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Biomedical subjects

A Roessner

Publications and source records attributed to A Roessner.

At least 55 records · Page 3Linked to original sources
PubMed2000

High telomerase activity and high HTRT mRNA expression differentiate pure myxoid and myxoid/round-cell liposarcomas.

Molecular markers characterizing the transition of a myxoid to a more round-cell liposarcoma have not been described. To examine whether telomerase activity, hTRT and hTR mRNA expression were associated with tumor progression in myxoid liposarcoma, we investigated a total of 28 myxoid liposarcomas (13 pure myxoid tumors, 14 mixed-type tumors, and 1 pure round-cell variant) from 19 patients. Telomerase activity was detected by using the fluorescent PCR-based TRAP-assay. Expression of hTRT and hTR mRNAs was determined by the semi-quantitative RT-PCR. On the basis of only one tumor sample per patient, telomerase activity was found in 9 of 9 myxoid/round-cell liposarcomas and in 3 of 10 pure myxoid tumors. Elevated hTRT expression was found in 13 of 17 liposarcomas. All telomerase-positive tumors showed hTRT expression, whereas there were 3 cases showing hTRT expression without telomerase activity. HTR mRNA expression was elevated in all 19 liposarcomas. Thus, only the levels of telomerase activity and of hTRT mRNA expression differentiated pure myxoid liposarcoma and myxoid/round-cell liposarcoma (p < 0.003 and p = 0.029, respectively). We believe that high levels of telomerase activity and of hTRT expression are associated with tumor progression from low-grade pure myxoid to higher-grade malignant round-cell liposarcoma, and may consequently represent a useful prognostic marker for this histological sub-type of soft-tissue tumors.

Biomarkers↗
PubMed2000

Matrix metalloproteinases and TACE play a role in the pathogenesis of endometriosis.

Endometriosis, a benign gynecologic disorder, occurs in about 10% of women in reproductive age and in up to 50% of women with infertility. The basic etiologic factors causing this disease are unknown as yet. Matrix metalloproteinases (MMP) are involved in degradation of the extracellular matrix (ECM). Their proteolytic activity is regulated by tissue inhibitors of metalloproteinases (TIMPs). Tumor necrosis factor-alpha converting enzyme (TACE) is a membrane-bound disintegrin metalloproteinase that processes the membrane-associated cytokine proTNF-alpha to its mature soluble form. TNF-alpha induces the secretion of several MMPs. In order to study the expression of MMP-1, -2, -3 and -9, TIMP-1 and -2, TACE and TNF-alpha in endometrium and endometriotic tissue, we investigated formalin-fixed paraffin sections of endometriotic tissues and normal endometrium with immunohistochemical techniques and in situ hybridisation. Furthermore, quantitative PCR was used for quantification of TACE-mRNA in fresh tissue. We found in this study significant higher protein expression of MMP-1 and TACE and significant lower protein expression of TMP-1 and -2 in endometriotic tissue compared to endometrium. This data may suggest that high TACE expression causes the increased conversion of membrane-bound proTNF-alpha into its soluble form, which stimulates the increased secretion of MMP-1. The simultaneous deficiency of TIMP-1 and -2 in endometriotic tissue suppose an additional proteinase inhibitor imbalance in endometriosis.

ADAM Proteins↗
PubMed2000

Is typing of metaplasia at the squamocolumnar junction revealing its aetiology?

Until recently, intestinal metaplasia (IM) at the squamocolumnar junction (SCJ) was ascribed to Barrett's mucosa (BM), which arises from gastro-oesophageal reflux. Recent studies, however, have shown that IM at the SCJ can also be induced, for example, by Helicobacter pylori (HP). The aim of this study was to investigate whether the type of IM might be helpful in the differentiation between these two aetiologies. Biopsies from the antrum, corpus and immediately below the Z-line were taken from 443 patients. Eighty-three of them showed IM below the Z-line. In these, the endoscopic aspect of the Z-line was classified as either unremarkable (n=49) or suspected of BM (n=34). Typing of IM was done using Gomori's aldehyde fuchsin-Alcian blue staining. Overall, age, HP status and erosive oesophagitis had no influence on the IM type. Type-III IM (n=24) was more frequent in men (P=0.0371) and related to endoscopic BM (P<0.0001). Type-I/II IM (n=59) was associated with an unremarkable Z-line (P<0.0001) and was linked to multifocal gastric IM (P=0.016) and HP (P=0.0011). In conclusion, it was shown that, in the presence of a normal Z-line, especially in the absence of HP, type-III IM is suggestive of BM. The diagnosis of short or ultra-short segment BM should therefore include endoscopic, histological and histochemical characteristics.

