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F Wiener

Publications and source records attributed to F Wiener.

At least 37 records · Page 2Linked to original sources
PubMed1991

v-abl does not abolish IL-6 requirement by murine plasmacytoma cells.

Activation of c-myc by juxtaposition to an immunoglobulin locus and introduction of the v-abl oncogene act synergistically in generating a mouse plasmacytoma (PC). The question arose whether the effect of v-abl could be attributed to a deregulation of interleukin-6 (IL-6) production or responsiveness, in view of the fact that IL-6 exerts potent growth-stimulatory activity on PC cells. We studied the effect of IL-6 on the in vitro growth of primary PCs induced by pristane alone (TEPCs) or by pristane + A-MuLV (ABPCs). Five of 13 TEPCs and 3 of 7 ABPCs responded to IL-6. Macrophage supernatants prepared from both TEPCs and ABPCs had similar stimulatory effects on PC cells. From 30 primary PCs (including both TEPCs and ABPCs), we established 9 in vitro lines, 2 of which expressed v-abl. All were able to grow on macrophage feeder layers. Three types of behavior could be distinguished on the basis of growth in feeder-free cultures in the presence and absence of IL-6. Group I contained 4 IL-6-dependent lines. Group II contained 2 IL-6-independent lines (one v-abl expressor) that grew faster in the presence of IL-6. Group III consisted of 3 feeder-dependent lines (one v-abl expressor) that were not significantly stimulated by IL-6. These findings indicate that v-abl expression does not influence IL-6 dependence or responsiveness by itself. The supernatant of one line in group II was able to stimulate PC cells. All 6 lines of Groups I and II carried a typical (12;15) translocation, while all 3 lines in group III had a variant (6;15) or (15;16) translocation.

Abelson murine leukemia virus↗
PubMed1991

A new variant 15; 16 translocation in mouse plasmacytoma leads to the juxtaposition of c-myc and immunoglobulin lambda.

Mouse plasmacytomas (MPCs) induced by pristane oil, or by a combination of pristane oil and Abelson virus, carry one of two chromosomal translocations. The typical 12; 15 translocation leads to the juxtaposition of c-myc and immunoglobulin heavy-chain sequences, whereas the 6; 15 translocation links the kappa light-chain locus with the pvt-1 (plasmacytoma variant translocation) locus, located at least 75kb 3' of c-myc [Cory, S., Graham, M., Webb, E., Corcoran, L. & Adams, J. (1985). EMBO J., 4, 675-681]. Unlike the human Burkitt's lymphoma-associated translocation, the lambda/myc juxtaposed variant translocation has not been found previously in MPCs. Using unconventional MPC induction systems in which the tumor precursor cell was induced to proliferate in a secondary host, we have recently identified a 15; 16 translocation in six of the derived MPCs [Wiener, F., Silva, S., Sugiyama, H., Babonits, M. & Klein, G. (1990). Genes Chromosomes Cancer, 2, 36-43]. Chromosome 16 harbors the lambda light-chain gene. To explore whether the 15; 16 translocation represents the lambda/myc juxtaposition, we have mapped the breakpoints on chromosomes 15 and 16 by pulsed-field gel electrophoresis (PFGE). The pvt-1 region was mapped to approximately 220 kb 3' of c-myc. The breakpoint on chromosome 15 in ABPC-Ch-163-10, one of the six 15; 16 translocation-carrying MPCs, was situated approximately 80 kb 3' of c-myc and 140 kb 5' of pvt-1b, the major breakpoint cluster region of the previously analysed 6; 15 variant MPCs. The breakpoint on chromosome 16 was found to cut between the V1 and C3 regions of the lambda locus. Co-migration experiments showed that the C3 and the myc gene were juxtaposed head to tail on the 15; 16 translocation chromosome. On the reciprocal product V1 was juxtaposed to pvt-1.

Animals↗
PubMed1990

Abelson murine leukemia virus transforms preneoplastic Emu-myc transgene-carrying cells of the B-lymphocyte lineage into plasmablastic tumors.

