Search PubMed⌕ Search

Biomedical subjects

P Rudolph

Publications and source records attributed to P Rudolph.

At least 73 records · Page 4Linked to original sources
PubMed1997

Immunophenotyping of dermal spindle cell tumors: diagnostic value of monocyte marker Ki-M1p and histogenetic considerations.

Various studies have reported the utility of anti-CD34 staining in the differential diagnosis of dermal spindle-cell tumors. To investigate whether monoclonal antibody Ki-M1p might add practical diagnostic information, we examined a total of 120 cutaneous spindle cell neoplasms using a panel of markers. Anti-CD34 antibody QBEnd/10 consistently stained dermatofibrosarcomas, Kaposi's sarcomas, neurofibromas, and, to a lesser extent, hemangiopericytomas. A positive reaction was also found in > 18% of the dermatofibromas. Ki-M1p staining showed an intense immunoreaction in all dermatofibromas, whereas no reactivity was observed in dermatofibrosarcomas. In addition, a subset of cells was labeled in atypical fibroxanthomas and Kaposi's sarcomas. Neurofibromas, spindle-cell hemangioendotheliomas, and hemangiopericytomas were negative. Dermatofibrosarcomas and atypical fibroxanthomas also moderately expressed smooth muscle-specific actin. Immunohistochemically, a discrimination between dermatofibrosarcomas and neurofibromas was possible only by means of an antibody against the nerve growth factor receptor. We conclude that the combination of several antibodies, in particular anti-CD34 and Ki-M1p, may improve the accuracy of diagnostic immunohistochemistry in the field of cutaneous spindle cell tumors. We speculate that dermatofibroma is primarily a macrophage-rich inflammatory lesion in which cytokine secretion induces a secondary proliferation of fibroblasts, whereas dermatofibrosarcoma is likely to issue from primitive dermal cells of uncertain origin.

Antibodies, Monoclonal↗
PubMed1997

One single erythemagenic UV irradiation is more effective in increasing the proliferative activity of melanocytes in melanocytic naevi compared with fractionally applied high doses.

The effect of a single irradiation with UV light on the expression of Ki67 antigen, topoisomerase II alpha, proliferating cell nuclear antigen (PCNA), the melanocyte activation marker HMB-45 and protein p53 in melanocytic naevi was investigated 1 week after application of a single erythemagenic UV dose and after daily exposures with suberythemagenic doses over 4-6 weeks. To assess the effect of UV irradiation, one half of each naevus was shielded with black tape during the UV exposure, and the irradiated part and the non-irradiated parts were evaluated separately. Except for HMB-45, a double staining procedure was performed to distinguish between labelled melanocytes and keratinocytes. After semiquantitative assessment of the staining signal the irradiated part was compared with the non-irradiated part of the same naevus. Morphological changes and an enhanced proliferative/ reparative activity in melanocytes were much more frequent in the naevi irradiated with a single erythemagenic UV dose than in those given repeated suberythemagenic doses. In addition, the keratinocytes showed an increased labelling for PCNA and p53 after the single irradiation. These data may support the importance of intermittent UV exposure and sunburns in the development of both benign and malignant melanocytic lesions.

Adult↗
PubMed1997

Detection of human topoisomerase II alpha in cell lines and tissues: characterization of five novel monoclonal antibodies.

We report five novel monoclonal antibodies (Ki-S1, Ki-S4, Ki-S6, Ki-S7, and Ki-S8) reactive with a proliferation-related nuclear antigen. In immunoprecipitation and Western blot experiments using crude nuclear extracts, they recognized a protein of 170 kD that, after proteolytic digestion of the immunoprecipitate and sequencing of the resulting peptides, was identified as the alpha-isoform of human topoisomerase II. This was confirmed by testing the antibodies on a highly purified enzyme preparation. Crossreactivity with topoisomerase II beta was ruled out by testing the antibodies on crude extracts from yeast cells expressing the beta-isoform exclusively. The antibodies bind the antigen with different affinities and at different epitopes, apparently located within the carboxyl third of the enzyme. All five antibodies are suitable for archival material after adequate antigen retrieval, thereby enabling retrospective studies. This report illustrates the tissue and subcellular distribution of the antigen through the cell cycle by immunohistochemistry and confocal fluorescence microscopy. The antibodies will be useful tools in further analysis of morphological and functional aspects of topoisomerase II and may serve diagnostic purposes, as well as providing prognostic information in tumor pathology.

