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Biomedical subjects

F Brok-Simoni

Publications and source records attributed to F Brok-Simoni.

At least 55 records · Page 3Linked to original sources
PubMed1994

Biased representation of immunoglobulin heavy chain variable region subgroups in chronic lymphocytic leukemia.

The distribution of three immunoglobulin heavy chain variable region gene subgroups (VH1, 3 and 5) was investigated, using the polymerase chain reaction technique, in 53 patients with chronic lymphocytic leukemia. Thirty-seven patients displayed rearrangements of one of the above three gene segments. Over-representation of the VH5 subgroup was observed relative to its small size.

Antigens, CD↗
PubMed1994

In vivo clonal evolution of pre-B to B-cell acute lymphoblastic leukemia in childhood.

Two cases are described that provide further evidence for clonal evolution in pre-B-cell acute lymphoblastic leukemia. Two infants, whose lymphoblasts at diagnosis were morphologically subtyped as L1 and immunophenotyped as HLA DR+, CD19+, CD10+/- and C mu-, were induced and maintained in remission. One child relapsed 6 months after initiation of therapy. This time his lymphoblasts had L3 morphology and immunophenotyping demonstrated the appearance of surface immunoglobulins. The second child relapsed 18 months after initiation of therapy with a lymphomatous picture. He also had peripheral and bone marrow blasts with L3 morphology and surface immunoglobulins. A lymph node biopsy showed diffuse small non-cleaved lymphoma with a 'starry sky' appearance compatible with Burkitt's lymphoma. Only one case with a similar clonal evolution has been reported in the literature, but no surface immunoglobulins were demonstrated. The significance of clonal evolution in these cases and its potential practical implications are discussed.

Clone Cells↗
PubMed1993

Analysis of rearranged immunoglobulin genes indicating a process of clonal evolution in chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) is known to be a stable monoclonal neoplasm. In contrast to early studies demonstrating no more than two hybridizing immunoglobulin heavy chain bands corresponding to the two expected alleles, we have demonstrated an unexpected multiband pattern when the HindIII-digested DNA samples from 38 CLL patients were analysed by Southern blot hybridization using JH and C mu gene probes. In order to characterize the genetic basis for the multiband pattern, we molecularly cloned the immunoglobulin heavy chain genes of one of the patients whose leukaemic DNA sample demonstrated three hybridizing JH bands and a loss of the germline band. The cloned rearranged immunoglobulin genes could be divided, based on the restriction mapping and the hybridization with the various probes, into two basic patterns representing two alleles. In one of the cloned rearranged immunoglobulin genes a secondary rearrangement occurred that resulted in the addition of 300 base-pair long sequence into the switch region, and the creation of a HindIII restriction site. The results of the study suggest that clonal evolution occurs in some CLL, and that many of these neoplasms are indeed oligoclonal due to the accumulation of secondary genetic changes.

Antibodies, Neoplasm↗
PubMed1993

Detection and clinical relevance of genetic abnormalities in pediatric acute lymphoblastic leukemia: a comparison between cytogenetic and polymerase chain reaction analyses.

The E2A/PBX1 and the BCR/ABL fusion genes result from the t(1;19)(q23;p13) and the t(9;22)(q34;q11), respectively, and encode oncoproteins which are thought to play an important role in the development of acute lymphoblastic leukemia (ALL) subtypes associated with adverse prognosis. The use of the polymerase chain reaction (PCR) for the detection of these genetic rearrangements may offer advantages over cytogenetic techniques which are often unsatisfactory in patients with ALL and, furthermore, provide a useful tool for monitoring of residual disease. However, it has not yet been evaluated whether the employment of PCR at the time of diagnosis improves the detection rate of these clinically relevant genetic anomalies. We have developed a multiprimer-PCR protocol which facilitates the detection of each of the four chimeric E2A/PBX1 and BCR/ABL mRNAs in a single reaction. This protocol was used for the evaluation of bone-marrow or blood samples from 251 children with ALL in whom cytogenetic analyses had been performed. Of the 251 patients, 221 had a B-cell precursor immunophenotype. In this group, 21 patients (9.5%) carrying the E2A/PBX1 rearrangement and three patients (1.4%) with BCR/ABL transcripts were detected by PCR. Twelve of these cases had escaped the detection by conventional cytogenetic analysis. In two of 12 patients with a typical t(1;19)(q23;p13), no E2A/PBX1 transcripts were identified by PCR, thus suggesting the presence of different molecular rearrangements. Residual leukemic cells were detected by PCR in five of eight patients who were followed during complete clinical remission. The frontline use of PCR has an important impact on the timely diagnosis, therapeutic decisions, and monitoring of high-risk patients with B-cell precursor leukemia who carry the E2A/PBX1 or BCR/ABL fusion genes.

