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Biomedical subjects

M H Therkildsen

Publications and source records attributed to M H Therkildsen.

15 recordsLinked to original sources

Expression of histo-blood-group-A/B-gene-defined glycosyltransferases in normal and malignant epithelia: correlation with A/B-carbohydrate expression.

Malignant transformation of oral and bladder epithelia is often associated with loss of histo-blood-group-A- and -B-carbohydrate antigens, whereas these antigens, which are absent in normal adult distal colon (but present in fetal colon) reappear in malignant distal colon. In order to gain insight into the genetic basis of the biosynthetic regulation for these changes, we have correlated the expression of the A- and B-carbohydrate antigens with that of the A/B-gene-defined glycosyltransferases in colon, bladder and oral carcinomas by immunohistology. A newly developed anti-A/B-transferase monoclonal antibody (MAb) was used to demonstrate the in situ localization of transferase expression at the individual cell level with correlation to carbohydrate antigen expression, and gave the essential information that the transferase is derived from the ABO gene complex. The reappearance of A- and B-carbohydrate antigens in carcinomas of the distal colon was found to be unrelated to the expression of the A/B-transferase proteins, which were expressed throughout normal adult colon in accordance with previous enzymatic studies. In contrast, the loss of A- and B-carbohydrate antigens in malignant bladder and oral epithelia was accompanied by concordant loss of enzymes.

ABO Blood-Group System

Epidermal growth factor receptor expression on oral mucosa dysplastic epithelia and squamous cell carcinomas.

The expression of the receptor for epidermal growth factor (EGF) has been determined on oral squamous cell carcinomas. Immunoreactive receptor was localized using a monoclonal anti-EGF-receptor antibody which reacts with sequences in the external domain of the receptor. Frozen sections were studied from 40 patients with squamous cell carcinomas. In 16 sections from the patients with the squamous cell carcinomas, normal differentiated oral mucosa was included and in 7 of these the patients had received preoperative radiotherapy. Sections from 6 other patients with squamous cell carcinoma contained dysplastic epithelia. EGF-receptor-positive cells were present in the basal cell layer on normal differentiated oral mucosa. In sections from patients receiving preoperative radiotherapy the EGF-receptor-positive cells were also found in the spinous cells. In dysplastic epithelia nearly all cells stained for the receptor. The distribution and staining intensity of the EGF receptor varied in the oral squamous cell carcinomas, 36 were positive. The staining pattern in the carcinomas obtained from patients receiving preoperative radiotherapy was not altered qualitatively. Nearly all poorly differentiated cells were stained, but when the tumor was moderately to well differentiated a reduction in the extent of staining in certain areas was seen, paralleling the findings observed in the differentiated upper layers of the normal oral mucosa. This was most pronounced for the epithelial pearls, where the EGF-receptor-positive cells were localized to the undifferentiated cells in the periphery. The results of the present investigation confirm the presence of the EGF receptor on undifferentiated cells, with the extent of the staining reaction on oral squamous cell carcinomas varying inversely with cellular differentiation.

Adult

Malignant Warthin's tumour: a case study.

Malignant transformation of a benign Warthin's tumour (adenolymphoma) is extremely rare. The light microscopic and ultrastructural features of an adenocarcinoma arising in a Warthin's tumour in the parotid gland are described. Light microscopy demonstrated a transition zone from the benign to the malignant component, and the malignant cells revealed oncocytic features by both light- and electronmicroscopy.

Adenolymphoma

Altered expression of ABO (H) carbohydrate antigens is seen in pleomorphic adenomas.