Adult↗
PubMed2000

Distribution pattern of matrix metalloproteinases 1, 2, 3, and 9, tissue inhibitors of matrix metalloproteinases 1 and 2, and alpha 2-macroglobulin in cases of generalized AA- and AL amyloidosis.

Matrix metalloproteinases (MMPs) degrade basement membranes and connective tissue and play an essential role in the homeostasis of the extracellular matrix which is disrupted by the deposition of amyloid. This immunohistochemical study investigated the distribution pattern of matrix metalloproteinases (MMP-1, -2, -3, and -9) and their inhibitors [alpha 2-macroglobulin (alpha 2-M), tissue inhibitors of MMPs (TIMP)-1, and TIMP-2] in human AA- and AL amyloid deposits. Specimens of liver, kidney, and spleen from 22 autopsy cases were investigated. Nine patients had suffered from generalized AA amyloidosis, eight from generalized AL amyloidosis, and five from rheumatoid arthritis or tuberculosis with no histological evidence of amyloid. In all amyloidotic and non-amyloidotic patients, each protease and protease inhibitor was detected in almost every organ investigated. In the amyloidotic cases, there was no indication that a specific protease or protease inhibitor was absent or expressed, but a difference was observed in their spatial distribution patterns. The most noticeable difference was found in immunostaining of amyloid. Only MMP-1, -2, and -3, and alpha 2-M were present in AA amyloid deposits, and only TIMP-1 and TIMP-2 were found in deposits of AL amyloid. This is the first study to show that MMP-1, -2, and -3 are present in AA amyloid deposits. They may be involved in tissue remodeling or in proteolysis of the precursor and fibril proteins.

Adult↗
PubMed2000

Inducible nitric oxide synthase expression in human urinary bladder cancer.

Nitric oxide (NO) is generated by a family of enzymes, nitric oxide synthases (NOS), in a wide range of mammalian cells. NO produced by the inducible NOS isoform (iNOS) has been suggested to play an important role in tumor biology with both tumor promoter and anti-tumor activity. Here, the cellular localization of iNOS in tissue of 100 cases of urinary bladder cancer was assessed immunohistologically using a commercially available antiserum. Positive iNOS immunostaining was detected in all samples of tumor tissue, whereas nonmalignant tissue adjacent to malignant areas did not show any iNOS positivity. The tumor tissue revealed a highly inhomogeneous staining pattern. In addition to uniformly stained tumor specimens, we also found markedly iNOS-positive tumor islets in the midst of unstained tumor tissue and scattered individual tumor cells expressing marked staining. In some cases, the tumor tissue showed no or only weak staining intensity. In some instances, the superficial epithelial layer of papillary carcinomas was extremely immunoreactive, in other cases it was not. Thus we were unable to show a clear correlation to tumor grade or stage. Further studies with a diversity of tumor markers including molecular genetics techniques will be necessary to elucidate how and to what extent NO and bladder cancer of different grades and stages are functionally interrelated.

Animals↗
PubMed2000

Plasmacytoma of the tonsil with AL amyloidosis: evidence of post-fibrillogenic proteolysis of the fibril protein.

We report of a 58-year-old Caucasian man who was referred to the University Hospital with a greatly enlarged left tonsil which showed calcifications on computed-tomography scans. Histopathology revealed a plasmacytoma with secondary AL amyloidosis, ossifications, and multinucleated foreign-body-type giant cells. N-terminal sequencing of amyloid-fibril proteins purified from the formalin-fixed tissue showed the presence of two proteins of different size; these were of lambda-light-chain origin (subgroup V), measured approximately 15.2 kDa and 10.5 kDa, and had identical N-terminal ends (YVLTQPP). When the amyloid deposits were immunolabeled with a polyclonal antibody directed against lambda light chain, they showed two staining patterns: some deposits showed intense immunolabeling while others were not immunoreactive. Immunostaining of amyloid was completely absent after protease pre-treatment. Immunoelectron microscopy with gold-labeled secondary antibodies showed staining that was spatially related to amyloid fibrils and suggested that the antibody probably detected the fibril protein. Therefore, our hypothesis in this case is that the different immunostaining patterns are due to a post-fibrillogenic proteolysis of the fibril protein at the C-terminal end of the light chain, as indicated by the presence of two differently sized lambda-light-chain fragments with identical N-terminal ends.

Amyloidosis↗
PubMed2000

Mutation of p53 with loss of heterozygosity in the osteosarcomatous component of a dedifferentiated chondrosarcoma.

