Intimal sarcoma of the left iliac artery.
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Aged↗
Biomedical subjects
K Remberger
Publications and source records attributed to K Remberger.
Invasion of human cartilage by cultured multicellular spheroids of rheumatoid synovial cells--a novel in vitro model system for rheumatoid arthritis.
OBJECTIVE: A new 3-dimensional cell culture system was established to examine the invasion of rheumatoid synovial cells into cartilage. METHODS: Synovial cells from 20 patients with rheumatoid arthritis (RA) and 15 patients with osteoarthritis (OA) were co-cultured as multicellular spheroids with cartilage fragments. RESULTS: After 4 weeks the rheumatoid spheroids eroded the cartilage. The destruction of cartilage was supported by a high expression level of cathepsin D and matrix metalloproteinases. In contrast, the OA tissue showed attachment to the cartilage only. CONCLUSION: Our results indicate that spheroid/cartilage co-cultures seem to be a suitable in vitro model for the study of destructive cellular mechanisms that occur in RA.
Arthritis, Rheumatoid↗
Amplification of the genes BCHE and SLC2A2 in 40% of squamous cell carcinoma of the lung.
Gene amplification is a common genetic change in human cancer cells. Previously, we provided the first evidence for gene amplification at chromosome band 3q26 in squamous cell lung carcinoma. In this study, the following analyses were performed: (a) we evaluated biopsies and paraffin-embedded tissues of 16 additional squamous cell lung carcinomas for gene amplification using reverse chromosome painting. Of the 16 tumors, 3 tumors showed an amplification of the entire long arm of chromosome 3, and 3 tumors showed various amplifications on 3q, all of which involved chromosome band 3q26; (b) we tested eight genes encompassing region 3q25-qter in two different tumors to identify amplified genes on chromosome 3q. The genes SI, BCHE, and SLC2A2 were amplified in both tumors; and (c) we analyzed 15 additional paraffin-embedded tissues to determine the amplification frequency of these genes. Of the 15 squamous cell lung carcinomas, 6 showed amplification for at least 1 of the genes, with BCHE and SLC2A2 as the genes most frequently amplified. Together, our reverse chromosome painting data and our PCR analysis indicate gene amplification at 3q26 in 40% of all squamous cell lung carcinomas with BCHE and SLC2A2 as possible target genes of the amplification unit in squamous cell lung carcinoma.
Blotting, Southern↗
[Myocardial pump failure in dilated cardiomyopathy and pheochromocytoma].
Progressive dyspnoea developed in a 37-year-old woman over a period of 2 months. A chest x-ray and echocardiography revealed a massive dilatation of the heart with thrombi in both ventricles. The endomyocardial biopsy was classified as myocarditis in two different departments of pathology. The patient developed thromboembolic events and an untreatable heart failure which led to the patient's death. The necropsy revealed a dilated 600-gram-heart and thrombi in both ventricles. On histological and immunohistological examination of the heart, the original diagnosis was corrected to catecholamine-induced dilated cardiomyopathy.
Adrenal Gland Neoplasms↗
Prevalence of adrenal and extra-adrenal Conn syndrome in hypertensive patients.
