Determination of tissue polypeptide antigen (TPA) levels in different cancer types and controls.

The clinical significance of the radioimmunological determination of tissue polypeptide antigen (TPA) was studied in 1980 and 1981 in patients with different cancer types (cancer of the gastrointestinal tract, cancer of the genitourinary tract, cancer of the lung and other malignancies) as well as in patients with acute inflammatory diseases, other benign diseases and healthy controls. TPA levels were elevated in about 70% of patients with acute inflammatory diseases and in 50-80% of patients with malignancies having evidence of disease (ED). In all other groups, as healthy controls, benign diseases except inflammatory diseases and cancer patients who had no evidence of disease (NED) or partial remission (PR), TPA was above the normal range in 4-17%. Comparisons between cancer patients with ED and cancer patients with NED/PR, healthy controls and patients with benign diseases (without acute inflammatory diseases) have shown a significant difference (p less than 0.01). Data from a follow-up program from the years 1982 to 1984, including TPA determinations, are shown. TPA can be regarded as an additional 'marker' for proliferative processes. The test seems to be useful for monitoring cancer growth in advanced cancer patients who received chemo- or radiotherapy. Limitations result from the lack of tumor specificity of the marker TPA.

Determination of TPA levels in breast cancer and controls.

The clinical significance of radioimmunological determination of Tissue Polypeptide Antigen (TPA) has been studied on patients with breast cancer (n = 376), on "normal subjects" (n = 92), on benign diseases of the breast as well as on patients with inflammatory diseases (n = 98). TPA levels were elevated (120 U/l or higher) in the group with inflammatory diseases in 68% and in the group with breast cancer (stage IV with progression of disease) in 85%. In all other groups (healthy controls, benign diseases of the breast, breast cancer before operation, breast cancer stage I (NED), breast cancer stage II and III (NED), and breast cancer stage IV (PR/CR), TPA was higher only in 5-22%. TPA determinations seem not to be very useful for diagnostic purposes in breast cancer, but it can be regarded as suitable for monitoring proliferative processes in advanced breast cancer. Limitations result from lack of tumor specificity of the proliferation marker TPA. So far, follow-up studies after mastectomy in breast cancer and in patients with advanced breast cancer under chemotherapy have shown that CEA and TPA are concordant. There is no cross reactivity between CEA and TPA. The main component of the labeled tracer has an isoelectric point of 4.4 but there is some impurity in the tracer as it was shown in chromatofocusing.

[Leukocyte migration inhibition test using myelin basic protein in patients with malignant diseases]. / Der Leukozyten-Migrations-Inhibitionstest unter Verwendung von basischem Myelinprotein bei Patienten mit malignen Erkrankungen.

The leukocyte migration inhibition test in agarose technique was standardized as far as possible. The greatest interassay variance is not more than 10%, the greatest intraassay variance less than 5%. The test was carried out as a two-step technique in a homologous system. Such variances have not been obtained when an autologous system was used. Myelin basic protein was used as antigen. Migration inhibitions greater than 43% were measured in 66% of the controls (22 healthy persons, 22 patients with non malignant diseases), 30% of the patients with malignancies showed migration inhibitions of more than 43% (36 tumor patients without evidence of disease, 27 patients with tumors in progression). These results may reflect a stimulation of the lymphocytes by using myelin basic protein as antigen under the conditions we have used.

The electrophoretic mobility test with myelin basic protein, binding of 125I-MBP to lymphocytes, and gel electrophoresis pattern of supernatant during incubation.

Lymphocytes from seven patients with malignancies, from seven patients with non-malignancies, and from five healthy persons were incubated with 125I-labeled MBP. Binding of MBP of lymphocytes was monitored from 0.5 to 20h. The binding ranged from 4 to 7% of the total MBP present and remained fairly constant during the first 4h of incubation. It dropped considerably at 20h. Mean percentages of MBP binding were lower in cancer patients than in persons without malignancies. After incubation, the supernates were examined by gel electrophoresis. The electrophoretic pattern was similar in comparing groups with different diagnoses. A considerable loss of MBP in the terminal supernatant (20h) was found. When tested in the electrophoretic mobility test (EM test) with stabilized erythrocytes, supernatant derived from cancer patients produced a somewhat higher mean slowing effect than did superntes from other patients and controls.

[Radioimmunoassay for human myoglobin: methodology and diagnostic significance in myocardial infarction (author's transl)]. / Radioimmunologische Bestimmung von Human-Myoglobin in der Diagnostik des akuten Myokardinfarkts.

