Search PubMed⌕ Search

Biomedical subjects

R Ackermann

Publications and source records attributed to R Ackermann.

At least 73 records · Page 4Linked to original sources

Molecular biology of dissemination in bladder cancer--laboratory findings and clinical significance.

Recent molecular biology investigations have demonstrated that tumor progression and dissemination in bladder cancer is a highly complicated phenomenon, consisting of multiple distinct steps and regulated by a great number of different genes. Some of these genes involved in the specific steps of tumor progression and dissemination have been identified. Several oncogenes, e.g., the epithelial growth factor receptor (EGF-R), and tumor-suppressor genes, e.g., the p53 gene, have been found to correlate significantly with tumor progression. The decreased expression of cell-adhesion molecules such as E-cadherin appears to facilitate tumor-cell detachment in the primary tumor, whereas expression of the intercellular adhesion molecule (ICAM)-1 might be of relevance for cell attachment at the metastatic site. Tumor invasion through the basement membrane has been correlated with a decreased expression of laminin and elevated urinary levels of acidic fibroblast growth factor. Although the complex processes related to dissemination are far from being completely understood, the finding of differential expression of distinct genes appears to provide the first targets for therapeutic intervention.

Animals↗

Color Doppler sonography of the prostate.

Digital rectal examination, prostate-specific antigen and transrectal sonography (TRS) are the main diagnostic tools for evaluating men at risk for carcinoma of the prostate (PCa). PCa has a hypoechoic echo pattern via TRS in 60- 85% of cases. Hypoechoic areas are observed, however, in benign prostatic hyperplasia (BPH) as well. For this reason, TRS yields a low specificity and sensitivity in detecting PCa in screening programs. Additional data, independent of the grey scale information available via TRS, can be obtained by using the innovative technology of color Doppler sonography. This imaging modality allows simultaneous real-time sonographic visualization and evaluation of vascular structures. The present study analyzes to what extent the analysis of blood flow perfusion of prostatic parenchyma can provide further information concerning the pathologic alterations occurring in abnormal prostate tissue. Blood flow phenomena were reproducibly demonstrated in the prostate and in the periprostatic tissue with the color-coded Doppler sonography (CD-TRS). 31 patients with the diagnosis of BPH could be separated into two different groups according to the findings with TRS and CD-TRS. In contrast, patients with histologically proven PCa (n = 16) had subjectively increased perfusion rates. Blood flow phenomena were analyzed using computer-calculated resistive index and pulsatility index as evaluations of flow and frequency. A preliminary analysis of the wave-form characteristics shows that flow in the prostate gland is associated with a high resistive index in both PCa and BPH. The mean frequency demonstrated in the pulsatility index appears to be high in PCa, but low in BPH cases. Further studies are needed to verify the described factors' abilities to differentiate prostate tissue as either PCa or BPH.

Humans↗

Angiocentric lymphoma of the kidney in the acquired immunodeficiency syndrome.

Angiocentric lymphoma, which is the malignant counterpart of angiocentric immunoproliferative lesions, comprises a rare group of non-Hodgkin's lymphomas of T-cell origin. It is characterized by marked invasion and destruction of small vessels by lymphomatoid cells, predominantly in the lungs. The prognosis is poor and many patients die within several months. To our knowledge primary involvement of the genitourinary tract has not been previously reported. We report a case of a solitary primary angiocentric lymphoma of the kidney in a patient with the acquired immunodeficiency syndrome. Therapy consisted of nephrectomy without adjuvant treatment. Histological characteristics as well as diagnostic and therapeutic options are discussed.

Acquired Immunodeficiency Syndrome↗

Expression of the c-kit proto-oncogene and its ligand stem cell factor (SCF) in normal and malignant human testicular tissue.