BACKGROUND: Primary aldosteronism (PA) is caused by an adrenal aldosterone-producing tumor (A-APT) or adrenal hyperplasia. An extra-adrenal APT (E-APT) as a cause of PA has been reported in 5 cases. Autopsy studies show a high incidence of ectopic adrenocortical tissue. We did a prospective study of the prevalence of A-APTs and E-APTs and the biochemical features of E-APTs in patients with PA. METHODS: Hypertensive patients (N = 3900) referred to our unit were screened for PA by measuring renin activity, urinary aldosterone-18-glucuronide, tetrahydroaldosterone, and 18-hydroxycorticosterone (18-OH-B). Primary aldosteronism was found in 257 cases. The differentiation between A-APTs and adrenal hyperplasia was based on the results of postural response of renin, plasma aldosterone, 18-OH-B, computed tomography, isotope scanning, or adrenal venous aldosterone. Ultrasound examination of the abdomen was used to screen for E-APT. RESULTS: The cause of PA was bilateral adrenal hyperplasia in 101 cases, unilateral adrenal hyperplasia in 2, an A-APT in 146, and an E-APT in 1. The site of aldosterone production was uncertain in 7 patients who had normal adrenal glands on computed tomography but refused to undergo isotopic scanning and adrenal venous catheterization. Ultrasound examination disclosed normal retroperitoneum in 4 of the 7 cases but could not rule out E-APT in 3 cases. The biochemical features of the patient with the E-APT were similar to classic A-APT, with low renin, high aldosterone, and high 18-OH-B values without appropriate response to posture or to short-term volume expansion. The excision of the E-APT in the right kidney resulted in normalization of blood pressure and renin, aldosterone, and 18-OH-B levels. CONCLUSION: Although E-APT is rare, it should be considered in the interests of specific therapy for PA because aldosterone-secreting malignant ovarian tumors also have been reported.
Adrenal Cortex Neoplasms↗
Differentiation pathways and histogenetic aspects of normal and abnormal prostatic growth: a stem cell model.
A stem cell model is presented for the organization of the prostatic epithelium that may explain normal and abnormal growth in the human prostate. This model is based on recent data indicating that: 1) The three basic cell types encountered in the prostatic epithelium--i.e., secretory luminal, basal, and endocrine paracrine (EP) cells--are linked in the precursor progeny relationship. 2) The proliferative compartment of the normal and hyperplastic epithelium is located in the basal cell layer. 3) The proliferative compartment of the prostatic epithelium is androgen-independent but contains andro-responsive target cells. 4) During the malignant transformation of the prostatic epithelium, the proliferative zone is inverted and shifts to luminal cell types. 5) Formation of neoplastic basement membrane (BM) material is crucial for the development of the invasive phenotype in prostate cancer. 6) The proliferative activities in prostate cancer are exclusively restricted to exocrine cell types, whereas endocrine differentiated tumor cells are postmitotic cells. 7) The majority of exocrine tumor cells are androgen-responsive in contrast to endocrine differentiated cell types that consistently lack the nuclear androgen receptor (AR). In this model, a small stem cell population located in the basal cell layer gives rise to all epithelial cell lineages encountered in the normal, hyperplastic, and neoplastic prostate. The differentiating process from basal cells to secretory luminal cells via intermediate phenotypes is induced by circulating androgens, and largely depends on the presence of androgen-responsive target cells in the basal cell layer. Accordingly, the abnormal growth of the secretory epithelium in benign prostate hyperplasia (BPH) may be related to an increase in the total number of androgen-responsive basal cells in the proliferative compartment. Prostate cancer derives from transformed stem cells located in the basal cell layer that acquire secretory luminal characteristics under androgenic stimulation. During tumor invasion, the malignant phenotypes adhere via specific receptors to newly formed BM-material, which, in turn, may facilitate their passage through the extracellular matrix. The occurrence of endocrine differentiation in prostate cancer reflects the pluripotency of its stem cells. The widespread absence of nuclear AR in endocrine differentiated tumor cells clearly indicates that this phenotype belongs to those cell clones in prostate cancer, that are initially androgen-independent and refractory to hormonal therapy. Accordingly, the progressive emergence of endocrine cell clones during tumor progression may represent one mechanism by which prostate cancer cells escape hormonal control.
Adenocarcinoma↗
Differential expression of 5 alpha-reductase isoenzymes in the human prostate and prostatic carcinomas.
