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Biomedical subjects

F Wiener

Publications and source records attributed to F Wiener.

At least 73 records · Page 4Linked to original sources
PubMed1984

High resolution banding analysis of the involvement of strain BALB/c- and AKR-derived chromosomes No. 15 in plasmacytoma-specific translocations.

Plasmacytomas were induced in (BALB/c X AKR 6;15) X BALB/c backcross mice where one of the BALB/c-derived chromosomes No. 15 was replaced by the AKR(6;15)-derived Robertsonian 6;15 chromosome. (BALB/c X AKR 6;15)F2 mice that were homozygous for Rb 6;15 were mated to BALB/c mice. Plasmacytomas were induced in the progeny by intraperitoneal injection of pristane. The cytogenetic marker permitted the distinctive identification of the two chromosome 15 homologues, including the distal segment involved in the plasmacytoma-specific translocations. 7 of the 10 plasmacytomas contained the typical t(12;15) translocation. The BALB/c-derived 15 chromosome served as the donor of the translocated segment in six of them. In the seventh, the Rb 6;15 chromosome of the AKR strain was the donor. The remaining three tumors contained the same type of intrachromosomal rearrangement. It arose by the pericentric inversion of the Rb 6;15 chromosome, leading to a variant plasmacytoma-associated rcpt (6;15) translocation. Unlike the usual 6;15 variant that arises by a reciprocal exchange between two separate chromosomes, it was generated by an exchange of the distal segments of a single chromosomal element. High resolution banding analysis of the tumors showed that all translocated breakpoints on chromosomes 15, 12, and 6 were identical with the previously described breakpoints characteristic for the typical 12;15 and the variant 6;15 translocation in murine plasmacytomas. It is known that the distal segment of chromosome 15 carries the c-myc oncogene (23). The PC-associated translocations cut across the 5'-exon of c-myc in the majority of the cases (24,26). The severed oncogene is transposed to the Ig-region on the recipient chromosome. Since the BALB/c strain is highly sensitive to PC-induction, we were interested to examine the question whether its chromosome 15 is preferred as the oncogene donor in AKR X BALB/c backcross mice that carry cytogenetically distinguishable 15 chromosomes. Our results show that this is not the case, since the same segment of the AKR-derived chromosome 15 could also serve in the same capacity. This is in contrast with T cell leukemogenesis where we have previously found that the trisomization-associated duplication of chromosome 15 occurred in a highly asymmetrical fashion, depending on the donor strain of No. 15 (9-11).

Animals↗
PubMed1984

Hemizygous interstitial deletion of chromosome 15 (band D) in three translocation-negative murine plasmacytomas.

Three murine plasmacytomas that were exceptional in lacking the characteristic (12;15) or (6;15) translocations were studied by G banding and high-resolution banding. One of every two chromosomes 15 (two of four in tetraploid tumors) was shortened in all three tumors. High-resolution banding analysis revealed that this was due to an interstitial deletion in the 15D band region. The two breaks responsible for the deletion have been tentatively localized to the interface of bands D2/3' and within band D2. One of the three plasmacytomas, ABPC45, had a rearranged c-myc gene. All three tumors contained a greater abundance of 2.4-kilobase myc RNA transcripts than normal spleen or thymus. The c-myc gene is located in the 15 D2/3 band region. We suggest that it may have joined the centromeric portion in the deletion plasmacytomas. This transposition may have led to its constitutive activation, as in the more frequent translocation-carrying plasmacytomas.

Animals↗
PubMed1983

Fusion of DNA region to murine immunoglobulin heavy chain locus corresponds to plasmacytoma-associated chromosome translocation.

Murine plasmacytomas frequently exhibit a translocation of the distal region of chromosome 15 to the end of chromosome 12, where the immunoglobulin heavy chain locus resides. A candidate for the DNA across the chromosome fusion point is a cloned region of non-immunoglobulin DNA which in most plasmacytomas has recombined near the alpha heavy chain constant region gene. That the incoming DNA, provisionally designated LyR (lymphoid rearranging) DNA, does derive from chromosome 15 is shown here by blot analysis of DNA from two panels of somatic cell hybrids: hybridomas between an AKR T-lymphoma (Tikaut) and CBA mouse cells with a cytogenetically distinctive chromosome 15, and between mouse and Chinese hamster cells. LyR DNA segregated with chromosome 15 in all lines and the results assign LyR to the distal two thirds of that chromosome. This assignment, together with the previously reported high frequency of recombination between LyR and C(alpha) in plasmacytomas and associated alteration of LyR transcription suggests that translocation activates a LyR gene involved in plasmacytoma oncogenesis. Moreover, LyR rearrangement in certain T-lymphomas, such as the Tikaut line examined here, also implicate that gene in oncogenesis of some T-lymphomas.