Recent findings suggest an important role of the proto-oncogene c-kit, a surface membrane receptor of the tyrosine kinase family, and its ligand stem cell factor (SCF) in normal spermatogenesis and possibly in the pathogenesis of certain testicular germ cell tumors. To further investigate this potential role, the expression of c-kit and SCF was studied in normal and malignant human testicular tissue specimens at the mRNA and protein level by Northern blot analysis and immunohistochemistry, respectively. The detection of the c-kit receptor in normal human germ cells and its natural ligand SCF in Sertoli cells suggests the presence of a local trophic regulatory system that may be active in human spermatogenesis. Additionally, c-kit expression was detected in the seminoma but not in the nonseminoma subtype of human testicular germ cell tumors (GCT). Stem cell factor was not expressed at the mRNA level in tissue from either subtype of GCT as determined by Northern blot analysis; however, the protein was detected immunohistochemically in the cytoplasm of rare tumor cells.

Cell Adhesion Molecules↗

Dual-parameter immunoflow cytometry--a new technique in the noninvasive diagnosis of bladder cancer.

The introduction of monoclonal antibodies into the diagnosis of transitional cell carcinoma (TCC) has been a further step toward the use of biological parameters to support conventional cytological diagnosis of this tumor entity. Several investigators have demonstrated the high sensitivity and good specificity of immunocytology. Nevertheless this technique is hampered by the inconvenient and time-consuming microscopic analysis. The purpose of this study was to combine the advantages of immunocytology with the capabilities of an automated flow-cytometric system. Since all monoclonal antibodies (mAbs) currently used for immunocytology cross-react with granulocytes a preselection of urothelial cells becomes necessary for immuno-flow cytometry (immuno-FCM). Based on earlier analyses mAb Due AUT 2, reactive against urothelium and not against granulocytes, was chosen to preselect for urothelial cells. mAb Due ABC 3 was used to discriminate between normal and malignant urothelial cells. Initial experiments including 10 barbotage specimens from patients with histologically proven TCC and concomitant urinary tract infection yielded a high sensitivity (90%) of immuno-FCM. In 10 control patients with malignancies other than bladder TCC and benign diseases ABC 3 expression was not increased. Flow-cytometric examination of irrigation specimens from 10 patients with a history of bladder cancer but without cystoscopic and cytologic evidence of tumor recurrence showed abnormal results in 6 patients. Rebiopsy and/or cystectomy confirmed tumor recurrence in 5 of these patients and in 1 patient with negative immuno-FCM. Ongoing prospective trials will further define the clinical impact of this approach in the diagnosis and follow-up of patients with bladder cancer.

Antibodies, Monoclonal↗

High-intensity focused ultrasound (HIFU) in the treatment of benign prostatic hyperplasia (BPH).

Transurethral resection of the prostate (TURP) and open adenectomy are regarded the golden standard in the management of patients with symptomatic benign prostatic hyperplasia (BPH). Various alternative treatment forms (microwaves, laser, radiofrequency, focused ultrasound) have been introduced recently. They all aim at reduction of morbidity related to TURP keeping a comparable efficacy at the same time. Since December 1992, 50 patients with BPH have been treated by high intensity focused ultrasound (HIFU-P) at our department. Six weeks following HIFU-P mean Qmax improved from 5.7 ml/s to 11.6 ml/s. Post voiding residual volume (RV) dropped from 215 ml to 100 ml, the International Prostate Symptom Score (IPSS) from 19.8 to 9.9. Both, IPSS and RV further improved during the following weeks. Follow-up data one year after treatment demonstrate that results remained stable in the majority of patients. Urinary tract infections were observed in 3 patients, macrohematospermia in all and macrohematuria (caused by the suprapubic catheter) requiring blood transfusion in 1 patient.

Aged↗

[High energy focused ultrasound in treatment of benign prostatic hyperplasia].

Transurethral resection of the prostate (TURP) and open adenectomy are regarded the "golden standard" in the treatment of benign prostate hyperplasia (BPH). Various alternative treatment forms (microwaves, laser, radio frequency, focused ultrasound) have been introduced recently. They are all aimed at reducing the morbidity related to TURP while achieving comparable efficacy at the same time. Since December 1992, 35 patients with BPH have been treated with high-intensity focused ultrasound (HIFU-P) in our department. By 6 weeks after HIFU-P, mean Qmax had improved from 6.5 ml/s to 12.1 ml/s. Residual volume dropped from 207 ml to 95 ml, IPSS from 20.1 to 9.7. Both subjective as well as objective improvements remained stable after 3 and 6 months. Urinary tract infections were observed in 3 patients, macrohemato-spermia in all, and macrohematuria (caused by the suprapubic catheter) requiring blood transfusion in 1 patient.

