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Biomedical subjects

K Havemann

Publications and source records attributed to K Havemann.

At least 235 records · Page 13Linked to original sources

A modified spectrophotometric test for nitroblue-tetrazolium reduction of granulocytes and monocytes and its application for testing inhibition of monocytes by serum components in tumor patients.

For evaluation of serum-factor involvement in monocyte function, we established a modified quantitative spectrophotometric-nitroblue tetrazolium (NBT) test. We investigated the stimulation of human peripheral monocytes and granulocytes by zymosan, endotoxin, and Corynebacterium parvum in vitro. In addition, polymorphonuclear neutrophil (PMN) function in a patient with non-Hodgkin lymphoma was studied during the course of polychemotherapy and intravenous application of Corynebacterium parvum (C. parvum). In non-Hodgkin lymphoma (n = 15) and bronchogenic carcinoma (n = 11) the NBT-reduction of autologous monocytes in presence of autologous serum in relation to a AB serum was decreased compared to a control group of age-matched healthy blood donors. The sera from patients with these neoplasms inhibited NBT-reduction of monocytes from healthy donors. This inhibition showed a correlation to the presence of immune complexes in patients with bronchogenic carcinoma.

Antigen-Antibody Complex↗

Chemical characterization of macrophage cytotoxicity factor, macrophage migration inhibitory factor, T-helper cell-replacing factor and colony-stimulating factor from culture supernatants of concanavalin A-stimulated murine spleen cells.

Supernatants from Concanavalin A-stimulated murine spleen cells were subjected to hydrophobic interaction chromatography on phenyl-Sepharose. Macrophage cytotoxicity factor (MCF), macrophage migration inhibitory factor (MIF), T-helper cell-replacing factor (TRF) and colony-stimulating factor (CSF) were bound at high ionic strength and were released stepwise at low ionic strength. CSF thus could be separated from MCF, MIF and TRF and the bulk of other proteins. Chromatograhy of pools containing MCF, MIF and TRF on Sephadex did not lead to a separation of the three activities which were all found in a molecular weight range of 25.000-55.000. Isoelectric focusing of these pools in pH range from 4 to 9 gave two peaks for MCF in a single sharp peak at pH 5.3. The results demonstrate that the four biological activities can be distinguished on a chemical basis and are accessible for purification and chemical characterization.

Animals↗

[Immunotherapy in bronchial carcinoma].

In bronchogenic carcinoma the clinical trials performed with nonspecific immune stimulation, either in its systemic or local form, suggest that in patients with early manifestations (e.g. adjuvant therapy after operation) the time of relapse may be delayed. A similar effect is perhaps obtained in studies employing tumor antigen preparations. Whether the cure rate is increased is questionable at this time. These rather disappointing results should induce us to consider other approaches to tumor immunotherapy. Results obtained in small cell bronchogenic carcinoma suggest that a manipulation of humoral immunity (e.g. by influencing circulating immune complexes) may be an additional therapeutic concept.

Antibody Formation↗

[Significance of tumor markers in the diagnosis and treatment of bronchial carcinoma].

In bronchogenic carcinoma a variety of tumor markers have been described in the last few years. These markers are oncofetal proteins like the carcinoembryonic antigen (CEA), pregnancy-associated antigens like the pregnancy-associated alpha 2-glycoprotein (alpha 2-PAG), and the beta-chorionic gonadotropin (beta-HCG), or normal proteins like isoferritin, coeruloplasmin and hormones. In addition, many attempts have been made to isolate tumor-specific antigens and proteins from lung tumor tissues. The clinical application of the different tumor markers for early diagnosis, staging and therapy control of lung cancer patients is described.

Antigens, Neoplasm↗

Incidence of circulating immune complexes in patients with lung cancer and their effect on antibody-dependent cytotoxicity.

