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F Wiener

Publications and source records attributed to F Wiener.

At least 55 records · Page 3Linked to original sources
PubMed1988

Further studies on chromosome 15 trisomy in murine T-cell lymphomas: mapping of the relevant chromosome segment.

Trisomy 15 is the most common chromosomal aberration in murine T-cell lymphomas. The relevant chromosomal region responsible for the growth advantage of the 15-trisomic cell has not been defined. In order to map this region, we have induced thymic lymphomas by chemical carcinogens (DMBA or MNU) in mice with 2 different constitutional translocations, T(7;15)9H homozygotes and [T(7;15)9H X T(5;15)4Ad] FI hybrids. Twenty-two tumors developed in 90 carcinogen-treated mice. Among the 14 cytogenetically analyzed thymic lymphomas, 4 were diploid and 5 were aneuploid, with no chromosome-15-associated changes. Five lymphomas showed partial duplication of chromosome 15. Four of them have duplicated the segment distal to the C/DI breakpoint of T9H, while the 5th carried an interstitial duplication of the D2 sub-band of the T(7;15) translocation chromosome. These findings suggest that the duplication of the D 2/3 region, known to contain the c-myc and the pvt-I genes (Banerjee et al., 1985), rather than other regions of chromosome 15, contributes to the development and/or progression of murine T-cell leukemias.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Intravenous glucose tolerance test in gestational diabetes and pregnancy: 'manual' versus computerized assessment.

In order to assess the reliability of 'manual' versus computerized interpretation of the intravenous glucose tolerance test (IVGTT), fifty-five women, aged 19 to 41, underwent an IVGTT. Fifteen subjects had overt diabetes mellitus, sixteen were evaluated for gestational diabetes and twenty-four were healthy controls, fourteen of whom were pregnant. Each IVGTT was analysed by two trained physicians independently and by a simple computerized program, and the k' values obtained were compared, using the Student t-test for paired data. Significant difference (p less than 0.005) was found comparing either the 'manual' assessments or the 'manual' versus computer calculations. It is concluded that the IVGTT test must be interpreted using a simple computerized program, especially in borderline cases of pregnancy where the traditional 'manual' analysis might result in misclassification or misdiagnosis of the patient.

Adult↗
PubMed1988

6;7 chromosomal translocation in spontaneously arising rat immunocytomas: evidence for c-myc breakpoint clustering and correlation between isotypic expression and the c-myc target.

Our previous studies have shown that spontaneously arising immunocytomas in the LOU/Ws1 strain of rats contain a t(6;7) chromosomal translocation in all seven tumors studied (F. M. Babonits, J. Spira, G. Klein, and H. Bazin, Int. J. Cancer 29:431-437, 1982). We have also shown that the c-myc is located on chromosome 7 (J. Sümegi, J. Spira, H. Bazin, J. Szpirer, G. Levan, and G. Klein, Nature (London) 306:497-499, 1983) and the immunoglobulin H cluster on chromosome 6 (W.S. Pear, G. Wahlström, J. Szpirer, G. Levan, G. Klein, and J. Sümegi, Immunogenetics 23:393-395, 1986). We now report a detailed cytogenetic and molecular analysis of nine additional rat immunocytomas. The t(6;7) chromosomal translocation is found in all tumors. Mapping of the c-myc breakpoints showed that in 10 of 14 tumors, the c-myc breakpoints are clustered in a 1.5-kilobase region upstream of exon 1. In contrast with sporadic Burkitt's lymphoma and mouse plasmacytoma, only 1 of 14 tumors contains the c-myc breakpoints in either exon 1 or intron 1. Analysis of the sequences juxtaposed to the c-myc show that immunoglobulin H switch regions are the targets in at least five tumors and that there is a strong correlation between the secreted immunoglobulin and the c-myc target. Unlike sporadic Burkitt's lymphoma and mouse plasmacytoma, at least two rat immunocytomas show recombination of the c-myc with sequences distinct from immunoglobulin switch regions.

Animals↗
PubMed1987

The role of chromosome 15 in murine leukemogenesis. II. Relationship between tumorigenicity and the dosage of lymphoma vs. normal-parent-derived chromosomes 15 in somatic cell hybrids.

