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Biomedical subjects

A Makris

Publications and source records attributed to A Makris.

At least 55 records · Page 3Linked to original sources
PubMed1996

Thoracolumbar burst fractures: correlation between post-traumatic spinal canal stenosis and initial neurological deficit.

Forty five patients (27 males and 18 females) aged 18 to 62 years, with thoracolumbar burst fracture treated between 1980 to 1994 were studied retrospectively. The purpose of the study was the identification of the existing correlation between the posttraumatic spinal canal stenosis and the initial neurological deficit. The presence of Dall and Stauffer type II fracture statistically constitutes an important factor, with negative involvement, in the diagnosis of the initial neurological status. In thoracolumbar spine, there is an inversely proportional relation with statistical importance between the level of injury and the post-traumatic spinal stenosis-as the burst fracture is sited higher, smaller canal encroachments by fragments will produce the same neurological deficit.

Adolescent↗
PubMed1995

The Barthel Index in assessing the response to palliative radiotherapy in malignant spinal cord compression: a prospective audit.

A prospective study of functional assessment of response to palliative radiotherapy (RT) in malignant spinal cord compression (SCC) is reported. The relevant components of the Barthel Activities of Daily Living Index (ADLI: walking, transfer, and bladder and bowel control) were used to assess functional capacity, and compared with a standard neurological assessment. Fifty-one consecutive patients (38 men, 13 women; mean age 63.9 years) were assessed, all of whom were treated by primary or postoperative radiotherapy. Five of the 51 patients had had decompressive laminectomy prior to RT. Median survival was 34 days (range 2-570). Walking improved in only five of 12 patients who had an improvement in motor power. The ability to transfer from bed to chair improved in 11 patients. Ambulation at presentation was the single most important determinant of outcome. Of the eight patients ambulatory at presentation, all were alive at 1 month and seven remained ambulatory. Of the 43 non-ambulatory patients, only four were able to walk following treatment (all prostatic carcinomas). Only four patients regained urinary continence, and none regained bowel control after this was lost. Functional assessment using ADLI and standard neurological examination provide a more useful guide to outcome in malignant SCC than neurological examination alone.

Adolescent↗
PubMed1995

AH/PH domain-mediated interaction between Akt molecules and its potential role in Akt regulation.

The cytoplasmic serine-threonine protein kinase coded for by the c-akt proto-oncogene features a protein kinase C-like catalytic domain and a unique NH2-terminal domain (AH domain). The AH domain is a member of a domain superfamily whose prototype was observed in pleckstrin (pleckstrin homology, or PH, domain). In this communication, we present evidence that the AH/PH domain is a domain of protein-protein interaction which mediates the formation of Akt protein complexes. The interaction between c-akt AH/PH domains is highly specific, as determined by the failure of this domain to bind AKT2. The AH/PH domain-mediated interactions depend on the integrity of the entire domain. Akt molecules with deletions of the NH2-terminal portion (amino acids 11 to 60) and AH/PH constructs with deletions of the C-terminal portion of this domain (amino acids 107 to 147) fail to interact with c-akt. To determine the significance of these findings, we carried out in vitro kinase assays using Akt immunoprecipitates from serum-starved and serum-starved, platelet-derived growth factor-stimulated NIH 3T3 cells. Addition of maltose-binding protein-AH/PH fusion recombinant protein, which is expected to bind Akt, to the immunoprecipitates from serum-starved cells induced the activation of the Akt kinase.

Amino Acid Sequence↗
PubMed1995

Randomized trial of chemoendocrine therapy started before or after surgery for treatment of primary breast cancer.