BACKGROUND: Steroid 5 alpha-reductase is essential for the intracellular accumulation of dihydrotestosterone (DHT), which mediates androgen effects on target tissue. METHODS: In the present study, we describe the differential expression and cellular localization of 5 alpha-reductase 1 and 2 isoenzymes in the human prostate, and untreated and hormone-resistant prostatic carcinomas. The secretory epithelium of normal and hyperplastic glands showed strong nuclear 5 alpha-reductase 1 reactivity. Accordingly, the DHT forming 5 alpha-reductase process in secretory luminal cell types may be mediated predominantly by the type 1 isoenzyme. The androgen-independent basal cell layer variably expressed type 1 and 2 isoenzymes in nuclear and cytoplasmatic compartments. This suggests that circulating androgens are involved to control the basal cell layer, which represents the proliferative compartment of the human prostate. RESULTS: When compared with benign prostate tissue, increased 5 alpha-reductase reactivity was detected in prostate cancer, particularly in high-grade tumors and androgen-insensitive states of the disease. In cancerous lesions, the type 1 isoenzyme tended to shift to the cytoplasm, while the nuclear staining remained unchanged or slightly increased. Referring to the type 2 isoenzyme, increased cytoplasmatic and nuclear enzyme activity was detected in malignant cells when compared with adjacent benign prostate tissue. Even endocrine differentiated tumor cells that consistently lacked the nuclear androgen receptor variably expressed 5 alpha-reductase immunoreactivity. CONCLUSIONS: Although the functional significance of the differential subcellular localization of type 1 and 2 isoenzymes is currently unknown, the present data suggest that prostate cancer retains the DHT forming 5 alpha-reductase process in high-grade lesions and recurrent disease. Accordingly, circulating androgens may be still significant in these hormone-refractory malignancies.
Androgens↗
A novel site of DNA amplification on chromosome 1p32-33 in a rhabdomyosarcoma revealed by comparative genomic hybridization.
Cytogenetic analysis of a human embryonal rhabdomyosarcoma revealed a near-diploid karyotype with structural chromosome aberrations not involving the typical rearrangements of rhabdomyosarcomas, plus a large number of double minutes. Comparative genomic hybridization revealed a previously undescribed site of DNA amplification on the short arm of chromosome 1 (band 1p32-33).
Child↗
[Leydig cell tumors of the testis--clinical and morphologic aspects].
Leydig cell tumors are the most common tumors of the gonadal stroma. They account for 3% of all testicular tumors. Whereas in 10% of adult cases malignancy occurs, the clinical course in children is benign. During childhood the tumor presents with precocious pseudopuberty, in adults with testicular swelling and gynecomastia. We report on 17 cases of Leydig cell tumor, paying special attention to clinical and morphological aspects.
Adult↗
DNA amplification on chromosome 3q26.1-q26.3 in squamous cell carcinoma of the lung detected by reverse chromosome painting.
Multiple genetic lesions have been reported in small cell lung carcinoma (SCLC), while considerably less information is available on squamous cell carcinoma (SCC). We used reverse chromosome painting to screen a total of nine SCCs for DNA amplifications. In three of the nine SCCs, hybridisation signals were found at chromosome region 3q26.1-q26.3, which does not contain any known oncogene. In one of the three SCCs, there were additional hybridisation signals at 1q, 5p and 6p21.1. The high frequency of a consistent amplification (3q26.1-q26.3) in SCC strongly indicates a novel gene at 3q26.1-q26.3 that is important in the pathology of SCC.
Aged↗
Pulmonary capillary hemangiomatosis as a rare cause of pulmonary hypertension.
Pulmonary capillary hemangiomatosis (PCH), first described by Wagenvoort et al. in 1978, is a rare cause of pulmonary hypertension which occurs predominantly in young adults. In the literature only 18 cases have been reported. In 1988 Langleben et al. proposed a hereditary form of PCH with probable autosomal-recessive transmission. Histologic findings include irregular small nodular foci of thin-walled capillary-sized vessels which diffusely invade the lung parenchyma, the bronchial/bronchiolar walls and the adventitia of large vessels. We report on a case of PCH in a 24 year old man who presented the clinical signs of interstitial lung disease.
Adult↗
Constitutive expression of c-fos and c-jun, overexpression of ets-2, and reduced expression of metastasis suppressor gene nm23-H1 in rheumatoid arthritis.
