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Biomedical subjects

K Havemann

Publications and source records attributed to K Havemann.

At least 253 records · Page 14Linked to original sources

Biological and immunological aspects of small cell carcinoma of the lung in relation to ectopic hormone production.

Small cell carcinoma share morphological and functional characteristics with normal Kulchitsky cells (K-cells) of the bronchial tree. This tumor is thought to reflect a neoplastic transformation of the pulmonary APUD cells because of the morphological similarities with K-cells, the association with paraneoplastic syndromes and the high incidence of ectopic hormone production. The peptide hormones produced and secreted by small cell carcinoma can be used as tumor markers to guide diagnosis and to monitor chemotherapy. They may be of particular value in following the course of a patient and in detecting early recurrences. Some of the hormonal substances produced by the tumor have the biochemical characteristics of prohormones. The difference between the abnormal hormones and their physiological counterparts probably will lead to the development of more specific marker assays. On the other hand, some of the atypical hormones have autoantigenic properties, as they occur in circulating immune complexes of patients with small cell carcinoma. The correlation between ectopic hormone production and host immunity might be of importance for the development of future treatment modalities.

Antigen-Antibody Complex↗

[Treatment of metastasising soft-tissue sarcoma with a uniform combination chemotherapy of cyclosphosphamide, vincristin, adriamycin and DTIC ("CyVADIC") (author's transl)].

Combination chremotherapy with cyclophosphamide, vincristin, adriamycin and DTIC (CyVADIC") was used from 1974 to the middle of 1977 on 12 patients with various forms of metastisising soft-tissue sarcoma. An objective response was observed in seven of eleven patients. Full, although brief, remission occurred in two of six patients with fibrosarcoma and persists in one with an undifferentiated sarcoma. Partial remission was induced in one patients each with fibrosarcoma and alveolar-cell sarcoma. Mean survival time was 18 months. Those responding to treatment had a longer average survival time than those refractory to it. No statistically significant conclusions can be drawn because of the small number of patients, but these observations suggest that this combined treatment can favourable influence previously therapy-refractory forms of metastasising soft-tissue sarcoma.

Adult↗

Carcinoembryonic antigen and ferritin in patients with lung cancer before and during therapy.

Carcinoembryonic antigen (CEA) levels were determined in 114 patients with confirmed lung cancer at the time of diagnosis using the CEA Ire-Sorin radioimmunoassay. Elevated CEA values were found in 47%. Most of the patients with high CEA levels had clinically detectable metastases. Ferritin was detectable by the Laurell-electrophoresis in the serum of 58 out of 81 (72%) of the patients with confirmed lung cancer at the time of diagnosis. Ferritin levels were significantly higher in patients with metastases. Serial measurements of CEA and ferritin during radio- and chemotherapy showed that the assay may be useful to evaluate the effects of therapy. Because of some false negative results both CEA and ferritin determinations should be used only in context with other clinical and laboratory findings.

Carcinoembryonic Antigen↗

Proteolytic cleavage of human IgG molecules by neutral proteases of polymorphonuclear leukocytes.

The effect on human IgG of the elastase-like (ELP) and chymotrypsin-like (CLP) neutral proteases derived from human polymorphonuclear leukocytes was studied. By incubating ELP with monoclonal IgG proteins, two immunochemically and electrophoretically distinct components were formed which were similar, but not identical, to the Fc and Fab fragments produced by papain digestion. When an IgG protein was incubated under similar conditions with CLP enzyme, no proteolysis was observed. IgG proteins differed in their susceptibility to proteolysis by ELP. These differences were related to the subclasses IgG1-IgG4. The IgG1 and IgG3 proteins were readily cleaved by ELP, but the IgG2 and IgG4 proteins were more resistant. Although free light chains differ in susceptibility to proteolysis by ELP, our studies showed that neither the type (kappa or lambda) nor the subgroup of light chain affected the susceptibility of complete IgG molecules to cleavage by this enzyme.

Animals↗

Preparation of colony stimulating activity from large batches of human urine and production of antisera against it.

In vitro induction of myelopoetic colonies from mouse bone marrow has been used for measurement of leucopoetic colony stimulating activity (CSA) isolated from large batches of human urine. After high flow dialysis in artificial kidneys and immediate adsorption to DEAE-Cellulose, followed by purification on Con A-Sepharose, treatment with insoluble Papain and gelfiltration on Sephadex G 100, enrichment of CSA was about 6,000-fold. An important step of the enrichment procedure was the separation from a CSA-inhibiting protein, probably combining with CSA. Specific activity was further increased by preparative polyacrylamide gel electrophoresis to 5.3 X 10(6) units per mg protein. The total enrichment exceeded 25,000-fold. The final purification product consisted of a group of closely related proteins with high specific activity. Antisera raised with one of the electrophoretic fractions suppressed bioactivity in each of the different purification steps including the final CSA fractions differing in electrophoretic mobility. The antisera furthermore inhibited CSA in human lung and monocyte conditioned media but had only very little effect on partially purified CSA from stimulated human lymphocytes as well as CSA derived from mouse lung conditioned medium.

Chromatography, Gel↗

Effect of neutral proteases from human granulocytes on colony forming cells in vitro.

Marked inhibition of colony formation is observed after incubation of mouse and human bone marrow cells with the human granulocytic neutral proteases elastase and chymotrypsin as well as with pancreatic chymotrypsin. The corresponding enzymes inactivated with diisopropylfluorophosphate were almost inactive. Incubation of different colony inducing agents either resulted in no change or in an increase of their colony stimulating activity. The data suggest a direct proteolytic action of the proteases on colony forming cells which may alter receptor sites for colony stimulating activities.

