Search PubMed⌕ Search

Biomedical subjects

H Graeff

Publications and source records attributed to H Graeff.

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

Immunolocalization of urokinase-type plasminogen activator in adenomas and carcinomas of the colorectum.

Carcinogenesis in the human colon is associated with a marked increase in the tissue content of the urokinase-type plasminogen activator (u-PA). This study was performed to determine the type of cells responsible for the u-PA increase in carcinomas of the colon and in their precursor lesions, the adenomas, by immunohistological evaluation applying monoclonal antibody 3689 directed to the beta-chain of u-PA. Normal intestinal mucosa (n = 17) showed hardly any staining of u-PA, but some lamina propria cells were faintly positive. Carcinomas (n = 17) and adenomas (n = 16) showed a considerable and comparable staining intensity of u-PA in neoplastic columnar epithelial cells, and this staining was found to be diffuse and cytoplasmic. In a majority of the neoplastic tissues the u-PA staining was found to be patchy and not related to known risk markers of malignancy such as dysplasia in the adenomas, or to prognostic determinants such as Dukes' classification or differentiation in the carcinomas. The observation of strong u-PA positive lamina propria cells in adenomas but infrequently observed in normal mucosa and carcinomas was noteworthy. u-PA staining intensity of the tissue sections was found to correlate well with the u-PA antigen level in the tissue extracts determined by ELISA (r = 0.52, P = 0.0001) but poorly with the u-PA activity determined enzymatically (r = 0.28, P = 0.05). In conclusion, the u-PA increase in neoplasia of the human colon can be attributed to an increased diffuse cytoplasmic content of u-PA in neoplastic columnar epithelial cells.

Adenocarcinoma↗
PubMed1991

Thromboembolism in gynecologic oncology.

The risk of thrombo-embolic complications increases in surgical gynaecological oncology as a consequence of difficult and long-lasting interventions. In gynaecologic operations without any drug prophylaxis thrombosis has been reported by 24-29%, whereas in operations of progressed oncological findings thrombo-embolic complications arise in almost every second case. Such complications have to be taken seriously due to difficulty treatable sequelae (post-thrombic syndrome) and due to potentially lethal pulmonary embolism. Furthermore, they are important causes of postoperative early mortality. Diagnosis of a deep thrombosis is insecure even for experienced clinicians. We have various diagnostical means at our disposal, such as phlebography, sounding and 125-iodine-fibrinogen-testing. Differentiated drug medication for the prevention and therapy of thrombo-embolism is definitely indicated. There are also different kinds of physical and drug-aided means, which can be applied according to the individual situation.

Coumarins↗
PubMed1991

Biological and clinical relevance of the urokinase-type plasminogen activator (uPA) in breast cancer.

Tumor cell invasion and metastasis is a multifactorial process, which at each step may require the action of proteolytic enzymes such as collagenases, cathepsins, plasmin, or plasminogen activators. An enzymatically inactive proenzyme form of the urokinase-type plasminogen activator (pro-uPA) is secreted by tumor cells which may be converted to an enzymatically active two-chain uPA-molecule (HMW-uPA) by plasmin-like enzymes. Action of proteases on pro-uPA may generate the enzymatically active or inactive high-molecular-weight form of uPA (HMW-uPA). Some proteases (plasmin, cathepsin B and L, kallikrein, trypsin or thermolysin) activate pro-uPA by cleaving the peptide bond Lys158 and IIe159. Other proteases (elastase, thrombin) cleave pro-uPA at different positions to yield enzymatically inactive HMW-uPA. HMW-uPA may be split into the enzymatically active LMW-uPA and the enzymatically inactive ATF (amino terminal fragment). ATF may be cleaved between peptide sequence 20 and 40 within the receptor binding domain of uPA (GFD). Such impaired ATF does not bind to uPA-receptors. Action of the bacterial endoproteinase Asp-N from Pseudomonas fragi mutant on pro-uPA or HMW-uPA, however, generates intact ATF which efficiently competes for binding of HMW-uPA or pro-uPA to receptors on tumor cells. High uPA-antigen content (pro-uPA, HMW-uPA, or LMW-uPA) in breast cancer tissue (not in plasma) indicates an elevated risk for the patient of recurrences and shorter overall survival. Thus pro-uPA/uPA-antigen content in breast cancer tissue serves as an independent prognostic parameter for the outcome of the disease. Cathepsin D is also an independent prognostic factor for recurrences and overall survival. High content of cathepsin D in breast cancer tumors is, however, not correlated with elevated levels of pro-uPA/uPA indicating that synthesis and release of cathepsin D and pro-uPA/uPA are independent events.

Binding Sites↗
PubMed1990

Role of plasmin in the degradation of the stroma-derived fibrin in human ovarian carcinoma.

The aim of this study was to evaluate the type of enzymes involved in tumor-associated fibrinolysis of the stroma component fibrin in ovarian cancer patients. For this purpose, the high-molecular-mass fibrin degradation products (HMM-XDP) were isolated from malignant ascitic fluid by protamine sulfate precipitation and further purified by gel filtration and acid precipitation. After reduction with 2-mercaptoethanol, the peptide chain components were separated by reverse-phase high-performance liquid chromatography (RP-HPLC). The nature of these components was elucidated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and N-terminal amino acid sequence analysis and compared with fibrin-derived fragments formed in vitro. The results indicate that plasmin is the essential protease involved in the degradation of the stroma-derived fibrin portion found in ovarian cancer ascites.

Amino Acid Sequence↗
PubMed1990

[Macrosomia of the fetus and clinical relevance].

