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Biomedical subjects

F Brok-Simoni

Publications and source records attributed to F Brok-Simoni.

At least 19 recordsLinked to original sources
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↗
PubMed1988

More than two immunoglobulin heavy chain J region genes in the majority of infant leukemia.

Congenital and infant leukemia are rare conditions associated with a very poor prognosis due to the high frequency of adverse clinical and laboratory parameters. As the occurrence of multiple immunoglobulin heavy chain hybridization band in childhood leukemia has been associated with poor prognosis, we studied whether it was present in this type of leukemia as well. Seven cases were examined, 4 of them less than 7 months of age. The immunophenotype was lymphoid in 5 and hybrid in 2. Most had abnormal karyotypes. In 5 of the 7, including all with congenital leukemia, an immunoglobulin heavy chain J region multiband pattern was found by Southern blot. The multiband pattern, whether primary or due to clonal evolution, seems to be associated with poor prognosis.

Adolescent↗
PubMed1987

PGI*3(Israel), a new, unstable allele in the phosphoglucose isomerase system.

Phosphoglucose isomerase (PGI) and 16 other biochemical genetic markers were studied in an Israeli-Arab family previously described for hereditary deficiency of adenylate kinase (AK) and glucose 6-phosphate dehydrogenase (G6PD). In this inbred family a rare PGI*3 allele was observed in 11 of 32 members tested, indicating an autosomal codominant inheritance. The electrophoretic mobility of this allele is similar to that of the PGI*3 allele found in Indian populations, but unlike the Indian allele, it has a very low specific activity and heat stability. This PGI*3 allele, designated PGI*3 (Israel), seems to be a different unstable mutation and along with AK and G6PD deficiencies seems to be associated with severe anaemia.

Alleles↗
PubMed1987

Molecular analysis of Burkitt's leukemia in two hemophilic brothers with AIDS.

In two hemophilic brothers infected by the human immunodeficiency virus (HIV), Burkitt's leukemia developed within 1 year. Both patients were treated by aggressive chemotherapy, and both are still in complete remission for 23 and 14 months, respectively. Sera from both brothers contained anti-HIV antibodies. However, DNA extracted from the tumor cells, when analyzed by Southern blot using a cloned HIV probe, did not reveal HIV-related sequences. Hybridization experiments with an Epstein-Barr virus (EBV) probe revealed the presence of EBV-specific sequences in the tumors' DNA. In both patients' tumors rearranged c-myc genes were found. The rearrangements occurred in both genes 3' to the third exon of c-myc, thereby suggesting that a variant chromosomal translocation took place in both cases. Indeed, karyotype analysis of the malignant cells of one of the patients revealed the variant t(2:8) translocation. In contrast to the majority of Burkitt's tumors carrying this translocation, which are kappa light-chain producers, cells of our patient expressed lambda chains. Furthermore, in both cases the lymphoblasts carried IgG on the surface, again an unusual finding in Burkitt's tumors. Finally, because both patients had an identical HLA phenotype, the role of genetic factors in the development of such tumors should be considered.

Acquired Immunodeficiency Syndrome↗