A Alimov

Publications (10)25.27 Total impact

• Article: Mutation analysis of MEN1, HRPT2, CASR, CDKN1B, and AIP genes in primary hyperparathyroidism patients with features of genetic predisposition.

  O Vierimaa, A Villablanca, A Alimov, M Georgitsi, A Raitila, P Vahteristo, C Larsson, A Ruokonen, E Eloranta, T M L Ebeling, J Ignatius, L A Aaltonen, J Leisti, P I Salmela
  [show abstract] [hide abstract]
  ABSTRACT: Primary hyperparathyroidism (PHPT), a common endocrine condition, is usually caused by sporadically occurring parathyroid adenoma. A subset of patients carry germline mutations in genes such as MEN1 (multiple endocrine neoplasia type 1), HRPT2 (hyperparathyroidism 2), and CASR (calcium-sensing receptor) predisposing to syndromic forms of PHPT or familial isolated hyperparathyroidism (FIHP). Recently, germline mutations in two novel genes AIP (aryl hydrocarbon receptor-interacting protein) and CDKN1B (cyclin-dependent kinase inhibitor 1B) have been found to be associated with endocrine tumors. The purpose of this study was to evaluate the role of MEN1, HRPT2, CASR, AIP, and CDKN1B genes in PHPT patients with clinical features suggestive of genetic predisposition. Medical records of patients treated for PHPT from 1974 to 2001 at Oulu University Hospital were reviewed. Patients with multiglandular or recurrent/persistent disease, other MEN1- related manifestations, aged 40 yr or younger at onset or with a family history of PHPT/MEN1-related tumor were invited to the study. Twenty patients with previously diagnosed MEN1 were excluded. Participants were interviewed and blood samples obtained for biochemical screening and mutation analysis of MEN1, HRPT2, CASR, AIP, and CDKN1B. Of the 56 invited patients, 29 took part in the study. One patient was found to carry the c. 1356_1367del12 MEN1 founder mutation. Mutations in other genes were not detected. Apart from MEN1, mutations in other genes predisposing to PHPT seem to be rare or non-existing in Northern Finnish PHPT patients. No evidence was found for a role of AIP or CDKN1B in PHPT predisposition.
  Journal of endocrinological investigation 04/2009; 32(6):512-8. · 1.57 Impact Factor
• Article: Loss of parafibromin expression in a subset of parathyroid adenomas.

  C Juhlin, C Larsson, T Yakoleva, I Leibiger, B Leibiger, A Alimov, G Weber, A Höög, A Villablanca
  [show abstract] [hide abstract]
  ABSTRACT: Inactivation of the hyperparathyroidism-jaw tumour syndrome (HPT- JT) gene, HRPT2, was recently established as a genetic mechanism in the development of parathyroid tumours. Its encoded protein parafibromin has tumour-suppressor properties that play an important role in tumour development in the parathyroids, jaws and kidneys. Inactivating HRPT2 mutations are common in HPT- JT and parathyroid carcinomas, and have been described in a few cases of parathyroid adenomas with cystic features. In this study, 46 cases of cystic parathyroid adenomas previously investigated for HRPT2 mutations were characterized with regard to MEN1 gene mutations, cyclin D1 expression and parafibromin expression. In normal tissues and cell lines, parafibromin was ubiquitously expressed. Furthermore, parafibromin was detected as a dominating nuclear and a weaker cytoplasmic signal in transfected cell lines. In the three parathyroid tumours with inactivating HRPT2 mutations parafibromin expression was not detectable, and in one of two cases with aberrantly sized parafibromin the protein was delocalized. Both high and low cyclin D1 levels were found among HRPT2-mutated and -unmutated tumours, suggesting that these events are not mutually exclusive in parathyroid tumour development. The presented data suggest that in the majority of benign parathyroid tumours the expression of parafibromin remains unaltered, while the loss of parafibromin expression is strongly indicative of gene inactivation through mutation of the HRPT2 gene.
  Endocrine Related Cancer 07/2006; 13(2):509-23. · 4.36 Impact Factor
• Article: Combined LOH/CGH analysis proves the existence of interstitial 3p deletions in renal cell carcinoma.