PURPOSE: To evaluate in a randomized clinical trial systemic chemoendocrine therapy used as primary (neo-adjuvant) treatment before surgery in women with primary operable breast cancer. PATIENTS AND METHODS: Patients aged less than 70 years with clinically palpable, primary operable breast cancer diagnostically confirmed by fine-needle aspiration cytology (FNAC) and suitable for treatment with surgery, radiotherapy, cytotoxic chemotherapy, and tamoxifen were considered eligible. Patients randomized to neoadjuvant treatment received four cycles of chemo-therapy for 3 months before surgery followed by another four cycles after surgery, and were compared with patients randomized to adjuvant therapy who received eight cycles of chemotherapy over 6 months after surgery. RESULTS: Of 212 patients who were randomized to receive either adjuvant (n = 107) or neoadjuvant (n = 105) chemoendocrine therapy, 200 are now assessable for response. The two groups are comparable for age, menopausal status, disease stage, and surgical requirements. The overall clinical response rate was 85%, with a complete histologic response rate of 10%. There was a significant reduction in the requirement for mastectomy in patients who received neoadjuvant treatment (13%) as compared with those who received adjuvant therapy (28%) (P < .005). Symptomatic and hematologic acute toxicity was low and similar for adjuvant and neoadjuvant therapy. The median follow-up period for patients in this trial is 28 months, during which time four patients have relapsed locally and 20, including one of the local relapses, have developed metastatic disease, 19 of whom have died. The follow-up period is too brief to evaluate relapse rate or survival duration. CONCLUSION: This trial confirms previous reports of a high rate of response to neoadjuvant therapy, but is the first to include small primary cancers and to show, in the context of a randomized trial, a reduction in the requirement for mastectomy. Until disease-free and overall survival data are available from the larger National Surgical Adjuvant Breast and Bowel Project (NSABP)-18 trial, such neoadjuvant treatment cannot be recommended outside of a clinical trial.

Adult↗
PubMed1994

Tpl-2 acts in concert with Ras and Raf-1 to activate mitogen-activated protein kinase.

Mitogenic signals initiated at the plasma membrane by extracellular factors acting on receptor tyrosine kinases or G protein-coupled receptors are transmitted to the nucleus through an intricate signaling network. Components of this network participate, upon stimulation, in a complex array of phosphorylation-dependent protein-protein interactions which leads to the formation of transient multimolecular complexes. Complexes containing products of the protooncogenes ras and raf-1 and the protein kinase MEK-1 activate the mitogen-activated protein kinases (MAPKs), which play a central role in the integration of different mitogenic signals by directly phosphorylating cytoplasmic and nuclear targets. In this report we present evidence that the kinase encoded by the tumor progression locus 2 gene (Tpl-2) contributes to the activation of the MAPK cascade. MAPK activation induced by the Tpl-2 protein is blocked by dominant negative mutants of Ras and Raf-1, whereas a kinase-deficient Tpl-2 mutant down-regulates mitogenic signals induced by v-Ha-Ras or v-Raf. These data suggest that Tpl-2 activates the MAPK cascade, perhaps through its participation in the assembly of Ras/Raf-1-containing multimolecular complexes.

3T3 Cells↗
PubMed1993

Identification of the gene encoding the mitochondrial elongation factor G in mammals.

Protein synthesis in cytosolic and rough endoplasmic reticulum associated ribosomes is directed by factors, many of which have been well characterized. Although these factors have been the subject of intense study, most of the corresponding factors regulating protein synthesis in the mitochondrial ribosomes remain unknown. In this report we present the cloning and initial characterization of the gene encoding the rat mitochondrial elongation factor-G (rEF-Gmt). The rat gene encoding EF-Gmt (rMef-g) maps to rat chromosome 2 and it is expressed in all tissues with highest levels in liver, thymus and brain. Its DNA sequence predicts a 752 amino acid protein exhibiting 72% homology to the yeast Saccharomyces cerevisiae mitochondrial elongation factor-G (YMEF-G), 62% and 61% homology to the Thermus thermophilus and E. coli elongation factor-G (EF-G) respectively and 52% homology to the rat elongation factor-2 (EF-2). The deduced amino acid sequence of EF-G contains characteristic motifs shared by all GTP binding proteins. Therefore, similarly to other elongation factors, the enzymatic function of EF-Gmt is predicted to depend on GTP binding and hydrolysis. EF-Gmt differs from its cytoplasmic homolog, EF-2, in that it contains an aspartic acid residue at amino acid position 621 which corresponds to the EF-2 histidine residue at position 715. Since this histidine residue, following posttranslational modification into diphthamide, appears to be the sole cellular target of diphtheria toxin and Pseudomonas aeruginosa endotoxin A, we conclude that EF-Gmt will not be inactivated by these toxins. The severe effects of these toxins on protein elongation in tissues expressing EF-Gmt suggest that EF-Gmt and EF-2 exhibit nonoverlapping functions. The cloning and characterization of the mammalian mitochondrial elongation factor G will permit us to address its role in the regulation of normal mitochondrial function and in disease states attributed to mitochondrial dysfunction.

