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Biomedical subjects

G Niedobitek

Publications and source records attributed to G Niedobitek.

At least 109 records · Page 6Linked to original sources
PubMed1991

Epstein-Barr virus infection in oral hairy leukoplakia: virus replication in the absence of a detectable latent phase.

Epstein-Barr virus (EBV) infects both B lymphocytes and oropharyngeal epithelium, and it has been argued that the true reservoir of virus persistence in vivo is the self-renewing basal epithelial compartment. The identification of oral hairy leukoplakia (HL) of AIDS patients as a clinically apparent focus of EBV replication in lingual epithelium therefore provides a means of studying the EBV-epithelial cell interaction in situ. Replicative EBV DNA and productive cycle antigens are restricted to the upper, more differentiated epithelial layers in HL, and here we have applied highly sensitive in situ hybridization and immunohistological methods to examine the lower basal/suprabasal layers for evidence of latent EBV infection. We could not detect EBV DNA in these layers using an in situ DNA hybridization protocol which, on reference B cell lines, detected 1 viral genome/cell. Likewise, using sensitive in situ RNA hybridization for both the small non-polyadenylated EBER RNAs (abundant transcripts seen in all known forms of EBV latency) and the latent membrane protein (LMP) mRNA (the most abundant viral mRNA in B lymphoblastoid cell lines), the basal/suprabasal cells in HL were consistently negative; immunohistological staining with specific monoclonal antibodies also gave no evidence of latently infected LMP-positive cells. When the biopsy extracts were analysed by immunoblotting with selected human antisera, in addition to abundant productive cycle antigens, a band of constant size (66K) was observed which also reacted with immunopurified antibodies monospecific for one of the latency-associated nuclear antigens, EBNA 1; the cellular origin of this EBNA 1 could not be ascertained, but it is possible that in HL the protein is expressed during the productive cycle. The absence of demonstrable EBV latency in the basal/suprabasal cells of HL suggests that this is purely a virus replicative lesion which is sustained by continual re-infection of the maturing epithelium, not by the maturation of latently infected cells from the basal compartment.

Antigens, Viral↗
PubMed1991

Differentiation-associated expression of the Epstein-Barr virus BZLF1 transactivator protein in oral hairy leukoplakia.

The BZLF1 protein of Epstein-Barr virus (EBV) is a key immediate-early protein which has been shown to disrupt virus latency in EBV-infected B cells. We have generated a monoclonal antibody, BZ1, to BZLF1 which reacts in immunohistology, immunoblotting, and immunoprecipitation and which recognizes both the active, dimeric form and the inactive, monomeric form of the protein. Biopsies of oral hairy leukoplakia, an AIDS-associated lesion characterized by high-level EBV replication, were examined by immunohistochemistry using the BZ1 monoclonal antibody. A differentiation-associated pattern of BZLF1 expression was observed, BZ1 reacting with nuclei of the upper spinous layer of the lesion. This finding suggests that the BZLF1 promoter may be regulated by the degree of squamous differentiation. A comparison of in situ hybridization to EBV DNA and viral capsid antigen staining with BZ1 reactivity suggested that BZLF1 expression precedes rampant virus replication. The inability to detect EBV in the lower epithelial layers of oral hairy leukoplakia raises questions concerning the nature of EBV latency and persistence in stratified squamous epithelium.

Antibodies, Monoclonal↗
PubMed1991

Presence of vasoactive intestinal peptide receptors in nasal mucosa.

In recent years several tachykinins have been identified in the airway sensory nerves. Since the physiological and pathophysiological effects of neuropeptides depend on their functionally relevant concentrations and presence of specific receptors in the target tissue, specimens of enlarged turbinates and nasal polyps were removed in 11 patients and examined for the presence of vasoactive intestinal peptide (VIP) receptors. An intensive color reaction was observed in the cytoplasm of the tubular mucosa cells in polyps and turbinates as well as in the epithelium and submucosal glands. Since both these tissues reacted with VIP receptor antibody, noncross-reacting antibody against dendritic reticular cells (DRC 6-B7), nonspecific binding is possible, however it also must be speculated that the unspecific binding is overlaying specific binding. In addition a large number of cells located diffusely or in close association in the subepithelium and interstitial tissue stained only with VIP-specific antibody, indicating specific receptor binding. The color reaction is limited to the cell membrane and the cytoplasm of these cells was clearly eosinophilic. These cells were located in close proximity of the blood vessels, very indicative for active migration. Since VIP-positive nerves are also located near the blood vessels an activation process of these cells with subsequent release of enzymes and other active proteins is possible, thus influencing the inflammatory response.