Antibodies, Monoclonal↗
PubMed1997

Prognostic significance of the proliferative activity in neuroblastoma.

The prognostic significance of the immunohistochemically assessed growth fraction in neuroblastomas was determined in relation to tumor grade and tumor stage. A total of 101 cases of neuroblastoma were examined with the monoclonal antibodies PC10 against proliferating cell nuclear antigen (PCNA) and Ki-S5 against the Ki-67 protein. Patients were followed for a mean time of 4.8 years. Expression of both PC10 and Ki-S5 was found to be significantly linked to tumor grade and tumor stage. Prognostically favorable stage IVs was associated with low PCNA and Ki-S5 levels. For ganglioneuroblastoma, significant differences were found between the diffuse and the composite type. In univariate analysis of stage III and IV tumors, Ki-S5 and PCNA scores were significantly correlated with disease-free survival (P < 0.0015), allowing definition of a subset of cases with favorable outcome. As to Shimada's group with poor prognosis, significant differences in the clinical course were found for low and high Ki-S5 scores (P = 0.036) but not for PCNA. In multivariate analysis, only patient age, Shimada's grade, and Ki-S5 scores achieved prognostic significance. We conclude that proliferation marker Ki-S5 may provide substantial prognostic information and might become a useful adjunct for predicting the clinical courses of neuroblastoma.

Adolescent↗
PubMed1997

Prognostic relevance of a novel proliferation marker, Ki-S11, for soft-tissue sarcoma. A multivariate study.

In 132 soft-tissue sarcomas and 52 benign soft-tissue tumors, cellular proliferation was examined by immunohistochemistry using monoclonal antibodies Ki-S11 (Ki-67 antigen) and Ki-S1 (topoisomerase II alpha) and by flow cytometric analysis of the S-phase fraction (SPF). Malignant tumors were graded histologically according to the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system. Patient age, sex, tumor location, histological type, and DNA ploidy were considered as additional prognostic variables. Consistent immunoreactivity was seen in approximately 95% of the cases, and determination of SPF was possible in approximately 60% Ki-S11 and Ki-S1 immunolabeling indices correlated in a linear manner. All proliferation parameters yielded significant differences between benign and malignant tumors. Ki-S11 and Ki-S1 immunoreactive scores also co-varied significantly with SPF, mitotic count, and histopathological grade. In univariate analysis, immunohistochemical proliferation indices, histopathological grade, mitotic count, and SPF were predictive of overall survival and the development of metastases. In multivariate analysis, immunolabeling scores of proliferation markers, grade, and SPF emerged as independent predictors of global survival and systemic progression. We conclude that the immunohistochemical assessment of proliferation, being more readily performable and more easily assessable than the equally relevant S phase fraction, may add appreciable information to the current prognostic models for soft-tissue sarcoma.

Adolescent↗
PubMed1997

Value of p53 expression, cellular proliferation, and DNA content as prognostic indicators in renal cell carcinoma.

OBJECTIVE: In renal cell carcinoma (RCC) little is known about the basic mechanisms of cell proliferation and differentiation leading to growth, invasion, and eventual metastasis. In the present study, the prognostic significance of proliferative activity, p53 activity, and ploidy is analyzed. METHODS: In 90 patients with RCC overexpression of the p53 protein. DNA ploidy and proliferation status as determined by the monoclonal antibodies Ki-67 and Ki-S5 were analyzed in addition to tumor malignancy grade and stage and correlated with the clinical course. RESULTS: During the follow-up period (average 38 months) 23% of the patients had a progressive course. Only the Ki-S5 index correlated with stage, grade, and clinical course. Ploidy, p53, and Ki-67 correlated neither with tumor stage and grade nor with the clinical course. CONCLUSION: The proliferation activity determined with the monoclonal antibody Ki-S5 represents the most promising prognostic factor of the pathological indicators considered for the clinical course of RCC.

