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Biomedical subjects

T Löning

Publications and source records attributed to T Löning.

At least 109 records · Page 6Linked to original sources

[Experiences with monoclonal antibody orthoclone OKT3 following liver transplantation].

In 7 patients 10 cycles (5 to 21 days, dosage: 30 to 430 mg, median 138 mg) of OKT3 therapy were performed after liver transplantation. In all patients reactivation of an EBV-infection with hepatitis was observed. Two patients treated with high dosages (430 mg respectively 195 mg) developed lymphoproliferative lesions. In one patient with persistent EBV-infection (dosage: 360 mg) a B-cell-lymphoma was diagnosed. This patient died 26 months after transplantation.

Female↗

[Demonstration and biological significance of viral and cellular oncogenes in uterine carcinomas].

Premalignant and malignant lesions of the cervix uteri and endometrium were analyzed for the presence of human papillomavirus (HPV) DNA and c-myc or c-erbB2/neu oncogene expression. HPV DNA was detected by PCR in 100% of the cervical carcinomas and CIN lesions, but also in endometrial lesions (3/8 adenocarcinomas, two hyperplasias and one adenomyosis uteri). Myc-overexpression was found in 25-30% of the cervical carcinomas and severe dysplasias, but not in endometrial lesions. C-erbB2 was overexpressed in 4/11 endometrial carcinomas and 3/19 CIN3 lesions. The implications of these results are discussed.

Biomarkers, Tumor↗

[Mycosis fungoides and Sézary syndrome: diagnostic and prognostic relevance of cellular antigen expression].

Mycosis fungoides and Sézary syndrome (cutaneous T-cell lymphomas [CTCL]) are recognized, especially in the early stages, as being a potentially difficult diagnostic problem when they have to be histologically differentiated from a series of inflammatory disorders (ID). The diagnostic value of immunophenotyping is controversial; almost all studies have been semiquantitative. The prognostic implications of the antigen expression in CTCL are not known. To acquire more insight into these problems, the expression of differentiation-associated and activation/proliferation-associated antigens was examined in cryostat sections from 35 patients with conclusively diagnosed CTCL and 19 patients with ID. Positive cells were calculated as numbers/mm2 tissue section. The results were analysed statistically. Single antigen expressions were not helpful for differentiation between CTCL and ID. High percentages (89%-96%) of patients with CTCL stages I, II, and III and patients with ID could be classified correctly (discriminant analysis) by combined quantitative assessment of the expression of antigens Ki67 and Ki1/CD30 in the dermis and CD25 in the epidermis. In later stages (IVa, IVb) the note of correct classifications was worse because of the decrease in discriminating properties of the respective antigens. The biological role of antigen expressions was analyzed together with the clinical parameters (age, stage of disease). Stage was the parameter with the most significant influence on patient survival. CD1a-positive epidermal cells (Langerhans cells) were the only cell population that was significantly (P = 0.011) associated with survival. Death resulting from CTCL was significantly (P = 0.003) less frequent in patients with epidermal CD1a-positive cell densities higher than 90 cells/mm2 in comparison with patients with lower numbers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Epidermal Langerhans' cell densities influence survival in mycosis fungoides and Sézary syndrome.

Because Langerhans' cells (LC) (CD1a-positive epidermal cells) have been discussed to be involved in the pathogenesis of mycosis fungoides and Sézary syndrome, the authors examined the influence of densities of Langerhans' cells and, concurrently, of other phenotypes retrospectively on survival of 35 patients. Cell densities were assessed on cryostat sections (alkaline phosphatase antialkaline phosphatase-technique) of the respective diagnostic biopsy specimens. Additionally, two clinical parameters (age, stage of disease) were evaluated. CD1a-positive epidermal cells were demonstrated to be the only cell population being significantly associated (P = 0.011) with survival. Death resulting from mycosis fungoides and Sézary syndrome was significantly (P = 0.003) less frequent in patients with epidermal CD1a-positive cell densities higher than 90 cells/mm2 (optimal break point) as compared with patients with lower numbers. These results suggest that Langerhans' cells have a significant impact on prognosis of patients with mycosis fungoides and Sézary syndrome. They play an important role in the host defense mechanisms against these lymphomas rather than to favor their progression as proposed recently.

Adult↗

Immunohistochemical investigation and northern blot analysis of c-erB-2 expression in normal, premalignant and malignant tissues of the corpus and cervix uteri.

