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Biomedical subjects

W Arnold

Publications and source records attributed to W Arnold.

At least 325 records · Page 18Linked to original sources

The tetracycline resistance transposons Tn1721 and Tn1771 have three 38-base-pair repeats and generate five-base-pair direct repeats.

The 10.7 kilobase (kb) tetracycline resistance transposons Tn1721 and Tn1771, isolated from disparate sources, are completely homologous on the basis of heteroduplex analyses. Both transposable elements are capable of forming multiple duplications of a 5.3 kb portion encompassing the resistance genes (tet region). A model accounting for both, recA-independent translocation and recA-dependent amplification, postulates two direct and one inverted repeat as essential constituents of the transposons. DNA sequence analyses of Tn1721 and Tn1771 have substantiated this model. They demonstrated three identical 38 base pair repeats identically in both transposons dividing them into a "minor transposon" and a tet region. Identical sequences of at least 87 base pairs providing recombination "hot spots" for gene duplication have been found at the ends of the repetitious tet region. Translocation of Tn1721 and Tn1771 generates five base pair direct repeats at the respective sites of insertion. On the basis of the heteroduplex molecules and sequences analyzed the two transposons are identical.

Base Sequence↗

Coronavirus-associated antibodies in nasopharyngeal carcinoma and infectious mononucleosis.

Coronavirus-like particles are found within the cytoplasm of NPC tumor cells, within the cytoplasm of the tumor cells of the regional metastases, and within tumor cells grown on nude mice. For the immunologic identification of the coronaviruses, the cultures of human tracheal epithelium (MRC-C) were used and inoculated with a known coronavirus strain. Whereas blood sera from NPC patients (n = 73) contain significantly elevated antibody titers against corona viruses, unselected sera from patients without NPC showed a low antibody titer (n = 83). Only patients suffering from infectious mononucleosis (n = 40) showed a titer pattern similar to that of NPC patients. For demonstration of antigen-antibody reaction within the NPC tumor cell cytoplasm, sera with a high antibody content against coronaviruses deriving from other than NPC patients or anticoronavirus sera from rabbits were used. By indirect immunofluorescence, the NPC tumor cells showed a bright cytoplasmic fluorescence. No fluorescence was seen when tumor cells were exposed to human sera with known low or absent corona antibody titer or to normal rabbit sera. The results indicate that next to a DNA virus infection (EBV), an RNA virus infection (coronavirus) may play a role in NPC as well as in infectious mononucleosis.

Antibodies, Viral↗

Extremely underwound chromosomal DNA in nucleoids of mouse sarcoma cells.

The superhelical properties of chromosomal DNA from cells of a mouse sarcoma were investigated in neutral sucrose gradients containing ethidium bromide. Removal of negative supercoiling from the DNA of the sarcoma cells required a substantially higher dye concentration than was necessary in the case of DNA from cultured mouse fibroblasts. The calculated value of the mean superhelical density in malignant cells (sigma = -0.14) appears abnormally high compared with the value (sigma = -0.09) obtained for DNA of mouse fibroblasts. Chromosomal DNA from mouse sarcoma cells is therefore concluded to be highly deficient in helical turns.

Animals↗

The significance of serologic, histologic, and immunohistologic findings in the prognosis of 88 asymptomatic carriers of hepatitis B surface antigen.

Eighty-eight asymptomatic carriers of hepatitis B surface antigen (HBsAg) were followed with biochemical, serologic, histologic, and immunohistologic studies over a period of four years. None of the 78 HBsAg carriers with normal or minimally changed liver tissue, antibody to hepatitis B e antigen (HBeAg) in serum, and no intranuclear hepatitis B core antigen (HBcAg) developed a chronic inflammatory liver disease. Four individuals lost circulatory HBsAg, and at least two individuals terminated their HBsAg carrier state. Seven asymptomatic HBsAg carriers with chronic hepatitis were characterized by HBeAg in serum and intranuclear HBcAg. However, three HBsAg carriers with chronic hepatitis and an absence of intrahepatocellular HBcAg were positive for antibody to HBeAg over the observation period. The mechanism that leads to chronic hepatitis in these patients remains to be determined.