Adult↗
PubMed1996

Prognostic indicators for response to therapy and survival in patients with metastatic renal cell cancer treated with interferon alpha-2 beta and vinblastine.

OBJECTIVES: Only one third of all patients with metastatic renal cell carcinoma respond to immunochemotherapy. Improved patient selection could render such treatment unnecessary in many cases. The goal of the study was to test various factors for their prognostic value as predictors of success of immunochemotherapy and patient survival in metastatic renal cell carcinoma. METHODS: Fifty patients with metastatic renal cell carcinoma were subjected to immunochemotherapy with interferon alpha-2 beta and vinblastine. Different variables such as age, sex, location of metastasis, primary or late metastasis, performance status, histologic status, overexpression of the p53 protein and cell proliferation as assessed by immunohistochemistry, and deoxyribonucleic acid-ploidy were considered as potential prognostic factors for response to immunochemotherapy and survival. RESULTS: Thirty percent (15) of the cases responded to therapy: 2 complete and 13 partial remissions. In univariate analysis, the proliferative activity (Ki-S5 labeling index) emerged as the statistically most significant prognostic factor (P = 0.0013) for prediction of successful immunochemotherapy in metastatic renal cell carcinoma. The second most significant factor was the location of metastases (P = 0.015), whereas all other parameters did not achieve statistical significance. As to overall survival, responsiveness to therapy was the most significant predictor (P = 0.0003), followed by Ki-S5 scores (P = 0.025). All other factors, including the sites of metastasic spread (P = 0.21), were not statistically relevant. CONCLUSIONS: Proliferation status in terms of Ki-S5 immunoreactive scores appears to be a valuable predictor of the responsiveness to immunochemotherapy. Overall survival appears to depend essentially on disease progression and tumor cell proliferation. Other alleged prognostic factors, such as performance status, sarcomatoid histology, and metastasis location, were not significant in this study.

Adult↗
PubMed1996

p53 expression, proliferation marker Ki-S5, DNA content and serum PSA: possible biopotential markers in human prostatic cancer.

OBJECTIVES: The biology of prostate cancer is poorly understood. Despite established prognostic criteria, a confident prediction of the clinical outcome is not always possible. Therefore, additional and more precise information is highly desirable. In the present study, we compared potential biologic markers with the laboratory, clinical, and histopathologic parameters of prostate-specific antigen (PSA) level, tumor stage, and tumor grade. METHODS: Paraffin-embedded material from 62 radical prostatectomies for prostate carcinoma was examined immunohistochemically using monoclonal antibody Ki-S5 to determine the tumor growth fraction and antibody DO-1 to assess p53 protein overexpression. Deoxyribonucleic acid-ploidy was analyzed by flow and image cytometry. Preoperative PSA levels were assessed by standard method. The tumors were categorized according to the Gleason grading system and staged postsurgery after the TNM classification. RESULTS: The p53 expression, proliferation rate (Ki-S5), and rate of aneuploidy correlated closely with stage (P < 0.05) and Gleason score (P < 0.01). However, divergences were occasionally observed. The ploidy status correlated closely with proliferative activity and p53 expression. Conversely, no correlation was seen between these parameters and serum PSA content, the latter being significantly associated with the tumor stage alone. CONCLUSIONS: The results characterize proliferation marker Ki-S5, p53 expression, and ploidy status as tumor biopotential markers, whereas PSA provides diagnostic information. Use of these investigative methods promises to provide additional information relevant in prognosis and therapy selection. Nonetheless, their precise prognostic value will have to be established in further studies.

Aged↗
PubMed1995

Diagnostic assessment of two novel proliferation-specific antigens in benign and malignant melanocytic lesions.