Somatic cell hybrids were generated between an MCF-virus-induced 15-trisomic T-cell lymphoma of AKR origin with a proviral insertion near the c-myc locus, and normal diploid fibroblasts or lymphocytes of CBAT6T6 origin. Three lymphoma/fibroblast fusions were performed. Six independently-derived clones from 2 fusions were tested for tumorigenicity. Three of the 6 clones were weakly malignant (take incidence 20% below), and 3 were strongly malignant (take incidence over 80%). All 3 lymphoma/lymphocyte hybrids and 6 derived clones were strongly malignant. All hybrids contained a nearly complete chromosomal complement of both parental cells. This was confirmed at the molecular level by determining the ratio of germ-line (G) vs. rearranged (R) myc-carrying Eco RI fragments that showed the expected 1.9-2.7:1 proportion. Malignant segregants selected from the weakly malignant lymphoma/fibroblast hybrids by in vivo inoculation showed changed 15-chromosome ratios. Four out of the 6 clones showed amplification of the lymphoma-derived 15-chromosome that carries the R-myc fragment and a concomitant decrease in the average number of the G-myc-carrying chromosomes. This was deduced from the fact that the G:R ratio was between 2 and 3:1 in the in vitro hybrids but became inverted (1:2-3) in the tumors. Two tumors showed no amplification of R-myc. G-myc was decreased. One of these tumors showed a change in the G:R ratio from 2.5:1.0 to 1.2:1.0, while the other was essentially unchanged (1.9:1.0 in the in vitro clone and 2.2:1.0 in the derived tumor). These findings support the notion that both the amplification of the lymphoma-derived 15-chromosome with the retrovirally rearranged c-myc carrying fragment and/or the loss of the G-myc-carrying 15-chr can contribute to the tumorigenic potential of the hybrids.

Animals↗
PubMed1987

Avian v-myc replaces chromosomal translocation in murine plasmacytomagenesis.

Deregulation of c-myc expression in association with chromosomal translocations occurs in over 95% of murine plasmacytomas, rat immunocytomas, and human Burkitt lymphomas. Infection with a murine retrovirus (J-3) containing an avian v-myc rapidly induced plasmacytomas in pristane-primed BALB/cAn mice. Only 17% of the induced plasmacytomas that were karyotyped showed the characteristic chromosomal translocations involving the c-myc locus. Instead, all of the translocation-negative tumors demonstrated characteristic J-3 virus integration sites that were actively transcribed. Thus, the high levels of v-myc expression have replaced the requirement for chromosomal translocation in plasmacytomagenesis and accelerated the process of transformation.

Animals↗
PubMed1987

Computerized classification of congenital malformations using a modified Bayesian approach.

The diagnostic classification of children with dysmorphic features involves over 200 syndromes and 232 findings, with an average of about 15 findings per syndrome. A knowledge base expressed in terms of Boolean combinations of findings is impractical. The normal Bayesian method requires a very large incidence matrix with the vast majority of cells being zero. A modified Bayesian method is proposed in which each syndrome is described in terms of its associated findings, whose incidence P (S/D) are designated as essential (0.90), prevalent (0.90), occasional (0.70) or rare (0.15), whilst P(S/-D) ranged from (0.08) to (0.10). The Bayesian calculation determines the probability of the presence P(D/S) or the absence P(-D/S) of each syndrome. The differential diagnosis consisted of all syndromes whose presence has a probability greater than 0.85. One hundred and thirty-one cases from the Hanna Khoushi Developmental Pediatrics Center at Haifa's Rothschild Hospital were considered. Of the 42 cases for which the center's specialists reached a diagnosis, the system listed the correct diagnosis for 91%. The system reached a diagnosis in about half of the remaining 89 cases. The medical literature is arranged by syndrome whilst the computer allows a case by case approach, thereby avoiding the need for the physician to consider each syndrome to see if it fits his case. This study shows that our modified Bayesian analysis is a valid method for shortening the physician's search in an area of great diagnostic complexity.

Bayes Theorem↗
PubMed1986

Computer-aided diagnosis of odontogenic lesions.

4 cysts and 8 tumors of odontogenic origin have been described for the computer in terms of the prevalence of the associated clinical and radiological findings. Symptom prevalence as given in the literature and modified by our own experience was stated quantitatively as incidence ratios so that Bayes' formula could be used to calculate the probability of each disorder for each set of patient data. The model was applied to 48 cases whose lesions were identified by histopathology following surgery. In all cases, the actual lesion was listed in the computer-produced differential diagnosis, in 94% of the cases the lesion headed the list, and in 75% a probability of 0.85 or greater was achieved. The model can thus be applied to patients awaiting surgery to obtain a reliable differential diagnosis for guiding the medical staff in the proper management of the patient.

Adolescent↗
PubMed1986

Cardiogenic oscillation and phase III caused by pressure-volume heterogeneity: a model.

