[A subcutaneously implantable catheter in hematologic malignancy--a comparison with a conventional central venous catheter].
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Adolescent↗
Biomedical subjects
J Spira
Publications and source records attributed to J Spira.
The evaluation of 4-hydroxy-3-methoxyphenylglycol sulfate as a possible marker of central norepinephrine turnover. Studies in healthy volunteers and depressed patients.
Much evidence indicates that urinary 4-hydroxy-3-methoxyphenylethyleneglycol (MHPG) is an insensitive measure of central norepinephrine metabolism. This conclusion, however, seems to apply mainly to total urinary MHPG, since previous findings point to the possibility that the major proportion of urinary MHPG sulfate originates in the CNS, while most urinary MHPG glucuronide originates in peripheral organs. To examine this hypothesis, experiments were performed by which we altered MHPG turnover in man at two different stages: firstly, strong physical exercise (ergometer) increased the urinary excretion rate of MHPG glucuronide and not that of MHPG-sulfate; secondly, ethanol (l g/kg), which is known to block the metabolism of MHPG to vanilmandelic acid in the liver, increases the urinary excretion rate of the glucuronide and not that of sulfate. Both experiments indicate that alteration of peripheral norepinephrine turnover changes the urinary excretion of MHPG glucuronide only and not that of sulfate, thus providing strong, albeit indirect, evidence for a primarily central origin of MHPG sulfate. Preliminary experiments in 32 depressed patients showed little difference in both MHPG fractions compared with healthy controls, apart from a slightly reduced excretion rate of glucuronide. These findings fail to provide any evidence of central, and only small changes in peripheral norepinephrine metabolism in depression.
Adult↗
Mapping of the c-myc, pvt-1 and immunoglobulin kappa genes in relation to the mouse plasmacytoma-associated variant (6;15) translocation breakpoint.
A variant mouse plasmacytoma (MPC)-associated translocation chromosome has arisen by pericentric inversion and exchange of the distal segments of a Robertsonian 6;15 fusion chromosome in the CAK TEPC 1198 mouse plasmacytoma, as described earlier. In situ hybridization was performed on the normal and the inverted Rb chromosomes, using myc and kappa probes. On the normal Rb chromosome, myc was in the 15 D2/3 region, whereas kappa hybridized in the 6 C2 area, as expected. On the inverted Rb chromosome, myc remains on the centrometric side of the translocation breakpoint on the chromosome 15-derived portion, whereas kappa has moved to the chromosome 6-derived segment that joined the same breakpoint on the telomeric side. Taken together with our recent demonstration that the murine c-myc locus is oriented 'head up' on chromosome 15, and with the results of Cory and co-workers concerning the relationship between the kappa gene and the associated pvt-1 region in the CAK TEPC 1198 tumor, the following conclusions can be drawn: (i) in the variant translocation of the CAK TEPC 1198 MPC, the breakage occurs 3' of the c-myc gene, as in the human Burkitt lymphoma-associated variant translocations; (ii) the pvt-1 gene on chromosome 15 is distal to the myc gene; (iii) the kappa light chain locus is oriented 'head up' on mouse chromosome 6 and faces pvt-1 and, beyond it, c-myc, in a head-to-tail configuration.
Animals↗
A new approach to gene mapping by in situ hybridization on isolated chromosomes.
A new technique was developed for in situ hybridization on isolated murine chromosomes. The safety and relative rapidity of the method is due to the ready availability of large numbers of isolated "target" chromosomes with well preserved morphology. Its applicability was demonstrated by mapping c-myc to band 15D of Robertsonian (6;15) fusion chromosomes. This localization coincides with the cytogenetic mapping of the translocation breakpoints in mouse plasmacytomas that carry the typical rcpt (12;15) translocation.
Animals↗
Triplication of one chromosome No. 15 with an altered c-myc containing EcoRI fragment and elimination of the normal homologue in a T-cell lymphoma line of AKR origin (TIKAUT).