Aged↗

The effect of father absence on the psychiatric hospitalization of Navy children.

Some Navy families are subject to unusual stress in that the active duty parent may be deployed for several months at a time. This study examined children and adolescents from Navy and civilian families who were admitted to a private psychiatric hospital. Deployment of the father placed Navy children and adolescents at risk for psychiatric hospitalization, but mainly in non-intact families where step-parents or single parents were present. Deployment may strain an already vulnerable family structure in selected Navy families.

Adolescent↗

Protein synthesis elongation factor EF-1 alpha expression and longevity in Drosophila melanogaster.

It has been proposed that the decline in protein synthesis observed in aging organisms may result from a decrease in elongation factor EF-1 alpha. Transgenic Drosophila melanogaster flies carrying an additional copy of the EF-1 alpha gene under control of a heat-inducible promoter have an extended lifespan, further indicating that the EF-1 alpha gene may play an important role in determining longevity. To test this hypothesis, we have quantitated EF-1 alpha mRNA, EF-1 alpha protein, and the EF-1 alpha complex-formation activity in these transgenic flies. Furthermore, we have tested whether the transgene construct is functional--i.e., whether transgenic mRNA is induced when flies are grown at higher temperature. The results show that although there is a clear difference in mean lifespan between the EF-1 alpha transgenic (E) flies and the control transgenic (C) flies, E flies do not express more EF-1 alpha protein or mRNA than C flies kept at the same experimental conditions. Although the transgene can be induced when E flies are heat-shocked at 37 degrees C, transgenic mRNA is not detectable in E flies aged at 29 degrees C. In both lines, the loss in catalytic activity with age is the same. We conclude that the E flies examined here do not live longer because of overexpressing the EF-1 alpha gene.

Animals↗

Determination of acenocoumarol in human plasma by capillary gas chromatography with mass-selective detection.

A method for the determination of acenocoumarol in human plasma by capillary gas chromatography-mass-selective detection is described. After addition of a structurally related analogue as the internal standard, the compounds are extracted from plasma at acidic pH into toluene, back-extracted with a basic solution and re-extracted from hydrochloric acid solution with toluene, which is then evaporated to dryness. The compounds are converted into their methyl derivatives, which are determined by gas chromatography using a mass-selective detector at m/z 324 for acenocoumarol and m/z 338 for the internal standard. The reproducibility and accuracy of the method were found to be suitable over the acenocoumarol concentrations range 2.2-74 nmol/l. The method could be considered as selective for acenocoumarol in the presence of its major metabolites in plasma.

Acenocoumarol↗

P53 accumulation in precursor lesions and early stages of bladder cancer.

Recent investigations have demonstrated alterations of the p53 tumor-suppressor gene in a considerable number of transitional-cell carcinoma (TCC) specimens. Thus far, these investigations have been restricted to either papillary TCC or invasive bladder cancer. To obtain further information on a possible involvement of p53 in bladder cancer development or tumor progression, investigations of precursor lesions and early stages of this disease are required. Immunohistochemical examination of 6 dysplasias and 24 carcinomas in situ (TIS) showed p53 accumulation, which is suggestive of p53 inactivation, in 2 (33%) and 9 (38%) of these specimens, respectively. This ratio was similar in 9 T1 lesions (33%) and in 14 cases of muscle-infiltrative disease (35%). In papillary tumors, p53 accumulation was observed exclusively in 3/10 moderately differentiated or high-grade lesions but not in 1 Ta G1 tumor. The expression of p53 accumulation was a consistent finding. The examination of tumor recurrences yielded either the presence or the absence of p53 overexpression in the primary and recurrent tumors of 7/8 patients. Similarly, in multifocal TCC, p53 accumulation was also either present or absent in 10/11 cases examined. These results suggest the existence of at least two different subgroups of TCC, with p53 accumulation being present in one of these groups. The observation of p53 accumulation in dysplasia and in TIS is a prerequisite for a possible involvement of p53 in bladder cancer carcinogenesis, although it does not prove this assumption.

