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Biomedical subjects

H Dudek

Publications and source records attributed to H Dudek.

At least 37 records · Page 2Linked to original sources

Myb and Ets proteins cooperate in transcriptional activation of the mim-1 promoter.

In the generation of the acutely transforming avian retrovirus E26, both myb and ets genes have been transduced, leading to the production of a Gag-Myb-Ets fusion protein. This co-occurrence of v-myb and v-ets oncogenes suggests that the two might have a functional relationship. To look for such a relationship, we tested the transcriptional activation activity of Myb alone or with coexpressed Ets-1 or Ets-2. Using the promoter of the v-Myb-inducible mim-1 gene as a target, we found that full-length c-Myb gene products were poor activators of transcription, while an oncogenic (truncated) form of this protein was a strong trans-activator. However, coexpression of Ets-2 with full-length or truncated forms of Myb greatly increased trans-activation. Coexpression of Ets-1, Fos, Jun, or Myc with Myb did not increase trans-activation of the mim-1 promoter. The ability of Myb and Ets-2 to transactivate was cooperative, since Ets-2 alone gave little or no activation. Bacterially synthesized Ets-2 protein was found to bind specifically to the mim-1 promoter, suggesting that it may be a target for both Myb and Ets proteins. Thus, Myb and Ets proteins can cooperate in transcriptional activation, and their co-occurrence in the E26 virus may reflect a functional relationship between these two oncoproteins. Truncated forms of Myb may have a reduced need for cooperating factors such as Ets-2, and this might constitute an important mechanism associated with oncogenic activation.

Amino Acid Sequence↗

Mutational analysis of Max: role of basic, helix-loop-helix/leucine zipper domains in DNA binding, dimerization and regulation of Myc-mediated transcriptional activation.

The Max protein forms a heterodimeric complex with the Myc family of proteins and binds to DNA in a sequence-specific manner. We investigated the role of the helix-loop-helix (HLH), leucine zipper (LZ) and basic domains of Max in protein complex formation, DNA-binding activity and transcriptional regulation. We mutagenized the basic, HLH and LZ domains of Max and studied the ability of the normal and mutant proteins to bind to DNA as both homo- and heterodimers and their ability to heterodimerize with Myc. Helix-1 and helix-2 regions of Max were found to be critical for homodimer formation and subsequent DNA binding, while the LZ was essential for heterodimer formation. In transient transfection assays the Myc protein functioned as a transcriptional activator while Max protein repressed the trans-activation observed with Myc.

Base Sequence↗

Murine myeloid leukemias with aberrant myb loci show heterogeneous expression of novel myb proteins.

Using a panel of anti-myb antibodies, we have examined the c-myb proteins present in the NFS-60 and ABPL-1, ABPL-2, and ABPL-4 tumor cell lines, all of which have an altered myb locus due to viral insertional mutagenesis. As predicted from previous DNA and RNA analysis, NFS-60 cells produce myb protein with a truncated C-terminus and a normal N-terminus. The three ABPL tumor cell lines studied here were previously shown to have undergone similar rearrangements towards the 5' end of myb locus and were expected to synthesize identical myb RNAs and proteins. These cell lines were found to produce myb proteins with N-terminal modifications. Surprisingly, however, the three cell lines were found to synthesize a heterogenous array of myb proteins of different sizes. These observations suggest that oncogenic activation of myb in ABPL tumors may involve additional changes in the coding region in addition to those occurring at the N-terminus.

Animals↗

Identification of two translational products for c-myb.

The c-myb gene is the normal cellular homolog of v-myb, the oncogenic component of Avian Myeloblastosis Virus (AMV). The c-myb gene has previously been shown to code for a single protein species of about 75 kd. However, accumulating evidence indicates that this gene could code for multiple mRNAs as a result of differential splicing. This was first detected in the ABPL-2 tumor line and was later shown to occur in normal cells. To test if indeed these differentially spliced mRNAs code for a new protein species that went hitherto undetected, a series of antibodies directed against specific domains of the myb protein, including the putative sequences that could be generated from the alternatively spliced mRNAs were generated. Immunoprecipitation analysis using these antibodies show that both normal and tumor cell lines synthesize at least two myb proteins, one of 75 kd and the other of 89 kd.

