PubMed Health⌕ Search

Biomedical subjects

T Goldmann

Publications and source records attributed to T Goldmann.

33 records · Page 2Linked to original sources
PubMed2001

The prognostic value of the expression of collagenase IV, cathepsin D and metallothionein in squamous cell carcinomas of the skin determined by immunohistochemistry.

We analyzed 53 specimens from primary squamous cell carcinomas of the skin for the expression of collagenase IV, cathepsin D and metallothionein by means of immunohistochemistry along with histological data. We compared tumors that metastasized (30) with tumors that did not (23) during a follow-up period of at least 5 years. The expression of the two proteolytic enzymes cathepsin D and collagenase IV was also assessed at the invading front of the tumors. Statistical analyses revealed significant differences for the overall expression of cathepsin D (P < 0.05), expression of cathepsin at the invading front (P < 0.05) and the tumor thickness (P < 0.01). The results showed that cathepsin D may be a prognostic factor for squamous cell carcinomas of the skin. We then combined the results of parameters with statistically significant differences by multiplication. The prognostic value of such a combined risk-factor score showed higher confidence than any of the single parameters alone: a sensitivity of 63.3%, a specificity of 87.0% and an efficiency of 73.6%. This kind of combined risk-factor score might be used to more accurately detect patients at high risk of metastasis.

Aged↗
PubMed2001

Localization of ceramide and glucosylceramide in human epidermis by immunogold electron microscopy.

Ceramides and glucosylceramides are pivotal molecules in multiple biologic processes such as apoptosis, signal transduction, and mitogenesis. In addition, ceramides are major structural components of the epidermal permeability barrier. The barrier ceramides derive mainly from the enzymatic hydrolysis of glucosylceramides. Recently, anti-ceramide and anti-glucosylceramide anti-sera have become available that react specifically with several epidermal ceramides and glucosylceramides, respectively. Here we demonstrate the detection of two epidermal covalently bound omega-hydroxy ceramides and one covalently bound omega-hydroxy glucosylceramide species by thin-layer chromatography immunostaining. Moreover, we show the ultrastructural distribution of ceramides and glucosylceramides in human epidermis by immunoelectron microscopy on cryoprocessed skin samples. In basal epidermal cells and dermal fibroblasts ceramide was found: (i) at the nuclear envelope; (ii) at the inner and outer mitochondrial membrane; (iii) at the Golgi apparatus and the endoplasmic reticulum; and (iv) at the plasma membrane. The labeling density was highest in mitochondria and at the inner nuclear membrane, suggesting an important role for ceramides at these sites. In the upper epidermis, ceramides were localized: (i) in lamellar bodies; (ii) in trans-Golgi network-like structures; (iii) at the cornified envelope; and (viii) within the intercellular space of the stratum corneum, which is in line with the known analytical data. Glucosylceramides were detected within lamellar bodies and in trans-Golgi network-like structures of the stratum granulosum. The localization of glucosylceramides at the cornified envelope of the first corneocyte layer provides further proof for the existence of covalently bound glucosylceramides in normal human epidermis.

Cell Membrane↗
PubMed2001

Diagnostic value of immunohistochemically detected surfactant--apoprotein-A in malignant tumors located in the lungs: report of two cases.

We report two cases of patients suffering from multiple tumors in the lungs with questionable origin. In these cases, the expression of Surfactant-apoprotein-A (SP-A) by the tumor cells has been a helpful feature in the process of diagnosis by indicating primary carcinomas of the lungs. Surfactant-apoprotein-A is expressed by the pneumocytes II in lung tissue and a portion of non-small cell lung carcinomas and has not yet been found to be expressed by other tumors when detected immunohistochemically by use of the monoclonal antibody PE-10. We analyzed formalin-fixed, paraffin-embedded specimens of different malignancies with pulmonary location for the expression of SP-A by the use of PE-10 with other antibodies against additional epitopes such as the thyroid transcription factor-1. In normal lung areas a distinct staining of the pneumocytes II has been observed. All the control sections of primary and metastatic nonlung-carcinoma specimen in our study remained negative. The monoclonal antibody PE-10 used in this study provides high specificity when compared to the results obtained with polyclonal antibodies. One of the two cases reported, a mucinous carcinoma of the lungs, had been negative for thyroid transcription factor-1 but positive for SP-A. Thus, SP-A detected by immunohistochemistry using the monoclonal antibody PE-10, together with other parameters such as thyroid transcription factor-1, may be a useful tool for individual diagnosis of malignomas located in the lungs with a questionable primary origin. Ann Diagn Pathol 5:84-90, 2001.

Adenocarcinoma, Mucinous↗
PubMed2001

HOPE fixation: a novel fixing method and paraffin-embedding technique for human soft tissues.