We investigated a dedifferentiated chondrosarcoma of a 61-year-old woman with an osteosarcomatous high-grade component for p53 alteration. The low-grade cartilaginous and the high-grade osteosarcomatous components of the tumor were macrodissected and evaluated separately by immunohistochemistry and molecular biology. We used PCR-SSCP analysis and direct sequencing to screen exons 4-8 for p53 mutations. The p53 intron 1-polymorphism was investigated for loss of heterozygosity. A functionally relevant p53 missense mutation in codon 193 of exon 6 (A-to-T transversion) with loss of wild-type allele was detected only in the dedifferentiated component. Using the monoclonal antibody DO-1, immunohistochemistry failed to show p53 overexpression. This evidence of p53 mutation may be regarded as at least a co-factor that "switched" the preexisting low-grade conventional chondrosarcoma to a highly malignant dedifferentiated tumor.

Chemotherapy, Adjuvant↗
PubMed2000

Radiographic findings in osteoarthritis of the knee joint are not correlated with cartilage histomorphology or immunohistochemistry.

The purpose of this study was to investigate whether radiographic joint space narrowing (JSN) of the lateral knee compartment predicts the histomorphological or immunhistochemical grading in cases of osteoarthritis of the knee joint. The lateral joint space was measured on weight-bearing radiographs. Femoral osteochondral plugs of 29 patients undergoing total knee replacement were obtained from lateral condyles. All these patients had severe osteoarthritis of the medial compartment, with the lateral compartment showing different stages of osteoarthritis. The specimens were histomorphologically evaluated with the Mankin score, and the expression of the cartilage-degrading enzymes MMP1 and MMP3 was measured. There was no correlation between the joint space and histomorphological or immunohistochemical data, whereas the enzyme expression was correlated with histomorphological grading. We conclude that radiographic assessment alone is not sufficient to evaluate the cartilage damage of the lateral condyle.

Arthroplasty, Replacement, Knee↗
PubMed2000

RB protein expression in human endometrial carcinomas--an immunohistochemical study.

The aim of the current study was to investigate the immunohistochemical expression of the retinoblastoma protein (pRB) in formalin-fixed, paraffin-embedded specimens obtained from 62 patients suffering from endometrial cancer. The avidin-biotin-peroxidase detection system with microwave pretreatment and the mouse anti-human NCL-RB1 monoclonal antibody were used. Heterogeneous nuclear immunostaining for the pRB was generally observed in the glandular cells in 59 out of 62 (95%) endometrial carcinomas, while stromal components were unreactive. In one case of stage Ic endometrioid adenocarcinoma, a small percentage of glandular cells (5%) stained positively with the anti-RB antibody, while two other tumors (stage IIa adenosquamous carcinoma and stage IIIa endometrioid adenocarcinoma) were pRB negative. In the cases with concomitant hyperplastic and neoplastic endometrial lesions, pRB immunoreaction was heterogeneous in the hyperplastic endometrial cells and in the adjacent neoplastic endometrium. Moreover, eight cases of endometrial carcinoma harboring K-ras codon 12 gene point mutation overexpressed pRB (more than 80% of glandular endometrial cells were positive) immunohistochemically, while none of three pRB negative slides had a K-ras gene alteration. Our data support the view that the pRB is expressed in most of the human endometrial neoplasms, but the lack of pRB immunoreactivity may correspond with the retinoblastoma gene rearrangements in a subset of advanced endometrial carcinomas.

Adenocarcinoma↗
PubMed2000

Expression of stromelysin and urokinase type plasminogen activator protein in resection specimens and biopsies at different stages of osteoarthritis of the knee.

This study aimed at assessing the possible diagnostic value of cartilage biopsies as a convenient marker for cartilage matrix degradation. We therefore examined cartilage specimens from 56 patients with primary osteoarthritis (OA) of the knee. Resection and biopsy cartilage specimens obtained during joint replacement surgery were used for this study. In addition to histomorphology, immunohistochemistry (ICH) was performed to determine the expression levels and distribution patterns of stromelysin and u-PA protein. The latter data were compared with the degree of histomorphological changes in osteoarthritic cartilage samples, based on a modified version of Mankin's grading score. Compared to the cartilage resection specimens, the biopsies showed comparable expression patterns for both proteinases: the strongest signals were noted in the superficial zone and, as matrix destruction increased, also in the chondrocytes of the transition and deep zones. The strongest signals were ascertained in cell clusters beneath deep matrix fissures. At the immunohistochemical level, we found a direct correlation in the expression of MMP-3 and u-PA between resection specimens and biopsies. Furthermore, in both types of cartilage samples, we noticed a positive relationship between the expression of both proteins and the Mankin score. Analysis of the expression levels revealed significant differences between deep, transition and superficial zones. Histomorphological and immunohistochemical examinations of MMP-3 and u-PA in biopsies of osteoarthritic cartilage turned out to be useful for estimating the pathological changes within osteoarthritic knee joints. Therefore, in future, cartilage biopsies from osteoarthritic knee joints might serve as a diagnostic tool and thus have an influence on further therapeutic strategies.

