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Biomedical subjects

K Remberger

Publications and source records attributed to K Remberger.

At least 73 records · Page 4Linked to original sources
PubMed1995

Human endogenous retrovirus K10: expression of Gag protein and detection of antibodies in patients with seminomas.

The human endogenous retrovirus K10 (HERV-K10) has been identified in the human genome by its homology to retroviruses of other vertebrates (M. Ono, T. Yasunaga, T. Miyata, and H. Ushikubo, J. Virol. 60:589-598, 1986). Using PCR amplification, DNA cloning, sequencing, and procaryotic expression, we were able to demonstrate that HERV-K10 encodes a 73-kDa protein which was processed by a HERV-K10-encoded protease to yield proteins p22/p26, p30, and p15/16. Analysis of the teratocarcinoma cell line Tera 1 or tumor tissues by immunoblotting demonstrated that the 80-kDa polyprotein of HERV-K10 gag and a processed protein of 39 kDa were expressed. In addition, a major protein of 39 kDa and additional species of 30, 22, 19, and 17 kDa could be detected in the supernatant of Tera 1 cells, suggesting that HERV-K10 Gag proteins are either secreted or processed to probably incomplete viral particles. In addition, the gag gene of HERV-K10 was expressed in the baculovirus system. Using this recombinant system to test antisera from patients with different diseases and healthy individuals, we were able to detect antibodies against the N-terminal part of HERV-K10 Gag in 2 to 4% of groups of tumor patients with titers ranging between 1:80 and 1:640, while approximately 0.1 to 0.5% of healthy individuals exhibited antibodies with lower titers. In contrast, patients with seminoma had antibody titers in the range of 1:2,560 at the time when the tumor was detected. Immunohistochemistry using specific rabbit sera or monoclonal antibodies against HERV-K10 Gag revealed that the Gag protein is expressed in the cytoplasm of the tumor cells. Furthermore, an 80-kDa protein corresponding to the HERV-K10 Gag polyprotein could be detected in tumor biopsies. For the first time, these data indicate that HERV-K10 Gag proteins are synthesized in seminoma cells and tumors exhibit relatively high antibody titers against Gag. So far, no information on which role HERV-K10 plays in the development of this tumor exists.

Antibodies, Viral↗
PubMed1995

A new subset of mineralocorticoid hypertension with excess of 21-deoxyaldosterone and Kelly's-M1 steroid: clinical and morphological findings.

Ten cases of adrenal adenomas, one case with unilateral adrenal hyperplasia, and another case with apparent bilateral are reported, in whom an alternative pathway of aldosterone via 21-deoxyaldosterone is operative. They all manifested hypertension, low renin activity, low normal potassium values, as well as high urinary excretion rates of 21-deoxyaldosterone and its related metabolite Kelly's-M1 steroid. In all cases, urinary aldosterone metabolites (aldosterone-18-glucuronide and tetrahydroaldosterone) and aldosterone precursor 18-hydroxycorticosterone levels were normal. Hence, the adrenal lesions give rise to hyper-21-deoxyaldosteronism. 21-Deoxyaldosterone is a weak mineralocorticoid, and its elevated production in the presence of normal aldosterone can induce a pathological state of hypermineralocorticoidism. Adrenalectomy resulted in normalization of hypertension in six of eight and amelioration in two of eight cases. Six of seven adenoma cases examined as well as the case of unilateral adrenal hyperplasia were sensitive to ACTH. One of the seven adenomas and, as expected, the case with apparent bilateral hyperplasia were angiotensin responsive. Histologically and electron microscopically, the operated adenomas consisted predominantly of clear cells, characterized by mitochondria with tubulo-vesicular internal structure similar to those of the zona fasciculata (in contrast, our classical Conn's adenoma with normal 21-deoxyaldosterone excretion exhibited a more heterogenous histological appearance and were, in terms of ultrastructure, more similar to cells of the zona glomerulosa). Ultrastructurally and immunocytochemically, the clear cells of 21-deoxyaldosterone adenomas showed features of both the zona glomerulosa and the zona fasciculata and are, hence, considered to be hybrid cells. We conclude that the determination of 21-deoxyaldosterone and Kelly's-M1 should be considered in the diagnosis of mineralocorticoid-induced forms of hypertension, especially when an adrenal adenoma has been detected with an imaging procedure.