Carcinoma in Situ↗

Cell surface expression and serum levels of intercellular adhesion molecule-1 in renal cell carcinoma.

Intercellular adhesion molecule-1 (ICAM-1) is the natural ligand of the T-lymphocyte adhesion molecule LFA-1 (lymphocyte-function-associated antigen-1). ICAM-1 is involved in target cell recognition by T-lymphocytes, LAK cells and natural killer cells. The molecule has also been detected on a variety of normal cells and on human tumors. Renal cell carcinoma (RCC) is one of the few tumors that respond to immunotherapy, but clinical results are generally disappointing. We therefore analyzed, by immunohistochemistry, the expression of ICAM-1 in pairs of normal kidneys, RCC, and RCC metastases. Moreover, serum ICAM-1 was determined in RCC patients and compared with surface expression of cell-bound ICAM-1. Strong glomerular expression of ICAM-1 was observed in all specimens of normal kidney examined. Proximal tubuli were weakly stained in the majority of specimens. Of the tumors, 80% stained positive for ICAM-1. Although ICAM-1 was detected on the majority of extrarenal tumor specimens examined, staining was generally weaker in the metastases. Patients without metastases at initial presentation more frequently expressed ICAM-1 in their primary tumors than did patients with metastases. Levels of serum ICAM-1 (sICAM-1) were significantly higher in RCC patients than in controls with non-malignant renal diseases. Patients with an unfavorable prognosis, e.g. with advanced tumor stage or metastasis at initial presentation, had higher levels of sICAM-1 than patients with low-grade and/or low-stage tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Antibody responses to the three genomic groups of Borrelia burgdorferi in European Lyme borreliosis.

The antibody responses to the three genomic groups of Borrelia burgdorferi (B. burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii) were determined in 97 German patients with various manifestations of Lyme borreliosis. The geometric mean antibody titers in each patient group, determined by ELISA, were similar with each antigen preparation. By Western blotting, however, patients with meningopolyneuritis tended to respond to more spirochetal polypeptides of B. garinii, the group 2 strain, whereas those with arthritis recognized more antigens of B. afzelii, the group 3 strain (P < .03), as did those with acrodermatitis. Only 1 patient each with erythema migrans, arthritis, or acrodermatitis had weak reactivity with outer surface protein A (OspA), and none responded to OspB. It is concluded that differences among the three groups of B. burgdorferi may result in variations in the antibody response in European Lyme borreliosis.

Antibodies, Bacterial↗

Immunohistochemical studies on the expression of HLA class I antigens in renal cell carcinoma: comparison of primary and metastatic tumor tissue.

HLA class I expression was studied in 43 specimens of normal renal tissue, 48 primary renal cell carcinomas (RCCs), and 12 metastases by immunofluorescence, using two different monoclonal antibodies (MoAbs; IOT2c, W6/32). Homogenous staining of all normal renal tissues was observed, as expected. From the panel of 48 renal tumors, 40 had a strong expression of HLA class I antigens when tested with both MoAbs, 7 tumors had only weak expression of HLA class I and were regarded as 'HLA class I negative', and 1 tumor showed homogenous staining when tested with one MoAb (IOT2c) but was negative when the other was used (W6/32). This was the only case in which different results with the two MoAbs were found. Reduced expression of HLA class I antigens was observed in 5/12 metastases, and in 1 metastasis no expression of HLA class I could be seen. The staining chartacteristics of 10 metastases in comparison with the respective primary tumors were as follows: same HLA class I score 7/10; loss of HLA class I 3/10; gain of HLA class I 0/10. In RCC, a complete loss of HLA class I expression is a rare phenomena, which was observed in 0/48 primary tumors and in 1/12 metastases. Reduced expression of HLA class I antigens occurs in about 15% of primary tumors but is more frequent (50%) in metastases; however, if this is relevant for cytotoxicity by T lymphocytes is unknown.

Carcinoma, Renal Cell↗