Search PubMed⌕ Search

Biomedical subjects

F Brok-Simoni

Publications and source records attributed to F Brok-Simoni.

At least 37 records · Page 2Linked to original sources
PubMed1998

Fast-FISH detection and semi-automated image analysis of numerical chromosome aberrations in hematological malignancies.

A new fluorescence in situ hybridization (FISH) technique called Fast-FISH in combination with semi-automated image analysis was applied to detect numerical aberrations of chromosomes 8 and 12 in interphase nuclei of peripheral blood lymphocytes and bone marrow cells from patients with acute myelogenous leukemia (AML) and chronic lymphocytic leukemia (CLL). Commercially available alpha-satellite DNA probes specific for the centromere regions of chromosome 8 and chromosome 12, respectively, were used. After application of the Fast-FISH protocol, and microscopic images of the fluorescence-labelled cell nuclei were recorded by the true color CCD camera Kappa CF 15 MC and evaluated quantitatively by computer analysis on a PC. These results were compared to results obtained from the same type of specimens using the same analysis system but with a standard FISH protocol. In addition, automated spot counting after both FISH techniques was compared to visual spot counting after standard FISH. A total number of about 3,000 cell nuclei was evaluated. For quantitative brightness parameters, a good correlation between standard FISH labelling and Fast-FISH was found. Automated spot counting after Fast-FISH coincided within a few percent to automated and visual spot counting after standard FISH. The examples shown indicate the reliability and reproducibility of Fast-FISH and its potential for automatized interphase cell diagnostics of numerical chromosome aberrations. Since the Fast-FISH technique requires a hybridization time as low as 1/20 of established standard FISH techniques, omitting most of the time consuming working steps in the protocol, it may contribute considerably to clinical diagnostics. This may especially be interesting in cases where an accurate result is required within a few hours.

Aneuploidy↗
PubMed1997

Central nervous system involvement at diagnosis in a case of pediatric CD30+ anaplastic large cell lymphoma.

Central nervous system (CNS) involvement in Ki-1/CD30 lymphoma is extremely rare, in contrast to the frequent involvement in other types of pediatric non-Hodgkin's lymphoma. No mechanism has yet been proposed to explain the sparing of the blood brain barrier in Ki-1/lymphoma. We present a 2-year-old boy who was admitted to the Department of Pediatric Hemato-Oncology due to lethargy, progressive breathing difficulties, massive diffuse lymphadenopathy, hepatosplenomegaly, and ichthyosis-like skin involvement with epidermolysis. A lymph node biopsy was compatible with Ki-1/CD30 anaplastic large cell lymphoma (ALCL). Bone marrow aspirate and biopsy demonstrated reactive hyperplasia. Cytogenetic analysis displayed hyperdiploid cells with 1p(-) in most cells. Cerebrospinal fluid examination showed pleocytosis with CD30+ cells. Possible mechanisms which could enable CNS involvement in this unusual case are discussed.

Central Nervous System Neoplasms↗
PubMed1997

Absence of p53 mutations in malignant mesotheliomas.

Mutations in the p53 gene are the most common genetic alterations found in human malignancies. In this study, a search was done for mutations in the conserved regions of the p53 gene in malignant mesotheliomas. Thirteen malignant mesotheliomas collected over the preceding 12 yr and maintained in paraffin blocks were examined by polymerase chain reaction (PCR) followed by both single-strand conformation polymorphism (SSCP) and denaturing gradient-gel electrophoresis (DGGE). Direct sequence analysis was performed in cases suspected for mutations. No mutations in exons 5 to 8 of the p53 gene were detected. Our results suggest that malignant transformation of human mesothelioma cells does not require inactivation of p53 by point mutations in the conserved regions of the gene.

Adult↗
PubMed1996

In vitro proliferative advantage of bone marrow cells with tetrasomy 8 in Ewing sarcoma.

We describe a case of a 14.5-year-old boy with a clinically aggressive pelvic Ewing sarcoma. The tumor cells showed the presence of a typical t(11;22)(q24;q12) aberration and gains of chromosomes 8, 10, 14, and 21. To determine the size of the trisomy and tetrasomy 8 clones an interphase analysis by fluorescence in situ hybridization with a centromere-specific chromosome 8 probe was performed. Significant quantitative differences between metaphase and interphase data were obtained. It was shown that culturing of bone marrow cells leads to enrichment of tetrasomy 8 population that may be explained by the proliferative advantage of the tetrasomy 8 cells.

Adolescent↗
PubMed1996

The characterization and localization of the mouse thymopoietin/lamina-associated polypeptide 2 gene and its alternatively spliced products.