We have developed a novel method for tissue fixation, including subsequent paraffin-embedding and sectioning, that allows the complete pathological analysis of all types of human soft tissues. Furthermore, it maintains additional positive features relevant to immunohistochemistry and molecular pathology. The so-called HOPE-technique (Hepes-Glutamic acid buffer mediated Organic solvent Protection Effect) comprises a protection-solution with an organic buffer, acetone as the only dehydrating agent, and pure paraffin of 52-54 degrees C melting temperature. Although the exact mechanism of protection has still to be elucidated, it seems rather unlikely that chemical bindings occur during the whole process of fixation, which is described and compared with the standard formalin-paraffin technique. Essentially, HOPE-fixed sections show formalin-like morphology. However, the sections are somewhat difficult to handle because of their fragility. This is due to the absence of any type of protein cross-linking and the dynamic processes of immersion and outflow of the HOPE protection solution. HOPE-fixed sections provide an excellent preservation of proteins and antigenic structures for differential analysis by immunohistochemical and/or enzyme histochemical techniques. However, their most remarkable feature is the extremely low degradation of nucleic acids (DNA and RNA) combined with good results obtained by in situ hybridization techniques. In conclusion, HOPE fixation may become a valuable additional tool in modern pathology.

Cross-Linking Reagents↗
PubMed2001

EnVision+, a new dextran polymer-based signal enhancement technique for in situ hybridization (ISH).

Seventy paraffin-embedded cervical biopsy specimens and condylomata were tested for the presence of human papillomavirus (HPV) by conventional in situ hybridization (ISH) and ISH with subsequent signal amplification. Signal amplification was performed either by a commercial biotinyl-tyramide-based detection system [GenPoint (GP)] or by the novel two-layer dextran polymer visualization system EnVision+ (EV), in which both EV-horseradish peroxidase (EV-HRP) and EV-alkaline phosphatase (EV-AP) were applied. We could demonstrate for the first time, that EV in combination with preceding ISH results in a considerable increase in signal intensity and sensitivity without loss of specificity compared to conventional ISH. Compared to GP, EV revealed a somewhat lower sensitivity, as measured by determination of the integrated optical density (IOD) of the positively stained cells. However, EV is easier to perform, requires a shorter assay time, and does not raise the background problems that may be encountered with biotinyl-tyramide-based amplification systems. (J Histochem Cytochem 49:1067-1071, 2001)

Cervix Uteri↗
PubMed2000

DNA-printing: utilization of a standard inkjet printer for the transfer of nucleic acids to solid supports.

The use of total cDNA as a probe for hybridization enables the transcription level of a large number of genes to be analyzed at the same time. Some effort has been spent to develop high density gene arrays on different solid supports to facilitate this hybridization. We achieved a high resolution by utilizing inkjet printer technology as a useful alternative to blotting the target genes onto a membrane. By the use of an ordinary inkjet printer model we show that it is possible to print DNA onto hybridization membranes and hybridize using either specific genes or total cDNA as probes. The high resolution of these prints (300 dpi) might be used in the future to construct complex micro-arrays to analyze simultaneously large numbers of genes.

Animals↗
PubMed2000

A receptor-type protein tyrosine phosphatase PTP zeta is expressed in human cutaneous melanomas.

We describe the expression of a receptor-type protein tyrosine phosphatase PTP zeta (or RPTP beta) in human cutaneous melanomas as detected by means of immunohistochemistry. The expression of PTP zeta has been described to be restricted to the central nervous system. In developing mice brain high levels of PTP zeta have been detected indicating its developmental importance; PTP zeta is also expressed in glioblastoma and neuroblastoma. By the use of immunohistochemistry we detected PTP zeta in human primary and metastatic melanomas. The melanocytes of healthy skin remained negative. Due to the developmental origin of the melanocytes from neural crest, this represents a further example for transformed cells switching back to express molecules related to their ontogenetic history. These promising initial results have to be verified in larger scaled studies; the inclusion of nevi will be necessary to further elucidate the role of PTP zeta in melanocyte transformation and melanoma development.

Antigens, Neoplasm↗
PubMed1999

Epipodite and fat cells as sites of hemoglobin synthesis in the branchiopod crustacean Daphnia magna.

In contrast to the malacostracan crustaceans that use hemocyanin as the oxygen carrier, a number of branchiopod crustaceans, such as the water flea Daphnia magna, utilize hemoglobin (Hb) as the respiratory protein. By means of in situ hybridization (ISH) techniques with subsequent signal amplification using catalyzed reporter deposition, sites of Hb synthesis were localized in Daphnia magna. Based on a previously reported Hb-cDNA sequence, a specific ISH probe was designed and hybridized with the Hb-mRNA in histological sections of adult D. magna. The detection of Hb-mRNA was tissue specific and revealed that Hb is synthesized in fat cells, which play a role in fat and glycogen metabolism, and in epithelial cells of the epipodites, which are involved in osmoregulation. Sites of Hb synthesis have been identified in several invertebrate phyla, including Annelida and Nematoda. However, this is the first example in the class Crustacea, and only the second in the phylum Arthropoda.