Adolescent↗
PubMed1992

Erythrocyte glutathione and tumour response to chemotherapy.

There is much evidence that tumour glutathione (GSH) concentration is an important factor in resistance to cancer chemotherapy. Since measurement of tumour GSH would require an invasive procedure in every patient, we have tried to find out whether GSH concentrations in peripheral-blood erythrocytes are related to the response to chemotherapy and thus whether they reflect those in tumour cells. Erythrocyte GSH concentrations were measured by spectrophotometry in peripheral blood from 28 patients with advanced breast cancer and 40 patients with other tumours before and after treatment with various conventional chemotherapeutic regimens. The mean pretreatment GSH concentration was lower in patients who showed a complete or partial response to chemotherapy than in those with stable or progressive disease in both the breast-cancer group (8.69 [95% confidence interval 5.99-11.39] vs 2.32 [1.23-3.41] mumol/g haemoglobin; p less than 0.01) and the group with other tumours (5.94 [4.14-7.74] vs 2.83 [1.71-3.95] mumol/g; p less than 0.01). The correlation of erythrocyte GSH concentration with response rate suggests that this measurement may be helpful in prediction of response to therapy.

Antineoplastic Agents↗
PubMed1992

Detection of adeno-associated virus type 2 in human peripheral blood cells.

The non-pathogenic human parvovirus, adeno-associated virus (AAV) is helper virus-dependent. However, it integrates into the cellular genome in the absence of its helper viruses. Therefore it could become a useful vector for gene therapy. Previous studies and our own results have shown that 40 to 80% of adults are seropositive for AAV and that seroconversion occurs during the first few years of life, but little is known about the route of natural infection with the virus. We used the polymerase chain reaction to detect the AAV-2 genome and identify AAV sequences within peripheral blood leukocytes (PBLs). We could detect AAV in PBLs of two of 55 healthy blood donors, and two of 16 haemophilic patients. AAV DNA replication and viral protein production in PBLs propagated in tissue culture were also examined. AAV DNA replicated very efficiently in the presence of helper adenovirus, but capsid proteins were produced at a lower level and the yield of infectious virus was very low. Our findings prove that in vivo infection of PBLs occurs, and that PBLs could mediate the spread of AAV infection to different body tissues.

Capsid↗
PubMed1991

Identity of rearranged LINE/c-MYC junction sequences specific for the canine transmissible venereal tumor.

The canine transmissible venereal tumor is a naturally occurring neoplastic disease that affects the external genitalia of both sexes and is transmitted during coitus. Cytogenetic and immunologic studies demonstrated that tumors from different parts of the world are very similar, suggesting that they are transferred from one animal to another by the transplantation of viable cells. We found that the c-MYC oncogene was rearranged in this tumor by the insertion of a transposable genetic element sequence (known as LINE, long interspersed element) 5' to the first exon. The amplification of a DNA segment located in the junction of the LINE genome and c-MYC upstream sequences enabled the testing of the similarity of transmissible venereal tumor samples collected independently in different parts of the world. Oligonucleotide primers flanking the LINE/c-MYC junction were used to amplify a 340-base-pair segment and nested primers amplified a 280-base-pair segment. A fifth oligonucleotide used as a probe contained the actual junction sequence. All of the tumors analyzed revealed the existence of the specific bands, which were absent in normal canine DNA samples. The amplified segments obtained from all of the tumors analyzed were identical in size and nucleotide sequence, suggesting transmission of the original rearranged cell itself, as opposed to independent events of LINE insertion in a "hot spot."

Animals↗
PubMed1991

EBV genome and immunoglobulin gene rearrangement in the differential diagnosis of nasopharyngeal carcinoma and lymphoma.

Head and neck tumors include nasopharyngeal carcinoma (NPC) and lymphoma. The differential diagnosis of these tumors is based on histology, immunocytochemical staining, and EBV serology. In rare cases it might be difficult to distinguish between NPC and lymphoma in HE section or biopsies. DNA hybridization with cloned EBV and human immunoglobulin gene fragments allows the detection of EBV-related sequences and immunoglobulin gene rearrangements. The presence of EBV genome supports the diagnosis of NPC or EBV related BL, while rearrangement of immunoglobulin genes points to B-cell lymphoma. The diagnosis in 11 patients suspected of head and neck tumors was carried out by hybridization of DNA extracted from the tumors and assayed with cloned EBV and IgHCJ DNA probes. One patient proved to have EBV-associated BL based on positive hybridization with EBV probes and immunoglobulin rearrangement, presenting a unique hybridization with cloned EBV DNA BamHI W fragment, with bands of 3.2 and 3.9 kb. BL was confirmed in this patient by demonstration of c-myc rearrangement. A second patient was negative in hybridization with EBV, and positive for immunoglobulin rearrangement, and therefore was diagnosed as having B-cell lymphoma. In seven patients NPC was confirmed by hybridization with EBV-DNA probes. In two patients, both NPC and B-cell lymphomas were excluded.