Biopsy↗
PubMed2000

Mdm2 gene amplification in gastric cancer correlation with expression of Mdm2 protein and p53 alterations.

Mdm2, localized on chromosome 12, is considered a negative regulator of p53 function and seems to play a role in the pathogenesis of a variety of tumors. The mdm2 amplification in advanced-stage gastric carcinoma has not yet been investigated. Mdm2 amplification was determined in 43 gastric carcinomas, and the genetic results were correlated with mdm2 protein expression, p53 alterations, and clinicopathologic data. The tumors were classified according to Lauren: 20 intestinal-type tumors, 19 tumors of diffuse growth inclusive of a primary small cell carcinoma, and 4 carcinomas with mixed differentiation. Staging was based on the pTNM classification system. Mdm2 and p53 were demonstrated by immunohistology on formalin-fixed and paraffin-embedded tumor tissue. The mdm2 oncogene was amplified by nonradioactive hybridization of tumor DNA with an mdm2 cDNA probe. The Southern blots were evaluated densitometrically. For p53 mutation screening, we analyzed the highly conservative regions of the p53 gene (exons 4 to 8) with the use of the polymerase chain reaction-single-strand conformation polymorphism technique. Polymerase chain reaction products with band shifting were directly sequenced. Mdm2 amplification was demonstrated in 18 tumors (41.8%). The mdm2 gene was amplified more frequently in carcinomas with a diffuse growth pattern. Gastric carcinomas of the intestinal type, however, showed a higher frequency of p53 alterations. There was no statistical significance of the molecular genetic and immunohistologic results of the mdm2/p53 status to staging as well as to age and sex of the patients. The mdm2/p53 pathway is a part of the carcinogenesis of gastric carcinoma. Only approximately 20% of gastric carcinomas failed to show mdm2 and/or p53 alterations. The upregulation of the mdm2 oncogene and the accompanying inactivation of the tumor suppressor gene 53 seem to play a role above all in carcinomas of the diffuse type.

Adult↗
PubMed2000

Rosai-Dorfman disease and generalized AA amyloidosis: a case report.

We report on a patient who, at 31 years of age, was found to suffer from sinus histiocytosis with massive lymphadenopathy (SHML; Rosai-Dorfman disease) with nodal and extranodal involvement as described previously. Five years later the patient presented with nephrotic syndrome caused by a generalized AA amyloidosis, and he subsequently died from pulmonary thromboembolism owing to renal vein thrombosis. Retrospective analysis of serum levels of C-reactive protein (CRP) showed that during the last 3 years before his death, he had a persistently elevated CRP level ranging from 73 to 161 mg/L, despite antiinflammatory treatment with prednisolone, methotrexate, or 6-mercaptopurine. These figures indicate that the patient was probably suffering from a permanent acute phase response which, in the absence of any other evidence of a chronic inflammatory disease which commonly causes AA amyloidosis, was most likely owing to SHML.

Adult↗
PubMed2000

Expression of cathepsin K in chordoma.

Invasive growth of chordoma is accompanied by severe destruction of adjacent bone tissue, a fact that requires high proteolytic activity at the tumor invasion fronts. In this context, cathepsin K is a candidate molecule. It is a protease with high collagenolytic and elastinolytic activity and previously thought to be restricted to osteoclasts and osteoclast-mediated bone resorption. In this study, 44 cases of chordoma of sphenooccipital localization, and 10 embryo-fetal specimens including chorda dorsalis were studied immunohistochemically for their expression of cathepsin K. In 4 additional snap-frozen chordoma cases, the enzyme expression was investigated by reverse transcription polymerase chain reaction and enzyme histochemistry. Ten chondrosarcomas of the skull base served as controls. Various concentrations of cathepsin K mRNA could be seen in all snap-frozen chordoma specimens. The protease was immunohistochemically expressed by the tumor cells. The immunoreactions were accentuated at the tumor invasion fronts. Enzyme histochemistry indicated a strong tumor cell-associated cathepsin K activity in invasive tumor components. In contrast to chordoma, cathepsin K was not significantly expressed in chorda dorsalis and chondrosarcoma of the skull base. In chondrosarcoma, protease expression was limited to osteoclastic cells localized between infiltrative tumor components and regular bone trabeculae. This study shows the significant expression and activity of cathepsin K in chordoma and implicates an important and direct role of this protease in the infiltrative growth of this tumor. This protease expression occurred during neoplastic transformation and did not appear in chorda dorsalis.