Adenoma↗
PubMed1994

Monoclonal antibodies directed against the Epstein-Barr virus-encoded nuclear antigen 1 (EBNA1): immunohistologic detection of EBNA1 in the malignant cells of Hodgkin's disease.

Monoclonal antibodies directed against the Epstein-Barr virus nuclear protein 1 (EBNA1) were used to examine conventional paraffin sections from a series of EBV-associated lymphoproliferative disorders by immunohistochemistry. The presence of latent EBV infection in tumor cells was determined by in situ hybridization for the Epstein-Barr virus early RNAs (EBERs). Of those EBER-positive cases a total of 28 of 40 cases of Hodgkin's disease, 3 of 3 cases of Burkitt's lymphoma, and 8 of 8 cases of human immunodeficiency virus-associated cerebral B-cell lymphoma expressed detectable amounts of EBNA1. In the positive cases, expression was confined to the tumor cells. No reactivity was detected in EBV-negative cases of the above tumors or in 8 cases of EBV-negative cases of large cell anaplastic non-Hodgkin lymphoma. This report provides the first unequivocal evidence for the expression of the EBNA1 protein in the tumor cells of Hodgkin's disease and validates an important reagent with which to analyze the role of EBV in various virus-associated malignancies.

Amino Acid Sequence↗
PubMed1994

Asymmetric expression of protein kinase CK2 subunits in human kidney tumors.

Renal clear cell carcinomas and the corresponding ipsilateral control tissues were investigated for protein kinase CK2 activity and subunit ratio. The average protein kinase CK2 activity from 21 different kidney samples was 318 U/mg and that from the corresponding tumors 610 U/mg. The subunit ratio of protein kinase CK2 alpha in tumors/normal tissue (T/N) was 1.58 and that of the protein kinase CK2 beta (T/N) was 2.65. The data suggest that the generally described increase in protein kinase CK2 activity in tumor cells may to some extent result from a deregulation in subunit biosynthesis or degradation. This at least partly owing to the presence of excess enzymatically active protein kinase alpha-subunit but also to a significantly higher presence of the non-catalytic beta-subunit.

Adenocarcinoma, Clear Cell↗
PubMed1994

The proliferative function of basal cells in the normal and hyperplastic human prostate.

To obtain more insight into the proliferative function of basal and secretory cell types in human prostate, we studied the immunoprofile of three well-characterized proliferation-associated antigens (Ki-67, PCNA, MIB 1) in normal and hyperplastic prostate tissue. Distinction between labeled basal and secretory cell types was made by simultaneous demonstration of the proliferation-associated antigens and basal cell-specific cytokeratins in identical sections. In normal and hyperplastic acini, approximately 70% of labeled cells were of the basal cell phenotype. These data clearly suggest that the proliferative compartment of the normal and hyperplastic epithelium is located in the basal cell layer. Compared to normal and hyperplastic conditions, severe proliferative abnormalities were detected in high-grade prostate intraepithelial neoplasias (PIN), as documented by the extension of the proliferative compartment up to the luminal border. Conversely, approximately 70% of proliferating cells detected in atypical hyperplasias that progressed in invasive carcinomas were localized in the remaining basal cell layer. These findings may indicate the proliferative role of basal cells in the epithelial renewal, and the development of hyperplastic and neoplastic disorders in the human prostate.

Antibodies, Monoclonal↗
PubMed1994

Multidirectional differentiation in the normal, hyperplastic, and neoplastic human prostate: simultaneous demonstration of cell-specific epithelial markers.