Animals↗
PubMed1993

Tumor progression locus 2 (Tpl-2) encodes a protein kinase involved in the progression of rodent T-cell lymphomas and in T-cell activation.

The Tpl-2 locus, cloned by provirus tagging from one of three sublines of the Moloney leukemia virus-induced rat thymoma 2769, defines a gene encoding a protein kinase associated with progression in 22.5% of the tumors. Tpl-2 is expressed primarily in spleen, thymus, liver, and lung. Provirus integration occurs in the last intron of the gene, leading to the expression of a truncated mRNA that terminates in the proviral long terminal repeat and encodes a protein with an altered C-terminal domain. Strong evidence that this genetic change confers growth advantage to affected cell clones was provided by the finding that, during cultivation of all three sublines derived from tumor 2769, cells were selected that harbored independent provirus insertions in the Tpl-2 locus. Exposure of normal rat spleen cells to Con A induces the expression of enhanced levels of Tpl-2 within the first 60 min from the time of exposure suggesting that, in normal splenocytes, Tpl-2 may be involved in the transition from a quiescent to the G1 phase of the cell cycle.

Amino Acid Sequence↗
PubMed1993

Structure of a Moloney murine leukemia virus-virus-like 30 recombinant: implications for transduction of the c-Ha-ras proto-oncogene.

Tumor progression locus 2 (Tpl-2) encodes a novel serine-threonine protein kinase which is activated by provirus integration in the late stages of oncogenesis in Moloney leukemia virus (MoMuLV) induced rat T-cell lymphomas. In this report, we present evidence that the provirus integrated in the Tpl-2 locus in 1 of 10 T-cell lymphomas harboring a Tpl-2 rearrangement (2779) is a recombinant between MoMuLV and virus-like 30 (VL30) sequences (Mo-VL30). Recombination between MoMuLV and VL30 may contribute to the transduction of ras, as suggested by the finding that VL30 flanks the ras oncogene in all of the ras transducing viruses isolated from rats to date. The Mo-VL30 recombinant described here represents evidence that recombination between MoMuLV and VL30 can be uncoupled from the transduction of ras, and it may precede the transduction. Sequence comparison between clones of Mo-VL30, Harvey sarcoma virus (Ha-MSV), and genomic c-Ha-ras revealed that all three share a 124-bp region of 87.3% homology. This region was detected at nucleotide positions -1845 to -1720 of c-Ha-ras and 20 bp 5' of the recombination breakpoint between VL30 and ras in Ha-MSV. On the basis of the sequence comparison between VL30, Ha-MSV, and c-Ha-ras, we are proposing a model which explains how VL30 may have facilitated the transduction of c-Ha-ras and perhaps the other ras proto-oncogenes. According to this model, the sequence homology between VL30 and c-Ha-ras targets this gene for transduction by promoting the integration of the provirus in this locus through homologous recombination.

Animals↗
PubMed1993

Genomic organization and expression of Tpl-2 in normal cells and Moloney murine leukemia virus-induced rat T-cell lymphomas: activation by provirus insertion.

