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Biomedical subjects

D Haag

Publications and source records attributed to D Haag.

At least 37 records · Page 2Linked to original sources
PubMed1983

Antibodies to intermediate filament proteins in the immunohistochemical identification of human tumours: an overview.

Intermediate-sized filament proteins (IFP) are tissue specific in that antibodies to keratin, vimentin, desmin, glial fibrillary acidic protein (GFAP) and the neurofilament proteins can distinguish between cells of epithelial and mesenchymal origin as well as of myogenic and neural origin respectively. Malignant cells retain their tissue-specific IFP, which makes it possible to use these antibodies in tumour diagnosis. Carcinomas are exclusively detected by antibodies to keratin. Monoclonal antibodies to keratin have allowed the differentiation between subgroups of epithelial tumours until now between adenocarcinomas and squamous cell carcinomas. Lymphomas, melanomas and several soft tissue tumours are distinctly recognized by antibodies to vimentin. On the other hand, rhabdomyosarcomas and leiomyosarcomas are positive for desmin, while astrocytomas give a strong reaction with GFAP antibodies. Thus, antibodies to IFP are useful tools for differential diagnosis in surgical pathology.

Antibodies↗
PubMed1983

Coexpression of keratin- and vimentin-type intermediate filaments in human metastatic carcinoma cells.

Metastatic tumor cells of epithelial origin present in effusions from human serous cavity fluids (ascites or pleural fluid) were examined for their intermediate-sized filament types by using antibodies to keratin, vimentin, and desmin in the indirect immunofluorescence technique. Solid epithelial tumors (both primary carcinomas and their metastases) contain keratin intermediate-sized filaments exclusively. However, when these cells are present in ascitic or pleural fluid, they also express vimentin, which occurs in a fibrillar organization. The possible effects of this additional, but temporary, cytoskeleton on metastatic growth or aggressiveness (or both) are discussed.

Carcinoma↗
PubMed1983

Preservation of morphological, functional, and karyotypic traits during long-term culture and in vivo passage of two human skin squamous cell carcinomas.

Two cell lines (SCL-I and SCL-II) derived from squamous cell carcinomas of human skin were investigated during 4 years in culture. Both lines were tumorigenic in nude mice, and cells could be recultivated from xenografts. Growth in agar remained poor, but both cell lines developed abnormal stratified epithelial structures in organotypical cultures. The morphological and particularly ultrastructural characteristics remained typical in both cultures and xenografts. Keratinization slightly decreased, but nude mouse tumors differentiated as the original tumors, and this was reflected in keratin expression. Six major polypeptides (Mr 61,000, 57,000, 54,000, 51,000, 49,000, and 45,000) were similarly identified in both tumors and cell lines, also after animal passage, which was further substantiated by two-dimensional gel electrophoresis, but quantitative variations were found with different growth conditions. A distinct keratin cytoskeletal network was visualized in both lines by immunofluorescence, but only a few cells in SCL-II also expressed vimentin. Flow cytometry demonstrated 2c DNA stem lines for original tumors and derived lines. Early passages were hypodiploid by cytogenetic analysis of banded chromosomes. In SCL-I, a shift to tetraploidy occurred before passage 20 and remained stable throughout. In SCL-II, an incomplete shift to near tetraploidy and a stem line deviation were apparent, but later passages, nude mouse tumors, and cells recultured therefrom were hypodiploid (2c) again. Chromosome studies further revealed distinct stable marker chromosomes which showed additional structural aberrations with time in culture and after animal passage. Thus, phenotypically and genotypically, each squamous cell carcinoma and its derived cell line were distinct, and characteristics were preserved over long time periods in vitro and through in vivo passage.

Animals↗
PubMed1982

J-chain-producing immunoblastic lymphoma in a case of Richter's syndrome. Immunohistochemical evidence for a gradual malignant transformation of a single B-cell clone and flow cytophotometric data.

A 66-year old male with Richter's syndrome died 52 month after diagnosis of chronic lymphocytic leukaemia (CLL). The clinical course was characterized by a marked IgM hypoglobulinaemia which paralleled a chronically relapsing Herpes simplex infection. Autopsy showed a large retroperitoneal and intraabdominal tumour mass and well defined supradiaphragmatic lymphomas. Histological examination revealed a composite tumour consisting of CLL B-cell type (B-CLL) and immunoblastic malignant lymphoma of B-cell type (B-IbL). The lymphocytes bear mu-chains on their surface and to a lesser extend within their cytoplasm, the obviously defective immunoblasts produce J chains exclusively. Flow cytophotometric data seem to indicate an identical diploid stem line of the two tumours. The majority of the cells are in G0/1 phase. The CLL rarely produces mitoses, however, the IbL has a mitotic rate of 7% and a considerable proportion (33%) of cells in the phase of DNA-synthesis. This is the fourth malignant lymphoma and the second immunoblastic lymphoma to be reported that produces J chain in the absence of immunoglobulin.

