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Biomedical subjects

G Krieger

Publications and source records attributed to G Krieger.

At least 55 records · Page 3Linked to original sources

Characterization of Raji cell binding IgG in patients with metastatic breast cancer.

The aim of the present study was to isolate and characterize the immune complexes detected by the Raji cell assay in metastatic breast cancer. However, the Raji cell binding material could not be separated from monomeric IgG by Sephacryl S-300 gel chromatography in any of the 16 sera investigated. The parallel elution profile of monomeric IgG and the Raji cell binding activity suggested that anti-Raji cell antibodies, rather than immune complexes of low molecular weight, were present in these sera. This was further substantiated by pepsin digestion of the Raji cell binding IgG fractions. The binding of F(ab')2 fragments was quantitatively comparable to the binding of undigested IgG, and the bound F(ab')2 fragments could be visualized by immunofluorescence at the cell membrane. The presence of antibodies against Raji cells was further confirmed by the complement-dependent cytotoxicity assay. These antibodies did not react with untransformed lymphocytes and there was no correlation with anti-Epstein-Barr virus antibodies. The incidence of cytotoxic anti-Raji cell antibodies in breast cancer was 12% compared to 20% in malignant lymphoma, to 0% in normals and patients with degenerative cardiovascular diseases, and to 5% in patients with auto-immune diseases.

Antibodies, Neoplasm↗

[Rearrangements of immunoglobulin and T-cell-antigen receptor genes as diagnostic markers in lymphatic neoplasms].

During recent years cloning of the genes encoding the immunoglobulin (Ig) and T-cell (TCR) antigen receptor has made it possible to analyze clonal expansions of B- or T-cells at the molecular level. We here describe the usefulness of the Ig- and TCR-gene rearrangements in selected cases of malignant lymphoma. In contrast to all other cases investigated, one non-Hodgkin's lymphoma (NHL) exhibited the infrequent phenomenon of oligoclonality, i.e. three distinct B-cell clones were discerned by Southern blot analysis. Detection of clonal TCR- and Ig-gene rearrangements unequivocally documented bone marrow involvement in four of eight NHL-patients, where conventional histologic and cytologic examination remained inconclusive. As expected, analysis of bone marrow DNA revealed clonal Ig-gene rearrangements in three cases with clear histologic evidence of bone marrow infiltrations by the NHL. In one case of a patient with acute mixed lymphoid-myeloid lineage leukemia a previously identified clonal Ig-gene rearrangement vanished after successful chemotherapy. Analysis of Ig- and TCR-gene rearrangements promises to be a very useful diagnostic tool in selected cases of lymphoid neoplasia.

Acute Disease↗

[Juridical aspects of new treatment methods].

We distinguish between subjectively and objectively new methods of medical attendance. Subjectively new are methods carried out by the specific physician for the first time, because he is just entering his profession or because he has never applied this techniques before. Objectively new methods are derived from medical investigation leading to other medical attendances than usually. With regard to new medicaments, the law is codified. As for objectively and subjectively new methods of medical attendance, the physician must observe the common principles like information of the patient, his consent, necessity of treatment, as well as competent performance.

Clinical Trials as Topic↗

[False diagnosis--a nevus and its juridical consequences].

Not only therapy but also diagnosis requires high quality on the physician's part. He has to make a diagnosis according to the symptoms of the sickness as well as the patient's anamnesis applying all necessary resources of medical science. The right diagnosis at the beginning of treatment is an essential precondition for the proper information of the patient. During medical attendance, as well, the physician has to apply all possibilities of diagnosis. He is responsible for all damages brought on by a false diagnosis or by not making a diagnosis at all.

Diagnosis, Differential↗

Binding characteristics of three complement dependent assays for the detection of immune complexes in human serum.

