The specificity of the method in 30 patients with no history of bladder cancer was 93%. CONCLUSIONS: DPI-FCM appears to be a highly reliable method of recognizing tumor cells in bladder barbotage specimens even in patients with concomitant urinary tract infection. The procedure may be of value in monitoring bladder cancer patients for tumor recurrence.

ATP-Binding Cassette Transporters↗
PubMed1998

Epididymal metastasis of a prostatic carcinoma.

We report the case of a 73-year-old patient who presented with a local recurrence of a prostatic carcinoma which had metastasized to the right epididymis. The histopathological examination of the resected tissue after transurethral resection of the prostate 8 years before revealed a pluriformal adenocarcinoma of the prostate, but the patient refused any kind of therapy at that time.

Adenocarcinoma↗
PubMed1997

[Surgical therapy of locally confined prostate carcinoma].

Since prostate specific antigen (PSA) has been established as marker for screening, a dramatic increase of prostatic cancer incidence has been observed over the past years. A further consequence of PSA-measurements lies in the observation that nowadays the majority of newly diagnosed prostatic carcinoma is in a clinically localized stage and therefore amendable to radical prostatectomy in a curative intervention. An important task yet to be solved is to find parameters able to estimate the malignant potential of the tumor preoperatively. Long-term results of radical prostatectomy are explained and the possibilities for reduction of intra- and perioperative complications are discussed.

Biomarkers, Tumor↗
PubMed1997

Screening for renal carcinoma associated mutations in the von Hippel-Lindau tumor suppressor gene by temperature gradient gel electrophoresis.

Renal cell carcinoma is the most common neoplastic disease of the adult kidney and occurs in its sporadic and hereditary form. Approximately 57% of all renal carcinomas of the clear cell type analyzed revealed a mutation in the von Hippel-Lindau disease (VHL) gene. In the present work, temperature gradient gel electrophoresis (TGGE) is presented as a rapid and precise polymerase chain reaction (PCR)-employing methodology for the detection of mutations in the VHL gene. The theoretical efficiency of TGGE to detect mutations in every base pair of the gene was calculated. According to computer analysis, at least 92% of all known mutations in the VHL gene are detectable. This calculated figure appears to be in agreement with the experimental results. Primary difficulties in analyzing exon 1 of the VHL gene were overcome by the employment of psoralen-cross-linked PCR fragments. In addition, TGGE analysis was used in screening for possible mutations in thirteen renal carcinoma samples. With this protocol TGGE is successfully added to the array of methods for the screening of VHL mutations.

Aged↗
PubMed1997

c-myc in bladder cancer. Clinical findings and analysis of mechanism.

The c-myc gene product is known to be involved in the regulation of cell proliferation and differentiation. Altered c-myc gene expression is a common event in a variety of tumors. This study was designed to investigate c-myc overexpression in transitional cell carcinoma (TCC). The first part was designed to investigate the frequency of c-myc overexpression in relation to tumor stage and tumor grade. A second set of experiments was directed at the mechanisms underlying c-myc overexpression in TCC. A total of 185 paraffin-embedded urothelial tissue specimens were investigated immunohistochemically for c-myc overexpression. A single case of overexpression (6%) was observed in normal urothelial tissue (n = 16). c-myc overexpression was also infrequent in carcinoma in situ (TIS) (7/39 = 18%). In contrast, papillary urothelial tumors (n = 65) yielded c-myc overexpression in 38 cases (58%). Investigation of infiltrating bladder tumors revealed c-myc overexpression in 56% of T1 tumors and 59% of muscle-infiltrating tumors. The staining pattern in multifocal tumors was heterogeneous in 10 of 18 cases. Similarly, only 12 of 28 patients with tumor recurrences showed the same c-myc staining pattern in the primary tumor and in tumor recurrences. c-myc overexpression did not correlate with tumor grade or tumor progression. Nevertheless, the high frequency of c-myc overexpression in urothelial carcinoma suggests an important role for this protein in urothelial carcinoma. Therefore, the mechanism underlying c-myc overexpression was further investigated in six bladder carcinoma cell lines. Southern blot experiments under standardized conditions showed no significant gene amplification. The comparison of c-myc mRNA expression to that of histone H3 as a measure of cell proliferation revealed a moderate correlation (r = 0.45) in the six cell lines examined. These data suggest that in accord with its established role as a cell cycle competence factor, c-myc may be necessary but not sufficient for the induction of proliferation in urothelial carcinoma.

Aged↗
PubMed1997

Alterations of the metastasis suppressor gene nm23 and the proto-oncogene c-myc in human testicular germ cell tumors.