E mu-myc transgenic mice were back-crossed to BALB/c mice up to back-cross generation 3. The offspring that included transgene-carrying and -negative mice in approximately equal proportions were randomly divided into 2 groups. Thirty-four mice (group I) were treated with pristane, followed by A-MuLV, and 40 (group II) were injected with A-MuLV alone. Altogether, 16 lymphoid tumors developed in group I and 17 in group II. Nine of the tumors in group I and 4 in group II appeared as ascitic tumors. The ascites contained lymphoblasts and 10 to 45% plasmacytoid cells. These tumors were designated as plasmablastic lymphomas (PLs). All tumors except one were transgene-positive and did not carry translocations. An exceptional tumor in group I carried a variant 6;15 translocation but not the transgene. It obviously corresponds to the regular Abelson + pristane-induced plasmacytoma. Among 11 tested PLs, 10 had a single retroviral insertion site, while one tumor showed 3. Among 18 untreated transgenic descendants (group III), chosen randomly during serial back-crosses, 15 (83%) developed lymphomas, with no sign of plasmacytoid differentiation. The incidence was comparable in all 3 groups, assuming 50% of the mice in groups I and II to be transgenic. The time distribution of tumor development was also similar. Spleen cells from transgene-carrying mice with no clinical sign of lymphoma were infected in vitro with A-MuLV and transplanted i.p. into BALB/c recipients. PLs developed in 26 of 31 pristane-treated recipients, but in only one of 18 untreated recipients. One of 6 PLs tested was monoclonal, whereas the remaining 5 were oligoclonal. They all expressed v-abl. These results show that some of the preneoplastic B-cells that expressed constitutively active myc transgene turned into plasmablasts after infection with A-MuLV. Full development of their neoplastic potential was facilitated by the presence of pristane-granuloma.

Animals↗
PubMed1990

The "missing" mouse plasmacytoma (MPC) associated translocation T(15;16) occurs repeatedly in new MPC induction systems.

A reciprocal translocation between chromosomes 15 and 16 has been detected in seven murine plasmacytomas induced by a combination of pristane and Abelson virus. Six of the tumors were induced in a new, unconventional experimental system based on transfer of uninfected or Abelson virus infected bone marrow and spleen cells, respectively, into pristane treated mice. All six tumors were of donor type. The seventh tumor appeared in a conventional pristane + Abelson virus treated mouse. This tumor was unusual in carrying both the 15;16 variant translocation and the typical 12;15 translocation, in the same tumor cells. In the new 15;16 variant, the breakpoint of chromosome 15 was at the interphase of the D2/3 sub-bands, as in mouse plasmacytomas with the previously well-known typical 12;15 and variant 6;15 translocations. The breakpoint on chromosome 16 was mapped to band 16B1, corresponding to the presumed cytogenetic site of the Ig-lambda gene. In three of the seven tumors with the 15;16 translocation, the derivative chromosome 15 had undergone a duplication, a feature that has not been previously encountered in the MPC-associated 12;15 and 6;15 translocation carriers. The reciprocal derivative chromosome 16 was lost from one of the seven tumors. We postulate that the 15;16 translocation results in juxtaposition of the myc gene to lambda sequences, probably in a similar orientation as previously described for the variant 6;15 translocation.

Abelson murine leukemia virus↗
PubMed1990

A murine plasmacytoma with a variant (15;16)(D2/3;B1) translocation that involves the c-myc and lambda light chain gene-carrying chromosomes.

A murine plasmacytoma (MPC) with a reciprocal translocation between chromosomes 15 and 16 with breakpoints in 15D2/3 and 16B1 is reported. The breakpoint on chromosome 15 is identical to the breakpoint in the MPC-associated typical (12;15) and kappa variant (6;15) translocation. Therefore it probably involves the c-myc gene as well. Unlike the Burkitt lymphoma (BL) system, a lambda/myc variant translocation has not been described in the MPC system. Chromosome 16 is known to carry the lambda gene. Therefore, the 15;16 translocation probably represents the "missing" lambda/myc variant in MPC, suggesting that the lambda gene is localized at 16B1.

Animals↗
PubMed1990

Alterations in the domain structure of tissue-type plasminogen activator change the nature of asparagine glycosylation.