The aim of this study was to gain a thorough insight into the proliferative activity of benign and malignant melanocytic tumors. A total of 314 cases were examined by immunohistochemistry on paraffin-embedded material. The growth fraction was assessed by means of two monoclonal antibodies, Ki-S1 and Ki-S5, which react with two different proliferation-specific nuclear antigens. Additionally, HMB-45 was used as a marker of melanocytic activation. Statistically significant differences (P < 0.01) in the proliferation rates were found between common acquired nevi, Spitz's/Reed's nevi, primary cutaneous melanomas, and metastatic melanomas, whereas dysplastic nevi were hardly distinct from other nevi of the compound type. In melanoma, the growth fraction correlated well with the tumor stage but poorly with HMB-45 expression and mitotic count. Along with tumor progression, an increasing heterogeneity of proliferation indices was observed. Our results provide no evidence for a progression from dysplastic nevi into melanoma. They indicate that the assessment of the proliferative activity may be of considerable diagnostic help in cases of uncertain histology and that it might contribute to an alternative concept for the classification of melanocytic tumors.

Adolescent↗
PubMed1994

Hepatic and serologic toxicity of systemic interleukin-2 and/or interferon-alpha. Evidence of a risk-benefit advantage of subcutaneous therapy.

A total of 107 cancer patients were treated with 148 cycles of subcutaneous (SC) immunotherapy employing interleukin-2 (rIL-2) and/or interferon-alpha (rIFN-alpha). The systemic toxicities of SC cytokine therapy were retrospectively evaluated with regard to hepatic and metabolic adverse effects, and compared to adverse effects previously reported upon high- or intermediate-dose intravenous (IV) rIL-2 therapy. Our study cohorts consisted of 15 patients who received SC rIL-2 at doses of 4.8-14.4 million IU/m2/day on 5 days per week for a total of 8 weeks, 20 patients who received rIFN-alpha 2b at 3.0-6.0 million U/m2/day thrice weekly for a total of 6 weeks, and 72 patients who were given SC rIFN-alpha 2b at 6.0 million U/m2/day thrice weekly plus SC rIL-2 at 14.4-18.0 million IU/m2/day on days 1 and 2, followed by 4.8 million IU/m2/day, 5 days per week for 6 consecutive weeks. These treatment regimens were well tolerated in the outpatient setting; no toxic deaths occurred, and none of the patients developed life-threatening toxicity. Upon SC rIL-2/rIFN-alpha combination therapy, we observed mild decreases in plasma protein and albumin levels (mean nadir +/- standard deviation, 67 +/- 5 g/L and 38.8 +/- 3.9 g/L, respectively), minor albeit significant increases in serum total bilirubin levels (mean peak +/- standard deviation, 7.8 +/- 3.1 mumol/L), serum aspartate aminotransferase (25.9 +/- 9.9 U/L), alanine aminotransferase (42.0 +/- 45.9 U/L), alkaline phosphatase (301 +/- 255 U/L), lactate dehydrogenase (230 +/- 64 U/L), gamma-glutamyl transpeptidase (147 +/- 141 U/L) activities and triacylglyceride (2.6 +/- 0.9 mmol/L) concentrations. Cholinesterase activities (mean nadir +/- standard deviation, 42.6 +/- 13.7 kU/L), and serum cholesterol levels (4.4 +/- 0.9 mmol/L) decreased upon SC rIL-2/rIFN-alpha combination therapy. These mild clinical side effects and laboratory changes were in marked contrast to a multitude of dose-limiting and life-threatening adverse reactions described upon IV rIL-2 therapy. It is concluded that low-to intermediate-dose SC rIL-2/rIFN-alpha combination therapy as used in this study, can be given in the outpatient setting with good practicability and excellent safety.

Adult↗
PubMed1994

Penetration of spin-labeled dihydrolipoate into the skin of hairless mice. Modification of epidermal and dermal polarity.

Electron paramagnetic resonance (EPR) imaging with the modulated field gradient technique is a novel method to investigate skin biophysical and biochemical properties employing specific nitroxide spin probes. Using this method, a distinct increase in polarity from epidermis towards lower dermis is observed with the spin label dit-butylnitroxide (DTBN). With proxylmaleimide a considerable increase in mobility is found, when epidermis is compared with dermal compartments. The effect of the natural antioxidant dihydrolipoate on skin membrane polarity was studied. Skin penetration of spin labeled dihydrolipoate was investigated by EPR imaging. The results indicate that dihydrolipoate also increases membrane polarity. The biophysical and biochemical changes in the epidermis and dermis as revealed by spatial imaging, provide indirect evidence for skin penetration of dihydrolipoate. This conclusion was supported by the finding that spin labeled derivatives of dihydrolipoate and lipoate were detected inside epidermis and dermis by EPR imaging. This study demonstrates the feasibility of EPR imaging to investigate pharmacodynamic and pharmacokinetic properties of spin labeled drugs in skin.