OBJECTIVES: To identify genes that are involved in the development and progression of rheumatoid arthritis (RA). METHODS: We used a multiple gene analysis system and a set of available genes participating in processes such as proliferation, differentiation, tumour progression, and metastasis, to identify their RA related expression. Synovial tissues from 22 patients with RA were evaluated in comparison with those from six patients with osteoarthritis and two patients with non-inflamed joints as controls, using northern blot and reverse transcriptase polymerase chain reaction experiments. RESULTS: Our data confirm the role of c-fos and c-jun as constitutive signal transmitters in solid RA tissues, thus demonstrating the potential of the approach. Activation of both genes persisted through multiple passages of the cells in tissue cultures derived from the synovial lining of RA tissues. There was an increased expression of ets-2 in 30% of RA samples and an up to 30-fold decreased expression of the potential metastasis suppressor gene nm23-H1 in 90% of RA tissues, compared with control tissues. CONCLUSIONS: The data presented show for the first time a significant decrease of nm23-H1 expression in RA, which is possibly involved in local invasiveness, and a strong activation of the ets-2 nuclear oncogene in about one third of RA tissues, which may also be part of a pathway leading to advanced disease stages. The constitutive expression of c-fos and c-jun in RA tissue most probably results from a continuing inflammatory stimulus. These findings with cell cultures suggest an intrinsic activation mechanism of these early response genes in RA.
Arthritis, Rheumatoid↗
Proliferation enhancement by spontaneous multiplication of chromosome 7 in rheumatic synovial cells in vitro.
Mosaic trisomy of chromosome 7 is known to occur in a variety of non-neoplastic hyperproliferative disorders. In long-term cell cultures established from rheumatic synovium with mosaic trisomy 7, we observed a continuous increase in the proportion of cells with trisomy 7 to over 50% by the 10th in vitro passage. Simultaneous in situ hybridization with a repetitive chromosome-7-specific DNA probe and fluorescent Ki-67 labelling showed a strong correlation between trisomy 7 and an elevated proliferation index in cultured rheumatic synovial cells. Moreover, we observed a fraction of rapidly proliferating cells with up to eight copies of chromosome 7 as the sole cytogenetic change. Frequent somatic pairing of centromeres of two chromosomes 7 in interphase nuclei suggests either atypical non-disjunction with a persisting centromere or selective endoreduplication of chromosome 7.
Arthritis, Rheumatoid↗
Differential expression of the pS2 protein in the human prostate and prostate cancer: association with premalignant changes and neuroendocrine differentiation.
The distribution of the estrogen inducible pS2 protein was investigated in benign and malignant prostate tissue by the avidin-biotin complex method. Prostate tissue obtained from 20 patients without clinical and histological evidence of malignant disease consistently lacked pS2 immunoreactivity. Conversely, nonneoplastic tissue from 36 total prostatectomies with locally advanced prostate cancer showed a variable degree of pS2 reactivity in normal or hyperplastic glands and in prostatic intraepithelial neoplasia (PIN) adjacent to the cancerous lesions. This suggests that the pS2 gene expression detected in nonmalignant tissue may be related to early premalignant changes of prostate glands harboring significant carcinomas. In prostate cancer the pS2 protein was detected in close association with neuroendocrine (NE) differentiation as assessed by Chromogranin A (Chr A) immunoreactivity. Double labeling techniques showed that pS2 immunoreactivity recognizes both endocrine (Chr A-positive) and adjacent exocrine (Chr A-negative) cell types within NE foci. Whereas pS2 expression was consistently confined to NE differentiation in untreated tumors, carcinomas that relapsed after hormonal therapy showed increased pS2 immunoreactivity, even in the absence of NE features. The differential expression of the pS2 peptide in nonneoplastic tissue from patients with and without malignant disease indicates that pS2 immunohistochemistry may be useful in the diagnostic evaluation of negative biopsy specimens. Furthermore, the results suggest that the immunohistochemical spectrum of pS2 in prostate cancer may include endocrine differentiated and presumably related cell populations.
Carcinoma↗
Endocrine-paracrine cell types in the prostate and prostatic adenocarcinoma are postmitotic cells.