The formation of N-linked oligosaccharides of eukaryotic glycoproteins starts with the attachment of a common precursor at the recognition site Asn-X-Ser/Thr. Subsequent processing, by yet unknown controlling factors, leads to the formation of three different glycans: the high mannose type, the complex type and the hybrid type. In order to gain insight into the processing mechanisms, we studied the glycan pattern of a panel of related molecules constructed by insertion, duplication or deletion of the domains encoded by the cDNA of a fibrinolytic glycoprotein, tissue-type plasminogen activator (t-PA). These variant molecules are identical in regard to the glycosylation sites originally situated in particular domains, but differ with respect to the sequential alignment of the domains. The variant and native t-PA genes were transfected into mouse C127 cells and their carbohydrate structures analyzed by the susceptibility to specific endoglycosidases and by reaction with sugar-specific lectins. We found that with one exception, all mutant activators lack the high mannose glycan found at asn 117 of native t-PA. The exception was a molecule that retains the original domain arrangement up to and through the glycosylation site at asn 117. These results demonstrate for the first time that structural alterations in the primary sequence distal to the actual glycosylation site can result in altered processing of N-linked oligosacharides.

Amino Acid Sequence↗
PubMed1990

The use of knowledge-based information systems for interpreting specialized clinical chemistry analyses--experience from erythrocyte enzymes and metabolites.

A knowledge-based information system has been constructed to facilitate and standardize the interpretation of data obtained from specialized analyses in clinical chemistry. For illustration the system was applied to metabolic studies of erythrocytes from patients in whom hereditary disorders are suspected to explain the presence of a haemolytic anaemia or a polycythaemia. The study includes assay of the catalytic activity of 10 different enzymes and the concentration of some key metabolites. The knowledge-based system is an excellent tool for documentation, updating and transfer of knowledge of the interpretative process. This will reduce the risk of changes in this process being made without sound motivation and documentation. Furthermore, the statistical and graphic features of the system provide data for long-term quality assessment and insights into reference sample groups which are used to update decision levels.

Anemia, Hemolytic↗
PubMed1990

A combined data- and knowledge base system for the interpretation of metabolic investigations of erythrocytes from hemolytic and polycythemic patients.

A knowledge based-information system has been constructed to facilitate and standardize the interpretation of data obtained from specialized analyses in laboratory medicine. For illustration the system was applied to metabolic studies of erythrocytes from patients in whom hereditary disorders are suspected to explain the presence of a hemolytic anemia or polycythemia. The study includes assay of the catalytic activity of ten different enzymes and the concentration of some key metabolites. The knowledge based system is an excellent tool for documentation, updating and transfer of knowledge about the interpretative process. This will reduce the risk that changes in this process are made without sound motivation and documentation. Furthermore, the statistical and graphic features of the system provide data for long-term quality assessment and insights into reference sample groups which are used to update decision limits. A few cases are used to illustrate the advantages of the system.

Anemia, Hemolytic↗
PubMed1989

Plasmacytoma induction in radiochimeras.

We have induced plasmacytomas (MPC) in BALB/c radiochimeras (RCh) repopulated with syngeneic hemopoietic cells carrying distinctive chromosomal markers. A group of 38 RCh that received 0.5 ml pristane, followed by Abelson virus infection 2-3 weeks later, developed 7 tumors (18.5%) of donor origin after a relatively short latency period (X = 83 +/- 8.3 days). In contrast, only 3 (2%) MPCs were observed in 149 RChs that received 0.5 ml pristane 3 times at monthly intervals. Two of them originated from host cells. Pristane-treated RChs developed a less extensive oil granuloma (OG), compared with pristane-treated intact mice. This may explain the low incidence of MPC in the former. Our findings also suggest that Abelson virus can overcome the postulated deficiency of OG. MPC induction in the pristane + Abelson-virus-treated RCh system will facilitate the further characterization of the MPC precursor cell and the localization of genetic resistance vs. susceptibility factors at the donor vs. host level.

Animals↗
PubMed1989

The accelerating role of Abelson murine leukemia virus in murine plasmacytoma development: in vitro infection of spleen cells generates donor-type tumors after transfer to pristane-treated BALB/c mice.