Circulating immune complexes were determined in patients with lung cancer by the C1q deviation test and by column chromatography on Sepharose 6 B. Immune complexes could be demonstrated by the two different methods in 50--80% of patients' sera at the time of diagnosis. Patients with extended disease had more immune complexes than patients with limited disease. Serial determinations showed a good correlation between immune complex levels and clinical course of disease. The size of the immune complexes present in patients' sera was determined by sucrose density ultracentrifugation and by column chromatography in the region between 10 S and 30 S. Furthermore in this study no inhibition of antibody-dependent cell-mediated cytotoxicity by circulating immune complexes could be seen.

Antibody-Dependent Cell Cytotoxicity↗

A radioassay for proteolytic cleavage of isolated cartilage proteoglycan. 2. Inhibition of human leukocyte elastase and cathepsin G by anti-inflammatory drugs.

20 non-steroidal anti-inflammatory drugs and other agents were evaluated for their effectiveness in directly inhibiting the proteolytic activity of human leukocyte elastase and cathepsin G. The proteolysis of hide powder azure by leukocyte granule extracts was used for initial testing, and selected drugs were then studied further using a radioassay of the proteolysis of isolated proteoglycan by purified leukocyte elastase and cathepsin G. The results indicated that at drug concentrations likely to be attained to vivo, phenylbutazone may significantly inhibit elastase, while gold thiomalate and mucopolysaccharide polysulfonic acid ester (MPSE; Arteparon) could limit the action of cathepsin G. Oleic acid may provide a useful starting point for development of agents specifically designed to inhibit cartilage erosion.

Anti-Inflammatory Agents↗

[Transfer factor (TF) treatment of patients with HBs-Ag-positive chronic active hepatitis. A prospective, controlled study (author's transl)].

It is a clinically and experimentally well supported working hypothesis that infection with hepatitis B virus may result in chronic active hepatitis in patients with suspected immune deficiencies. On this basis, a pilot study was performed in order to evaluate the effect of "specific" transfer factor (TF) in the treatment of HBS-Ag-positive chronic active hepatitis. From the leukocytes of 500 ml venous blood each of 40 volunteers that had completely recovered from acute virus hepatitis B within the last 6 months, a unique TF pool (40 units of TF) was prepared according to the method of Lawrence. Preexaminations indicated that this preparation was able to enhance cellular immune reactions in vitro. Thirteen patients with HBS-antigenemia and chronic active hepatitis (i.e., two liver biopsies within the last 6 or more months with the histological criteria of chronic aggressive hepatitis according to de Groote, elevated serum levels of bilirubin, alkaline phosphatase, transaminase activities, and/or gamma-globulines) were randomized: Seven received s.c. injections of two units of TF each on days 1 and 15, the other six saline. Conversion of skin reactions to some ubiquitous antigens occurred in the TF group, but no significant and constant drop of HBS-Ag serum titers was observed. Although some of the biochemical parameters seemed to ameliorate in the TF group, the differences versus the control group did not prove to be significant within the limited number of patients under observation. The in vitro reactivity of patients' lymphocytes to HBS-Ag, tested by means of the 3H-thymidine uptake, was never found enhanced after TF application. In the used doses, "specific" TF was not effective in the treatment of HBS-Ag-positive chronic active hepatitis; unfavorable side-effects were not observed.

Adult↗

[Circulating immune complexes of patients with malignant lymphomas (author's transl)].

Using the 125J-Clq deviation method according to Sobel, the polyethylenglycol precipitation test of Nydegger, and a Sepharose 6B column chromatography in a modification of MacLennan's method, circulating immune complexes (CIC) have been detected in 20--27% of patients with Hodgkin's lymphoma, in 8% of patients with non-Hodgkin lymphoma of low, and in 20--40% with high malignancy. CIC appeared in advanced stages of the diseases and correlated well with the activity of the disease. CIC disappeared in remissions and reappeared during reactivation of the disease. CIC were only found in patients with general symptoms, i.e. B-symptoms. The pathogenetic role of CIC in the initiation of B-symptoms and in tumor spread is still not fully explained. The antibody part of the CIC is IgG, the antigenic component has not yet been characterized.

Adult↗

Lymphocyte proliferation to phytohemagglutinin (PHA) in hepatitis B antigen-positive and -negative hepatitis.