Neuroendocrine (NE) differentiation frequently occurs in common prostatic malignancies and has potential prognostic and therapeutic implications. In a recent study we were able to provide immunohistochemical evidence that endocrine-paracrine cell types represent an androgen-insensitive cell population in prostate cancer, documented by the consistent lack of the pertinent receptor. In this study we investigated the proliferative activity of endocrine-paracrine cell types in normal, hyperplastic, and neoplastic prostate tissue. Using double-label techniques for the endocrine marker chromogranin A (chr A) and the proliferation-associated MIB-1 antigen, we evaluated the proliferative status of endocrine-paracrine cell types in the prostate and prostatic adenocarcinoma showing marked NE differentiation. In this series of carcinomas and in nonneoplastic tissue the proliferative activities were exclusively restricted to nonendocrine cell populations, whereas endocrine-paracrine cell types characterized by Chr A consistently lack MIB-1 immunoreactivity. This may indicate that prostatic endocrine-paracrine cell types do not participate in the cell cycle during normal, hyperplastic, and neoplastic prostatic growth. Based on the present information, the endocrine phenotype can be considered to be an androgen-insensitive, postmitotic subpopulation in the prostate and prostate cancer.
Adenocarcinoma↗
Influence of indomethacin and difluoromethylornithine on human tumour growth in nude mice.
Biopsy material from six human colorectal carcinomas was transplanted to 114 nude mice. A treatment protocol was established which included no treatment (control, C), indomethacin (I), difluoromethylornithine (D) or a combination of both (ID). The influence of the various drugs on tumour weight and protein kinase CK2 activity was monitored. CK2 activity was measured because in all tumours examined so far the enzyme activity was found to be enhanced several-fold when compared to the non-neoplastic tissue of the same patient. More than half of the investigated tumours showed a conspicuous reduction in weight after drug treatment, and I and the combination of D/I were significantly effective using the mixed model analysis. Furthermore, we have tried to discover whether there is a change in the subcellular localisation of protein kinase CK2 subunits associated with drug treatment. We analysed the tumours and the non-neoplastic control tissues by immunohistochemistry using antibodies directed against the CK2 subunits and against the proliferation marker Mib. In addition, we have also investigated the behaviour of the nucleolar protein B23 which has also been shown to be enhanced several-fold in rapidly proliferating tissue and which is also a substrate for CK2. The immunohistochemical data suggest that, irrespective of the drug treatment and the observed reduction in CK2 activity, the CK2 subunits remain localised in the nucleus.
Animals↗
Adamantinoma of long bones. A histopathological and immunohistochemical study of 23 cases.
The clinical and histological data of twenty-three cases of adamantinomas of the long bone collected by the Working Group on Bone Tumors at the DKFZ/FRG are reported including immunohistochemical observations in twenty-one of the cases. Females and males between 5 and 67 years (mean, 25.4 years) were affected equally (11/12). All adamantinomas were positive for cytokeratins often in coexpression with vimentin, at least focally. Although exhibiting varying histological patterns, no correlation between histology and clinical course was seen. However, sex and mode of initial therapy seem to influence an unfavorable clinical outcome. All three decreased patients were males receiving marginal or delayed surgery. This underlines the low-grade malignant character of adamantinoma. To assure the histological diagnosis pathologists should employ immunohistochemistry for demonstrating the sometimes sparse epithelial cell nests when radiology is suggestive for adamantinoma. Correct diagnosis should lead to resection with wide surgical margins.
Adolescent↗
Morphogenetic aspects of normal and abnormal prostatic growth.
Studies of cancerogenesis in the human prostate have been hampered by a number of factors, including the complex composition of the prostatic epithelium by three different cell types, the lack of good animal models and the relative inaccessibility of the gland. More information about the basic biology of epithelial cell types in the development of the various neoplastic disorders of the prostate gland is required. This article reviews recent data about differentiation and proliferation processes in the human prostate and proposes a stem cell model that may explain the morphogenisis of normal and abnormal prostatic growth.
Cell Differentiation↗