The effect of heterogeneity of pressure-volume (PV) behavior of lung units and the effect of the pulsations of the heart on expired N2 following a single breath of O2 were studied mathematically in a model of the lung. The lung was pictured as consisting of three compartments, one of high compliance (HC) and another of low compliance (LC), both affected by cardiac pulsations, and a third, nonoscillatory compartment (NC). Three sigmoid PV curves were assigned to the three compartments, for both acini and airway (generation 10-23), so that total compliance summed up to 200 ml/cmH2O. Bifurcation of NC was at generation 5/6 and that of HC and LC at any chosen generation. A steepness constant, K, was defined to characterize the sharply descending portion of the sigmoid PV curve. For a ratio of the steepness constant for the oscillatory compartments, KHC/KLC = 1, a sloping alveolar plateau was produced. The plateau was concave for KHC/KLC greater than 1 and slightly convex for KHC/KLC less than 1. Cardiogenic oscillations (CO) of the expired N2 were produced by alternate flows from either NC or HC and LC. CO diminished in fast expiration, and a phase shift between the heart pulsation and the CO was seen; both agree with experimental findings.

Heart↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

Activation of the c-myc oncogene by the immunoglobulin heavy-chain gene enhancer after multiple switch region-mediated chromosome rearrangements in a murine plasmacytoma.

Presented is a detailed molecular analysis of the rearranged c-myc oncogene from ABPC45, an unusual plasmacytoma that was originally classified as translocation-negative. Previous data obtained by high-resolution chromosome banding suggested that this tumor was a member of a small group distinguished by the absence of rcpt (12;15) or (6;15) and further characterized by a band deletion near the c-myc locus on chromosome 15. However, genomic Southern blotting and analysis of the cloned oncogene in the present study reveal that (i) chromosome 12 sequences lie 365 base pairs 5' of the rearranged c-myc; (ii) this DNA consists of immunoglobulin alpha switch region and 5' immunoglobulin mu switch region sequences that are rearranged in an aberrant fashion; and (iii) the immunoglobulin heavy-chain gene enhancer element now resides approximately 2.5 kilobase pairs 5' of c-myc. We infer from these and other data that the rearrangement of c-myc in ABPC45 occurred via a multistep switch region-mediated process and that a reciprocal translocation has indeed taken place. Unlike many other plasmacytomas, this event did not interrupt the normal c-myc transcription unit. Rather, disruption of gene regulation is manifested in part by a change in relative usage of the two promoters normally used by the unrearranged gene. In contrast to several of its counterparts in Burkitt lymphomas, DNA sequence analysis of the translocated c-myc gene of ABPC45 reveals that it has not acquired point mutations in the noncoding first exon. These results strongly imply that a cis-acting regulatory element normally located 5' of exon 1 is lost and that heavy-chain constant region or enhancer sequences exert similar cis effects on translocated c-myc loci.

Animals↗
PubMed1985

Gene localization on sorted chromosomes: definitive evidence on the relative positioning of genes participating in the mouse plasmacytoma-associated typical translocation.

Experiments have been carried out to establish the relative position of the mouse Ig heavy chain locus and the c-myc oncogene. In mouse plasmacytoma with the typical rcpt(12;15) chromosome translocation the c-myc oncogene is juxtaposed to one of the heavy chain genes in a head-to-head orientation. Since the relative orientations of the c-myc locus and the Ig heavy chain gene cluster on the corresponding mouse chromosomes had not been settled, it was not known whether the rearranged c-myc gene is transposed to chromosome 12 or remains on chromosome 15. To decide which of the two alternatives is correct, we separated the translocation chromosomes by fluorescence-activated chromosome sorting. The separated chromosomal fractions were hybridized with myc-specific DNA probes corresponding to the first or second/third exons in a chromosome spot assay. The results presented here indicate that the c-myc gene in mouse plasmacytoma carrying the typical translocation, as in the human Burkitt lymphoma analogous translocation, transposes to the chromosome carrying the Ig heavy chain locus. These results also establish the orientations of the Ig heavy chain locus and the c-myc locus on their normal chromosomes.

Animals↗
PubMed1985

Influence of genotype and the organ of origin on the subtype of T-cell in Moloney lymphomas induced by transfer of preleukemic cells from athymic and thymus-bearing mice.