Seventy specimens of normal endometrium (n = 13) and cervix (n = 12), endometrial hyperplasia (n = 4), cervical dysplasia (n = 20), endometrial (n = 11) and cervical carcinoma (n = 8) and uterine metastases of mammary carcinomas (n = 2) have been analysed for c-erB-2 expression with immunohistochemistry employing a monoclonal anti ERBB-2 antibody and Northern-blot hybridization using single stranded RNA probes. In comparison with the c-erbB-2 mRNA expression level found in normal samples, two advanced and poorly differentiated endometrial adenocarcinomas (FIGO IV) and two ductal mammary carcinomas which had metastasized to the uterus, together with three carcinomas in situ of the cervix, showed c-erbB-2 enhanced transcription level. All other endometrial samples including adenomatous hyperplasia and nine endometrial carcinomas (FIGO I), and all other lesions of squamous epithelial origin displayed transcriptional activities at or below the baseline level. Immunohistochemical study of ERBB-2 protein expression showed staining in most samples, although different in distribution and intensity. Staining of endometrial glands was seen in unevenly distributed cells or cell clusters. In contrast, for endocervical glands, labelling was observed distinctly on basally located cells (reserve cells) and at the subapical side of luminal cells. Faint labelling of the basal cell layer was also observed in squamous epithelia. It was more pronounced in severe cervical dysplasia and carcinoma in situ. In carcinomas of glandular origin, dedifferentiation was accompanied by an increase in cytoplasmic labelling, whereas the intensity of staining was not related to differentiation in squamous cell carcinomas. While data derived from Northern blots are suggestive of c-erbB-2 overexpression to indicate an advanced and dedifferentiated state of tumours of glandular origin, staining with an anti-ERBB-2 antibody occurred in both normal and atypical squamous and glandular epithelia and may indicate regular proliferation and/or differentiation-associated events.

Adenocarcinoma↗

Expression of c-erbB2 and c-myc in squamous epithelia and squamous cell carcinomas of the head and neck and the lower female genital tract.

Normal tongue and cervical mucosa, premalignant cervical and vulvar lesions, primaries and metastases of squamous cell carcinomas from the oral, laryngeal, cervical and vulvar mucosa were analyzed for c-erbB2 and c-myc transcription with northern-blots using 32P single-stranded RNA probes. Transcription of c-erbB2 and c-myc could be detected for almost all tissues including normal samples. A slightly enhanced transcription level was found in three cervical intraepithelial neoplasias of Grade III (CIN III) but in none of the malignant lesions. Increased transcription of c-myc was observed in premalignancies and malignancies. It was more frequent in oral and laryngeal squamous cell carcinomas (SCC) (8 of 9 cases) than in genital SCC (3 of 11 cases) or premalignancies (3 CIS of 14 CIN/VIN). No relationships of c-myc enhanced transcription level with tumor grading and staging were noticed. Thus, mere oncogene expression is a widespread phenomenon in tissues of different histogenesis and quantitative analysis is necessary prior to ascribe any diagnostic or prognostic relevance. Moreover, the frequency of tumors with enhanced transcription may vary for phenotypically closely related tumors of different organs.

Adult↗

Study of neu-protein expression in mammary Paget's disease with and without underlying breast carcinoma and in extramammary Paget's disease.

Correlation between neu/c-erbB-2/Her-2 gene amplification and overexpression of the neu gene product has been reported in tumors of glandular origin, especially ductal breast carcinomas. Formalin-fixed and dewaxed sections from 23 cases of mammary (MPD) and 9 cases of extramammary (EPD) Paget's disease were immunohistochemically stained by means of the monoclonal antibody 3B5 directed against an intracellular domain of the neu gene protein. All MPDs exhibited a distinct membrane staining of tumor cells independent of the presence of ductal breast carcinomas found in 18 cases. All these breast carcinomas also were positive for neu staining. In contrast to MPD, all EPDs were negative. Normal epidermis was always negative. Northern blot analysis sustained the immunohistologic findings in that the presence of neu mRNA could be demonstrated in two of three cases with MPD. Negativity in one case was due to dilution effects by nontumor cells. Our results suggest that Paget cells of mammary and extramammary localization, although very similar phenotypically, derive from different genetic accidents. Furthermore neu positivity in all MPDs and all underlying ductal carcinomas suggests common genetic alterations for both tumors. However the finding of five neu protein-positive MPDs without associated ductal breast carcinomas may suggest a somewhat different transformation process.

Breast Neoplasms↗

[Thoracic chordoma].

Usually chordomas involve the intracranial and sacrococcygeal sites of the skeleton. We describe the uncommon localisation in the thoracic spine.

Adult↗

In situ detection of human papillomavirus types 13 and 32 in focal epithelial hyperplasia of the oral mucosa.