Adult↗

Knowles pinning of experimental femoral neck fractures: biomechanical study.

This experimental study demonstrates the rigidity and durability of Knowles pin fixation of femoral neck fractures. Embalmed proximal femora were utilized. A "fracture' was created by osteotomy, then reduced and fixed with Knowles pins. Four groups of reduction and pin configurations were created ("optimal reduction and pinning,' "poor reduction,' "inadequate pinning,' and "comminution') to simulate the clinical situation. With the Materials Testing Systems(MTS) machine, 3 months of walking by a patient with a femoral neck fracture were simulated. Results suggest that Knowles pinning of a femoral neck fracture can provide adequate support for immediate full weight-bearing ambulation until fracture healing. Stability and durability of fixation are compromised by loss of cortical bone support by "comminution,' short nonparallel pins not engaging the subchondral bone, and osteoporosis evidenced by a low Singh index.

Biomechanical Phenomena↗

Significance of antibody to hepatitis Be antigen (anti-HBe) in HBsAg-negative individuals.

A study was initiated to assess the significance of antibody to hepatitis Be antigen (anti-HBe) in HBsAg-negative individuals. Anti-HBe was demonstrated in the majority of sera positive for anti-HBs and anti-HBc. All sera positive for anti-HBs and negative for anti-HBc and most sera positive for anti-HBc but negative for anti-HBs were anti-HBe-negative. This implies that the antibody response to HBeAg is of shorter duration than that to HBsAg and HBcAg. Anti-HBe may help to discriminate between various states of hepatitis B virus infection found to be associated with anti-HBc-positive but HBsAg- and anti-HBs-negative sera. 2 individuals were anti-HBe-positive but HBsAg-, anti-HBs- and anti-HBc-negative, this finding is not understood.

Antibodies, Viral↗

Inhibition of hepatitis B virus deoxyribonucleic acid polymerase by the 5'-triphosphates of 9-beta-D-arabinofuranosyladenine and 1-beta-D-arabinofuranosylcytosine.

9-beta-D-Arabinofuranosyladenine (ara-A), 1-beta-D-arabinofuranosylcytosine (ara-C), and their 5'-triphosphates (ara-ATP and ara-CTP) were tested for ability to inhibit the hepatitis B virus (HBV)-associated deoxyribonucleic acid (DNA) polymerase. Ara-C did not inhibit the HBV DNA polymerase at the concentrations tested, ara-A did so by 50% at a concentration of 30 mM, with the inhibition noncompetitive with respect to deoxyadenosine 5-triphosphate (dATP). Ara-ATP and ara-CTP inhibited the DNA polymerase test competitively with respect to dATP and dCTP, respectively. Both compounds were also active after initiation of the DNA polymerase reaction. The inhibition caused by ara-ATP and ara-CTP was shown to be reversible, with no evidence that ara-ATP or ara-CTP was incorporated into the HBV DNA.

Arabinofuranosylcytosine Triphosphate↗

Follow-up of anti-HBc titers in healthy HBsAg carriers and patients with chronic inflammatory liver diseases.

Sera of 85 asymptomatic HBsAg carriers found among blood donors were tested for anti-HBc titers and were retested 4 years later. The results were correlated with the histological findings of first and final biopsy. None of 75 HBsAg carriers with normal or minimally changed liver tissue, 71 of them anti-HBe positive, developed chronic inflammatory liver disease. 4 HBsAg carriers eliminated HBsAg from the serum after a 1-to 3-year HBsAg-carrier state and 2 developed antibody against HBsAg in the sequel. In 65 of 75 cases we found unchanged anti-HBc titers. The geometrical mean titer (GMT) was 1:7,800 in the first and 1:7,000 in the final examination with a range of 1:400 and 1:25,600 in the group of HBsAg carriers with normal liver, and was 1:14,200 and 1:10,300, respectively, with a range of 1:800 and 1:51,200 in HBsAg carriers with minimal changes. In both groups the decrease of anti-HBc concentration within 4 years was not significant. The group of 10 HBsAg carriers with chronic hepatitis did not differ from healthy HBsAg carriers in respect to anti-HBc titers. Anti-HBc titers varied between 1:6,400 and 1:25,600, the GMT was 1:13,700 and 1:12,800, respectively. It is speculated that in healthy HBsAg carriers shedding of serologically undetectable quantities of complete and/or defective HBcAg from liver cell nuclei which contain HBcAg not detectable by immunofluorescence maintain the production of anti-HBc.