Abdominal Neoplasms↗
PubMed1982

DNA-flow-cytometric measurements on the normal, atrophic, hyperplastic and neoplastic human endometrium.

DNA distribution patterns and the fractions of the cell cycle phases were determined by means of flow-through cytometry in 87 samples of normal, atrophic, hyperplastic and carcinomatous human endometrium. The S-phase fractions vary during the normal menstrual cycle between 1 and 3% and reach a periovulatory maximum between 4.4 and 4.7%. Atrophic endometrium and regressive glandular cystic hyperplasia have little DNA synthesis (1.01% and 1.68% S-phase fractions respectively). Proliferating glandular cystic hyperplasia reveals 3.38% S-phase fraction, whereas adenomatous hyperplasia has an increased number of DNA-synthesizing cells (4.81%). The well-differentiated endometrial carcinoma shows no cytophotometrically detectable differences in comparison to adenomatous hyperplasia. All endometrial samples except for poorly differentiated endometrial carcinoma showed a diploid to tetraploid DNA distribution pattern. The poorly differentiated endometrial carcinoma displays two different types: one rapidly growing diploid-tetraploid tumor with 8.0 to 9.6% S-phase fractions, and another type with stemline deviations, polyploid nuclei and less pronounced synthetic activity.

Adenoma↗
PubMed1982

Phenotypic and genotypic characteristics of a cell line from a squamous cell carcinoma of human skin.

A human cell line (SCL-1) from a poorly differentiating cutaneous squamous cell carcinoma (SCC) ws studied through 20 passages during 2 years. Cells maintained their original morphology with low degree of keratinization, as indicated by light and electron microscopy. The keratin peptide pattern resembled the type in SCC tumors, and the corresponding filaments were detected by immunofluorescence at all passage levels. Cells did not grow in soft agar but formed tumor-like nodules in an "organotypic" culture assay (on lifted collagen gels) and grew invasively after transplantation to immunosuppressed inbred C3H mice. After injection into BALB/c nu/nu mice, tumors of SCC morphology were formed. The hypodiploid tumor stem-line was maintained for about 10 passages, when a shift to hyperploidy started, as determined by chromosome and DNA flow microfluorometric analyses. Two stable marker chromosomes (in 100 and 70% of the metaphases, respectively), involving chromosomes 7 and 9, strongly indicated a monoclonal origin of this cell line.

Aged↗
PubMed1981

Growth kinetics of human lung tumours in nude mice.

In order to investigate the growth characteristics of xenografts of human tumours in nude mice, we heterotransplanted 22 human tumours of the lung into nude mice. We noted growth in 11 of these tumours (50%). The histological appearance of most of the tumours growing in the first passage in nude mice was comparable with that of the donor tumours. In further passages, however, a progressive dedifferentiation was noted in many tumours, depending on their growth rate. With the aid of growth curves and cell cycle kinetics (FMF analysis) it is shown that the growth kinetics of these tumours is affected by the transplantation and that the growth rate of such xenografts in nude mie is different from that of the original tumour in the patient.

Animals↗
PubMed1980

Flow microfluorometric deoxyribonucleic acid (DNA) analysis supplementing routine histopathologic diagnosis of biopsy specimens.

Flow microfluorometric DNA analysis was applied on a routine basis additionally to the conventional pathologic diagnostics of biopsy samples. The evaluation of the DNA distributions for the determination of the fractions of cells in different stages of the cell cycle was complicated by varying portions of background debris, which was generally found to be present in suspensions of single dispersed cells prepared from solid tissues. By means of computerized subtraction of exponentially decreasing corrections, it was possible to clear the original flow microfluorometric distributions. The contribution of background debris was found to cause erroneous overestimation, particularly in the evaluation of low S-phase fractions. By means of the corrections, even samples containing more than 65 per cent nuclear fragments could be evaluated with sufficient accuracy. The correct evaluation of the S-phase fraction possibly could indicate the degree of differentiation and proliferative activity of tissues. Low S-phase fractions within the range of normal regeneration were found in benign alterations and well differentiated carcinomas. In contrast, S-phase fractions up to 40 per cent were present in poorly differentiated tumors with extended cellular atypia, largely varying nuclear size and staining properties. The combination of conventional pathologic diagnostics with quantitative determination of the fractions of cells within the stages of the cell cycle in biopsy samples on a routine basis could supplement the diagnoses by therapeutically relevant information.

Biopsy↗
PubMed1976

[Correlations between metric, cyto and histomorphological factors and thermographic findings in breast neoplasms].