17 cases of focal epithelial hyperplasia of the oral mucosa (FEH, Heck's disease) were investigated for the presence of human papillomavirus (HPV) nucleic acid sequences by means of in situ DNA hybridization using biotinylated DNA probes of HPV types 1, 6, 11, 13, 16, 18, and 32. Ten of 17 cases were positive for HPV 13 DNA in contrast to 6 of 17 positive cases obtained after application of the HPV 32 probe, with a double infection in one case. The results of our study suggest, that HPV 13 and HPV 32 are very specifically found in lesions of FEH and can be detected in a high percentage of cases using in situ hybridization.

Adult↗

[Cytomegalic inclusion disease of the salivary glands in sudden infant death syndrome].

The parotid gland and/or the submandibular gland in SIDS cases (180 from Berlin und 75 cases from Hamburg) were examined by means of HE staining, immunohistochemical analysis, in situ hybridization and electron microscopy. The SIDS cases were taken from the last 10 years; the age of the children ranged from 2 weeks to 1 year. Typical cytomegaly inclusion bodies were recognized in 10% (18 cases from Berlin; more girls than boys) and 7% (6 cases from Hamburg; more boys than girls). Our files indicate that the frequency of CMV infection was not age-dependent within the first 12 months of life. Using immunohistochemical analysis and in situ hybridization, virus substances were detected in cytomegal cells as well as in morphologically uninfected cells. The literature on the clinical and epidemiological aspects of cytomegaly indicates that a localized CMV infection of the salivary glands does not sufficiently explain the sudden death of these infants; however, it should be emphasized that cytomegaly can influence the immunological status of the organism.

Cytomegalovirus↗

Histiocytic differentiation in benign and malignant bone tumors.

In this study fresh frozen tissue samples of benign osseous tumors (five non-osteogenic fibromas, one fibrous dysplasia, one chondromyxoidfibroma), tumors of uncertain biological behaviour (eight cases of histiocytosis X, two giant-cell tumors), and of malignant intraosseous tumors (two malignant fibrous histiocytomas, two malignant histiocytosis, four osteosarcomas, one chondrosarcoma and two Ewing sarcomas) were studied with a panel of monoclonal antibodies reactive with monocyte/macrophages and various types of dendritic cells. In addition, tumors were further defined with a broad spectrum of antibodies against filamentous proteins and lymphocyte differentiation antigens. The specimens were stained with a triple-layer immunoalkaline phosphatase protocol. Tumors stained with these antibodies could be roughly divided into two groups. The first group comprised tumors with one predominant cell population reactive with one particular monoclonal antibody. In this group, cases of histiocytosis X were found to be consistently labelled with CD-1 antibodies. The giant-cell tumors showed a very homogeneous staining with certain monocyte/macrophage antibodies (Ki-M8). Nevertheless, even in these tumors, heterogeneity was demonstrated by the occurrence of cells with monocytic differentiation in histiocytosis X and conversely by the occurrence of cells with differentiation antigens of the dendritic cell system in giant-cell tumors. An exception has to be made for the two cases of malignant histiocytosis examined. These tumors were selectively labelled with antibodies against monocyte/macrophages (Ki-M8, IOM-1). The second group comprised tumors showing a high degree of heterogeneity demonstrated by the varying amounts of tumor cells reacting with the applied markers of the monocyte/macrophage and dendritic cell systems. In most cases it was difficult to ascribe labelled cells to the tumor cell population as opposed to an "innocent bystander" inflammatory cell population. This distinction was especially difficult in malignant fibrous histiocytomas underlining the current concept that these tumors are of primitive mesenchymal rather than true histiocytic origin.

Adolescent↗

Immunohistochemistry (S 100, KL 1) and human papillomavirus DNA hybridization on morbus Bowen and bowenoid papulosis.

In this study 55 paraffin embedded samples defined as Bowen's disease or bowenoid papulosis were investigated with antibodies against S 100 protein and keratins (KL 1). S 100-positive cells were quantified and related to defined section area of the epidermal compartment by computer-assisted image analysis. The density of S 100-positive cells was compared with normal skin and was particularly related to growth patterns and keratinization of the different lesions under study. S 100-positive dendritic cells were found to be reduced overall in bowenoid lesions when compared with normal skin. Lesions with high counts of S 100-positive dendritic cells most frequently showed a solitary growth pattern with highly conserved architecture and differentiation and no tendency to stromal invasion. In contrast, cases with low counts of S 100-positive cells very often showed multifocal development, a high degree of architectural disturbance and dedifferentiation. In this group, stromal invasion (cases of invasive carcinoma associated with Bowen's disease) was seen more often. Interestingly, this latter group of cases also revealed a peculiar keratin pattern. Frequently, the basal cell layer was decorated with KL 1 antibody, which usually recognizes only suprabasaly located keratinocytes. No differences between Bowen's disease and bowenoid papulosis were found in terms of densities of S 100-positive dendritic cells and keratin pattern. In our experience, extragenital Bowen's disease and genital Bowen's disease can not be distinguished on purely morphological grounds or with the immunocytochemical approach presented here. Interestingly, when employing in situ hybridization with HPV 16 probes three of seven samples of genital Bowen's disease harboured HPV 16 DNA, whereas six cases of extragenital disease were negative.