Cell surface carbohydrate antigens show changes in relation to differentiation, maturation and malignant transformation. The expression of type 2 chain ABH carbohydrate structures of the ABO histo-blood group system was investigated in 28 pleomorphic adenomas (PA) and normal parotid glands in order to study possible changes in the glycosylation pattern. The distribution of carbohydrate structures was investigated by immunohistological stainings of formalin-fixed paraffin-embedded material using monoclonal antibodies (MAbs) with well-defined specificity. A strong interindividual variation was found in the normal tissue as well as in the tumors. In normal tissue, acinus and duct cells all expressed elongated carbohydrate structures. The yoepithelial cells did not stain with any of the MAbs investigated. In the PAs, staining was seen in the ductular structures and myoepithelial cells. In contrast to normal tissue, the tumors expressed the short precursor molecule sialylated N-acetyllactosamine. Furthermore, the PAs showed loss of H and A antigens, and a reduced expression of Le(y) compared to normal tissue. The ductular structures as well as the modified myoepithelial cells expressed binary N-acetyllactosamine, which in the normal tissue could only be found in the striated and excretory ducts. Thus our study has shown that aberrant glycosylation is not only a feature of malignant neoplasms but also occurs in pleomorphic adenomas.

ABO Blood-Group System

Immunohistochemical detection of epidermal growth factor receptor in laryngeal squamous cell carcinomas.

Laryngeal squamous cell carcinomas from 15 consecutive preoperatively irradiated patients were investigated for the expression of epidermal growth factor receptor (EGF receptor). The study was performed on frozen sections by means of the 5-layer APAAP technique employing an antibody recognizing the extracellular part of the EGF receptor. In sections from 9 of the patients with laryngeal squamous cell carcinoma, normal differentiated epithelia were included. Sections from 6 of these patients, in addition, contained dysplastic epithelia. Expression of EGF receptor-like material was demonstrated in the basal cell layer of normally differentiated laryngeal epithelial and in dysplastic epithelia. Fourteen of the squamous cell carcinomas proved EGF receptor positive. Nearly all cells in the poorly differentiated carcinomas showed positive staining with the antibodies. In moderately to well differentiated carcinomas a reduction in the extent of staining was seen in certain areas. Especially for the epithelial pearls, the staining reaction was localized to the undifferentiated cells in the periphery. This finding corresponds to the staining pattern observed in the basal cell layers of normal epithelial. The present investigation confirms the expression of EGF receptor-like material in normal laryngeal epithelial, dysplastic epithelial and squamous cell carcinoma. The staining pattern was similar to that observed in oral squamous cell carcinomas, predominantly varying inversely with cellular differentiation.

Carcinoma, Squamous Cell

Malignant epithelial tumors in the minor salivary glands, the submandibular gland, and the sublingual gland. Prognostic factors and treatment results.

Ninety-five malignant tumors in the submandibular gland, the sublingual gland, and the minor salivary glands seen in a 25-year period were reviewed. The patients were retrospectively staged using the Union Internationale Contre le Cancer (UICC) classification. The most frequent tumor was adenoid cystic carcinoma, followed by adenocarcinoma. The submandibular gland was the most frequent location. Five-year and 10-year crude survival rates were 62% and 43%, respectively. Clinical stage was the most important prognostic factor. Survival was not correlated with location of tumor, although recurrence and metastases occurred more frequently in patients with cancer of the submandibular gland. Histologically, the 5-year and 10-year survival was significantly better for patients with adenoid cystic carcinoma compared with the other types; however, although still significant, this difference diminished at 10 years, confirming the need for a long observation time for patients with this tumor.

Adolescent

Undifferentiated carcinoma of the salivary gland in Greenlandic Eskimos: demonstration of Epstein-Barr virus DNA by in situ nucleic acid hybridization.

Paraffin sections of 11 undifferentiated salivary gland carcinomas of lymphoepithelioma type (malignant lymphoepithelial lesion) arising in Greenlandic Eskimos (Inuit) were examined for the presence of Epstein-Barr virus (EBV) using in situ nucleic acid hybridization with a 35S-labeled EBV-specific probe. Epstein-Barr virus genomes were detected in each case in malignant epithelial cells, but were not found in lymphoid stroma or in residual benign salivary epithelium. Eight undifferentiated salivary gland carcinomas from non-Eskimo patients (including two with lymphoepithelioma-like features) were negative for EBV-DNA. Our results confirm the existence of a consistent and specific association between EBV and tumor cells of undifferentiated salivary gland carcinoma of lymphoepithelioma type arising in Greenlandic Eskimos.