The prostatic epithelium is composed of three distinct cell populations: secretory luminal, basal, and endocrine-paracrine cells. It is currently unknown whether these basic epithelial cell types are related in a hierarchical pathway of differentiation or are independent and separate entities. In the present study we used double-label techniques for cell-specific markers to search for multidirectional differentiation in normal, hyperplastic, and neoplastic prostate tissue. In normal and hyperplastic conditions subsets of basal cells revealed synchronous expression of basal cell-specific cytokeratins and the prostate-specific antigen, indicating intermediate differentiation between basal and secretory luminal cell types. Furthermore, endocrine-paracrine cells of the closed type focally showed simultaneous expression of chromogranin A and basal cell-specific cytokeratins. These findings highlight the phenotypic plasticity of the basal cell layer in the human prostate. In prostatic adenocarcinoma co-expression of exocrine (prostate-specific antigen) and endocrine (chromogranin A) markers was detected frequently in subsets of malignant cells. Conversely, this amphicrine phenotype was rarely found in hyperplastic glands. The occurrence of multidirectional differentiation within the prostatic endocrine cell system may indicate that endocrine-paracine cells derive from pluripotent stem cells of endodermal origin. Furthermore, the phenotypic plasticity of basal cells suggests that this epithelial compartment houses stem cell populations that give rise to all epithelial cell lineages encountered in the normal, hyperplastic, and neoplastic human prostate.

Adenocarcinoma↗
PubMed1993

Clonal chromosome aberrations in cell cultures of synovial tissue from patients with rheumatoid arthritis.

Cytogenetic analysis of primary cell cultures and/or passages 1-3 of synovial tissue from seven patients with rheumatoid arthritis was performed. As the only recurrent chromosome aberration, trisomy 7 was found in six of seven cultures. In four cultures, trisomy 7 occurred as a clonal change in up to 20% of the analyzed cells, with an increase of the proportion of cells with +7 with the duration of the in vitro culture. Apart from this recurrent change, a variety of partly clonal, partly nonclonal numerical and structural chromosome aberrations were observed in all cases. These findings support the view that clonal chromosome aberrations may play a role in the pathogenesis of invasive growth of the synovial tissue in rheumatoid arthritis although the localized synovial hyperproliferation is not a true neoplastic process.

Arthritis, Rheumatoid↗
PubMed1993

Widespread distribution of nuclear androgen receptors in the basal cell layer of the normal and hyperplastic human prostate.

The role of the basal cell layer in organogenesis, epithelial renewal and development of benign prostatic disorders is largely unknown. The objective of the present study was to investigate whether or not basal cells express the nuclear androgen receptor (AR). Computer-assisted image analyses of immunohistochemical double stainings were performed to localize AR and basal-cell-specific cytokeratins in identical sections. The results showed that the basal cells express nuclear AR widely in normal and hyperplastic conditions. When compared with the staining intensities detected in secretory luminal cells, the receptor was most frequently expressed at lower levels in basal cells, which may exhibit strong AR immunoreactivity focally. Basal cells with increased AR expression were most frequently detected in hyperplastic lesions including post-atrophic and atypical hyperplasia. The presence of nuclear receptors for both androgens and oestrogens or progestins in basal cells may indicate that these cells are targets of the hormonal imbalance which has frequently been implicated in the aetiology of benign prostatic hyperplasia.

Atrophy↗
PubMed1993

Androgen receptor status in endocrine-paracrine cell types of the normal, hyperplastic, and neoplastic human prostate.

Neuroendocrine differentiation is a frequent occurrence in common prostatic adenocarcinomas and may have prognostic implications in prostatic malignancies. In the present study, we used immunohistochemical double label methods to evaluate the nuclear androgen receptor (AR) status in endocrine-paracrine (EP) cells of normal, hyperplastic, and neoplastic prostate including tumours that recurred after hormonal and radiation therapy. In normal and hyperplastic glands, EP cells characterized by the panendocrine marker chromogranin A (Chr A) did not reveal AR-positivity. This may indicate that prostatic EP cells represent an androgen-independent cell population whose regulatory functions are not influenced by circulating androgens. Unequivocal co-expression of Chr A and AR was very rarely detected in subsets of endocrine differentiated tumour cells in treated and untreated specimens. The widespread absence of nuclear AR in neuroendocrine tumour cells suggests that this phenotype belongs to those cell clones in prostate cancer which are initially androgen-independent and refractory to hormonal therapy.