Cathepsin K↗
PubMed2000

[Second carcinomas in cancers of the mouth cavity, pharynx and larynx. Clinical, histopathologic and cell kinetic findings].

BACKGROUND: The mortality because of malicious tumours of the oral cavity, of the pharynx and of the larynx has considerably increased in the Federal Republic of Germany during the last two decades. The prognosis not only shows a high ratio of recidivations and formation of metastases, but also a typical field canceration. There is a high rate of incidence of multiple primary, resp. secondary tumours that may occur synchronously or metachronously. Up to now we have learnt only little about the mechanisms concerning the development of tumours and their spread on the cellular molecular level. METHOD: The subject of the present retrospective study was the analysis of patients suffering from an epithelioma of the oral cavity, the pharynx and the larynx and the following secondary carcinomatas. The control group were patients suffering from primary tumours of the same location and subsequent recidivation or metachronous metastasis. By determination of the degree of malignity and keratinisation of the DNA ploidy, of the immunohistological expression of p53 and the immunohistological proliferation marker MIB1 conclusions had to be drawn with regard to the biological behaviour of tumours. RESULTS: The evaluation of the clinical parameters of the 122 patients on the whole revealed a clear increase of new disease as well as a shifting to the younger age within the last five years. Surprisingly, most common were secondary tumours in case of larynx carcinomatas. Patients suffering from secondary tumours show a bad prognosis, however, their maximum survival does not differ considerably from that of patients suffering from recidivations, resp. metastases. Because of the early diagnosis of the secondary carcinomatas the prognosis will depend on the primary carcinoma in most of the cases. The prognosis data indicate that independently from the fact whether there is a primary or a subsequent tumour, the therapy to be applied can only be a combined therapy consisting of operation and ray-therapy. The present examinations confirm reports with regard to disturbance of the p53 regulation that also play an important role in case of the head-neck area. The parallel analysis of MIB1 as a proliferation marker showed in case of the primary carcinomatas a correlation of positive p53-immunocolour with moderate and strong proliferation. Tumours in the hypopharynx and larynx showed a significantly smaller proliferation than that of the oral cavity and oropharynx. In case of the primary and secondary tumours the proliferation is more common in case of the G3-tumours. CONCLUSIONS: The in total modest differences between the primary and secondary carcinoma with regard to the DNA-ploidy; the proliferation and the p53-expression presumably originate in their formation within the scope of a so-called field canceration. Because of the field canceration supposed for the mucous membranes of the upper aerodigestive tract, the check-ups of these patients performed in regular intervals must not be limited in any case to the area of the primary tumour. They will have to consider the entire visible area of the upper respiratory and esophageal tract.

Adult↗
PubMed2000

Retroperitoneal schwannoma presenting as an adrenal tumor.

A retroperitoneal tumor in the region of the adrenal gland was diagnosed in a 56-year-old woman. The patient had been suffering from a dull abdominal pain for nearly four weeks before consulting her family physician. Ultrasound, CT and MRI scans revealed a giant tumor of the right adrenal gland. Endocrine activity could not be demonstrated. The size of the tumor was suggestive of an adrenal carcinoma. The patient was referred for adrenalectomy and complete exstirpation of the retroperitoneal mass. The histological examination revealed characteristical findings of a benign schwannoma.

Adrenal Gland Neoplasms↗
PubMed2000

[Lipoma-like liposarcoma of the tongue].

BACKGROUND: Liposarcomas of the tongue are rare. To date only 7 cases have been reported. PATIENT: We report a new case of a well differentiated lipoma-like liposarcoma of the body of the tongue in a 71-year old woman. Complete uneventful resection was performed. Histologically the tumor consisted of fat cells with occasional lipoblasts and spindle cell areas. There is no sign of recurrence of the tumor 2 years later. RESULTS AND CONCLUSIONS: Liposarcomas of the tongue are rare neoplasms. All cases reported were histologically well differentiated. Liposarcomas have to be considered in the differential diagnosis of solid masses of the tongue.

Aged↗