Adult↗
PubMed1991

[Expression of latent membrane proteins (LMP) of Epstein-Barr virus in malignant lymphomas].

The presence of Epstein-Barr virus (EBV) DNA and antigens was assessed by polymerase chain reaction and immunohistology, respectively, in a total of 92 cases of Hodgkin's disease, angioimmunoblastic lymphadenopathy, CD30-positive anaplastic large cell (ALC) lymphomas, and AIDS-associated atypical lymphoproliferations (ALP). Proportions of the EBV DNA-positive lesions showed latent membrane protein (LMP) expression; some of the LMP-positive ALC lymphomas and ALP cases also displayed EBNA2 immunostaining. BZLF1-protein and gp250/350 immunoreactivity were absent in all instances indicating latent EBV infection. Since the LMP gene has transforming potential, our findings support the concept of a pathoetiological role for EBV in these lymphoproliferative lesions.

Acquired Immunodeficiency Syndrome↗
PubMed1991

[Lymphoid tissues and AIDS: role of lymphocytes and follicular dendritic cells (FDC)].

Currently discussed models of AIDS pathogenesis attribute a pivotal role to HIV-variants developing in T cells during the course of the disease resulting in an increasingly rapid depletion of the infected T cells. Such models do not however explain the morphological findings observed in AIDS lymphadenopathy. To clarify the significance of the hyperplasia and subsequent destruction of the lymphoid follicles in HIV-related lymphadenopathy, we used in situ hybridization in combination with immunohistological labelling techniques to identify the phenotype of HIV-infected cells in lymph nodes. In addition to few T helper cells, mainly in germinal centres, large amounts of HIV-RNA were found in CD4-negative follicular dendritic cells (FDC) rather than in macrophages or other cells. This finding is well in accordance with the recent observations made by other authors suggesting that purified FDC can be infected with HIV in vitro. Furthermore, TNF alpha expression is localized mainly in centroblasts (activated B cells) of germinal centres. TNF alpha, released by antigen-activated B cells in vitro, has been shown to induce HIV replication in latently infected T cells. On the basis of these observations we propose that latently infected CD4+ T cells, having entered germinal centres, start HIV replication under the influence of cytokines present in this microcompartment of all lymphoreticular tissues. Here the T cells infect FDC which, in turn, pass on the virus to new healthy T helper cells. This model may explain both peculiarities of the lymphadenopathy syndrome as well as the long latency period of HIV-infection, ultimately leading to AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1990

The T cell triggering molecule Tp103 is associated with dipeptidyl aminopeptidase IV activity.

Tp103 is a 103-kDa T cell activation molecule that defines an alternative activation signal for human T lymphocytes. It is absent from or present in only low amounts on resting T cells but is expressed strongly after activation. Cross-linking of Tp103 via a mAb CB.1 leads to triggering of functional activities in preactivated CD3+ T lymphocytes. By using mAb CB.1 in immunohistology we found that Tp103 is expressed in epithelial cells of various tissues, such as kidney, prostate, epidermis and on endothelia of liver, spleen, lungs, and most vessels, and in bile duct canaliculi in the liver. We found a carcinoma cell line expressing Tp103 and could precipitate a 110-kDa molecule from the surface of these cells. We considered several known molecules of similar distribution and molecular mass for identity with Tp103 and show here that Tp103 is probably identical to the proteolytic enzyme dipeptidyl aminopeptidase IV. When we purified Tp103 by affinity chromatography, typical dipeptidyl aminopeptidase IV activity copurified with Tp103. On activated T cells the enzymatic activity associated with Tp103 is expressed on the outside of the cell. We show that mAb CB.1 recognizes the same molecule as the anti-CD26 mAb anti-Ta1. The anti-Ta1 mAb was found to have T cell-activating activity too, but to differ in its requirements for triggering of T lymphocytes.

Antibodies, Monoclonal↗
PubMed1990

Thymic carcinoma. Report of five cases and review of the literature.

Among 54 mediastinal tumours we examined in the past 20 years, there were 5 cases of primary thymic carcinomas, each with widespread metastases. Histological features in three cases were consistent with lymphoepithelioma-like carcinoma. One case showed an epidermoid pattern with keratotic pearls resembling Hassall bodies. One undifferentiated carcinoma developed from a cortical thymoma. Epstein-Barr virus could not be detected in tumour tissue with in situ hybridization. A review of the literature revealed only 94 well-documented cases of thymic carcinoma. Both thymic carcinomas and thymomas are neoplasms of the thymic epithelial cells, but thymic carcinomas are obviously histologically malignant and usually not associated with any parathymic syndromes. Epidermoid and lymphoepithelioma-like carcinomas are described along with special forms, such as small- and clear-cell carcinomas, basaloid, sarcomatoid, mucoepidermoid, and adenocystic carcinoma. Compared to the other forms, lymphoepithelioma-like carcinoma has a poor prognosis in regard to metastases and rate of survival. Some thymic carcinomas may develop from pre-existing thymomas.