Animals↗

CML patients in blast crisis have breakpoints localized to a specific region of the BCR.

Chronic myelogenous leukemia (CML) is associated with the Philadelphia (Ph) chromosome, which results from a reciprocal translocation between chromosomes 9 and 22. This activates the abl oncogene by moving it from chromosome 9 and combining it with sequence located on chromosome 22. The new fusion gene, with chromosome 22 sequence at its 5' end and chromosome 9-abl sequence at its 3' end, generates a new messenger RNA (mRNA) and protein that are implicated in the pathogenesis of CML. The breakpoint near the c-abl locus on chromosome 9 can occur within a large area. In contrast, the breakpoints on chromosome 22 are concentrated within a 6 kilobase (kb) region termed the breakpoint cluster region (bcr). This study was designed to determine whether chronic-phase and blast crisis patients had identifiable differences in the structure of their Ph chromosomes. Restriction mapping of the chromosome 22 translocation breakpoints performed for 26 patients showed that the breakpoints of eight of the nine patients in blast crisis were in the 3' portion of the bcr, whereas the breakpoints in the 17 patients in the chronic phase were clustered in the 5' portion of the bcr. This suggests a strong correlation between a 3' bcr breakpoint and blast crisis in CML.

Blast Crisis↗

Effects of in vivo manganese administration on calcium exchange and contractile force of rat ventricular myocardium.

The purpose of this study was to investigate the effect of prolonged (14 days) intragastric administration of Mn2+ (0.25 mmol/kg daily) on Ca2+ exchange and contractility of rat ventricular myocardium. Left-ventricular pressure and its first derivative (dP/dt) were recorded by means of a balloon catheter inserted via the left atrium into the left ventricle of the rat heart perfused by Langendorff method. Ca2+ exchange in the stimulated and rested ventricular myocardium was investigated with the aid of 45Ca under the conditions of complete equilibration of preparations with a solution containing 45Ca2+. The "cellular" 45Ca2+ content was calculated by subtraction of 45Ca2+ dissolved in the free water of extracellular space from the total tissue 45Ca2+ content. The cellular 45Ca2+ content in the stimulated (60/min) ventricles of control rats (without Mn2+) was 0.83 +/- 0.09 mmol/kg wet weight (w.w.). Ten minutes of rest resulted in a gain of 0.06 mmol 45Ca/kg w.w. (not statistically significant). Fourteen days' exposure to Mn2+ resulted in an increase of the mean 45Ca content to 1.61 +/- 0.09 mmol/kg w.w. in the stimulated preparations and to 1.35 +/- 0.06 mmol/kg w.w. in the rested ones (p less than 0.001). Thus, the control rest preparations did not change their Ca2+ content, while in the rats treated with Mn2+ the rest resulted in an increase at exchangeable Ca by 52%. The maximal ventricular developed pressure (Pmax) after 14 days of Mn2+ administration was increased by 35% and dP/dtmax was 228% of the value in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Lipoma of the corpus callosum].

The authors present a case of lipoma of corpus callosum in a 25-years old patient. The results of psychological testing, plain skull X-ray. EEG investigation, images of CT, MRI of the brain and right carotid angiography are presented. The patient refused surgical treatment. His neurological state after discharge from hospital was good.

Carotid Artery, Internal↗

[Clinico-radiological analysis of surgically treated sciatica cases].

An analysis included 187 patients treated surgically for sciatica due to vertebral disk pathologies. Nerve roots compression was noted in all examined patients, including 54% of left-sided compression, 43% of right-sided, and 3% of bilateral compression. Majority of cases involved nerve roots in L5 (51%) and L4 (36%) segments of the spine. Intra-operationally 139 (87%) out of 160 abnormal radiculographies have been confirmed. Disk disease was diagnosed in 11 patients despite the lack of changes in radiculography. It may be explained by the extremely lateral prolapse of the vertebral disk. Long term course of the disease and clinical picture decide on surgery in such cases.

Adolescent↗