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Biomedical subjects

J Lenz

Publications and source records attributed to J Lenz.

At least 91 records · Page 5Linked to original sources

Localization of the leukemogenic determinants of SL3-3, an ecotropic, XC-positive murine leukemia virus of AKR mouse origin.

SL3-3 is a potent leukemogenic retrovirus that closely resembles the non-leukemogenic virus Akv. Both viruses were isolated from AKR mice, have ecotropic host ranges, and form plaques in the XC assay. They differ at only 1 to 2% of the nucleotides in the viral genomes but differ markedly in virulence properties. SL3-3 induces leukemia in a high percentage of inoculated AKR, C3H, CBA, and NFS mice, whereas Akv does not induce disease in any of these strains. To determine which region of the genome accounts for the leukemogenic potential of SL3-3, we constructed recombinant genomes between molecular clones of SL3-3 and Akv. Recombinant, viral DNA genomes were cloned and then were transfected onto NIH 3T3 fibroblasts to generate infectious virus. The recombinant viruses were tested for leukemogenicity in AKR/J, CBA/J, and C3Hf/Bi mice. We localized the primary leukemogenic determinant to a 3.8-kilobase fragment of the SL3-3 genome containing the viral long terminal repeat, 5' untranslated sequences, gag gene, and 5', 30% of the pol gene. Reciprocal recombinants containing the equivalent region from Akv, linked to the env gene and the remainder of the pol gene from SL3-3, did not induce leukemia. We conclude that the primary virulence determinant of SL3-3 lies outside the region of the genome that encodes the envelope proteins gp70 and p15E.

AKR murine leukemia virus↗

[Effect of various vagal functional conditions on the blood flow of abdominal organs].

In 21 mongrel dogs blood flow was measured in different gastrointestinal organs under fasting conditions, vagal stimulation with 2-desoxy-D-glucose and vagotomy. The examinations were performed in anaesthesia with the microsphere method. Basal blood flow was found in corpus, fundus and antrum below 0,5 ml/g X min, whereas in the region of the small curvature values of 0,7 ml/g X min were observed. Vagotomy decreases flowrates especially in the mucosa of the stomach except in the region of the antrum. There a significant increase was measured. The stimulated bloodflow shows a similar effect by a vagotomy, but on an elevated lovel. Observations over the time of 3 weeks revealed that bloodflow changes due to vagotomy are not long lasting over that time. Only a decrease can be observed in the region of the antrum. Also in the other abdominal organs bloodflow changes due to vagotomy are terminated to a short time interval. Except the bloodflow changes in the gallbladder lasts longer than 4 weeks. From this investigation the conclusion can be drawn that vagotomy does not cause long lasting and radical bloodflow changes in the abdomen.

Animals↗

[Changes in microcirculation of various layers and regions of the stomach wall following selective proximal vagotomy. Animal experiments using radioactive-labeled plastic particles].

Changes of the blood flow in the different layers and regions were determined with radioactively labelled microspheres after proximal vagotomy. Under normal conditions and vagal stimulation a significant reduction of the flow in corpus and antrum up to 74% can be observed at least over the time of 3 weeks. This decrease of bloodflow in the stomach together with a reduction in secretion can possibly be responsible for the successful treatment of diffuse bleeding in erosive gastritis by selective vagotomy.

Animals↗

Nucleotide sequence of the Akv env gene.

The sequence of 2,191 nucleotides encoding the env gene of murine retrovirus Akv was determined by using a molecular clone of the Akv provirus. Deduction of the encoded amino acid sequence showed that a single open reading frame encodes a 638-amino acid precursor to gp70 and p15E. In addition, there is a typical leader sequence preceding the amino terminus of gp70. The locations of potential glycosylation sites and other structural features indicate that the entire gp70 molecule and most of p15E are located on the outer side of the membrane. Internal cleavage of the env precursor to generate gp70 and p15E occurs immediately adjacent to several basic amino acids at the carboxyl terminus of gp70. This cleavage generates a region of 42 uncharged, relatively hydrophobic amino acids at the amino terminus of p15E, which is located in a position analogous to the hydrophobic membrane fusion sequence of influenza virus hemagglutinin. The mature polypeptides are predicted to associate with the membrane via a region of 30 uncharged, mostly hydrophobic amino acids located near the carboxyl terminus of p15E. Distal to this membrane association region is a sequence of 35 amino acids at the carboxyl terminus of the env precursor, which is predicted to be located on the inner side of the membrane. By analogy to Moloney murine leukemia virus, a proteolytic cleavage in this region removes the terminal 19 amino acids, thus generating the carboxyl terminus of p15E. This leaves 15 amino acids at the carboxyl terminus of p15E on the inner side of the membrane in a position to interact with virion cores during budding. The precise location and order of the large RNase T(1)-resistant oligonucleotides in the env region were determined and compared with those from several leukemogenic viruses of AKR origin. This permitted a determination of how the differences in the leukemogenic viruses affect the primary structure of the env gene products.

AKR murine leukemia virus↗

Molecular cloning of a highly leukemogenic, ecotropic retrovirus from an AKR mouse.

SL3-3 is a leukemogenic, ecotropic retrovirus produced by a T-cell line derived from a spontaneous lymphoma of an AKR mouse. We have isolated a molecular clone of its DNA provirus from infected NIH 3T3 fibroblasts. Cloned proviral DNA produced infectious virus upon transfection onto NIH 3T3 cells. Virus derived by transfection induced lymphomas at high frequency in AKR/J, C3H(f)/Bi, CBA/J, and NFS/N mice. Heteroduplex and RNase T1 fingerprinting analyses showed that the genomes of SL3-3 and the non-leukemogenic virus, Akv, contain no major substitutions relative to one another and differ by only a few base changes. These results unambiguously show that SL3-3 is a highly leukemogenic virus and that major rearrangements of the genome relative to Akv are not required for virulence.

AKR murine leukemia virus↗