Animals↗
PubMed1983

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↗
PubMed1983

Computerized medical reasoning in diagnosis and treatment of acid-base disorders.

A system is described for aiding the clinician in the management of acid-base disorders. The medical knowledge required for interpretation of blood gas measurements, etiologic diagnosis, and treatment selection for acid-base disorders is structured into decision pathways consisting of a series of inferences. Each inference is defined by a medical logic module which specifies the different combinations of criteria, patient data and/or previously confirmed inferences, sufficient for confirming or rejecting the inference. A method is provided for converting numerical observations to the appropriate logical statement used in the modules. Patient data are compared to the medical logic and a status report lists the input data, acid-base diagnosis, and the suggested therapy. After initial testing on patient data, the medical logic was updated to express the medical policy of our clinical specialists. The system was applied to 54 patients and the system's conclusions were in full agreement with our staff in 93% of the cases, and in partial agreement in the other cases. The modular structure of the system's medical knowledge allows full expression of all the nuances of medical policy in our unit and facilitates updating to encompass the latest developments in acid-base management. The system can be integrated readily into existing computerized patient monitoring systems.

Acid-Base Imbalance↗
PubMed1982

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↗
PubMed1982

Non-random chromosomal changes involving chromosomes 6 and 7 in spontaneous rat immunocytomas.

G-banding analysis of seven Ig-secreting spontaneous rat immunocytomas showed a consistent translocation of the distal part of the q-arm of chromosome 7 to the telomeric end of chromosome 6. The breakpoints were assigned to q3.3 on chromosome 7 and q3.2 on chromosome 6. Previously, we found a similar translocation pattern in mouse plasmacytomas induced by different agents. The distal part of the q-arm of chromosome 15 was translocated to the telomeric end of chromosome 12, known to carry Igh, the immunoglobulin heavy chain cluster. The banding homologies between the chromosomes involved in the translocation in the two species suggest that a similar mechanism is responsible for plasmacytomagenesis in both. We also predict that the rat Ig heavy chain gene cluster will be located to the terminal segment of chromosome 6.

Animals↗
PubMed1982

Computerized medical decisions in evaluating the diabetes patient.

A system for computer simulation of medical reasoning is described which has been applied to classifying diabetic patients and assessing the complications due to disease. Medical knowledge is formulated into modular, interrelated inference pathways. Each module states the inference and the Boolean combinations of criteria sufficient for confirming or rejecting it. Patient data is compared to the medical logic and a status report is produced which presents the clinical findings, confirmed inferences, the diabetes evaluation score for each body system and request for additional data at the follow-up visit. After initial testing the medical logic was easily updated to fully express medical policy in our clinic. The system provides an objective and consistent method for evaluating the diabetic patient.

Diabetes Complications↗
PubMed1982

Computer systems for facilitating management of the critically ill.

The Shock Research Unit has applied computer technology to the care of the critically ill and injured patient since 1961. The requirements for patient monitoring were initially explored with a process control computer (IBM) 1710). In the current system, a Xerox Sigma-5 computer is utilized for monitoring EKG, hemodynamic, respiratory, and biochemical signals. Electronic preprocessing increases the efficiency and speed of data acquisition and signal analysis. Provisions are made for recording narrative data as part of a commitment to evolve an automated patient record. Bedside displays include both tabular and graphic summaries of patient status and trends. A computer accessible archive of patient files is maintained. Clinical operation of the system has been facilitated by automation of afferent and efferent functions including flushing of catheters, servo-calibration of pressure measuring systems, automated urine collection and disposal, and computer controlled infusion of fluids and medications. We anticipate the continuing development of automated afferent and efferent components for feedback control of ventilators by automated sampling and measurement of arterial blood gases and infusion of fluids and medications in response to changes in monitored hemodynamic variables. Such automation, together with medical intelligence for priority alarms and interpretive displays, hold promise of increasingly potent and cost-effective systems to facilitate and improve care of the critically ill or injured patient.