Thymopoietins (Tmpos) are a group of ubiquitously expressed nuclear proteins, with sequence homology to lamina-associated polypeptide 2 (LAP2). Here we report the isolation and characterization of seven mouse Tmpo mRNA transcripts named Tmpo alpha, beta, beta', gamma, epsilon, delta, and zeta. The alpha, beta, and gamma Tmpo cDNA clones are the mouse homologs of the previously characterized human alpha, beta, and gamma TMPOs, respectively, whereas Tmpo epsilon, delta, and zeta are novel cDNAs. Additionally, the mouse Tmpo gene was cloned and characterized. It is a single-copy gene organized in 10 exons spanning approximately 22 kb, which encodes all of the described Tmpo cDNA sequences, located in the central region of mouse chromosome 10. The almost identical genomic organization between the human and mouse genes, and the novel alternatively spliced mouse transcripts, led us to reanalyze the human TMPO gene. The human beta-specific domain was found to be encoded by 3 exons designated 6a, 6b, and 6c and not by a single exon as described previously. These findings suggest that there may be more human transcripts than currently recognized. The possible involvement of the new growing family of Tmpo proteins in nuclear architecture and cell cycle control is discussed.

Alternative Splicing↗
PubMed1995

Analysis of microsatellite repeats in pediatric brain tumors.

Tumorigenesis has been shown to proceed through a series of genetic alterations involving protooncogenes and tumor suppressor genes. However, investigation of genomic instability of microsatellites has disclosed a new mechanism for human carcinogenesis, which is involved not only in hereditary nonpolyposis colon cancer (HNPCC) but also in a number of other malignancies. To determine whether microsatellite instability is involved in pediatric brain tumors, we screened 15 such tumors using seven microsatellite marker loci on six chromosomes 4, 5, 9p, 9q, 11, 14, and 17. Using the polymerase chain reaction method, DNA samples from the tumors and from normal peripheral blood leukocytes from each patient were compared for the allelic pattern produced at each locus. Our preliminary results indicate loss of heterozygosity at the fatty acid binding protein (FABP) locus, located on chromosomal arm 4q28-q31, the only trinucleotide repeat in the panel of markers used, for 3 of 15 cases, suggesting the presence of previously unidentified sequences relevant to brain tumorigenesis at or in the vicinity of this locus. We did not observe any microsatellite instability in these samples, indicating that the mechanisms operating in HNPCC are not active in this subset of pediatric brain tumors.

Brain Neoplasms↗
PubMed1995

Hexasomy of chromosome 8 and trisomy of chromosome 11 characterize two karyotypically independent clones in a case of acute non-lymphocytic leukemia. Conventional cytogenetic and FISH investigation.

A case of ANLL following a myelodysplastic syndrome, probably resulting from occupational exposure to ionizing irradiation, with two cytogenetically unrelated clones, hexasomy 8 and trisomy 11, was investigated by conventional cytogenetics and FISH. Significant quantitative differences between data obtained by metaphase and interphase analysis of the hexasomy 8 clone were observed. A difference in the sensitivity to chemotherapy of the two clones was found: while the hexasomy 8 clone markedly decreased in response to treatment, the trisomy 11 clone remained unchanged.

Aneuploidy↗
PubMed1995

Rearrangement of the immunoglobulin heavy chain gene in juvenile chronic myeloid leukaemia.

Five patients with clinical and laboratory features typical for juvenile chronic myeloid leukaemia (JCML) are presented. Rearrangement of the j joining region of the immunoglobulin heavy chain (Jh) was demonstrated in three children out of five analysed. As no Vh to DhJh nor kappa light chain rearrangements were demonstrated, it is reasonable to speculate that the transforming event of the stem cell happened at the stage when Dh to Jh rearrangement took place. As the monocytic lineage is prominent in JCML, it is suggested that the transforming event happens in a unique stem cell with intermediate differentiation towards the myelomonocytic as well as the B-lymphatic lineage. This stem cell, which is present at a certain stage of embryogenesis, disappears later. Such an early 'hybrid' cell is sometimes involved in leukaemias of early infancy, and may be the transformed cell in some cases of infantile leukaemia.

Base Sequence↗
PubMed1995

Preferred usage of specific immunoglobulin gene segments in chronic lymphocytic leukaemia cells of three HLA-identical sisters.

We report three family members, including a set of identical twins, who developed CD5 positive B-CLL. The patients are female Ashkenazi Jews sharing an identical HLA phenotype. Two of the HLA loci (B35 and Cw4) were common with those already described as being shared by Ashkenazi Jews with an increased incidence of CLL. The rearranged immunoglobulin genes of the malignant cells of all three patients were found to express genetically related VH regions belonging to the VH3 subgroup, and chromosomal studies suggest a process of clonal evolution in one of the twins.

Aged↗
PubMed1995

Demonstration of thymopoietin transcripts in different hematopoietic cell lines.

We have cloned and characterized the human thymopoietin (TP) coding region and studied the mRNA expression of this gene in different hematopoietic cell lines. The 150-bp PCR fragment that encodes the 49-amino-acid human TP peptide was isolated from genomic placental DNA. Its colinearity with the cDNA sequence suggests lack of introns within the coding region. TP mRNA expression was demonstrated in lymphocytes from all the differentiation stages investigated, as well as in a myeloid cell line (K-562). These findings suggest a further expansion of the proposed TP functions.

