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Biomedical subjects

H F Otto

Publications and source records attributed to H F Otto.

At least 19 recordsLinked to original sources

Venular endothelium binding molecules CD44 and LECAM-1 in normal and malignant B-cell populations. A comparative study.

Lymphocytes leave the blood via post-capillary venules by binding initially to their specialized endothelium. CD44 is a 80-90 kDa hyaluronate-binding glycoprotein involved in binding to endothelium of high endothelial venules (HEV). LECAM-1 is a 75-85 kDa glycoprotein with lectin activity interacting with human peripheral lymph node vascular addressin (PNAd) on HEV. This immunohistochemical study shows that CD44 and LECAM-1 are essentially coordinately expressed on B-lymphocytes. The mode and level of CD44/LECAM-1 expression dissect the peripheral B-cell development into stages that are closely linked to morphologically defined B-cell compartments. Although statistically correlated in B-cell leukaemias (p < 0.0009) and extranodal B-cell lymphomas (p < 0.003), expression of both molecules was less stringently coordinated in 127 B-cell neoplasms examined. B-cell chronic lymphocytic leukaemia, hairy cell leukaemia and mantle zone lymphoma were CD44/LECAM-1 positive, thus corresponding to their reactive counterparts. Correspondingly, follicular centre cell-derived lymphomas were devoid of both markers. Conversely, CD44 and LEC-AM-1 were infrequently detectable in extranodal malignant B-cell neoplasms, irrespective of their maturational state. Presence versus absence of CD44 and LECAM-1, alone or together, determined neither the leukaemic versus aleukaemic state nor the nodal versus extranodal tumour-forming phenotype of a B-cell tumour.

B-Lymphocytes

[Nomenclature-inherent problems in oncology exemplified with primary thymogenic tumors].

Controversy about thymic organogenesis and its complex ontogenesis and functions, have led to several contradictory classifications of primary thymic tumors. Apart from the mesenchymal tumors such as thymolipomas there are four cell types which may represent the cellular origins of primary neoplastic lesions of the thymus: Thymocytes (T-lymphoblastic lymphoma), thymic B-lymphocytes (thymic lymphoma of the B-cell type), epithelial cells (thymomas, thymic carcinomas), and neuroendocrine cells (carcinoid tumors of the thymus).

Carcinoid Tumor

Influence of major histocompatibility complex class I and II antigens on survival in colorectal carcinoma.

HLA-A,B,C and HLA-D molecules present antigenic peptides to the antigen-specific receptor of autologous T-lymphocytes. T-cell-mediated host-versus-tumor response might therefore depend on the presence of these molecules on tumor cells, although the absence of HLA-A,B,C determinants on a cell has been shown to increase its susceptibility to lysis by natural killer cells. To investigate whether the presence or absence of HLA-A,B,C and/or HLA-DR in colorectal carcinoma influences relapse rate and time of tumor-related death, 152 patients who underwent putatively curative surgical treatment were surveyed for a maximum of 65 months (mean, 48 months). As determined by immunohistochemistry, aberrant reduction or loss of HLA-A,B,C/beta 2-microglobulin molecules was more frequent in tumors of the proximal colon than of the rectosigmoid (P = 0.032) and in mucinous carcinomas than in nonmucinous ones (P = 0.022). An abnormal induction of the HLA-D-associated invariant chain (Ii) was more frequent in Dukes' A and B than in stage C (P = 0.046). Reduction/loss of HLA-A,B,C/beta 2-microglobulin was correlated with the absence of HLA-DR (P = 0.024) and Ii (P = 0.005). In contrast to the prognostic role of tumor stage and grade, the presence versus the absence of HLA-A,B,C/beta 2-microglobulin and HLA-DR/Ii molecules was not correlated with recurrence rate or survival. We conclude that in spite of an increasing amount of experimental data suggesting the contrary, the status of HLA-A,B,C and HLA-DR expression in colorectal carcinoma seems to be irrelevant in vivo, regarding survival and growth of residual tumor cells after putatively curative resection of the initial tumor burden.

Aged

Prevention of bleomycin-induced fibrosing alveolitis with indomethacin: stereological studies on rat lungs.

The prevention of the pulmonary toxicity of bleomycin (BLM) has been investigated in experimental models where pulmonary damage was induced with one intra-tracheal dose of BLM. The present investigation was carried out as a pre-clinical study in which BLM was administered systemically. The non-steroid anti-inflammatory drug indomethacin (INDO) was chosen as a possible candidate for pulmonary protection. Twenty female Wistar rats were treated daily with 4 mg/kg (7.3 units) BLM intra-peritoneally for 50 days and 20 rats with BLM and with 1 mg/kg INDO subcutaneously for 62 days. There were 20 animals as controls. Histological examination revealed fibrosing alveolitis in the BLM-treated group which was markedly suppressed in the combination group. Quantitative morphological (stereological) parameters demonstrate that BLM induced alveolar wall thickening (+45%), pulmonary fibrosis (+110%), and an increase of alveolar wall nuclei and of intra-alveolar macrophages (volume densities +43% and +133%, P less than 0.001). In contrast, after combination with INDO significant differences to the control group could not be detected except for a slight increase of intra-alveolar macrophages (+62%). Thus, INDO is a highly efficient agent in the prevention of BLM-induced pulmonary damage.