The fluid phase C1q binding, the solid phase C1q binding and the Raji cell assay are the most widely employed methods for the detection of complement fixing immune complexes in human disease. However, their binding characteristics for complexes formed in native serum have not been compared and studied in detail. For this purpose, Tetanustoxoid (TT): anti-TT complexes were formed closely to in vivo conditions by incubating sera of immunized people with TT. Then the molecular characteristics of those complexes, which could be detected by the 3 immune complex assays, were defined. The methods used are precipitation curve, gel chromatography and measuring the complexed antibody with a sensitive Elisa method. All 3 assays detected only complexes near the equivalence zone; the Raji cell assay being the most sensitive detecting 1.5 micrograms complexed antibody/ml serum followed by the solid phase (6 micrograms/ml) and the fluid phase C1q binding assay (50 micrograms/ml). As estimated by gel chromatography, both the C1q binding assays measured most sensitively complexes with a molecular weight distinctly over 2,000,000 daltons, whereas the Raji cell assay detected preferentially complexes in the range of 2,000,000 daltons. Smaller TT: anti-TT complexes with a molecular weight less than 600,000 daltons were not detectable by the 3 assays. In conclusion, the 3 assays, while differing in sensitivity, showed similar binding patterns with preference for high molecular complexes near equivalence. Subsequently, they might be insensitive to small complexes persisting in the circulation.

Antigen-Antibody Complex↗

[Intraoperative changes in extravascular lung water. Study on heart surgery patients].

The intraoperative changes in extravascular lung water (EVLW) were studied in 40 patients undergoing aortic-coronary bypass grafting. The patients were divided into two groups on the basis of preoperative ejection fraction (EF) values (group I: EF greater than 45%; group II: EF less than 45%). EVLW was measured using the double-indicator dilution method (thermo/dye). In a control study, changes in transthoracic impedance (ZoTh) were recorded. The initial EVLW value in group I was 4.3 +/- 0.4 ml/kg body wt. and in group II, 4.4 +/- 0.3 ml/kg body wt. After extracorporeal circulation, significant changes in EVLW could be observed (group I: from 4.5 +/- 0.5 ml/kg body wt. to 7.0 +/- 0.2 ml/kg body wt.; group II: from 5.1 +/- 0.8 ml/kg body wt. to 7.8 +/- 0.9 ml/kg body wt. (p less than 0.001). At the end of the operation, no changes in EVLW were observed in group I. However, in group II EVLW was significantly different to initial values (6.3 +/- 1.0 ml/kg body wt., p less than 0.01). The results obtained using the double-indicator method were identical with those obtained using the transthoracic impedance method. A marked correlation could be seen between length of ECC recording and EVLW values at the end of the operation, especially when the ECC time was 90 min or more (r = 0.84). Based on our results, it must be assumed that intraoperative damage to capillary membranes occurs if the ECC time is above 90 min.

Coronary Artery Bypass↗

Metastatic breast cancer with constantly low CEA blood levels. A subgroup with unfavorable prognosis?

The capability of breast cancer to secrete CEA might have biological significance. In 105 patients with metastatic breast cancer serial CEA determinations and clinical follow-up data were available during progression of disease up to death. In this series, 39 patients (37%) had constantly low CEA levels (less than 10 ng/ml), whereas 66 patients (63%) showed CEA values exceeding 10 ng/ml with progression. The patients with low CEA levels had significantly shorter median survival times (P = 0.001) after mastectomy (39 versus 65 months) and after recurrence (18 versus 28 months) than the patients with high CEA levels. This difference was due first to a poor-risk group of 13 patients with rapidly disseminating tumors, very short survival (less than 12 months), and low CEA levels. Secondly, there were more patients with pulmonary involvement and unfavorable prognosis and fewer patients with osseous metastases and long survival in the low-CEA group. In conclusion, there might be a subtype of breast cancer with rapid progression and low CEA secretion. This clinical observation has to be confirmed by histological grading and CEA staining of these tumors.

Antineoplastic Combined Chemotherapy Protocols↗

Immune complex-like material in the serum and plasma exchange in patients with metastatic cancer.