Tpl-2 is a gene encoding a protein kinase which is primarily expressed in normal spleen, thymus, and lung tissue and is activated by provirus insertion in Moloney murine leukemia virus-induced T-cell lymphomas during the late stages of oncogenesis. Tpl-2 is composed of eight exons and spans a 35-kb genomic DNA region. The provirus integrates reproducibly in the last intron and in the same transcriptional orientation as the Tpl-2 gene. This genetic change leads to the expression of enhanced steady-state levels of a truncated Tpl-2 RNA transcript which is predicted to encode a protein with an altered C-terminal domain. Tpl-2 is transcribed from two alternating promoters, P1 and P2. The RNA transcripts originating in the two promoters harbor different 5' untranslated regions derived from the alternate noncoding exons IA and IB. Utilization of the P2 promoter, which gives rise to exon IB containing Tpl-2 RNA transcripts, was detected primarily in tumor cells. The Tpl-2 protein was expressed in COS-1 cells as an N-terminal fusion with a 12-amino-acid hemagglutinin tag. Immunoprecipitation of transfected COS-1 cell lysates with antihemagglutinin or anti-Tpl-2 antibodies, followed by incubation with [gamma-32P]ATP, confirmed that Tpl-2 possesses protein kinase activity.

Animals↗
PubMed1993

New markers, D16FC1 and Tp12, differentiate between rat chromosomes 16 and 17.

Problems in differentiating rat chromosomes 16 and 17 cytogenetically can be resolved with unique probes mapped to these chromosomes. Using somatic cell hybridization and nonisotopic in situ hybridization, probes D16FC1 and Tp12 were localized to 16p16-->p15 and 17q12.1-->q12.2, respectively. The locations of these probes can serve as reference points to facilitate mapping of future probes to rat chromosomes 16 and 17.

Animals↗
PubMed1992

A molecular genetic linkage map of mouse chromosome 18 reveals extensive linkage conservation with human chromosomes 5 and 18.

An interspecific backcross between C57BL/6J and Mus spretus was used to generate a molecular genetic linkage map of mouse chromosome 18 that includes 23 molecular markers and spans approximately 86% of the estimated length of the chromosome. The Apc, Camk2a, D18Fcr1, D18Fcr2, D18Leh1, D18Leh2, Dcc, Emb-rs3, Fgfa, Fim-2/Csfmr, Gnal, Grl-1, Grp, Hk-1rs1, Ii, Kns, Lmnb, Mbp, Mcc, Mtv-38, Palb, Pdgfrb, and Tpl-2 genes were mapped relative to each other in one interspecific backcross. A second interspecific backcross and a centromere-specific DNA satellite probe were used to determine the distance of the most proximal chromosome 18 marker to the centromere. The interspecific map extends the known regions of linkage homology between mouse chromosome 18 and human chromosomes 5 and 18 and identifies a new homology segment with human chromosome 10p. It also provides molecular access to many regions of mouse chromosome 18 for the first time.

Animals↗
PubMed1991

Measurement of hepatitis B viral DNA in serum by solution hybridization and comparison with the dot-blot hybridization technique.

A recently introduced method for the detection of hepatitis B viral (HBV) DNA in the serum, using solution hybridization, was assessed for its sensitivity and specificity in 242 sera from patients with chronic HBV infection, and in controls. In 87 sera the results were compared with the classical dot-blot technique. The new method gave positive results in 82% (56/68) of all dot-blot-positive sera and in 97% (35/36) of those with strong positive dot-blot reactions. All 30 hepatitis B surface antigen (HBsAg) carriers positive for hepatitis B e antigen (HBeAg) were positive in the solution hybridization assay, with a mean HBV-DNA level of 172 +/- SE 36 pg/ml. Negative results were obtained in all 20 subjects negative for all HBV markers and in all 36 HBsAg+/anti-HBe+ carriers with normal aminotransferase activity, negative for hepatitis B core antigen (HBcAg) expression in the liver. By contrast 93% (66/71) of the anti-HBe+ patients with positive HBcAg expression in the liver were positive for serum HBV-DNA in the solution hybridization assay, with a mean level of 30.5 +/- SE 6.7 pg/ml. Of 14 sera with discrepant HBV-DNA results in the two assays, 12 were solution hybridization-negative/dot-blot-positive and 2 were solution hybridization-positive/dot-blot-negative. These results indicate that the new, simple method is specific, and suitable for the determination of serum HBV-DNA in clinical practice.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA Probes↗
PubMed1990