Blood Gas Analysis↗
PubMed1981

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↗
PubMed1981

The role of chromosome 15 in murine leukemogenesis. I. Contrasting behavior of the tumor vs. normal parent-derived chromosomes No. 15 in somatic hybrids of varying tumorigenicity.

G-banding analysis was carried out on a series of hybrids derived from the fusion of a chromosome 15-trisomic murine T-cell leukemia of AKR origin and normal diploid fibroblasts or lymphocytes of the CBT6T6 strain. Due to the 14;15 translocation involved in the generation of the T6 marker, the chromosomes No. 15 and 14 derived from the normal and the tumor parent can be distinguished cytogenetically. Highly tumorigenic, in vitro maintained hybrids, and high-tumorigenic segregants of originally low-tumorigenic in vitro hybrids, selected by in vivo passage, showed a similar cytogenetic pattern. It was characterized by the amplification of the tumor-derived chromosomes No. 15 from the expected 3 to 5.5 +/- 0.2 copies and a concomitant decrease of the normal derived T(14;15)6 from 2 copies to 0.9 +/- 0.2. All other autosomes except No. 14 showed only minor random variations, around the expected number of 4 copies. The tumor-derived chromosome 14 was amplified from the expected 2 to 3 copies. The low-tumorigenic hybrids showed the opposite pattern with a decrease in the number of the tumor-derived 15 chromosome from 3 to 2.6 +/- 0.1 and the maintenance of the two normal parent derived T(14;15)6 chromosomes. These findings suggest the existence of a qualitative difference between the 15 chromosomes derived from the tumor vs. the normal parent, due to mutation or proviral DNA insertion in the tumor-derived homologue. Amplification of the change locus and a decrease in the dosage of its normal counterpart appear to favor tumorigenicity.

Animals↗
PubMed1980

Non-random duplication of chromosome 15 in murine T-cell leukemias: further studies on translocation heterozygotes.

Four combinations of translocation heterozygotes with cytogenetically distinct chromosomes 15 were used to investigate whether the T-cell leukemia-associated duplication of chromosome 15 is a non-random or a random event. In leukemias of AKR x CBAT6T6F1 (Group 1) and C57BL x CBAT6T F1 (Group IV) crosses the duplication was non-random, affecting the AKR-derived chromosome 15 (Group 1) and CBAT6T6-derived T (14;15) 6 chromosome (Group IV), respectively. In contrast, in leukemias induced in CBA x CBA T6T6F1 combinations (Group III) - where both chromosomes 15 (normal and translocated) were CBA-derived-the duplication was random. Similarly, in the Rb6;15 x CBAT6T6F1 cross (group II) the duplication of chromosome 15 appeared to be random. The results supported the hypothesis that the genetic content of chromosome 15 rather than its translocated state is decisive for the preferential duplication of this chromosome in T-cell leukemogenesis. However, the genetic background of the strain from which chromosome 15 is derived may also influence the duplication pattern of individual tumors.

Animals↗
PubMed1980

Cytogenetic studies on abelson-virus-induced mouse leukemias.

The karyotype of Abelson-virus-induced murine leukemias was studied by G-banding. In contrast to the regular trisomy of chromosome 15 in most murine T-cell leukemias, Abelson leukemias were purely diploid, and remained diploid for up to seven consecutive passages in vivo. The hypothesis is advanced that integration into the recipient cell of the DNA copy of the large cellular insert, carried by the Abelson virus, may perform a function similar to the effects of gene duplication by trisomy in the more slowly developing murine leukemias.

Abelson murine leukemia virus↗
PubMed1980

Cytogenetic studies on IgA/lambda-producing murine plasmacytomas: regular occurrence of a T(12;15) translocation.

Seven IgA/lambda-producing murine plasmacytomas had the 12;15 translocation, previously found in IgA/kappa-producing plasmacytomas, and lacked the rcpT(6;15) translocation, also found in some kappa producers. The results suggest that the generation of the 12;15 translocation is an important, perhaps essential event during the genesis of plasmacytomas. The possibility that the distal region of chromosome 15 may contain a "supergene" area involved with the differentiation and/or normal responsiveness of various types of lymphoreticular cells, must be seriously considered on the basis of the present and previous evidence on plasmacytomas, as well as the extensive evidence now available on the role of chromosome 15-changes in the genesis of murine lymphomas. The involvement of chromosome 12 is of interest in view of the fact that it is known to carry the heavy-chain immunoglobulin determinants.

Animals↗