Adult↗

Penile/anal condylomas and squamous cell cancer. A HPV DNA hybridization study.

Acuminate condylomas from the penis (n = 17) and anus (six cases), three anal/penile giant condylomas, anal Bowen's disease (four cases), and intraanal squamous cell carcinomas with associated condylomatous changes (10 cases) including two verrucous carcinoma were studied for human papillomavirus (HPV) infections with nick translated, biotinylated cDNA probes for HPV 6, 11, 16 and 18. In addition, six cases of flat white penile lesions designated as lichen sclerosus et atrophicus were examined. Reannealed complementary DNA strands were detected in situ with either immunoenzyme or immunogold protocols. The in situ hybridizations resulted in 1/6 positive penile lichenoid lesions, 12/17 positive penile acuminate condylomas, 6/6 positive anal acuminate condylomas (including two condylomas with cellular atypias), 2/3 positive giant condylomas, 1/4 positive anal bowenoid lesions, and 4/10 positive keratinized squamous cell carcinomas, two of them being verrucous carcinomas. All penile/anal condylomas and two giant condylomas harboured HPV 6 and/or 11 DNA. The five positive carcinomas (carcinoma in situ/invasive cancer) contained HPV 6 and/or 11 in two cases (including the verrucous carcinomas), and HPV 16 and/or 18 in three cases (one carcinoma in situ, two invasive carcinomas). Recurrent malignancies were seen in one case to harbour the same HPV type as the primary lesions (HPV 16). In one particular patient, a double infection with HPV 16 and HPV 18 was demonstrated in distantly located malignant tumours. Our study confirms the restrictions and the value of non-isotopic hybridization methods applied to archival tissues, and extends the knowledge on the presence and distribution of HPV infections at anogenital sites.

Adult↗

Cutaneous T cell lymphoma: immunocytochemical study on activation/proliferation and differentiation associated antigens in lymph nodes, skin, and peripheral blood.

The expression of activation/proliferation antigens (CD 25, CD 30, Ki 67, transferrin receptor) in lymph nodes and skin were compared in nine patients with mycosis fungoides (MF) with patients with erythroderma not related to MF, and patients with reactive lymphofollicular hyperplasias (a total of 14 patients). A panel of differentiation antigens was analyzed in addition. Reactivities were revealed by the APAAP technique. Activation/proliferation antigen scores in lymph nodes were related to the clinical stages of MF in most instances (low scores in cases of MF stage I/II, high scores in 3/4 cases of MF stage III/IV). They differed markedly in cases of non-MF-erythrodermia with the exception of one patient, and in all cases of reactive lymphofollicular hyperplasia. Expression of activation/proliferation antigens in lymph nodes were different in most cases from those in skin and peripheral blood. For diagnostic use, the activation/proliferation antigen scores were superior to the cell differentiation antigen profiles. Among cellular differentiation antigens, only the extent of CD1+ cells provided some diagnostic information, since the number of these cells were markedly increased in all cases of dermatopathic lymphadenitis with/without MF when compared with reactive lymphofollicular hyperplasia. In the diagnosis of MF, immunohistochemistry of activation/proliferation or differentiation antigens cannot replace routine paraffin histology, but may provide supplement any data in equivocal cases.

Adult↗

Dendritic/Langerhans cells and prognosis in patients with papillary thyroid carcinomas. Immunocytochemical study of 106 thyroid neoplasms correlated to follow-up data.

Paraffin sections of 106 primary thyroid carcinomas were the subject of an immunocytochemical study to determine the density of infiltrates of S-100 protein-positive dendritic/Langerhans cells (LC), lysozyme-positive histiocytes, and LCA-positive lymphocytes. Evidence of dense infiltrates of LCs was found only in the majority of papillary thyroid carcinomas (PCs). The determination of the quantity of LCs proved to be a highly effective means of assessing the prognosis of these tumors. Irrespective of other morphologic and clinical features, no single instance of death resulting from cancer occurred among 23 PCs with dense LC infiltrates (including 6 tumors of stage pT4), while 9 of 53 (17%) of the remaining patients ultimately died from thyroid cancer. On the other hand, the degree of histiocytic and lymphocytic infiltrations was not associated with a distinct biologic behavior neither among PC nor among the remaining thyroid carcinomas. These findings suggest that LCs may play an important role in the immunologic defense mechanisms of the host against the tumor only in the papillary type of thyroid cancer.

Amidohydrolases↗