A radioimmunoassay was developed to determine serum myoglobin (SMb). 50 healthy persons showed values between 0 and 90 ng/ml. Serial tests of 10 patients following acute myocardial infarction or during angina pectoris (AP) indicated that SMb reached pathological values before CK and CK-MB (average 250 +/- 95 ng/ml at the time of hospitalisation which corresponds to 3.3 +/- 1.4 h after beginning of angina pectoris). At hospitalisation the simultaneously determined CK was within normal limits and reached pathological values only 6.2 +/- 1.9 h after the onset of angina. Maximum of SMb was 506 +/- 194 ng/ml occurring 8.8 +/- 2.8 h after beginning of AP, maximum of CK was 905 +/- 475 mU/ml occurring 20.0 +/- 7.8 h after AP. CK-MB and CK differed only slightly in their time course. One patient with severe AP had pathologically increased SMb values whilst all other enzymes were completely normal. Methodical and clinical results are discussed.

Amylase/creatinine clearance ratio and tubular proteinuria in acute pancreatitis.

Amylase/creatinine clearance ratio (CAm/CCr), urinary protein concentration and urinary protein pattern were studied in 102 samples from 27 patients with acute pancreatitis and in 46 controls. Raised CAm/CCr, proteinuria and a tubular protein pattern were present in 74, 56 and 96% of the patients, respectively. However, CAm/CCr and proteinuria and CAm/CCr and tubular protein pattern were not correlated. These results do not support the suggestion that an elevated CAm/CCr in acute pancreatitis is due to generalized tubular protein reabsorption failure presenting with tubular proteinuria.

Immunodiagnostics of malignant disease. VI. Electrophoretic mobility test (EMT) in malignant melanoma.

The electrophoretic mobility test (EMT) is an in vitro assay for demonstrating cellular immunity. In the presence of tumor antigens lymphocytes of tumor patients liberate lymphokines, which reduce the charge of indicator particles resulting in a measurable reduction of their eletrophoretic mobility. Lymphocytes of 174 patients were tested by EMT. The antigens used were a basic myelin protein termed encephalitogenic factor (EF) and a 3M KCl extract from melanoma tissue. In 91% of the cancer patients there was a positive lymphocyte response. In contrast to this the controls and non-malignant diseases showed a positive result in only 8.7% of the cases. Using the 3M KCl extract from melanoma tissue as tissue as antigen 1 of the benign controls, 3 patients with nonmalignant diseases and none of the 49 patients with malignant diseases reacted positively, whereas in the melanoma group 86% showed a positive lymphocyte response. The results show the possibility of demonstrating tumor specific immune reaction in the EMT.

Specificity of increased amylase to creatinine clearance ratio in acute pancreatitis.

The amylase to creatinine clearance ratio was found to be normal in 11 of 33 patients with acute pancreatitis. The ratio was elevated in 10 of 19 patients with renal insufficiency. Thus, it does not seem to be a specific index in the diagnosis of acute pancreatitis.

[Differentiation of the proteinuria by microelectrophoresis in continuous polyacrylamide-gradient gels (author's transl)]. / Differenzierung der Proteinurie durch die Mikroelektrophorese in kontinuierlichen Polyacrylamid-Gradientengelen

It is possible to differentiate the proteinuria of glomerulonephritis by means of microelectrophoresis in polyacrylamide-gradient gels. The advantages of this method (quick, cheap, concentration of the urine not required) led to its introduction into clinical use. Upon separating the urinary proteins according to their molecular weight and form, four patterns of proteinuria may be differentiated: low molecular, intermediate and high molecular. Those forms of glomerulonephritis which show constant morphological and clinical findings (e.g. minimal proliferative glomerulonephritis, mesangioproliferative glomerulonephritis with crescents) can be related to one of the four patterns of proteinuria, whereas the pattern of proteinuria in other forms of glomerulonephritis (e.g. (peri-)membranous glomerulonephritis, mesangioproliferative glomerulonephritis) are dependent on the phase of the disease.

RNA-dependent DNA polymerase from a cell line derived from the bone marrow of a patient with polycythemia vera.

A RNA-dependent DNA polymerase was isolated from a human cell line derived from the bone marrow of a patient with polycythemia vera. The purification procedure included chromatography on phosphocellulose and oligo(dT)-cellulose, and glycerol gradient centrifugation. The enzyme could be distinguished from polymerase A by salt elution from phosphocellulose, utilization of poly(rC) - oligo(dG) and its molecular size of about 70000, as determined by centrifugation. Throughout the purification procedure ribonuclease H activity was co-purified. Upon dodecylsulfate-polyacrylamide electrophoresis on microgradient gels two main bands with molecular weights of 68000 and 66000 and three minor bands were detected. The enzyme preferentially used poly(rA) - oligo(dT) as template-primer compared with poly(dA) - oligo(dT). It incorporated dGMP into polymer on poly(rC) - oligo(dG).