Adenocarcinoma↗
PubMed1993

Differential expression of alpha 6 and alpha 2 very late antigen integrins in the normal, hyperplastic, and neoplastic prostate: simultaneous demonstration of cell surface receptors and their extracellular ligands.

The very late antigens (VLAs) are alpha beta-heterodimeric transmembrane proteins that include surface cell receptors for laminin (VLA-6) and collagen (VLA-2), which mediate cell-matrix and cell-cell adhesion. We investigated the distribution of VLA-6 (alpha 6, beta 1) and VLA-2 (alpha 2, beta 1) proteins in normal, hyperplastic, and neoplastic human prostate tissue and lymph node metastases by the avidin-biotin complex method. In normal and hyperplastic glands we observed two staining patterns that differed according to the density of alpha 6- and alpha 2-receptors at the site of co-expression with their corresponding ligands (laminin, type IV collagen) in acinar basement membranes (BMs). Band-like deposits with high receptor density suggested strong anchorage of the prostate epithelium to acinar BMs, whereas the absence of this pattern most probably reflected reduced cellular attachment. Very late antigen-6 immunoreactivity showed the band-like pattern in approximately 70% of normal and hyperplastic glands compared with VLA-2, which showed the same pattern in only 5% of cases. In prostatic adenocarcinoma the band-like pattern significantly decreased with dedifferentiation and was consistently absent in grade III lesions. Compared with staining intensities in normal and hyperplastic conditions, grade I and II tumors maintained or overexpressed the VLA-6 receptor in 85% of cases, whereas the VLA-2 receptor was downregulated in approximately 70% of cases. Grade III tumors were characterized by a heterogeneous expression of VLA-6 and VLA-2 proteins, but frequently upregulated their receptors in corresponding lymph node metastases. Regardless of the staining intensity, all primary and metastatic carcinomas investigated expressed VLA-6 and VLA-2 receptors whose extracellular domains were extensively co-expressed with their ligands in neoplastic BM formations. These findings suggest that VLA-6 and VLA-2 receptors mediate attachment of tumor cells to neoplastic BM material, which, in turn, may endow these cells with an increased ability to invade the extracellular matrix.

Adenocarcinoma↗
PubMed1993

Ossifying renal tumor of infancy.

Ossifying renal tumor of infancy is a rare but distinctive tumor that presents as a mass in the pelvicaliceal system. It is usually suspected to be a calculus until surgical exploration reveals dense tumor attachment to the renal parenchyma. The histogenesis of this lesion has not been established. We present a case of this unusual neoplasm. A renal sparing procedure was performed on this biologically benign tumor. Followup after 20 months showed no evidence of recurrence.

Female↗
PubMed1993

[New aspects in histogenesis of hyperplasia and cancers of the prostate].

The prostatic epithelium has generally been described as consisting of three separate cell types--secretory, luminal, basal and endocrine-paracrine (EP) cells--that differ by their morphological features, functions and hormonal regulation. Compared with the gastrointestinal tract and other self-renewing tissue, little is known about differentiating and proliferative processes in the normal and hyperplastic human prostate. In the present report, we propose a stem cell model 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 are linked in precursor-progeny relationship as documented by the existence of intermediate phenotypes, 2. the basal cell layer represents the proliferative compartment in normal and hyperplastic conditions, 3. EP-cell types do not proliferate and lack the nuclear androgen receptor (AR), 4. basal cells may be potentially androgen-responsive as documented by the presence of AR, 5. formation of basement membrane (BM) deposits is crucial in the development of the invasive phenotype. 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 responsive target cells in the basal cell layer. Accordingly, the abnormal growth of the secretory epithelium in benign prostatic hyperplasia may be related to an increase in the total number of androgen-responsive basal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Oncogenic osteomalacia: imaging studies.