Carcinoma, Squamous Cell

Microwave-assisted frozen section diagnosis. A comparison between conventional cryostat technique and the combination of freezing and microwave-stimulated fixation.

The study evaluates the morphology of frozen tissue sections treated by microwave-stimulated fixation compared with unfixed cryostat sections. Furthermore, microwave fixation has been compared with fixation at room temperature. Improved preservation of nuclear structures (chromatin pattern and nucleoli) was found with the microwave combination, while other parameters were indistinguishable from the unfixed cryostat sections. Fixation at room temperature showed no difference compared with the unfixed cryostat sections. The combined method might be useful in rapid diagnosis of mesenchymal tumors, lymphoid proliferations and tumors of the CNS.

Cell Nucleus

A case of granulomatous sialadenitis of the submandibular gland.

Granulomatous inflammation of the major salivary glands is very rare and may be due to obstruction. Little attention has been paid to this condition. The reaction is caused by extravasation of mucus, as seen in the common mucocele of the minor salivary glands. A case of granulomatous inflammation of the submandibular gland caused by obstruction is presented. The etiology of granulomatous sialadenitis is reviewed.

Granuloma

The final outcome of patients presenting with their first episode of acute diarrhoea and an inflamed rectal mucosa with preserved crypt architecture. A clinicopathologic study.

When a patient presents with acute diarrhoea, the most important question is whether it represents the first episode of chronic inflammatory bowel disease (CIBD) or acute self-limited colitis (ASLC). The early changes in the rectal mucosa of patients with ASLC have been claimed to be highly diagnostic, the presence of an unspecific inflammatory infiltrate in the lamina propria and the absence of disturbances in the crypt architecture being the characteristic features. Thirty-two patients who in the period 1980-1984 presented with their first episode of acute diarrhoea and whose rectal mucosa showed these histologic features were followed up for 1.5-7 years. Forty-one per cent of the patients were finally classified as having ASLC and 28% as having diseases other than CIBD or ASLC. Thirty-one per cent eventually developed CIBD. Thus the features claimed to be diagnostic of ASLC could not predict the final outcome of the disease in patients presenting for the first time with acute diarrhoea. The histologic interpretation can provide significant information in these patients but should never replace a careful clinical judgement and, if doubt remains, further observation of the patients.

Acute Disease

Contribution of the trabecular component to mechanical strength and bone mineral content of the femoral neck. An experimental study on cadaver bones.

Both proximal femora from 10 females were acquired at autopsy. The trabecular component of the femoral neck of one specimen from each pair was evacuated, while the contralateral specimen was left intact as a reference. Bone mineral content (BMC) of the femoral neck, demonstrated only a slight (mean 4.8%) individual side to side variation. After evacuation of the trabecular component, BMC was reduced with mean 23.5%. Mechanical strength of the specimens, determined by applying a force to the femoral head perpendicularly to the axis of the femoral shaft, was reduced by mean 39.5%. Correlation between BMC and fracture strength was poor. There was no correlation between reduction in BMC and reduction in mechanical strength after evacuation, indicating that bone fracture strength is influenced by factors other than the mineral content.

Aged

Enzyme histochemical demonstration of hairy cell leukaemia in paraffin-embedded tissue sections.

Hairy cell leukaemia is a form of leukaemia difficult to diagnose since pancytopenia is often present. Hairy cells contain tartrate-resistant acid phosphatase, and this factor is utilised in the diagnosis of the condition. This study confirms that it is also possible to demonstrate tartrate-resistant acid phosphatase in leukaemic infiltrates in formalin fixed paraffin-embedded tissue sections.

Acid Phosphatase