An ouabain- and thioguanine-resistant subline (TIKAUT) of spontaneous AKR lymphoma, TKA, was trisomic for chromosome 15 and contained a single 33 kb EcoRI fragment, containing the oncogene c-myc. The original TKA lymphoma and derived in vitro line contained the same 33 kb fragment, as well as a normal 22 kb fragment. It has been concluded that the original 15-trisomic TKA tumor has duplicated a 15-chromosome that contained the changed fragment, while maintaining the normal fragment as well. Subsequently, in the derived TIKAUT line, the changed chromosome duplicated again, giving rise to three copies, and the normal homologue was eliminated altogether. This confirms our earlier somatic hybrid study showing that the duplicated 15-chromosome of a T-cell leukemia confers an advantage on the cell that favors tumorigenicity, whereas the normal homologue exerts a counteracting influence. Therefore, in the course of tumor progression, the changed chromosome tends to be amplified, whereas its normal homologue tends to be eliminated.
Animals↗
Correlation between tumorigenicity and banding pattern of chromosome 15 in murine T-cell leukemia cells and hybrids of normal and malignant cells.
The most common chromosomal aberration in murine T-cell lymphomas is trisomy of chromosome 15. It has now been shown that the chromosomal region 15E exhibits a variant early replication banding pattern after 5-bromo-deoxyuridine labeling during part of the preceding S-phase. This variation is restricted to T-cell tumors. Plasmacytomas bearing the specific translocation t(12;15) show a normal early replication banding pattern of chromosome 15. In T-cell tumors all three chromosomes 15 of one cell are of the same variant banding type. In hybrids between tumor and nontumor cells, the number of cells expressing the variant early replication banding pattern is related to the degree of malignancy. Chromosomes 15 in one cell never expressed the variant and the normal banding pattern simultaneously. All five to six chromosomes 15 from one hybrid cell are of the same banding type irrespective of their parental origin. With respect to the type of early replication banding pattern, there is complete reversibility; tumor-parent-derived chromosomes 15 change to normal, and normal-parent-derived chromosomes 15 change to tumor.
Animals↗
Robertsonian translocation studies on the significance of trisomy 15 in murine T-cell leukemia.
G-banding analysis was carried out on T-cell leukemias induced in various Robertsonian mice by 7,12 dimethylbenz(a)anthracene (DMBA), N-methyl-N-nitrosourea (MNU), or Moloney virus. Trisomy 15 was the only regularly seen chromosome aberration whether chromosome No. 15 was involved in a centric fusion or not. Translocated No. 15 chromosomes were not preferentially duplicated. These results show that it is not the translocated state of chromosome No. 15 but the genetic content that is of importance in leukemia development.
9,10-Dimethyl-1,2-benzanthracene↗
Non-random duplication of chromosome 15 in T-cell leukemias induced in mice heterozygous for reciprocal and Robertsonian translocations.
Two translocation--carrying stocks of mice, T(7;15)9H and Rb(4;15) were resistant to chemical leukemogenesis by 7,12-dimethylbenz(a)-anthracene (DMBA) or methylnitroso-N-urea (MNU). Lymphomas were induced in F1 hybrids derived from crossing these two stocks with various susceptible strains. In T-cell leukemias originating from F1 hybrids with Rb(4;15) as one parent and strain CBA or ASW as the other, the translocation chromosome was present in two copies. In trisomic tumors derived from Rb(4;15) X AKR F1 cross, the AKR-derived chromosome 15 was duplicated regularly. In contrast, all trisomic lymphomas of the T(7;15)9H F1 outcrosses showed duplication of the non-translocated chromosome 15 and not of the (7;15) translocation chromosome. It is suggested that the resistance of the T(7;15)9H stock to chemical induction of T-cell leukemia may be related to the position of the translocation on chromosome 15 (band D2). Our previous studies (reviewed by Klein, 1981) have indicated that this area may contain an oncogene that needs to be activated and subsequently undergo duplication in the course of leukemia development. In our previous studies on trisomic leukemias induced in heterozygotes (Wiener et al., 1979, 1980 b), we have found that duplication was non-random in all investigated crosses, unless the normal and the translocation marker carrying chromosomes were derived from the same inbred strain. A "duplication preference" scale could be established between chromosomes No. 15 derived from different strains. This suggested that the likelihood of leukemia development was different, depending on the genetic origin of chromosome 15. In the present study, we have found that the duplication of chromosome 15 occurred at random in the CBAT6T6 X C3H F1 cross. This is attributed to the close genetic relationship between the two strains, as indicated by their shared isoenzyme and other markers.