Animals↗

Degradation products of fibrinogen by elastase-like neutral protease from human granulocytes. Characterization and effects on blood coagulation in vitro.

We investigated the effect of elastase-like neutral protease isolated from human granolocytes on human fibrinogen. Dependent on enzyme concentration and time of incubation, the elastase-like protease induced a progressive degradation of fibrinogen. Analysis of the remaining polypeptide chains showed a high susceptibility of the Aalpha- and low susceptibility of the gamma-chain of fibrinogen towards the proteolytic action of the enzyme. The split products were characterized by polyacrylamide gel electrophoresis and two-dimensional immunoelectrophoresis. They showed antigenic determinants of fibrinogen and of plasmin-induced proteolysis products D and E. The cleavage fragments isolated by gel chromatography had distinct molecular weights. Coagulability of fibrinogen by thrombin was inhibited according to the concentration of the protease and the time of incubation. Split products of fibrinogen with higher molecular weight prolonged the coagulation time of native fibrinogen, whereas low molecular weight fragments were ineffective.

Blood Coagulation↗

Colony stimulating factor (CSF) in human mixed lymphocyte cultures: effect on human and mouse progenitor cells.

Supernatants from human two-way MLC, poor and rich in monocytes, were tested for their ability to induce colony growth of human and mouse progenitor cells in semi solid agar. Colony stimulating factor (CSF), with activity in both systems, indicated that allogenic lymphocytes require monocytes to produce CSF. Whereas human marrow showed an early kinetics of production, the liberation of CSF active on mouse marrow cells exhibited a delayed kinetics. These results, combined with other evidence, suggest that human lymphocytes produce two different factors.

Bone Marrow Cells↗

[Chemotherapy of gastrointestinal cancer (author's transl)].

Gastrointestinal cancer has proved exceedingly resistant to chemotherapy efforts. 5-Fluorouracil (5-FU) accepted as standard treatment, has provided only infrequent and incomplete antitumor effects. Other drugs as the nitrosoureas BCNU and CCNU or Mitomycin C do not match the effectiveness of 5-FU. Improvement in frequency of tumor regression have been recorded for gastric carcinoma with combinations of 5-FU and BCNU and 5-FU, adriamycin and Mitomycin C and for colorectal carcinoma with combination of 5-FU, methyl-CCNU and vincristine. There are also suggestions that such combination chemotherapy may produce increased survival when compared to untreated patients. The combination of 5-FU and streptozotocin in carcinoid tumors or adriamycin in primary hepatoma may be of some effectiveness.

Carcinoid Tumor↗

Demonstration of antibodies in patients' sera, directed against nonspecific cross-reacting antigen.

Nonspecific cross-reacting antigen (NCA), which strongly cross-reacts with carcinoembryonic antigen, was demonstrated to be an autoantigen. Antibodies directed against NCA were shown in different groups of patients, but high titers (greater than 1/64) were found only in cancer patients. A correlation between tumor mass, antigen load, and antibody titer apparently existed. Sera obtained from patients preoperatively and postoperatively differed significantly (P greater than 0.01) in the sense that titers were high only in sera sampled after the patients were treated. Nevertheless, the formation of these antibodies cannot be considered a cancer-specific phenomenon because of their existence also in patients with nonmalignant diseases.

Adult↗

[Therapy of testicular neoplasms].

It can be established that it is nowadays possible by means of an interdisciplinary therapy to achieve a full remission of more than 2 years in 80% of the malignant teratomas of stages I and II and in up to 40% of the teratomas of stage III, which possibly means a cure of the patient.

Bleomycin↗

[Combination chemotherapy in patients with disseminated bronchogenic carcinoma (author's transl)].

49 patients with disseminated bronchogenic carcinoma (small cell, 16;squamous cell, 17;large cell, 12;adeno, 4) were treated with a combination of adriamycin, cyclophosphamide, vincristine and DTIC. In a randomized series (21 patients) chemotherapy alone was compared to chemotherapy plus heparin. Partial remission was achieved in 8 patients with small cell carcinoma, in 5 patients with large carcinoma and in 2 patients with squamous cell carcinoma. The survival of patients who responded to therapy was greater than the survival of patients who did not respond to therapy. The duration of remission and the survival time was not longer in patients who had additional heparin therapy.

Antineoplastic Agents↗

[Treatment of alveolar soft part sarcoma (author's transl)].

Till now few reported cases of alveolar soft part sarcoma of the skeletal musculature which was classified for the first time by Christopherson in 1952 could not make plain a uniforme treatment. Radioresistance was also described as unsuccessful chemotherapy as early or excessiv surgical proceeding. Our own unusual observation of a case of this very rare malignant mesenchymal tumor may give a direction for a sensible therapy.

Adult↗

[Factor XIII deficiency in adults with acute leukemia: results of a substitution therapy with factor XIII (author's transl)].

A decrease in fibrin stabilizing factor (Factor XIII) is the most frequent coagulation disorder seen in adults with acute leukemia. Patients with prominent reduction of factor XIII (FSF) (less than 50%) were substituted with a factor XIII concentrate from human placenta, and factor XIII plasma concentration and bleeding tendency were followed up during the course of the disease. After substitution plasma, factor XIII activity went up to normal levels in most of the patients. As compared to the course of 12 patients with distinct factor XIII reduction without factor XIII therapy, there were less bleeding complications in 13 courses of patients with prominent reduction of factor XIII substituted with factor XIII concentrate and in 11 with normal or only slightly reduced factor XIII levels.

Acute Disease↗