Thymus, spleen, and bone marrow of 1-month-old neonatally Moloney murine leukemia virus-inoculated mice have been transferred to 400-R-irradiated syngeneic recipients of the opposite sex. The donor or recipient origin of T-cell lymphomas arising in the host animal was identified by the sex chromosome marker. Spleen and bone marrow of athymic BALB-nu/nu mice contain cells with the potential to develop into T-cell lymphomas upon transfer to thymus-bearing BALB/c recipients. Such lymphomas arise from at least two subsets of T-cells, one terminal deoxynucleotidyl transferase (TdT) positive and the other 20 alpha-hydroxysteroid dehydrogenase positive. The enzyme-negative precursor T-cells from the BALB-nu/nu spleen and bone marrow can thus mature to enzyme-positive cells and give rise to lymphoma in the thymus-bearing recipient. Preleukemic spleen and bone marrow, but not thymus, from CBA and BALB/c mice regularly contained cells with the potential to develop lymphoma. The subset of T-cell involved was influenced by the genotype since lymphomas arising after the transfer of CBA and BALB/c spleens were TdT positive and 20 alpha-hydroxysteroid dehydrogenase positive, respectively. In thymus-bearing mice, but not in nude mice, the transfer of preleukemic spleen cells gave lymphomas earlier than did transfer of bone marrow cells. This suggests that the more mature lymphoid cell population in the spleen of thymus-bearing mice may allow leukemic transformation to occur more rapidly than do the less mature cells in the bone marrow. In one-third of the cases, the virus produced by the preleukemic cells transferred induced new lymphomas involving recipient host cells. These de novo-induced lymphomas were all TdT positive. We suggest that leukemic transformation of TdT-positive cells may occur through a different mechanism than does transformation of cells bearing the 20 alpha-hydroxysteroid dehydrogenase marker.

20-Hydroxysteroid Dehydrogenases↗
PubMed1984

Further studies on the asymmetry of chromosome 15 duplication in trisomic leukemias of heterozygous origin: preferential status of the AKR chromosome.

Four combinations of translocation heterozygotes with cytogenetically distinct chromosomes 15 were used to investigate whether the T-cell leukemia-associated preferential duplication of the AKR-derived chromosome 15 (AKR-15) is determined by factors within this chromosome, or is due to genes within the AKR genotype, but outside chromosome 15. Two of the four combinations were also used to determine whether the AKR-15 duplication preference could be cancelled by MCF-viremia in permissive F1 hybrids. Chemically and virally induced 15-trisomic leukemias showed the same AKR-15 duplication preference, which was due to some autonomous property of AKR-15 itself. It was maintained in (C57BL 6;15 X C57BL) F1 leukemias, where 6;15 is the only AKR-derived chromosome propagated on the C57BL/background. In the (C57BL 6;15 X AKR) F1 hybrid cross where both chromosomes 15 are of AKR origin, duplication occurred at random. To approach the second question, MCF viremia was induced by neonatal virus inoculation into permissive (AKR 6;15 X B6Fv-In) F1 hosts. The preferential duplication status of the AKR-derived 6;15 remained unchanged.

Animals↗
PubMed1984

Chromosomal translocations activating myc sequences and transduction of v-abl are critical events in the rapid induction of plasmacytomas by pristane and abelson virus.

Plasmacytomas with short latent periods can be induced in BALB/c mice by a single intraperitoneal (i.p.) injection of 0.5 ml pristane followed 20-40 d later by an injection of Abelson virus. The karyotypes of 18 such tumors were determined; 10 of these had rcpt 12;15, 5 had rcpt 6;15 and 3 had no translocations, but two of these have been shown to have interstitial deletions of chromosome 15. The specific breakpoints were the same as described in pristane-induced plasmacytomas, i.e., at 15D2 /3, 6C2 , and 12F2 . Near diploid karyotypes and trisomy of chromosome 11 were frequently seen. All of the Abelson-plus-pristane-induced plasmacytomas (ABPC) were studied as transplanted tumors, contained integrated v- abl sequences, and actively transcribed v- abl mRNA. All but one of these tumors contained abundant myc RNA transcripts. The shortness of the latent periods of the ABPC suggests that the rcpt 12;15 and rcpt 6;15 occur soon after pristane administration and are present at the time Abelson virus is introduced. In this form of plasmacytomagenesis , activated v- abl genes appear to bypass other genetic changes that require a much longer period of time in pristane plasmacytomagenesis . Nonetheless, the consistent finding of chromosome-15 alterations and abundant myc expression in these plasmacytomas emphasize the apparent need for multiple events even in the genesis of some tumors induced by rapid transforming viruses.

Abelson murine leukemia virus↗
PubMed1984

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↗