X-ray und NMR imaging studies of a 34-year-old patient with tumor-induced hypophosphatemic osteomalacia (OM) are presented. Besides typical features of OM, periosteal new bone formation was noticed initially. After 17 months of conservative treatment with supplements of inorganic phosphorus and 1,25-dihydroxyvitamin D, bone density had increased but Looser's zones were still present, while periosteal new bone formation was strikingly less evident. At this time a tumor in the first left metatarsal space became palpable, was surgically excised and proved to be a low-grade synovial sarcoma with hypervascular and partially calcified structures. Six months later an X-ray survey showed no more signs of metabolic osteopathy. Preoperatively, the pronounced vascularity of the tumor could be demonstrated by angiography and NMR scanning.

Adult↗
PubMed1992

Distribution of basement membranes in primary and metastatic carcinomas of the prostate.

The presence of periacinar and pericellular basement membranes (BMs) has been reported recently in common prostatic adenocarcinomas. In this study we extended our investigations of BMs on lymph node and hematogenous metastases, primary prostatic cancer with unusual histologic features, and posttreatment tumors. In contrast to prostatic malignancies that derive from the transitional epithelium (squamous cell carcinoma, prostatic transitional cell carcinoma) and prostatic involvement by bladder cancer, inconspicuous stromal changes and distinct BM formations at the site of tumor invasion were observed in carcinomas deriving from the secretory epithelium (papillary ductal carcinoma) and from the basal cell (basal cell carcinoma). Even highly malignant anaplastic and small cell carcinomas, as well as irradiated and/or hormonally treated tumors, showed distinct BM formations in contact with the stroma. The same observations could be made in lymphatic and hematogenous metastases of different anatomic sites. These findings indicate that prostatic malignancies may retain BMs even in high-grade lesions, metastases, posttreatment tumors, and variants of prostatic adenocarcinoma.

Basement Membrane↗
PubMed1992

An electronic primer in dermatopathology.

We present an electronic primer in dermatopathology based on a full-text retrieval system which contains all the features of traditional handbooks of dermatopathology. The system including high-resolution black and white pictures with coloured overlays runs on every personal computer with VGA card and needs no additional software and hardware equipment. The representation of pictures is improved by using high-resolution VGA cards. The system is able to work like an electronic diagnostic consultant in dermatopathology.

Animals↗
PubMed1992

The 'female prostate': location, morphology, immunohistochemical characteristics and significance.

Using immunostaining for prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP), we can demonstrate prostate-analogous periurethral glands (the 'female prostate') in 66.7% of 33 cases. Histomorphologically, these glands resemble strongly the male prostate glands before puberty. They remain immature throughout life from the fetal period up to advanced age obviously because of a lack of an androgenic stimulus. The glands have long ducts leading into the urethra. A proper stroma component is missing. The immunohistochemical behavior of these glands also corresponds widely to that of the male prostate glands before puberty. No indications can be found for a proper biological function.

Acid Phosphatase↗
PubMed1992

Excessive collagen formation in fibrolamellar carcinoma of the liver: a morphological and biochemical study.

We have studied the excessive deposition of extracellular matrix in a patient with fibrolamellar carcinoma of the liver. The collagen matrix was predominantly composed of collagens I, III, and V. Since specific mRNAs for collagens I and III were detected by in situ hybridization, we also provide evidence that the fibroblastoid stromal cells were the major source of this collagen. Occasionally, also tumor cells could be shown to express collagen III-mRNA. Furthermore, some tumor cells showed positive signals for TGF-beta 1, while isolated stromal cells expressed interleukin-6. This cytokine expression may probably be related to the altered control of collagen gene expression.

Adolescent↗