Clinical significance of immune complex-like material in the serum was investigated in tumour patients undergoing plasma exchange with albumin-saline solution and subsequent chemotherapy. Immune complexes were detected by the Clq binding assay or the Raji cell radioimmunoassay in nine out of forty-five patients before this therapy. Levels of immune complexes were decreased to 10-30% of the initial value by plasma exchange depending on exchanged plasma volume. In contrast to other serum proteins like alpha 1-antitrypsin and alpha 2-macroglobulin, which showed protein specific increase during follow up after plasma exchange in all patients, recovery rates of immune complexes and IgG were highly individual but parallel in each patient. Clinical response to this protocol did not correlate with immune complex status, suggesting that removal of the measured immune complex like material had little clinical significance or was not longlasting enough to provide therapeutic benefit.

Albumins↗

The efficacy of large volume plasma exchange in chemotherapy resistant malignancies.

Chemotherapy resistance in cancer patients may be due to serum blocking factors, which can be diminished or eliminated by large volume plasma exchange (PE). This procedure was performed with the IBM blood cell separator in 69 patients resistant to chemotherapy. Immediately after PE the chemotherapy was given but it was reinstituted, if clinical evaluation revealed partial remission, minor response or no change. 37 out of 69 patients (53.6%) responded again, 32 (46.4%) did not. Response duration ranged from 2 to 45 weeks. Best clinical results were obtained in patients with colorectal cancer, 15 out of 23 showed improvement between 4 to 45 weeks. Serum blocking activity was measured using a modified mixed lymphocyte culture assay (MLC). There was a 80% positive correlation between clinical course of patients and MLC levels, if basic activity before the first PE was compared to MLC inhibition before the following PE's.

Adult↗

Critical aspects of the 125I-C1q binding assay for detecting immune complexes in tumor patients.

Clinical studies on C1q binding activity in tumor patients showed contradictory results and it was suggested that methodical problems might be partly responsible for those discrepancies. Therefore, precision of the C1q binding assay when testing tumor sera, influences of assay modifications on test results and possible interfering substances were investigated. Compared to aggregated human IgG and BSA: anti-BSA complexes as standards the C1q binding material in tumor sera was more unstable after freezing-thawing and distinctly more susceptible to methodical influences like testing with different 125I-C1q preparations or variations of PEG concentration and ionic strength of PEG solution. Addition of heparin and fibrinogen influenced the C1q binding of some tumor sera more than the C1q binding of standards and normal sera. Thus, instability and sensitivity to methodical influences of the C1q binding material have to be considered, when clinical studies using the C1q binding assay to detect immune complexes in tumor sera are interpreted.

Antigen-Antibody Complex↗

Chromatofocusing combined with the ELISA technique. A sensitive method for the analysis of immune complexes.

A sensitive method which permits analysis of IgG containing circulating immune complexes without detailed knowledge of the nature of the antigens and the specificity of the antibodies involved is described. Soluble BSA: anti-BSA were used as model immune complexes and isolated from serum. The procedure involves the use of gel chromatography for the separation of the high molecular weight fraction containing the immune complexes as measured by binding to 125I-labeled Clq, followed by absorption of the immune complex fraction to immobilized protein A-Sepharose CL-4B. After desorption from protein A-Sepharose the complexes were dissociated and separated into free antigen and antibody by chromatofocusing in the presence of urea. The isolated free antigen and antibody retained their immunological activity as shown by immunodiffusion, binding after their recombination to 125I-labeled Clq, and by recombining antigen and antibody with much enhanced sensitivity using a microplate ELISA system. By means of the ELISA recombination technique it is possible to analyze less than 1 microgram of BSA:anti-BSA model complexes. Application of this technique may provide more information about the nature of immune complex like material associated with diseases.

Animals↗

[Spontaneous occurrence of a factor VIII inhibitor in glomerulonephritis and immunoglobulin a deficiency].

A 24-year-old patient with isolated IgA deficiency and a 3-year history of minimal change glomerulonephritis with nephrotic syndrome developed acute hemorrhagic diathesis. A spontaneous inhibitor of factor VIII was diagnosed. Therapy with substitution and plasmapheresis was without prolonged effect. Only consistent immunosuppressive therapy normalized coagulation. The patient died from septic complications during immunosuppressive therapy.