Adult↗
PubMed1990

Detection of human papillomavirus type 16 DNA in carcinomas of the palatine tonsil.

Twenty eight tonsillar carcinomas of various histological types were investigated for the presence of Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human papillomavirus (HPV) types 6, 11, and 16 by in situ hybridisation using highly stringent procedures. In six cases an autoradiographic signal was obtained in the tumour cell nuclei with the HPV type 16 specific probe. No signal was obtained with any of the other probes. Immunohistochemical investigations with mouse monoclonal antibodies directed against the L1 protein of HPV type and a rabbit antiserum that detects common protein determinants of HPV gave negative results, thus indicating latent infection. Furthermore, a series of tonsils from controls with comparable age distribution was negative by both in situ hybridisation and immunohistology. These results indicate a possible role for HPV 16 in the aetiology of a proportion of tonsillar carcinomas.

Adult↗
PubMed1990

Ber-EP4: new monoclonal antibody which distinguishes epithelia from mesothelial.

A new monoclonal antibody, Ber-EP4, directed against a partially formol resistant epitope on the protein moiety of two 34 kilodalton and 39 kilodalton glycopolypeptides on human epithelial cells is described. Immunostaining of a wide range of normal and neoplastic human tissues and cell lines showed that all carcinomas and all non-neoplastic epithelial cells, except hepatocytes, parietal cells, and apical cell layers in squamous epithelia, homogeneously expressed Ber-EP4 antigen. As Ber-EP4 does not detect any normal or neoplastic non-epithelial cells, this antibody might prove valuable for the differentiation of the following (i) non-epithelial tumours from undifferentiated carcinomas; (ii) hepatocytes from bile duct cells in certain liver diseases; (iii) mesothelial cells from carcinoma cells in lung biopsy specimens; and (iv) reactive mesothelial cells from carcinoma cells in smears of serous effusions.

Adult↗
PubMed1990

Testicular sex cord stromal tumour with granulosa cell differentiation: detection of steroid hormone receptors as a possible basis for tumour development and therapeutic management.

A testicular sex cord stromal tumour with granulosa cell differentiation, typical of granulosa cell tumours of the adult type, was investigated immunohistologically on snap frozen and paraffin wax embedded material. The predominance of vimentin and the additional expression of cytokeratin subtypes 8 and 18, as well as the negative staining for epithelial membrane antigen, accorded with results previously reported, for ovarian granulosa cell tumours; the lack of expression of desmoplakin, however, was a distinctive feature. Together with negative staining for leucocyte common antigen, the antigen pattern facilitates the differential diagnosis between granulosa cell tumour and undifferentiated carcinoma or gonadal lymphoma, although its suitability for differentiating within the group of gonadal stromal tumours seems to be limited. The small growth fraction, shown by the monoclonal antibody Ki-67, is typical of the clinical behaviour of granulosa cell tumours. The expression of oestrogen and progesterone receptors, also recently found in testicular Leydig cell tumours, may provoke new approaches to the management of testicular granulosa cell tumours, as well as a new hypothesis on the development of these tumours.

Aged↗
PubMed1990

[Epstein-Barr virus and malignant lymphomas--studies on incidence and localization of viral DNA].

Tissue specimens from 198 cases of Hodgkin's disease and 151 non-Hodgkin lymphomas as well as 34 non-malignant lymph node biopsies were examined for the presence of Epstein-Barr virus (EBV) DNA by polymerase chain reaction. EBV-specific DNA sequences were detected in DNA extracts of 58% of Hodgkin's disease biopsies. Non-Hodgkin lymphomas and benign lymph node lesions were associated with EBV in far smaller proportions. In Hodgkin's disease biopsies, subsequent in situ hybridization revealed an exclusive localization of EBV DNA in the tumour cells, suggesting an involvement of EBV in the pathogenesis of Hodgkin's disease in a substantial proportion of cases.

Base Sequence↗
PubMed1990

[Demonstration of DNA tumor viruses in carcinomas of the upper respiratory tract].