  A Alimov, M Kost-Alimova, J Liu, C Li, U Bergerheim, S Imreh, G Klein, E R Zabarovsky
  [show abstract] [hide abstract]
  ABSTRACT: We have recently developed an allele titration assay (ATA) to assess the sensitivity and influence of normal cell admixture in loss of heterozygosity (LOH) studies based on CA-repeat. The assay showed that these studies are biased by the size-dependent differential sensitivity of allele detection. Based on these data, we have set up new criteria for evaluation of LOH. By combining these new rules with comparative genome hybridization (CGH) we have shown the presence of interstitial deletions in renal cell carcinoma (RCC) biopsies and cell lines. At least three out of 11 analysed RCC cell lines and three out of 37 biopsies contain interstitial deletions on chromosome 3. Our study suggests the presence of several regions on human chromosome 3 that might contribute to tumor development by their loss: (i) 3p25-p26, around the VHL gene (D3S1317); (ii) 3p21. 3-p22 (between D3S1260 and D3S1611); (iii) 3p21.2 (around D3S1235 and D3S1289); (iv) 3p13-p14 (around D3S1312 and D3S1285). For the first time, AP20 region (3p21.3-p22) was carefully tested for LOH in RCC. It was found that the AP20 region is the most frequently affected area. Our data also suggest that another tumor suppressor gene is located near the VHL gene in 3p25-p26.
  Oncogene 04/2000; 19(11):1392-9. · 6.37 Impact Factor
• Article: Loss of heterozygosity in tumor cells requires re-evaluation: the data are biased by the size-dependent differential sensitivity of allele detection.

  J Liu, V I Zabarovska, E Braga, A Alimov, G Klein, E R Zabarovsky
  [show abstract] [hide abstract]
  ABSTRACT: Normal tissue contamination of tumors may eclipse the detection of loss of heterozygosity (LOH) by microsatellite analysis and may also hamper isolation of tumor suppressor genes. To test the potential impact of this problem, we prepared artificial mixtures of mouse-human microcell hybrid lines that carried different alleles of the same chromosome 3 marker. After performing an allele titration assay, we found a consistent difference between the LOH of a high molecular weight (H) allele and the LOH of a low molecular weight (L) allele of the same CA repeat marker. It follows that normal tissue admixtures will be less of a problem when LOH affects a H allele than with a L allele. Random screening of 100 papers published between 1994 and 1999 revealed that the loss of a L allele was recorded at about half the frequency (52%) of loss of a H allele. To avoid this bias, we have developed rules for the evaluation of LOH data. We suggest that the loss of a L allele should be given more weight than the loss of a H allele in LOH studies using microsatellite markers.
  FEBS Letters 12/1999; 462(1-2):121-8. · 3.54 Impact Factor
• Source

  Available from: psu.edu

  Article: Compact Low Energy Cw Linac With High Beam Current

  A. Alimov, A. Chepurnov, O. Chubarov, D. Ermakov, K. Gudkov, B. Ishkhanov, I. Piskarev, V. Shvedunov
  [show abstract] [hide abstract]
  ABSTRACT: INTRODUCTION tuning plunger in the range of 24502 MHz. Loaded quality factor of the cavity Q l = 3500 with a coupling constant 1.0. The calculated value of intrinsic quality factor Q 0 = 9000, shunt impedance R = 1.4 MW . After the buncher the beam enters the first accelerator section with graded-b (S 1 ), which accelerates the beam up to 600 keV. The output beam of the first section passes through a cooled aperture (A) with a diameter of 10 mm, which serves as a low- energy filter, and enters the second accelerator section (S 2 ) with tapered-b which accelerates the beam up to the energy of 1.2 MeV. Beam power and current at the accelerator output are measured by the Faraday cup (FC). To focus the beam solenoidal lenses L 1 and L 2 are used. Beam alignment is carried out by steerers St 1 and St<F9.069
  04/1998;
• Article: Loss of heterozygosity on chromosome arm 3p in nasopharyngeal carcinoma.

  L F Hu, G Eiriksdottir, T Lebedeva, I Kholodniouk, A Alimov, F Chen, Y Luo, E R Zabarovsky, S Ingvarsson, G Klein, I Ernberg
  [show abstract] [hide abstract]
  ABSTRACT: We have examined 17 primary undifferentiated nasopharyngeal carcinoma biopsies for allelic loss on 3p, comparing the findings in tumors with those in normal lymphocyte DNA from the same patients. Ten polymorphic microsatellite markers were used between 3p13 and 3p26. Allelic loss was observed in 12 samples (70%). Two loci were most frequently affected: D3S1067 (3p21.1-14.3) in 60% and D3S1217 (3p14.2-14.1) in 58%. One tumor seemed to have a homozygous deletion at 3p26, detected by the D3S1297 marker. Analysis of the clinical data showed that an increased number of aberrations in 3p was correlated with more advanced tumor stages.
  Genes Chromosomes and Cancer 11/1996; 17(2):118-26. · 3.31 Impact Factor
• Article: Report of the sixth international workshop on human chromosome 3 mapping 1995.