Animals↗
PubMed1993

Expression of CD30 and nerve growth factor-receptor in neoplastic and reactive vascular lesions: an immunohistochemical study.

A total of 118 biopsies from 20 different types of benign, malignant and reactive vascular proliferations were examined for the expression of the CD30 antigen using the monoclonal antibodies BerH2 and HRS4 on paraffin-embedded sections. The results were compared with those obtained using an antibody directed against the partially homologous nerve growth factor-receptor. The vascular character of the lesions was assessed by means of endothelial markers and the expression of intermediate filaments was verified immunohistochemically. CD30 was expressed in the endothelial component of more than the half of all tumours, with the exceptions of Kaposi's sarcoma and teleangiectatic granuloma. There was a slightly higher rate of Ki-1 positivity in malignant lesions. Nerve growth factor-receptor could be demonstrated in a similar percentage in both endothelium and pericytes, but no correlation with CD30 could be established. We conclude, therefore, that these antigens are not adequate for the differential diagnosis of vascular lesions, nor do they help distinguish between benign and malignant lesions. Their expression seems to reflect different states of cellular function or activation. It does not necessarily occur simultaneously or in the same cell type.

Antibodies, Monoclonal↗
PubMed1993

[Determination of proliferation activity of prostate cancers by means of nuclear proliferation-associated formalin resistant Ki-S5 antigens].

In order to evaluate the growth fraction in normal, hyperplastic and neoplastic prostatic tissue, we examined paraffin sections of 55 cases of prostatic cancer containing areas of benign (BPH) and atypical hyperplasia (AH). Cellular proliferation was assessed by nuclear staining with the monoclonal antibody Ki-S5 directed against a formalin-resistant epitope of the Ki67 antigen. The proliferation rate was minimal in normal glands and BPH (mean 0.35%), rather low in AH and grade I carcinoma (0.5 to 15% compared to grade II carcinoma (1 to 40%) and peaking to near 80% labeled cells in grade III carcinoma. In the majority of the tumors, foci of increased cell growth could be detected by this method. Ki-S5 labeling indices correlated significantly with the histopathologic grading established by Dhom. Correlation with the clinical outcome will be the subject of subsequent retrospective studies.

Antigens, Neoplasm↗
PubMed1991

[Preventive measurement in Gottingen kindergartens from 1975-1990].

379 children, age 3 to 6, were examined for caries prevalence in kindergartens in Göttingen. 64% of subjects had healthy natural dentitions, the df-s value was 2.3. In 1990 the mean df-s value for 4-5 year old children was 10% lower than 1985 and 45% lower than 1983. Oral health had improved differently in the various institutions. The mean df-s was between 0.6 and 4.7.

Child↗
PubMed1988

Multinucleated giant cells generated in vitro. Terminally differentiated macrophages with down-regulated c-fms expression.

Although multinucleated giant cells (MGCs) are a known feature of granulomatous reactions, little is known about their destination and function. In this study human blood monocyte (BM)-derived giant cells were generated by lymphokine stimulation in vitro. Their immunophenotype and ultrastructural morphology resembled that of MGCs occurring in vivo. Mitotic activity within MGCs could not be established either in vitro or in vivo. Enzyme equipment of MGCs was elevated in comparison with monocyte-macrophages. In comparison with unfused monocyte-macrophages, MGCs did not reveal a higher level of interleukin-1 production or cytostatic activity. They showed, however, a 20-30-fold increase in the production of oxygen-free radicals in response to zymosan. Transcription of the proto-oncogene c-fms was enhanced in short-term cultivated BM and was rapidly down-regulated in MGCs after fusion had occurred. It is concluded that MGCs represent highly stimulated cells of monocyte-macrophage lineage at a terminal stage of maturation.

Antigens↗