In situ hybridization (ISH) using 35S-labeled probes was applied to the detection of viral DNAs in 115 epithelial tumours from various sites. Epstein-Barr virus (EBV) DNA was detected in 83% of undifferentiated nasopharyngeal carcinomas (NPC) while none of seven squamous cell NPC displayed an EBV-specific autoradiographic signal. Also, all other tumours investigated, including thymomas, thymic carcinomas, tonsillar carcinomas and medullary breast carcinomas were negative upon ISH to EBV-specific probes. These results suggest a unique association of undifferentiated NPC with EBV. 28 tonsillar carcinomas were further analyzed for the presence of human papillomavirus (HPV) DNA. Six carcinomas showed an HPV16-specific signal while hybridization to HPV6- and HPV11-specific probes yielded negative results. No HPV-DNA was detected in any of 30 tonsils with chronic inflammation, thus excluding that the finding of HPV16 in a proportion of tonsillar carcinomas is merely circumstantial. These results point to a possible etiologic role of HPV16 in the pathogenesis of some tonsillar carcinomas.

DNA Tumor Viruses↗
PubMed1990

High incidence of Epstein-Barr virus genomes in Hodgkin's disease.

Tissue specimens from 198 cases of Hodgkin's disease and 151 non-Hodgkin lymphomas, as well as 34 nonmalignant lymph node biopsies were examined for the presence of Epstein-Barr virus (EBV) DNA by polymerase chain reaction. Epstein-Barr virus-specific DNA sequences were detected in DNA extracts from frozen and/or paraffin-embedded tissues of 58% of Hodgkin's disease cases. High and low grade non-Hodgkin lymphomas as well as chronic lymphocytic leukemia biopsies contained EBV DNA in 26%, 14%, and 7% of the cases, respectively. Ten percent of the control lymph nodes with normal histology were EBV positive. In Hodgkin's disease biopsies, subsequent in situ hybridization revealed an exclusive localization of the viral DNA in the tumor cells. These findings suggest an involvement of EBV in the pathogenesis of Hodgkin's disease in a substantial proportion of cases.

Base Sequence↗
PubMed1989

Acquired resistance to Listeria monocytogenes is mediated by Lyt-2+ T cells independently of the influx of monocytes into granulomatous lesions.

Facultative intracellular bacteria induce specific T cell responses of both the CD4+ and the CD8+ subsets. The immunohistological study of the tissue responses to Listeria monocytogenes in T cell subset-depleted, Listeria-primed mice revealed that CD4+ cells not only represent the predominant lymphocyte population in granulomatous lesions but mediate the attraction and accumulation of blood-borne monocytes into inflammatory foci. On the other hand, CD8+ T cells are able to mediate protection in the absence of CD4+ T cells, invading monocytes, and granulomatous inflammation, and therefore appear to activate resident macrophages for listericidal activity.

Animals↗
PubMed1989

Demonstration of monoclonal EBV genomes in Hodgkin's disease and Ki-1-positive anaplastic large cell lymphoma by combined Southern blot and in situ hybridization.

Forty-two cases of Hodgkin's disease (HD) and 22 cases of Ki-1-positive anaplastic large cell (Ki-1 + ALC) lymphoma were examined by Southern blotting for the presence of Epstein-Barr virus (EBV) DNA. Seven cases of HD and one case of Ki-1 + ALC lymphoma scored positive with a probe specific for the internal repetitive region of the EBV genome. Subsequently, these viral genomes could be demonstrated to be monoclonal in origin using an EBV terminal region DNA probe. In situ hybridization revealed that in two HD cases, the EBV infected cells had the distinct morphology of Hodgkin and Reed-Sternberg cells, thus suggesting a direct pathoetiological relationship between EBV and some cases of HD.

Adolescent↗
PubMed1989

Vimentin expression of newly formed rat bile duct epithelial cells in secondary biliary fibrosis.

The intermediate filament profile and the growth fraction of hepatocytes and bile duct epithelial cells were studied in a rat model of biliary fibrosis secondary to common bile duct ligation and scission. Strong vimentin expression was observed in epithelial cells of newly formed bile ductules, while normal liver contained only few weakly positive bile duct epithelial cells. All epithelial cells reacted with a pan-cytokeratin antibody. A monoclonal antibody specific for human cytokeratin 7 selectively reacted with both normal and newly formed bile duct epithelial cells. The intermediate filament profile of hepatocytes was constant, showing no changes during proliferation or in periportal areas adjacent to excessive bile duct formations. The proliferation-associated antigen detected by the antibody Ki-67 was present in many hepatocytes, homogeneously distributed in the lobules, but was seen only in a small proportion of the epithelial cells of the newly formed bile ducts. We conclude that vimentin may serve as an indicator for cellular reorganization in the bile duct system, and that the epithelial cells of newly formed bile ductules in this particular model of secondary biliary fibrosis were most likely to be derived from an outgrowth of the biliary duct system and recruitment of preductular epithelial cells. No morphological or immunohistological evidence suggesting a derivation from hepatocytes by ductular metaplasia or from oval cells was obtained.

Animals↗