Interferon alfa-2b treatment of HBeAg negative/serum HBV DNA positive chronic active hepatitis type B.

A randomized controlled trial of recombinant interferon alfa-2b has been initiated in patients with chronic active hepatitis who were negative for serum hepatitis B e antigen but positive for serum hepatitis B virus DNA and hepatitis B core antigen expression in the liver. Twenty-five patients received interferon alfa-2b 3 million units thrice weekly for 14-16 weeks and 25 served as untreated controls. Seventeen patients in the treatment and 18 in the control group have already completed a 12-month period of observation. Interferon alfa-2b was well tolerated by all patients. At the end of therapy, complete responses, defined as disappearance of hepatitis B virus DNA from serum and return of alanine aminotransferase to normal, were observed in 10 (59%) of the 17 treated patients compared to none in the control group (p less than 0.01). Twelve months after the onset of interferon alfa-2b therapy, 11 (65%) of the 17 treated patients were complete responders compared to 2 (11%) of 18 in the control group (p less than 0.01). Fifty per cent (4/8) of complete responders to interferon alfa-2b therapy, followed for 16-24 months, experienced reactivations of hepatitis B virus replication with reappearance of serum hepatitis B virus DNA and a return of serum alanine aminotransferase activity. The response to interferon alfa-2b therapy appeared to be independent of pre-treatment serum alanine aminotransferase and hepatitis B virus DNA levels.

Alanine Transaminase↗
PubMed1989

Mutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection.

Some patients with chronic hepatitis B virus (HBV) infection are HB e antigen (HBeAg) negative, have circulating HBV particles, and often have especially severe chronic hepatitis. To test the hypothesis that the absence of HBeAg production may be due to a change in the nucleotide sequence of the pre-core region of the genome, 18 Greek and 3 non-Greek patients positive for HB surface antigen underwent direct sequencing of HBV-DNA amplified from sera. In 7 out of 8 HBeAg negative patients, two mutations (guanosine to adenosine) were found in the terminal two codons of the pre-core region, giving the sequence TAGGACATG. The remaining patient had the first mutation only. The sequence TGGGGCATG was found in 4 of 5 of the HBeAg positive patients. The first mutation results in a translational stop codon that is predicted to result in failure to produce HBeAg. The rest of the pre-core region in the HBeAg negative patients was otherwise homologous to that of the HBeAg positive patients and to known sequences.

Amino Acid Sequence↗
PubMed1989

Western blot analysis of porcine corpus luteum heparin binding proteins using antibodies to acidic and basic fibroblast growth factor.

The 105,000 X g supernatant from homogenates of porcine corpora lutea was chromatographed on a heparin Sepharose affinity column. Bound protein was batch eluted and analyzed on Western blots using antibodies to acidic and basic fibroblast growth factor (FGF). The antibody to acidic FGF reacted specifically with at least four protein bands ranging from 21 to 50 kDa. Three antibodies to human basic FGF (145 residues) generated against either the N-terminal sequence (1-12), the internal sequence (33-43), or the C-terminal end (135-145) also reacted specifically with a total of four different bands. The apparent molecular weights ranged between 20 and 55 kDa. The luteal extract also expressed message for acidic FGF. The results show that there may exist a family of FGF-like molecules in the corpus luteum and demonstrates for the first time the presence of acidic FGF in that tissue.

Animals↗