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Biomedical subjects

W Siegert

Publications and source records attributed to W Siegert.

At least 163 records · Page 9Linked to original sources

Non-Hodgkin's lymphomas presenting with gastrointestinal involvement.

Between 1978 and 1983 a total of 33 patients with non-Hodgkin's lymphoma (NHL) involving the gastrointestinal tract were seen in our institution. Pathological classification was performed according to Kiel. Low grade NHL was diagnosed in 17, high grade NHL in 16 patients. The most frequent histological entity was lymphoplasmocytoid immunocytoma (11 patients). The most common sites of origin were the stomach (23 patients) and the ileocecal region (6 patients). The majority of patients presented with stage I and II disease (20 of 33 patients). As a rule primary therapy consisted of surgery with curative intent. Most of the patients received additional chemotherapy or radiotherapy. Patients with limited disease and complete tumour resection showed long-term survival from 12+ to 57+ months (mean 32.9+ months). Patients with advanced disease (stage III and IV) and only palliative surgery or with lymphoblastic lymphoma had a probability of survival of less than 12 months.

Adolescent↗

Myopathic carnitine deficiency associated with lymphocytic malignant non-Hodgkin lymphoma and monoclonal immunoglobulin G-K.

A 47-year-old male patient suffered from recurrent myalgia, induced by fasting or physical exercise. Later, he developed progressive muscular weakness. Serum levels of creatine phosphokinase (CPK) were elevated to approx. 400 U/1. Muscle biopsies showed lipid storage myopathy and signs of acute fiber necrosis, muscle carnitine was decreased to below 20% of controls, carnitine palmitoyl transferase (CPT) activity was normal. Carnitine was also moderately decreased in a liver biopsy and in plasma. Urine excretion of carnitine was low, no elevation of short-chain dicarboxylic acids could be found. The patient was also found to suffer from a lymphocytic malignant non-Hodgkin lymphoma, a monoclonal immunoglobulin (Ig) G-k in plasma and lymphocytic infiltration of bone marrow were demonstrated. At that time no evidence had been obtained to indicate that these two diseases could be related to each other. Autoantibodies against skeletal muscle could not be demonstrated. Absorption of L-carnitine p.o. was normal, however, plasma levels of carnitine fell again rapidly. Administration of 3 X 2 g L-carnitine per day normalized the patient's plasma carnitine levels and led to an increase of plasma short-chain acylcarnitine and ketone bodies, particularly beta-hydroxybutyrate (B-HOB). However, no significant clinical improvement could be seen. Additional application of prednisone led to normalization of CPK serum levels.

Carnitine↗

A sensitive method for detecting cells coated with antibodies with human monoclonal rheumatoid factor produced in vitro.

A human monoclonal rheumatoid factor (RF) produced in vitro by an Epstein-Barr virus immortalized cell line has been used to detect and quantitate antibodies specifically bound to cells. The RF is purified from cell culture supernatant by a simple procedure and then radiolabeled. In this assay, the binding of 125I-labeled RF to cells coated with specific antibodies is determined. This RF method detects very low titers of antibodies directed against specific cellular antigens and also minorities of antibody coated tumor cells in mixtures with identical non-coated cells. The advantages of this unique human monoclonal antibody are discussed.

Animals↗

Hexose transport in Epstein-Barr virus (EBV) negative lymphoma lines and their EBV converted, virus genome carrying sublines.

Increased hexose uptake is a marker for viral transformation, as has been shown in non-human fibroblasts transformed by oncogenic viruses. If this phenomenon is a general expression of viral induced transformation it should also apply on different oncogenic virus-cell systems. Recently two human EBV-negative lymphoma lines were converted to a stable EBV-positive state by infection with EBV. According to their biochemical and biological properties they enable us to study events associated with EBV-transformation. We analysed the uptake of (3H) glucosamine and (3H) 2-deoxy-D-glucose into BJAB and Ramos and their EBV-converted sublines and found a clear increase of the rate of uptake of both sugars in the EBV-positive sublines. Control experiments confirmed that the increased uptake was due to alterations on the level of the hexose membrane carriers and not due to increased metabolism. The observation of increased hexose uptake in the only presented available virus transformed human cell system is a strong argument for the general importance of this transformation-associated membrane change.

Animals↗

Antifolate effect of triamterene on human leucocytes and on a human lymphoma cell line.