The putative metastasis suppressor genes nm23-H1, nm23-H2 and the c-myc proto-oncogene were investigated in testicular germ cell tumors (GCTs) using Southern and Northern blotting as well as semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and single strand conformation polymorphism (SSCP) analysis. When studying Bgl II RFLPs, allelic losses of the nm23 gene were found in 3/12 (25%) informative tumors, and all 3 had lymph node and/or distant metastases. A 2 to 7 fold nm23 mRNA overexpression was found in 22/34 (64.7%) tumors examined. RT-PCR revealed that this phenomenon is mainly a consequence of nm23-H2 overexpression. Overexpression of both the H1 and the H2 gene was predominantly found in the seminoma subtype and was not associated with tumor stage. Only 1/25 tumors, a seminoma with distant metastases, had a point mutation in the coding region of the nm23-H2 gene as demonstrated by SSCP analysis. None of the 8 seminomas and only 1/13 non-seminomas had c-myc overexpression. No abnormalities of the c-myc gene could be detected on the DNA level. Despite the fact that in previous investigations nm23-H2 was demonstrated to be a putative transcription factor for c-myc, no coexpression of c-myc and nm23-H2 was found by quantitative RT-PCR in this study.

Chromosome Aberrations↗
PubMed1997

Evaluation and follow-up of patients with N1-3 M0 or NXM1 prostate cancer in phase III trials.

OBJECTIVES: The aim of this discussion is to review the design and conduct of phase III trials in metastatic prostate cancer, to seek ways of improving their study design, accuracy, relevance to clinical practice, acceptability to patients, and ease of participation by clinicians. We also aim to try to set uniform definitions for the evaluation of the different endpoints used in clinical trials on metastasized prostate cancer. METHODS: The work was started by correspondence between the participants in the group for the year before the consensus meeting. Two comprehensive questionnaires were circulated and the answers were distributed to all the members of the group. The statements were finalized during the consensus meeting. RESULTS: There were some differing opinions concerning the methods of evaluation of endpoints for follow-up, such as time to tumor progression and time to treatment failure. After the consensus conference, there were no major disagreements within the group. CONCLUSIONS: The aim of phase III trials is to influence clinical management. To obtain a credible result they require a sound statistical basis with appropriate power and encompassing patients from small urologic practices as well as large or academic institutions. However, deviation from routine practice may affect the accrual rate, and the trial procedure should therefore be as similar as possible to routine management. Trials inevitably involve extra work and cost. Both should be kept to a minimum to encourage participation and hasten a timely conclusion. It is mandatory to create uniform ways of designing and evaluating clinical trials in prostate cancer.

Clinical Trials, Phase III as Topic↗
PubMed1997

P-element inserts in transgenic flies: a cautionary tale.

The fruitfly, Drosophila melanogaster, can be transfected with P-elements and induced to overexpress a transfected gene whose impact on lifespan can be measured. Here, it is reported that in previous experiments a transfected gene was not expressed. This suggested a new statistical analysis indicating that (1) the size of the insert, the position and the interactions of the insert with the genetic backgrounds into which the P-element are inserted have effects on lifespan similar to those attributed to overexpression; (2) these effects occur without expression of the transfected gene; and (3) effects of interactions with backgrounds and effects of positions are as large as responses to six generations of strong directional artificial selection. Reports of effects of overexpression of transfected genes on lifespan in Drosophila melanogaster may be experimental artefacts. Credible experiments on the phenotypic effects of transgenesis need proper controls for the effects of insert size and position and should estimate the magnitudes of interactions of treatment with genetic backgrounds.

Animals↗
PubMed1997

Avoiding complications of radical retropubic prostatectomy.

During the past 15 years radical retropubic prostatectomy (RRP) has become the treatment of choice for localized prostate cancer. Before the 1980s the procedure was characterized by a significant number of intraoperative, postoperative and long-term complications. Since then the operation has evolved continuously, using the results from anatomical studies, and has resulted in a marked reduction in the morbidity and mortality associated with this procedure. The modern, anatomical approach to RRP emphasizes the principles of direct visualization and identification of the anatomical structures in the pelvis. Management of the dorsal vein complex and techniques for apical resection of the prostate, combined with improved understanding of the pelvic floor anatomy, have contributed to a reduced frequency of postoperative incontinence. The identification and localization of the "erectile nerves' (autonomic branches of the pelvic plexus to the corpora cavernosa) in the neurovascular bundles outside the prostatic capsule and Denonvilliers' fascia enables nerve-sparing surgery. In selected cases, sparing of the neurovascular bundles is possible to preserve sexual function without compromising cancer control as the principal goal of RRP.

Blood Loss, Surgical↗
PubMed1997

FDG-PET evaluation of retroperitoneal metastases of testicular cancer before and after chemotherapy.

We describe a patient whose primary tumor was a testicular teratocarcinoma predominantly composed of embryonal carcinoma. Before chemotherapy, the retroperitoneal metastases demonstrated heterogeneous, increased glucose metabolism as measured by 2-[18F]fluoro-2-deoxy-D-glucose and PET (FDG-PET). After chemotherapy, FDG uptake was reduced to normal values despite increased tumor volume. Histology revealed a pure mature teratoma. This observation suggests that further studies are needed to determine whether tumor differentiation of testicular teratocarcinoma metastases can be assessed by measuring glucose metabolism.

Adult↗
PubMed1997

Analysis of the DCC tumor suppressor gene in testicular germ cell tumors: mutations and loss of expression.