9,10-Dimethyl-1,2-benzanthracene↗
Cytogenetic replication studies on murine T-cell leukemias with special consideration to chromosome 15.
Chromosomal replication was studied by means of the BrdU-Höchst-Giemsa-technique in three minute T-cell leukemias with special regard to chromosome 15. In all the three leukemic cell lines the normally early replicating band 15 E was undetectable whereas late replication in this region is completely unaltered. Furthermore, R-banding, the structural homologue of early replication banding, remains unchanged. This observation is interpreted as a shift in the time point of replication during the S-phase of region 15 E, though the exact timing of replication of this region in tumor chromosomes remains unresolved.
Animals↗
Chromosome 15 trisomy in spontaneous and carcinogen-induced murine lymphomas of B-cell origin.
G-banding analyses of 14 independently derived B-cell lymphomas showed the frequent occurrence of chromosome 15 trisomy. It was present in seven of nine spontaneous B-cell lymphomas, but in company with other trisomies, monosomies and marker chromosomes. In five carcinogen-induced primary B-cell leukemias, trisomy 15 was the dominating change. Taken together with the previously demonstrated importance of chromosome 15 trisomy for T-cell leukemogenesis and of the 12;15 translocation in plasmacytogenesis in the mouse, it appears likely that the distal part of chromosome 15 carries a cluster of genes, perhaps a supergene region, that may play an important role in the differentiation and/or the normal responsiveness of various lymphoreticular cell types to growth control.
9,10-Dimethyl-1,2-benzanthracene↗
Suppression and reappearance of N-tropic L virus production in somatic cell hybrids after introduction and loss of chromosomes carrying Fv-1b.
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Animals↗
Nonrandom chromosomal changes in thy-1-positive and thy-1-negative lymphomas induced by 7,12-dimethylbenzanthracene in SJL mice.
Leukemias were induced by 7,12-dimethylbenzanthracene feeding of intact, thymectomized, or Freund's adjuvant-pretreated SJL mice. Four of six Thy-1-positive thymomas that arose in intact mice had a pseudodiploid stemline with one morphologically similar or identical marker. Banding analysis showed that the marker had arisen by the translocation of the distal part of one chromosome 15 to one X chromosome [t(X;ter 15)]. Two normal No. 15 chromosomes were also present in the same metaphase plates. These four Thy-1-positive lymphomas were thus trisomic for the distal part of chromosome 15. All 8 Thy-1-negative lymphomas, originating in the spleen or lymph nodes of thymectomized or adjuvant-pretreatment mice, had a trisomy of chromosome 12 and also a trisomy of either chromosome 3 or chromosome 18. These results further stress the importance of gene dosage effects, related to the distal part of chromosome 15, in Thy-1-positive T-cell leukemogenesis. The cytogenetic difference between the Thy-1-positive and -negative leukemias supports our hypothesis that nonrandom chromosomal changes in murine leukemias are dependent on the target cell type, rather than the inducing agent.
9,10-Dimethyl-1,2-benzanthracene↗
Non-random duplication of chromosome 15 in murine T-cell leukemias induced in mice heterozygous for translocation T(14:15)6.
Trisomy of chromosome 15 is a highly regular feature of murine T-cell leukemogenesis. We have studied the chromosomal constitution of 7,12-dimethylbenza(a)anthracene (DMBA)-induced T-cell leukemias in C57BL X CBAT6T6 F1 mice. The CBAT6T6-derived chromosome T(14:15)6 was regularly duplicated whereas the C57BL-derived normal chromosome 15 was only present in one copy. It was concluded that the gene(s) that tend to duplicate in parallel with the neoplastic transformation of the prothymocyte to an overt leukemic cell have a greater chance of duplicating and/or may have a stronger promoting effect on leukemogenesis if stronger promoting effect on leukemogenesis if located on the CBA-derived, structurally rearranged T(14:15)6 than the corresponding genes located on the C57BL-derived normal chromosome 15.