Adolescent↗
PubMed1991

Lack of bcr rearrangement in juvenile chronic myeloid leukemia.

Juvenile chronic myeloid leukemia (JCML) is an unusual subtype of children's leukemia, characterized by unique clinical presentation. Recent studies revealed several biological features, distinguishing from those observed in adult type chronic myeloid leukemia (ACML). The majority of ACML cases are characterized by the presence of an hybrid bcr-abl rearranged gene. In an effort to elucidate the molecular basis of this unusual leukemia we looked for bcr rearrangement in six JCML cases. No bcr rearrangement was identified in any of the analyzed samples. Together with previous studies from JCML cases, JCML has a different mechanism of leukomogenesis from ACML.

Blotting, Southern↗
PubMed1991

Bone marrow cell populations mimicking common acute lymphoblastic leukemia in infants with stage IV-S neuroblastoma.

Immunophenotyping of bone marrow mononuclear cells of 2 infants with stage IV-S neuroblastoma revealed the presence of many lymphoblasts and immature lymphocytes. Immunophenotyping showed that a high percentage of bone marrow cells were positive for the HLA-DR, CD19, CD20 and CD10 phenotype, similar to common acute lymphoblastic leukemia cells. Within 6 months of follow-up, without any treatment, complete regression of the tumors was observed. The coexistence of these two unusual populations will be discussed.

Bone Marrow↗
PubMed1990

Phosphofructokinase deficiency (Tarui disease) associated with hepatic glucuronyltransferase deficiency (Gilbert's syndrome): a case and family study.

Tarui disease is a rare, genetically determined glycogen storage myopathy caused by the total lack of phosphofructokinase (PFK) enzymatic activity in the muscles and partially deficient enzymatic activity in the erythrocytes. We describe a patient with this disorder, who presented with exercise intolerance, painful cramps, elevation of muscle enzyme levels in the serum, compensated hemolysis with paradoxically elevated hemoglobin levels and gout with overproduction of uric acid. This patient had a partial hepatic uridine diphosphoglucuronate-glucuronyltransferase deficiency (Gilbert's syndrome). The coexistence of these two enzymatic deficiencies resulted in a complex clinical picture, especially during and after muscular effort. Screening of the patient's family revealed asymptomatic PFK deficiency in the erythrocytes of both parents and sister.

Adult↗
PubMed1989

Immunoglobulin heavy chain gene rearrangements in chronic lymphocytic leukaemia: correlation with clinical stage.

A search for a correlation between the clinical stage of chronic lymphocytic leukaemia (CLL) and the pattern of immunoglobulin heavy chain gene rearrangements was undertaken. DNA samples from the leukaemic cells of 38 CLL patients were analysed by Southern blot hybridization. Using probes for the immunoglobulin heavy chain J (JH) and C mu regions a marked heterogeneity of the hybridization patterns was observed in both regions. The number of JH hybridization bands varied from one to four and more than two were found in 58% of the patients. In 42% of the patients no germline JH genes were found. One to three additional C mu bands were observed in 34%, but the germline was preserved in all samples. There was no correlation between the clinical stage and the number of hybridizing JH bands; however, a significant correlation was found between the loss of JH germline band or a C mu multiband pattern and advanced stage of the disease. The genetic events in the immunoglobulin genes observed in advanced CLL patients are assumed to result from clonal evolution and tumour progression.

Adult↗
PubMed1989

Aplastic crisis due to human B19 parvovirus infection in red cell pyrimidine-5'-nucleotidase deficiency.

Two siblings with chronic hemolytic anemia due to red cell pyrimidine-5'-nucleotidase (P-5'-N) deficiency, presented within a few days of each other with a febrile illness and pancytopenia. The cause of the aplastic crisis was an acute infection with human B19 parvovirus (B19 HPV) as proven by immunoelectron microscopy and DNA hybridization. This is the first report on the association of B19-HPV-related aplastic crisis with P-5'-N deficiency.

5'-Nucleotidase↗
PubMed1989

A search for bcl1, bcl2, and c-myc oncogene rearrangements in chronic lymphocytic leukemia.

Three cellular or putative oncogenes: c-myc, bcl1, and bcl2 were previously found to be rearranged in some B cell malignancies due to chromosomal translocations. Data concerning the role of such genetic rearrangements in B-CLL are very scanty and limited to few cases in which bcl1 rearrangements were found. We studied DNA samples from 38 cases of B-CLL by Southern blot technique in order to find out the existence and frequency of such events. No bcl1 or bcl2 rearrangements were found in any of the studied cases; thus, involvement of these genes in CLL must be rare. In one patient who had an aggressive and resistant disease, c-myc rearrangement was found.

Adult↗