The inhibitory effect of triamterene and its metabolites on human leucocyte dihydrofolate reductase has been studied. Under test conditions with dihydrofolic acid 0.5 X 10(-5) M, triamterene 7 X 10(-5) M produced total enzyme inhibition, whereas the metabolites hydroxytriamterene and the sulphate ester of hydroxytriamterene were less effective inhibitors; at their maximum attainable concentration of 5 X 10(-5) M, dihydrofolate reductase was inhibited by 80% and 50%, respectively. Cultures of the BJAB-B95-8 human lymphoma cell line were incubated with various concentrations of triamterene. Because of their increased specific activity of dihydrofolate reductase, the cells were able to maintain normal DNA metabolism, as measured by the ratio of the incorporation rates of 3H-deoxyuridine and 3H-thymidine, as well as normal cell growth at 1 X 10(-6) M, and in some cases at 1 X 10(-5) M triamterene. At 8 X 10(-5) M triamterene, the strong inhibitory effect caused severe impairment of DNA metabolism and subsequently dissolution of the cell culture. The results are discussed in relation to the possible toxic side effects of long-term triamterene treatment in patients suffering from alcoholic cirrhosis, who may have impaired metabolism of triamterene and a concomitant severe folate deficiency.

Burkitt Lymphoma↗

Ectoenzymes on the surface of cells from human lymphoblastoid lines: 5'-nucleotidase and phosphatase.

Activities of the ecto-enzymes 5'-nucleotidase (5'-N) and phosphatase were determined on the surface of intact cells from 15 different established lines of human B- and T-lymphoblasts. Whereas all the lines express phosphatase, 10 of the lines were negative for 5'-N. 5'-N-negative cell lines are found among B as well as T cells, and they do not carry cryptic enzyme activity. In a 5'-N-positive line activity of this enzyme is correlated with growth showing a peak during the logarithmic phase. On the other hand, inhibition of 5'-N does not change the growth curve of this line. Neuraminidase treatment of the cell surface brings about an increase in phosphatase but not in 5'-N activity. 5'-N of two B-cell lines of human peripheral blood lymphocytes shows complete crossreactivity with an antiserum obtained against human placental 5'-N. However, the enzyme of one lymphoma line with B-cell properties (EHR-A-Ramos) does not cross-react with this serum. The results are discussed with respect to suitability of these lymphoblast lines as model systems for the study of immunodeficiencies.

B-Lymphocytes↗

Epstein-Barr virus-induced increase in the concanavalin-A receptor density of established EBV-negative lymphoma lines in vitro.

Infection of two human EBV-genome negative lymphoma lines with the EBV-variants P3HR-I and B95-8 converts the lines to permanent carriers of EBV-DNA and the EBV-determined nuclear antigen. This process is accompanied by a series of biologic changes similar to those in oncogenic transformation by known tumor viruses (e.g. polyoma, SV40, Rous SV). They include altered growth properties and membrane changes, one of which is expressed in an increased agglutinability by Con-A. Although most transformed cell systems are more agglutinable than the non-transformed counterparts it is controversial whether they possess similar or changed numbers of lectin receptors. Since little was known about lectin receptor densities of virus transformed lymphoma cells, we set out to determine the densities of Con-A receptors on the EBV-negative lymphoma lines BJAB and Ramos and their EBV-converted sublines by simultaneous recording of the cell membrane fluorescence of FITC-Con-A and the cell volume using the FLUVO-METRICELL flow cytometer. We found that EBV infection gave rise to cell lines with a significantly elevated Con-A receptor density compared to the EBV-negative parental lines. The similar changes found in a number of independently converted sublines suggest that they are due to the direct or indirect action of the viral genome.

Burkitt Lymphoma↗

Quantitative correlation between the Dane particle-associated DNA polymerase and the hepatitis B e antigen.

In order to evaluate the potential infectivity of blood of hepatitis B patients, the Dane particle associated DNA polymerase was determined, which is a reliable marker for the presence of complete viral particles. Enzyme activities were compared with hepatitis B e antigen (HBeAg) titers determined by radioimmunoassay. Detectable DNA polymerase activity was only present in HBeAg positive blood, preferentially in samples with high antigen titers (1 : 1000 and above). These samples therefore have to be considered as highly infectious. However, blood with low HBeAg levels and free of detectable polymerase activity can still be infectious, since the polymerase reaction is rather insensitive compared to the radioimmunological HBeAg determination.

DNA-Directed DNA Polymerase↗