Inactivation of the DCC (Deleted in Colon Carcinoma) tumor suppressor gene by allelic loss and/or reduced expression is associated with the development of colon cancer, gliomas, gastric and prostatic malignancies. In a total cohort of 51 testicular germ cell tumors (GCT) of different histologies we analyzed restriction fragment length polymorphism (RFLP) for DCC at two specific DNA sites in 37 GCT and DCC mRNA expression compared to that of the adjacent normal testicular tissue in 41 GCT, one Leydig cell tumor and one testicular metastasis of a non-small cell lung cancer (NSCLC). Two of 17 tumors (11.7%) informative for the Msp I polymorphic site of the DCC gene and 6/25 tumors (24.0%) informative for variable number of tandem repeat (VNTR) showed loss of heterozygosity (LOH). DCC expression was analyzed by semi-quantitative polymerase chain reaction after initial reverse transcription (RT-PCR). Thirty of 41 GCT (73.1%) and both, the Leydig cell tumor and the testicular metastasis of NSCLC, had a nearly complete or total loss of DCC mRNA expression. Six of 11 (54.5%) seminomas and 24/30 (80.0%) nonseminomas had this loss of expression. Twelve of 17 (70.5%) localized tumors, 9/13 (69.2%) tumors with lymph node involvement and 9/11 (82.2%) tumors with distant metastases showed decreased or absent DCC expression. This data suggests that inactivation of the DCC gene, especially the loss of DCC expression, is associated with the development and progression of human GCT.

Gene Expression Regulation, Neoplastic↗
PubMed1997

Chronic granulomatous disease masquerading as a bladder tumor: a potential source of diagnostic error.

Chronic granulomatous disease (CGD) is a rare inherited disease of childhood, characterized by recurrent bacterial or fungal infections. The underlying defect is a dysfunction of neutrophil granulocytes interfering with their ability to kill phagocytosed microorganisms. Genitourinary tract involvement has been reported in 38% of these patients. We report a case of CGD in whom the most important findings were urinary bladder tumors at different locations and a subsequent obstruction of the left ureter. A review of the pathogenesis of the disease, potential involvement of the urinary tract and treatment is presented.

Adult↗
PubMed1997

p53 and MDM2 in the development and progression of bladder cancer.

OBJECTIVE: Earlier investigations have demonstrated that inactivation of the p53 tumor suppressor gene might play a role in the development and progression of bladder cancer. Complex formation with the MDM2 oncogene product is one mechanism inactivating the p53 protein. Therefore, the MDM2 and the p53 protein were investigated to study potential interactions in bladder cancer. METHOD: 200 archival bladder tissue specimens from 92 patients were studied by immunohistochemistry using monoclonal antibodies DO-1 against p53 and IF2 against MDM2. RESULTS: No staining was observed for p53 or MDM2 in normal urothelium. Alterations of both genes were rare in dysplasia. p53 accumulation was observed in 27-44% of the tumor stages examined. MDM2 overexpression increased from 18% in carcinoma in situ to 49% in T1 tumors, but was present in only 22% of the advanced tumors. Alterations of both genes were more frequent in high-grade lesions. To investigate the prognostic impact of these alterations 61 patients with superficial bladder tumors were followed for at least 2 years (mean 51 months). Multivariate analysis demonstrated that multifocal disease and p53 accumulation were significantly correlated with tumor progression (p = 0.0099 and 0.0135). MDM2 overexpression alone had no prognostic significance. Patients with alterations of both genes had a very high risk of tumor progression (p = 0.0064). CONCLUSION: These results demonstrate a positive correlation between p53 accumulation and MDM2 overexpression in the progression of bladder cancer which may have prognostic value.

Carcinoma in Situ↗
PubMed1996

Collagen VI regulates normal and transformed mesenchymal cell proliferation in vitro.

Suggestions exist that, in addition to traditional growth factors, the extracellular matrix (ECM) of a cell can regulate its proliferation. This hypothesis was investigated with normal and transformed fibroblasts because they exhibit specific intracellular responses after adherence to ECM and produce large quantities of ECM proteins. Although cells cultured on different ECM proteins grew more rapidly than those on plastic, adherence and cell growth on an individual ECM protein were not correlated. To test if ECM can stimulate cell growth, soluble ECM proteins were given to cells after plating. In this culture system only collagen VI (CVI), at a concentration of 20 microg/ml in medium, increased 3T3 cell number to 402% of control by 72 h. Similar increases of human fibroblasts and HT 1080 cell numbers were noted. DNA synthesis of all three cell types increased 24 h after addition of soluble CVI. A mixture of CVI single chains, yielded by reduction and alkylation, was not stimulatory. However, this mixture efficiently inhibited the DNA synthesis induced by native CVI. Antibody inhibition studies showed that the region of CVI stimulating proliferation differs from the site bound by the integrin receptor alpha2beta1, which mediates cell adhesion to immobilized CVI. Heparin inhibited a portion of CVI-induced proliferation. These data demonstrate that CVI can stimulate mesenchymal cell growth via a pathway that is independent of the integrin alpha2beta1 and that the stimulatory region appears to be within the native helical portion of the collagen.

3T3 Cells↗