Antibodies, Viral↗

[Therapy of chronic hepatitis (author's transl)].

Chronic hepatitis can be subdivided in to two subgroups by new serological methods. Controlled prospective studies have shown that HBsAg-negative, autoimmune chronic active hepatitis (CAH), which is characterized by autoantibodies in the blood, responds favourably to prednisone therapy alone or in combination with azathioprine. Preliminary results seem to indicate, that the dosage used may be reduced slowly and therapy finally stopped after 3-4 years of treatment in most patients. If relapses occur, a lifelong therapy seems to be necessary. Prednisone alone or in combination with azathioprine does not influence the course of HBsAg-positive CAH and the development of cirrhosis. For that reason corticoids cannot generally be recommended in these patients. If there is however a severe course of the disease with frequent periods of necrotising inflammatory involvement prednisone therapy for a period of about 12 months may be helpful. Treatment with different compounds supposed to stimulate immunological processes like laevamisol and transfer factor has not yet produced any decisive improvement. Treatment with antiviral substances as interferon, abarinoside A-or chloroquine still needs to be investigated further.

Autoimmune Diseases↗

[Inhibition of hepatitis B virus associated DNA polymerase by antiviral agents: in vitro studies with clinical implications (author's transl)].

The complete hepatitis B virus (Dane particle) contains a circular doublestranded DNA with single stranded regions and an endogenous DNA polymerase. The HBV associated DNA polymerase closes the single stranded regions of the HBV-DNA in the presence of triphosphatase and a detergent. The DNA polymerase reaction can be inhibition by antiviral substances that exhibit different mode of actions: intercalating agents, phosphonoformiate and the triphosphates of arabinofuranosyladenine and arabinofuranosylcytosine. The value of these in vitro test for the therapy of HBsAg positive chronic liver disease is limited by the fact that is remains so far unclear whether the HBV associated DNA polymerase is a virus- or a host-coded enzyme, and whether virus- or host-coded enzymes are involved in HBV-DNA synthesis in vivo.

Antiviral Agents↗

[Immunopathogenesis and immunopathology of acute viral hepatitis (author's transl)].

The serological and immunohistological findings enable us to separate the different groups of hepatitis A, hepatitis B, and hepatitis non-A, non-B. Investigations on isolated hepatocytes and the findings concerning the immunopathogenesis of acute hepatitis. Further investigation will show whether the group of non-A, non-B hepatitis, is again heterogenous.

Acute Disease↗

Toxicologic and therapeutic examinations with ftorafur in different mouse strains.

Ftorafur, a derivative of the antimetabolite 5-Fluorouracil, was tested for its toxicologic and therapeutic effectivity in the mouse strains XVII/Berlin, F1 (NMRI X DBA/2), Balb/c -- +/+, Balb/c -- nu/+, Balb/c -- nu/nu. The LD values were similar in all strains tested, with a somewhat higher sensibility of the homozygous nude mice. In each case lethality was higher in male than in female animals. This tendency was confirmed by the always more pronounced leukopenia in male versus female mice after high doses of Ftorafur. Thrombocytes, hemoglobin and hematocrit were not influenced by Ftorafur treatment, whereas marked reticulopenias were observed. While in the L1210 model significant ILS values without distinct leukopenias were obtained, no convincing effectivity could be demonstrated in any of the other tumor models. The results confirm that it is possible to compare phenotypical normal with nude mice both with regard to dosage levels and therapeutic activity.

Animals↗