  S L Naylor, B Carritt, C Boileau, C Beroud, C Alexander, P Allderdice, A Alimov, T Ashworth, J Bonifas, P Bugert, [......], M Grompe, T Joensuu, A Jonasdottir, R Gizatullin, L Krols, R J Leach, S T Lott, A Killary, T Martinsson, L Messiaen
  Cytogenetics and cell genetics 02/1996; 72(4):255-70.
• Conference Proceeding: Compact low energy CW linac with high beam current

  A. Alimov, A. Chepurnov, O. Chubarov, D. Ermakov, K. Gudkov, B. Ishkhanov, I. Piskarev, V. Shvedunov, A. Shumakov
  [show abstract] [hide abstract]
  ABSTRACT: The present paper deals with the experimental investigation of electron capturing, design of a simple RF power system for multi-section accelerator, and beam acceleration at the prototype accelerator with two accelerator sections
  Particle Accelerator Conference, 1995., Proceedings of the 1995; 06/1995
• Article: Assignment and ordering of twenty-three unique NotI-linking clones containing expressed genes including the guanosine 5'-monophosphate synthetase gene to human chromosome 3.

  L Fedorova, M Kost-Alimova, R Z Gizatullin, A Alimov, V I Zabarovska, A Szeles, A I Protopopov, N V Vorobieva, V I Kashuba, G Klein, A V Zelenin, D Sheer, E R Zabarovsky
  [show abstract] [hide abstract]
  ABSTRACT: Twenty-three unique NotI-linking clones, mainly isolated from the NRL1 library, were mapped and ordered by fluorescence in situ hybridization to human chromosome 3. All these clones were partially sequenced around the NotI sites and thus represent sequence-tagged sites. The EMBL nucleotide database was then searched with sequences from the NotI-linking clones using the FASTA program. This search revealed that the NRL-090 clone (at 3q24) contains the gene encoding human guanosine 5'-monophosphate synthetase (GMPS-PEN). To our knowledge, this is the first localization of this gene. Clone NL1-320 (at 3p21.3) contains a gene encoding arginine tRNA (97.3% identity in 73 bp), while clones NRL-063, NRL-097 and NRL-143 contain expressed sequences with unknown functions. Other clones displayed 60-85% similarities to cDNAs, CpG islands and other genes.
  European Journal of HumanGenetics 5(2):110-6. · 4.40 Impact Factor
• Article: Somatic mutation and homozygous deletion of PTEN/MMAC1 gene of 10q23 in renal cell carcinoma.

  A Alimov, C Li, R Gizatullin, V Fredriksson, B Sundelin, G Klein, E Zabarovsky, U Bergerheim
  [show abstract] [hide abstract]
  ABSTRACT: We studied chromosome 10q loss of heterozygosity and PTEN/MMAC1 gene inactivation in renal cell carcinoma (RCC). Fifty-four cases of RCCs were analysed by three 10q RFLP markers. Forty one of them were heterozygous for at least one of the markers, of which fourteen showed LOH (34%). Six tumors which showed 10q deletion for RFLP markers and six randomly selected tumors without RFLP LOH were included in an extended study of 10q by eight microsatellite markers. Eight of these cases showed LOH with two smallest deleted regions (SRO) at 10q23 delineated by markers D10S541 and D10S579 while the other distal SRO is between markers D10S587 and D10S212 at 10q25-26. The five tumors with LOH covering 10q23 were selected for mutation analysis of PTEN/MMAC1 gene. One tumor without LOH of 10q23 was selected as a control. Using direct sequencing of nine exons, we found three different base pair changes in three tumors with LOH. Nine RCC cell lines were analysed for PTEN/MMAC1 gene inactivation. One homozygous deletion was detected in the cell line UOK147. No expression of PTEN/MMAC1 gene was detect by RT-PCR in the cell line UOK 147.
  Anticancer research 19(5B):3841-6. · 1.73 Impact Factor