Lymphocytes from patients with HBs-Ag-positive and -negative acute, chronic-persistent, and chronic-active hepatitis, from healthy controls and from patients with alcoholic liver cirrhosis were tested under standardized conditions. These included use of a single charge of Phytohemagglutinin (PHA-P) dissolved and diluted in one operation, of a single pool of homologous serum of the major blood group AB found free of HBs-Ag and cytotixic factor, and elaboration of PHA dose response curves in the presence of autologous and homologous serum in each case examined. During the early phase of acute virus hepatitis B and non-B, and in HBs-Ag-positive chronic persistent and active hepatitis, hyperresponsiveness of lymphocytes to PHA was observed independently of the source of the serum present in the culture. Lymphocyte responsiveness returned to normal in the later phase of acute hepatitis and depressed in alcoholic liver cirrhosis and in cases of HBs-Ag-positive chronic active hepatitis in which cirrhosis had developed. Although the cause of these alterations in lymphocyte responsiveness is not completely understood, the central role of a primary change of the lymphocytes themselves affecting their ability to react to PHA seems probable.

Acute Disease↗

[Circulating immune complexes in bronchogenic carcinoma: relation to extent of disease and to therapy (author's transl)].

In sera of 72 patients with lung cancer, 20 patients with various benign lung diseases and 34 age matched controls circulating immune complexes were determined by column chromatography on Sepharose 6 B and subsequent testing of the eluate for macromolecular IgG as well as by inhibition of radiolabelled C1q binding to sensitized sheep erythrocytes. Whereas in both control and benign lung disease-sera complexes could be detected in less than 5%, sera of lung cancer patients showed macromolecular IgG in 83% and C1q reactive material in 53% at the time of diagnosis. Patients with metastases exhibited a significantly higher percentage of positive reactions than those without metastases (macromolecular IgG 93%/68%, C1q 71%/28%). The size of the complexes increased with the extent of disease. So far, no signficiant changes in circulating immune complexes could be demonstrated id pretherapeutic values were compared with those after X-ray-, chemo- or immunotherapy with one exception, which is an increase of C1q reactive material after radiotherapy.

Antigen-Antibody Complex↗

ACTH-like activity in immune complexes of patients with oat-cell carcinoma of the lung.

Immune complexes could be isolated from sera of 7 patients with oat-cell carcinoma of the lung, but not from 5 normal controls, using zonal ultracentrifugation. After ultracentrifugation, fractions containing macromolecular IgG were absorbed on a protein A-sepharose column and the immune complexes were eluted and dissociated by glycin-HCl buffer at pH 3.5. The eluates were tested for the presence of tumour-associated proteins as carcinoembryonic antigen (CEA), non-specific crossreacting antigen (NCA), alpha2 pregnancy associated antigen (alpha2PAG) and isoferritin. Whereas none of these tumour-associated antigens could be demonstrated, an ACTH-like activity was detected in the immune-complex fractions of 4 patients with oat-cell carcinoma, by radioimmuno- and bioassay. Polyacrylamide electrophoresis of an immune-complex fraction from a patient with Cushing syndrome showed ACTH-like activities, with mol. wt of 110,000, 75,000, 30,000 and less than 20,000 (all glycoproteins) indicating the presence of different subfractions of big ACTH.

Adrenocorticotropic Hormone↗

Humoral factors modulating growth of granulocyte macorphage progenitor cells.

The kinetic of production of colony-stimulating activity (CSA) inducing mouse and human colony-forming cells (CFU-C) was tested in different human leukocyte culture systems. Stimulated and unstimulated cultures of spleen single cell suspensions, peripheral mononuclear leukocytes and acute monocytic leukemia (AMoL) cells were investigated. With the exception of the AMoL cells, stimulated cultures always revealed higher CSA levels than unstimulated controls. The spleen cell cultures exhibited the highest overall activity showing three molecular species of 70,000, 35,000 and 10,000 daltons activating human CFU-C to form colonies in the agar culture system. Furthermore it could be demonstrated that colony formation could be inhibited by low molecular weight fibrinogen degradation products obtained by digestion of fibrinogen with granulocyte-derived elastase.

Animals↗