Adult↗

[Determination of the carcinoembryonic antigen (CEA) for predicting the success of therapy in metastatic breast cancer].

In 53 patients with metastatic breast cancer and increased CEA serum levels (greater than 10 micrograms/l) the CEA titer within the first 8 weeks after commencement of chemotherapy was compared with results of therapy. Among 30 patients in whom CEA values had decreased by at least 30% of pretreatment values 12 showed remission, 15 no change and 3 progression of the malignancy. Among 23 patients with unchanged or increasing CEA values during therapy 19 had progression, 3 an arrest and one a remission of the disease. In the one patient with remission the course of the disease was unusual inasmuch as the CEA value increased to 240 micrograms/l serum and liver metastases regressed excessively at the same time. This lead to the assumption of CEA release by tumour necrosis during therapy. The results suggest that in metastatic breast cancer and increased CEA values remission generally cannot be expected should the CEA value remain unchanged or rise within the first 8 weeks after initiation of treatment. In contrast, a decrease of CEA within that time may be considered a prognostically favourable sign which, however, does not mean clinically relevant reduction of tumour size in every case. For evaluation of treatment sufficient precision of CEA determinations must be guaranteed.

Antineoplastic Agents↗

Clinical significance of circulating immune complexes in patients with metastatic breast cancer.

Serum circulating immune complexes (CIC) were repeatedly measured by means of the CIq binding assay (Cba) and the Raji cell assay (Rca) in 158 patients with metastatic breast cancer (mbc). Frequency of occurrence and levels of CIC were only slightly increased in mbc when compared to age-matched healthy women. They were identical to those of patients with localized breast cancer prior to mastectomy and to those of post mastectomy patients without evidence of recurrent disease. In mbc the results of the Cba and the Rca showed a poor correlation, whereas in a control group of patients with rheumatoid arthritis both tests showed significantly elevated levels of CIC. Patients with mbc were followed up clinically and biochemically by serially measuring CIC for an average of 10 months. Patients with positive CIC did not prove to be an unfavorable group regarding progression of disease and response to chemotherapy. When CEA and CIC levels were compared, CIC, unlike CEA, was a poor tumor marker. In conclusion, CIC as measured by CIq binding assay and Raji cell assay are not clinically significant tumor markers or prognostic indicators in patients with metastatic breast cancer.

Antigen-Antibody Complex↗

[Clinical significance of circulating immune complexes in patients with metastatic breast cancer].

In 68 patients with metastatic breast cancer a follow-up study was performed to correlate circulating immune complexes (CIC) as detected by the C1q binding assay and the Raji cell radio immunoassay with the state of disease. Clinical examinations and determinations of CIC were carried out all four to eight weeks over at least six months. 19 patients were positive for CIC in the C1q binding assay and 12 in the Raji cell radioimmunoassay. There was no correlation between the results of both tests. In comparison 26 patients out of 68 with rheumatoid arthritis were positive in the C1q binding assay and 32 in the Raji cell assay. In these patients the results of both tests correlated significantly. There was only in a few cases of metastatic breast cancer a positive correlation between levels of CIC and changes of tumor burden. Furthermore, CIC did not prove to be of prognostic value.

Antigen-Antibody Complex↗

[The professional secrecy of physicians (author's transl)].

Legal requirement concerning confidential medical communication has been an essential item of medical professional ethics for centuries. Today, it is based not only on criminal and procedural but also on constitutional law. The legal requirement of secrecy applies to all knowledge the physician gains in performing his medical duties. These informations must be secret, if they are known to only a limited number of persons. The requirement of secrecy is still in force after the patient's death. Only those personally concerned can release the physician from his professional discretion. The physician can also be justified to speak in special legal situations. In addition, there is a legal requirement of secrecy towards the supervising authority, towards the hospital agency as well as towards colleagues.

Confidentiality↗