Adipocytes↗
PubMed1999

The expression of proteolytic enzymes at the dermal invading front of primary cutaneous melanoma predicts metastasis.

The expression of three proteinases Cathepsin B (Cath. B), Cathepsin D (Cath. D) and Collagenase IV (Coll. IV) has been retrospectively analyzed within an immunohistochemical study on routinely fixed, paraffin embedded tissues from 147 primary cutaneous melanomas belonging to the classes pT3 and pT4. The development of these melanomas has been followed for at least five years. We compared the expression of these proteolytic enzymes in tumors that metastized during the follow-up-period with that in tumors that did not metastize. The expression at the dermal invading front of the tumors showed higher prognostic values (Cath. B chi 2 = 40.03, p < 0.001; Cath. D chi 2 = 90.95, p < 0.001; Coll. IV chi 2 = 44.46, p < 0.001) than the overall expression of these enzymes (Cath. B chi 2 = 5.63, p = 0.018; Cath. D chi 2 = 6.21, p = 0.010; Coll. IV chi 2 = 6.57, p = 0.010). The distribution of protease-expression inside the tumor turned out to be important for the prognostic value, which might also lead to higher prognostic confidence when applied to other tumors.

Cathepsin B↗
PubMed1999

Prognostic classification of malignant melanomas by combining clinical, histological, and immunohistochemical parameters.

In a retrospective study the prognostic relevance of clinical, histopathological, immunohistochemical, and flow-cytometric parameters in primary malignant melanomas was evaluated using both the receiver operating characteristic ROC procedure and the logistic regression model. The proteolytic enzymes collagenase IV, cathepsin B, and cathepsin D proved to be significant prognostic factors. Combining the results obtained with these enzymes with gender, anatomic site, tumour thickness, Clark's level, ulceration, pattern of invasive growth, and presence of large round cells resulted in greatly improved discrimination between metastasized and non-metastasized cases. It is anticipated that this method could allow for precise individual prognostic characterization and in particular for identification of high-risk patients for adjuvant therapy.

Adult↗
PubMed1998

Transparent polyamide: a promising new material for microscopic slides.

We report the use of transparent Polyamide as a new material for microscopical slides intended to be used for immunohistochemical stainings. Polyamide slides provide a strongly increased adhesion of the sections compared to conventionally coated glass slides. They are sensitive to mechanical scratches and become turbid during deparaffinization, and revert to transparency within about eight hours. Immunohistochemical stainings for Cathepsin D for which sections from primary cutaneous melanomas are used reflect the results obtained with glass slides, providing well-preserved histology. Other possible applications for slides manufactured from Polyamide include molecular in situ-techniques, such as in situ hybridizations.

Cathepsin D↗
PubMed1998

Tumor characteristics involved in the metastatic behaviour as an improvement in primary cutaneous melanoma prognostics.

We report the results of a retrospective immunohistochemical study on routinely fixed, paraffin embedded tissues from 147 primary cutaneous melanomas belonging to the classes pT3 and pT4, the development of which has been followed for at least five years. The parameters Cathepsin B, Cathepsin D, Collagenase IV, Metallothionein and PCNA were selected from previous studies on small collectives. All parameters showed statistically significant differences between tumors of the metastatic and the nonmetastatic group. Particularly conspicuous was the expression of Cathepsin B, Cathepsin D and Collagenase IV at the dermal invading front of the tumors. Based on this data we present a procedure of combining these data with established clinical-histological parameters such as tumor thickness and ulceration to an integrated individual risk factor that improves the certainty of melanoma prognosis.

Biomarkers, Tumor↗
PubMedDate not supplied

HOPE--a novel tool for the pathologist.

The growing demand for the detection of prognostic and diagnostic biomarkers by application of molecular-biological techniques has been slowed down to a large degree by the use of formalin and its influence onto antigenic structures and nucleic acids, although other reasons also exist. With regard to morphology a limitation in the possibilities, compared to frozen sections, takes place. With the introduction of the HOPE (Hepes glutamic acid buffer mediated Organic solvent Protection Effect) -fixation to date both have become possible; substantially enlarged possibilities concerning the detection of DNA, RNA and proteins in combination with excellent morphological results comparable to formalin-fixed tissues. We also highlight some aspects from our lung specific work during the last years. Immunohistochemical markers for differential diagnostics of malignancies in the lungs are discussed; their enhanced detectability using the HOPE-technique is pathbreaking for the future. The same holds true for the substantially enhanced detectability of germs (e.g. mycobacteria) in HOPE-fixed tissues.

Buffers↗