Amino Acid Sequence↗
PubMed1994

[Glucose phosphate isomerase deficiency with congenital nonspherocytic hemolytic anemia].

Glucose phosphate isomerase (GPI) deficiency is an unusual cause of hereditary nonspherocytic hemolytic anemia described in Israel in 2 families of Arab ancestry. The disease, inherited as an autosomal recessive disorder, manifests itself by symptoms and signs of chronic hemolysis which are often ameliorated by splenectomy. A variety of defective GPI variants, characterized by modified physicochemical and/or kinetic properties of the enzyme have been reported, suggesting extensive polymorphism for this enzyme deficiency. We recently diagnosed GPI deficiency in a 23-year-old Jewish Ashkenazi man. Since the age of 1 year, when a diagnosis of hemolytic anemia of undetermined etiology was made, he has required frequent blood transfusion. Since splenectomy, performed when he was 6 years old, the requirement for blood transfusions diminished drastically, restricted to hemolytic crises following intercurrent febrile illnesses. To the best of our knowledge, this is the first report of GPI deficiency in an Israeli family of Ashkenazi-Russian origin.

Adult↗
PubMed1994

CD10+ cell population in the bone marrow of patients with advanced neuroblastoma.

Immunocytologic analyses of bone marrow can provide clinically useful prognostic information in neuroblastoma. While analyzing the bone marrow with a panel of monoclonal antibodies, which detect neuroblasts and other defining B-, T-, and myloid lineage, we identified two infants with stage IV-S neuroblastoma whose bone marrow contained a large population of common acute lymphoblastic leukemia (ALL)-like cells. This population expressed HLA-DR, CD19(B1), CD10(CALLA), and occasionally CD20(B1). Since 1988, 17 additional patients with advanced neuroblastoma (IV-S, III, and IV) were studied by us. In 10 of the 19 patients, the bone marrow revealed an expanded CD10 population (20-70%). It appears that this group of patients has a better prognosis. Out of 9 patients who did not have an expanded CD10 population, 8 died within 9 months from diagnosis, whereas out of 10 patients with an expanded CD10 population only one died and the others are alive, 6-30 months from diagnosis (P < 0.001). An expanded CD10 population in the bone marrow of disseminated neuroblastoma patients may therefore serve as a prognostic factor. Apart from the prognostic value of this particular population in the single patient, its presence may shed light on the interrelationship between the immune system and the neuroendocrine compartment.

Adolescent↗
PubMed1994

Primary central nervous system Burkitt's lymphoma presenting as Guillain-Barré syndrome.

A rare case of CNS Burkitt's lymphoma presenting as acute Guillain-Barré syndrome is presented. A 6-year-old previously healthy female presented with acute onset of limb and truncal weakness, involvement of ocular and bulbar nerves, and areflexia. The clinical diagnosis of Guillain-Barré syndrome prompted treatment with intravenous gammaglobulin with no response. A lumbar puncture following revealed marked pleocytosis, elevated protein, and decreased glucose. Immunological, cytological, and molecular studies of these cells confirmed the diagnosis of Burkitt's lymphoma IgM, kappa with t(8;14) and rearrangement of the J and kappa immunoglobulin chains. Aggressive systemic and intrathecal chemotherapy were started and within 5 days remission was achieved. The child is in complete remission 2 years from diagnosis. Although very rare, CNS lymphoma should be taken into account in every patient presenting with the clinical features of acute polyneuropathy.

Acute Disease↗
PubMed1994

Congenital haemolytic anaemia associated with adenylate kinase deficiency.

Chronic haemolytic anaemia associated with adenylate kinase (AK) deficiency is very rare and only seven cases in five families have been described. We present six children of one family who are deficient of this enzyme and in three of them a combined G6PD deficiency was found. AK deficiency was transmitted by an autosomal recessive gene and heterozygous state was not accompanied by disease, whereas homozygously affected individuals present a congenital chronic non-spherocytic haemolytic anaemia with haemoglobin levels of 8-9 g/dl. Patients also deficient in G6PD suffer from a more severe haemolytic anaemia with haemoglobin levels around 6 g/dl. The AK-deficient children are also mentally retarded. Splenectomy performed in five of the six patients resulted in complete remission of the haemolytic process.

Adenylate Kinase↗
PubMed1994

Familial leukemia: description of two kindreds and a review of the genetic aspects of the disease.

We describe two kindreds of Arab ancestry characterized by multiple cases of acute lymphoblastic leukemia. Consanguinity and intermarriages were prevalent in the two families. Age, mode of presentation, characteristics of the leukemic cells, response to treatment and prognosis were remarkably similar among the patients. A short review of the literature on familial leukemia is given.

Child↗