The role of Abelson murine leukemia virus (A-MuLV) in the accelerated development of murine plasmacytomas (PCs) (Potter et al., 1973: Science, 132, 592-594) was studied in a new experimental system. Spleen cells from pristane-treated or untreated BALB/c mice carrying Robertsonian 6;15 fusion chromosomes were infected in vitro with helper-free A-MuLV overnight and subsequently transplanted into the peritoneal cavity of pristane-treated or untreated BALB/c mice. Donor-derived PCs developed in 4 out of 76 pristane-treated recipients [latent periods: 38-82 (mean 51) days] that had received spleen cells from pristane-treated donors, and also in 2 out of 41 pristane-treated recipients that had received untreated donor-derived spleen cells (latent periods: 65 and 120 days). Three of the PCs in the former and both PCs in the latter group were tested for integration and expression of the v-abl gene, with positive results. This indicates that the spleen contains PC-precursor cells that can be activated by A-MuLV even before the impact of pristane. All 6 donor-origin PCs carried a translocation involving chromosome 15, band D2/3. Four of these corresponded to a typical 12;15 translocation, one was a variant 6;15 translocation and the 6th may represent a previously unidentified translocation between chromosome 15 and the lambda gene-carrying chromosome 16. No PCs developed among 29 pristane-untreated recipients that had received pristane-treated donor-derived spleen cells. In addition to PCs, monocytic tumors developed in 37 (26%) of all recipients. Their development was independent of pristane treatment of recipients but was particularly frequent in those who had received spleen cells from pristane-treated donors.

Abelson murine leukemia virus↗
PubMed1989

Relationship between tumorigenicity and the dosage of lymphoma- vs. normal-parent-derived chromosome 15 in somatic cell hybrids between lymphoma cells with rearranged pvt-1 gene and normal cells.

Somatic cell hybrids were generated between YACUT, a doubly drug-resistant subline of YAC-1 (a Moloney-virus-induced T-cell lymphoma of strain A/Sn origin with 2 proviral insertions near the pvt-1 locus) and normal diploid fibroblasts of CBAT6T6 origin. Three independent fusions were performed. Three uncloned hybrid cultures and 9 independently-derived clones were tested for tumorigenicity by the inoculation of graded cell numbers into syngeneic hosts. One of 3 uncloned hybrid cultures and 3 of 9 clones were weakly tumorigenic (take incidence 0%), and 1 of 3 uncloned hybrid cultures and 6 clones were highly tumorigenic (take incidence greater than 80%). One weakly tumorigenic hybrid and 3 weakly tumorigenic clones carried 3 copies of the tumor-derived chromosome 15 and 2 copies of the normal fibroblast-derived t(14;15) chromosomes. In contrast, 2 highly malignant hybrid clones lost one copy of the normal-fibroblast-derived t(14;15), but contained increased numbers (3.44-4.44) of the tumor-derived chromosome 15. Four tumorigenic segregants selected from the weakly tumorigenic fibroblast hybrids by in vivo inoculation showed the same cytogenetic change as the highly tumorigenic hybrid clones, in that the ratio of the normal:tumor-derived chromosomes 15 changed from 1.18-1.55 to 4.11-5.71. Tumorigenicity was thus associated with a modified balance between the tumor vs. the normal-parent-derived 15-chromosomes. Instead of the usual 3:2 ratio, the tumor-derived 15-chromosomes increased disproportionately, whereas the relative number of the normal-parent-derived 15-chromosome decreased, as a rule. These results suggest that amplification of the lymphoma-derived chromosome 15 favors tumorigenicity, but that this effect is counteracted by some influence emanating from the normal-parent-derived homologous chromosome.

Animals↗
PubMed1989

A knowledge-based system for automatic interpretation of an analytical profile of complement factors.