Correlations between metric, cyto- and histomorphological characteristics and thermographical results of 119 carcinomas of the breast have been studied by statistical methods. For the purpose of semi-quantitative evaluation the chi2 of 14 characteristics were calculated from foursquare tables and summarized in a correlation matrix. The study revealed a significant increase of thermographically suspect pictures with increasing size, but this was independent of the depth (i.e. the distance from skin surface) of the tumors. The proportion of uncertain but not clearly suspect results was 35% with the infrared telethermovision method, in contrast to 8% with liquid crystal plate thermography. Thermographically non-suspect carcinomas (especially the negative cases with liquid crystal plate thermography) were rich in connective tissue or stroma in most cases. On the other hand, carcinomas with numerous mitoses, large cell nuclei, increased N/C-ratio and large and strongly stained nucleoli predominantly exhibited definitely suspect pictures. The significant correlation between number of mitoses, size and staining of nucleoli and the thermographic results emphasizes that, besides vascularization and altered thermo-regulatory functions, the metabolism of the tumor itself contributes to the temperature differences. The type of growth and histological grading indicate that tumors with unfavourable prognosis preferentially exhibit thermographically suspect results. The use of thermography as a screening method is restricted because of possible false negative results. On the other hand, its additional use is justified in view of the gain in information about the biological situation of suspect alterations of the breast.

Breast Neoplasms↗
PubMed1975

Isolation of single cell nuclei from human epidermis for cytophotometric DNA--measurements.

Diluted acetic acid was applied to dissociate human epidermis into its constituents. A simple procedure to gain isolated single cells for cytophometric determination of their nuclear DNA content is described. The method is suited for single cell cytophotometric measurements and for cytofluorimetric flow systems likewise. The losses of Feulgen--stainable nuclear DNA during preparation were studied in dependence on the incubation time of the cells in acetic acid. The kinetics of extraction of nuclear DNA by diluted acetic acid follow a reaction of the first order. It was possible therefore to formulate a simple mathematical correaction for the losses during the isolation of epidermal cells. Avoiding the disadvantage of cut nuclei in histological sections the method is used to study the DNA histograms of resting, regenerating and pathologically altered human epidermis.

Acetates↗
PubMed1975

[Malignant granular-cell tumor of the cerebral white matter: morphological, cytophotometrical and neurochemical studies (author's transl)].

This is a report of the second known case of a primary malignant granular-cell tumor of the cerebral hemispherical white matter. Two cell types may be distinguished apparently representing different developmental stages of otherwise identical tumor cells. Quantitative histochemical and biochemical studies have shown that tumor cells were containing markedly elevated levels of DNA and RNA. Only few ribosomes and polysomes could be detected, however, by electron microscopy. While cytophotometry disclosed only slightly elevated cytoplasmic proteins, there was a distinct increase in total protein concentration of tumor tissue per unit weight, as measured by conventional techniques. It is suggested that this increase is mainly attributable to structural proteins of cellular and subcellular elements of multiplicating malignant cells. A ratio of RNA to DNA in excess of 1 was found for white matter derived from the central tumor, while the ratios of control tissue were lowered to values far below one due to postmortem changes greatly reducing tissue concentrations of RNA. No detailed characterization of RNA was attempted. The nuclear DNA content of tumor cells reached values equivalent to chromosomal hexadekaploidy. This was in sharp contrast to control data from an Abrikossoff tumor of the oral cavity and from a neurohypophyseal tumorette ("choristoma"), respectively, displaying diploidy only associated with a much lesser increase of cytoplasmic RNA and proteins. Qualitative lipid studies were consistent with a marked active demyelination of the tumor centre as indicated by a severe reduction of cerebrosides and sulfatides and the presence of cholesterol esters. In addition there was a striking loss of phosphatidylethanolamine and a lesser one of sphingomyelin of white matter of both the tumor-stricken and the contralateral unaffected hemispherical regions, possibly suggesting a generally disturbed metabolism of myelin. It is not clear whether these general changes were resulting from the presence of the unilateral tumor or from precocious cerebral involution.

Brain Neoplasms↗
PubMed1975

The influence of non-cytotoxic concentrations of the herbicide 2,4-dichlorophenoxyacetic acid on the DNA synthesis in cultured vertebrate cells.

The influence of the herbicide 2,4-Dichlorophenoxyacetic acid on the growth of cultured chicken muscle cells was studied by observing morphological changes and by cytophotometric measurement of the DNA content of individual cells. DNA-synthesis curves were derived from the distribution of DNA values. No marked effects were observed at a concentration of 60 mug per liter. In contrast, doses of 600 mug per liter caused a loss in cell differentiation consisting of a partial lack of polar orientation, diminished formation of fibers, and an increase of the N/C ratio. The nuclear matrix of desoxyribonucleoprotein (DNP) changed to a more heteropycnotic structure. Isolated cell necroses were found after 44 hrs of exposure. When compared to the controls, the relative DNA synthesis time was found to be prolonged 1.5-fold. The number of cells in the G2 phase decreased during 44 hrs of exposure. It is concluded from these results that the dosedependent growth inhibition of 2,4-D on vertebrate cells in culture takes effect during DNA synthesis. The morphological changes of the nuclear structure suggests that 2,4-D directly affects the template activity of the DNP matrix.

2,4-Dichlorophenoxyacetic Acid↗