Animals

Proliferative activity of neuroendocrine tumours of the gastroenteropancreatic endocrine system: DNA flow cytometric and immunohistological investigations.

The proliferative activity of 16 tumour specimens from 13 patients with neuroendocrine tumours of the gastroenteropancreatic endocrine system was studied by DNA flow cytometry and immunohistology for the nuclear Ki67 proliferation antigen. Equivalent results were obtained with both methods, which showed the proliferative activity of gastroenteropancreatic neuroendocrine tumours to be heterogeneous. In four malignant small intestinal carcinoids and one extravisceral carcinoid localised in the retroperitoneum the percentage (index) of proliferating tumour cells as measured by DNA flow cytometry ranged from 2.9 to 36.2% corresponding to low, moderate, or high proliferative activity. In four malignant pancreatic endocrine tumours and their metastases indices ranged from 8.7 to 18.3%, corresponding to low, moderate, or high proliferative activity. In four benign pancreatic endocrine tumours indices ranged from 4.3 to 7.7%, all corresponding to low proliferative activity. This heterogeneity of proliferative activity may in part explain the heterogeneous results reported of chemotherapy treatment. As chemotherapy of tumours is largely affected by favourable cell cycling kinetics, individual diagnostic investigations of the proliferative activity of these neuroendocrine tumours may be of value for identifying patients suitable for this treatment.

Adult

Pulmonary tumor thrombotic microangiopathy with pulmonary hypertension.

Pulmonary tumor thrombotic microangiopathy is characterized by fibrocellular intimal proliferation of small pulmonary arteries and arterioles in patients with metastatic carcinoma. Its morphologic features, including precursor lesions, were studied in 21 patients diagnosed in 630 consecutive autopsy cases with carcinoma (3.3%). Nineteen of 21 patients had adenocarcinoma and 11 of these 19 patients had gastric carcinoma. The pathogenetic events start with microscopic tumor cell embolism. Tumor emboli do not occlude affected vessels but induce both local activation of coagulation and fibrocellular intimal proliferation, which lead into stenosis or occlusion. Hemodynamically, an increase in vascular resistance results in pulmonary hypertension. In three patients, metastatic carcinoma was unknown before death, and the condition was diagnosed as pulmonary hypertension of unknown origin. Thus, pulmonary tumor thrombotic microangiopathy should be considered in the differential diagnosis of primary pulmonary hypertension, particularly in patients with well-known carcinoma who develop acute or subacute cor pulmonale.

Adenocarcinoma

Solid-cystic tumour of the pancreas. An endocrine neoplasm?

Immunohistochemical studies and DNA flow-cytometric investigations were performed in a case of solid-cystic tumour of the pancreas in a 35-year-old woman. All tumour cells were immunoreactive for the neuroendocrine cell markers chromogranin A and neuron-specific gamma-enolase. Moreover, about 10% of tumour cells were immunoreactive for insulin, while hypoglycaemia was absent. Few tumour cells (less than 1%) were immunoreactive for somatostatin, and no cells were found to be immunoreactive for pancreatic polypeptide or glucagon. No immunoreactivity was present for duct cell marker carcino-embryonic antigen and only individual cells were reactive for alpha 1-antitrypsin. Nuclear DNA content of the tumour cells was diploid and the proliferative activity was low. In confirmation of some reports on neuroendocrine markers in solid-cystic tumour of the pancreas, our findings support the theory that the lesion is a hormonally inactive neuroendocrine pancreatic tumour.

Adult

Clinico-pathological features and surgical management of primary epithelial hepatic malignancies.

Between January 1983 and January 1990, 89 patients with primary epithelial hepatic malignancy were admitted to the Department of Surgery, University of Heidelberg, for surgical treatment. Histopathologically, tumours were hepatocellular carcinoma (HCC) 75, fimbrolamellar carcinoma (FLC) 1 and cholangiocellular carcinoma (CCC) 13. Concomitant liver cirrhosis was found in 61%. Among the cirrhotic patients, hepatitis-B infection was found in 65% and post-alcoholic cirrhosis in 30%. Pre-operative alpha-fetoprotein serum levels were elevated in 66% of the patients with HCC and none of the patients with CCC or FLC. The resectability rate was 35.9% (32/83). Twenty-six patients underwent curative resection; six were resected palliatively. In 44 patients exploratory laparotomy and biopsy only were performed. Thirteen patients remained without any surgical procedure. The hospital mortality rate after resection was 21.8%. Short-term prognosis depended predominantly on concomitant cirrhosis associated with peri-operative blood loss and extent of hepatic resection. Long-term survival rates after curative resection were 78%, 55% and 21% for 1, 3, and 5 years, respectively. Prognostic factors of long-term survival were investigated by the Kaplan-Meier method.

Adenoma, Bile Duct

[Pathology of Crohn disease in children].

Incidence, macroscopic and histological appearance, and systemic manifestation of Crohn's disease in children are discussed. The main criteria for the differentiation between idiopathic inflammatory bowel disease (Crohn's disease and ulcerative colitis) and acute self-limited colitis (infectious colitis) of the intestinal tract are reviewed. Finally, a description of the morphology of precancerous changes and their clinical implications in Crohn's disease (and ulcerative colitis) is given.

Biopsy