The clinical relevance of foetal macrosomia (i.e. birth weight greater than or equal to 4000 gms) was investigated retrospectively using the 1987 figures of the "Bayerische Perinatalerhebung". 8591 (total n = 101931; 8.4%) newborns met the criterion for macrosomia and were compared with two groups of normosomic newborns (birth weight 2500-2999 gms and 3000-3999 gms). The problems, which may obscure correct prenatal diagnosis are discussed. The incidence of operative deliveries and birth injuries was increased. The duration of the deliveries was not prolonged in our study in contrast to published reports. The neonatal transfer-rate to a neonatal centre was higher in newborns, delivered by Caesarean section, compared with newborns delivered by the vaginal route. The perinatal and the maternal morbidity was higher, the perinatal mortality lower in the macrosomic newborn. According to our data, macrosomia represents and elevated perinatal risk.

Asphyxia Neonatorum↗
PubMed1990

[Androgenization in postmenopause in rare ovarian tumors--2 case reports].

Androgen-producing tumours of the ovary are uncommon in postmenopausal women. We report on symptoms of two patients with androgenization due to a stromal-Leydig cell tumour and a steroid-cell tumour, respectively. Clinical signs and symptoms, laboratory findings and therapeutic consequences are discussed.

Aged↗
PubMed1990

Tumour-associated fibrinolysis: the prognostic relevance of plasminogen activators uPA and tPA in human breast cancer.

Prognostic variables in breast cancer are urgently needed to individualize adjuvant cytotoxic therapy, especially in those patients where metastases in the lymph nodes have not been detected (node-negative disease). So far histomorphological criteria, the determination of receptors for steroid hormones or EGF (epidermal growth factor), the protease cathepsin D or DNA-ploidy are used to distinguish between low- and high-risk patients. High-risk patients have a higher incidence of recurrences and/or shorter overall survival after surgery of the primary tumour than low-risk patients. High-risk patients (node-positive; hormone-receptor-negative) would receive adjuvant hormone therapy or chemotherapy. In the node-negative patient, adjuvant therapy is only recommended if a high content of cathepsin D and aneuploidy of the tumour (or high S-phase in diploid tumours) has been diagnosed. Determination of cathepsin D in tumour extracts as a variable in breast cancer patients is based on the fact that invasion and metastasis is correlated with elevated levels of tumour-associated proteases such as cathepsins B and D, collagenase IV and plasminogen activators. The urokinase-type plasminogen activator (uPA) which is secreted by tumour cells as an enzymatically inactive proenzyme (pro-uPA) seems to play a key role in mediating tumour cell invasion in cancer tissues. Receptor-bound uPA converts enzymatically inactive plasminogen into the serine protease plasmin which then degrades the extracellular matrix surrounding the tumour cells (tumour stroma). We localized pro-uPA/uPA immunohistochemically in paraffin-embedded formalin-fixed breast cancer tissue sections. Pro-uPA/uPA was detected in the cytoplasm and on the plasma membrane of the tumour cells reflecting receptor-bound pro-uPA/uPA.(ABSTRACT TRUNCATED AT 250 WORDS)

Aneuploidy↗
PubMed1989

Elastase released from human granulocytes stimulated with N-formyl-chemotactic peptide prevents activation of tumor cell prourokinase (pro-uPA).

Proteolytic enzymes released from granulocytes upon stimulation with the chemotactic N-formyl peptide FNLPNTL (in the presence of cytochalasin B) prevented activation of tumor cell single-chain urokinase-type plasminogen activator (pro-uPA) by plasmin. Elastase was identified by the use of eglin C (elastase inhibitor) and a monoclonal antibody to elastase as the functional proteolytic enzyme in granulocyte supernatants. Action of purified granulocyte elastase on pro-uPA generated enzymatically inactive two-chain uPA linked by disulfide bridges which was indistinguishable by SDS-PAGE from plasmin-generated HMW-uPA. The major elastase cleavage site in pro-uPA was located between Ile159 and Ile160. a minor one between Thr165 and Thr166. Elastase cannot substitute for plasmin in the proteolytic activation of pro-uPA to enzymatically active HMW-uPA. However, when pro-uPA was first activated by plasmin to form enzymatically active HMW-uPA, this enzymatic activity was not impaired by subsequent elastase treatment.

Amino Acid Sequence↗
PubMed1989

[Measuring fetal vascular resistance with the Duplex scanner--a new fetal stress test].

In 77 women (phi 41 week, less than 7 days before delivery) we compared the resistance index (RI) in the umbilical artery (UA), descending aorta (DA) and intracranial artery (ICA) with an oxytocin challenge test (OCT) and a non stress test (NST). Proof criterias were asphyxia resulting in operative deliveries and metabolic acidosis. The sensitivity in predicting metabolic acidosis was low in all tests, but a high and comparable specificity could be achieved in both the RI and OCT. In predicting fetal asphyxia the RI in the ICA had a high sensitivity, the RI in the UA and DA had the highest specificity of all tests. Centralisation and increased brain perfusion seem to detect fetal asphyxia as a result of placental insufficiency.

Acidosis↗
PubMed1989

[Hemorrhage, shock and infection].

Hemorrhage and sepsis may lead to multiple organ system failure caused by a redistribution of cardiac output and a reduction of tissue perfusion. The pathophysiologic changes caused by hemorrhage are frequently prevented by rapid diagnosis of the cause of the bleeding (e.g., vessel injury or coagulation disorder) and its therapy. The pathophysiologic changes in sepsis are mediated by toxins which affect almost every organ system. Knowledge of the predisposing factors, rapid recognition of signs and symptoms, and understanding of the underlying pathobiochemical and pathophysiologic changes are mandatory in the successful therapy of septic shock. The main therapeutic principle remains removal of the focus.

Female↗