9,10-Dimethyl-1,2-benzanthracene↗
Nonrandom chromosome changes involving the Ig gene-carrying chromosomes 12 and 6 in pristane-induced mouse plasmacytomas.
The karyotypes of pristane-induced mouse plasmacytomas were studied by G banding. Only primary tumors or early passage generations were analyzed. In contrast to murine T cell leukemias that showed a regular trisomy of chromosome 15, all plasmacytomas showed a consistent translocation of the distal part of chromosome 15 to either chromosome 6 [rcpT(6;15)] or 12 [T(12;15)]. The specific breakpoints were at 6C, 15D3/E ro D2/3 and 12F2. Early passage generations often showed a mixed population with two different translocations, suggesting polyclonal origin. Considered together with the known karyotypic features of murine and human lymphomas, these findings support the theory that the nonrandom chromosomal changes in lymphoproliferative malignancies are associated with the type of the target cell, rather than with the etiological agent. Moreover, the involvement of the chromosomes known to carry the heavy chain (12) and the light chain (6) determinants, respectively, raises the question of whether the translocations may be related to the DNA level rearrangements known to occur during the differentiation of normal plasma cells.
Animals↗
Is trisomy cause or consequence of murine T cell leukemia development? Studies on Robertsonian translocation mice.
Trypsin-Giemsa banding studies on T cell leukemias induced in Robertsonian translocation mice by dimethylbenz[a]anthracene and Moloney leukemia virus show a trisomy of chromosome 15 even in cases in which chromosome 15 has undergone centromeric fusion with chromosomes 1, 5, or 6. These results suggest that the duplication of gene(s) located on chromosome 15 is of critical importance for murine T cell leukemia development.
Animals↗
Cytogenetic mapping of the trisomic segment of chromosome 15 in murine T-cell leukaemia.
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Aneuploidy↗
Chromosome changes (trisomy 15) in murine T-cell leukemia induced by 1,12-dimethylbenz(a)anthracene (DMBA).
The banding pattern of DMBA-induced leukemias in C57BL/6 mice revealed a very constant chromosome pattern: the presence of trisomy 15 in almost all leukemic cells. This finding strongly suggests that chromosome 15 trisomy is the first detectable specific chromosome change associated with the development of DMBA-induced T-cell lymphomas. A similar association was previously shown with regard to development of radiation-leukemia-virus-induced T-cell lymphoma. It is conceivable that in tumors of diverse etiologies common cytogenetic changes may appear in the same common target-cell precursor, by a process of the "convergent microevolution" type.
9,10-Dimethyl-1,2-benzanthracene↗
Chromosome changes (trisomies #15 and 17) associated with tumor progression in leukemias induced by radiation leukemia virus.
An experimental system was developed that permitted nonrandom chromosome changes that occur in radiation leukemia virus (RadLV)-induced lymphomas to be followed during tumor progression. RadLV variant-induced preleukemia and leukemia cells originating from female inbred C57BL/6 mice were injected into male animals of the same strain. Since all donors were females and all recipients were males, the sex chromosome complements (XX and XY) were used to distinguish the preleukemia and leukemia cells from those of host origin. The G-banding analysis revealed that more than 50% of animals that were inoculated with preleukemia cells and that developed leukemia possessed tumor stem-lines of 41 chromosomes with a tristomy of chromosome #15. In animals inoculated with overt leukemia cells and in which tumor progression occurred, the G-banding an additional trisomy of chromosome #17. The cytogenic data strongly suggested that the trisomy of chromosome #15 was the first specific tumor-associated chromosome change that occurred in the process of conversion of RadLV-induced preleukemia cells to fully autonomous tumor cells.
Animals↗