A comprehensive assay to evaluate the complement system includes functional tests of both classical and alternative pathways and immunochemical measurements of C3, C4, B, C1-INA, and C3d. The purpose of this analytical profile is to screen for rare hereditary deficiencies and acquired abnormalities of complement and to define the activation pathway in cases of complement consumptive processes. Based on several years' experience, a routine was established in our laboratory to report the data to the clinician, together with a computer-generated interpretive statement. This routine was formulated into a knowledge base by specifying a series of decision rules for each of the complement disorders. After the rules were tested and updated against some 400 complement profile analyses, reasonable analytical comments were produced by the system. This knowledge-based system for reporting and interpreting complement results offers several advantages: the interpretative work is facilitated and made more reliable; a consistent interpretative comment is generated that is recognized and therefore more meaningful for the clinician; the communication of analytical procedures and policy is enhanced.

Artificial Intelligence↗
PubMed1989

Expected pressure-volume heterogeneity within the lung.

Using a model of the lung providing for pressure-volume (P-V) heterogeneity, we reproduced straight (allowing for some concavity or convexity) alveolar plateaus in the nitrogen washout curve with a slope identical to an experimentally measured one (1.2% N2/liter). In a two-unit lung, with one unit of high volume (H) at total lung capacity (TLC) and another of low volume (L) at TLC, three variables could be adjusted to produce the desired alveolar plateaus: the ratio of TLCL/TLCH; the ratio of functional residual capacity, FRCL/FRCH; and the ratio of the steepness constants of their sigmoid P-V curve, KL/KH. We searched for all possible combinations of the three variables that yielded the desired alveolar plateau. For any TLCL/TLCH ratio, there were two single-value solutions for the FRCL/FRCH ratio; thus, the family of solutions was represented by two surfaces in three-dimensional space. We extended the study to a smaller alveolar slope (0.6% N2/liter), assuming that the total slope (1.2% N2/liter) was partially caused by diffusion-convection interaction. We also studied a three-compartment lung as indicative of a multicompartmental lung. The results are discussed in relation to experimentally confirmed P-V heterogeneity. Granting our basic assumptions of P-V heterogeneity, the real physical lung characteristics may be a subsection of the range of theoretical solutions described herein.

Adult↗
PubMed1989

A knowledge-based information system for monitoring drug levels.

The expert system shell SMR has been enhanced to include information system routines for designing data screens and providing facilities for data entry, storage, retrieval, queries and descriptive statistics. The data for inference making is abstracted from the data base record and inserted into a data array to which the knowledge base is applied to derive the appropriate advice and comments. The enhanced system has been used to develop an intelligent information system for monitoring serum drug levels which includes evaluation of temporal changes and production of specialized printed reports. The module for digoxin has been fully developed and validated. To demonstrate the extension to other drugs a module for phenytoin was constructed with only a rudimentary knowledge base. Data from the request forms together with the S-digoxin results are entered into the data base by the department secretary. The day's results are then reviewed by the clinical pharmacologist. For each case, previous results may be displayed and are taken into account by the system in the decision process. The knowledge base is applied to the data to formulate an evaluative comment on the report returned to the requestor. The report includes a semi-graphic presentation of the current and previous results and either the system's interpretation or one entered by the pharmacologist if he does not agree with it. The pharmacologist's comment is also recorded in the data base for future retrieval, analysis and possible updating of the knowledge base. The system is now undergoing testing and evaluation under routine operations in the clinical pharmacology service. It is a prototype for other applications in both laboratory and clinical medicine currently under development at Uppsala University Hospital. This system may thus provide a vehicle for a more intensive penetration of knowledge-based systems in practical medical applications.

Data Interpretation, Statistical↗
PubMed1989

PC-based system for classifying dysmorphic syndromes in children.

A system is described running on any IBM-compatible personal computer operating under MS-DOS which permits an expert in pediatric dysmorphology to formulate dysmorphic features and syndromes in a knowledge base, and a user to enter, analyze, store and retrieve case data. For each case, the system calculates the Bayesian probability of the presence of each syndrome in the knowledge base and lists as the differential diagnosis those syndrome whose probability exceeds 90%. For explanatory purposes, the syndrome definitions can be displayed and compared to the case data. The system has been tested and used in the Department of Clinical Genetics at Uppsala University Hospital. The current scope of the system's knowledge was found to be of valuable assistance to the pediatric practitioner but it must be expanded and refined for use by a clinical geneticist. This study has shown the validity of the system's design and structure and further work is under way to extend its knowledge capability.

Abnormalities, Multiple↗