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Biomedical subjects

P Benn

Publications and source records attributed to P Benn.

At least 37 records · Page 2Linked to original sources
PubMed1992

Cytogenetic studies of bone marrow fibroblasts cultured from patients with myelofibrosis and myeloid metaplasia.

Cytogenetic studies of bone marrow fibroblasts and blood cells from peripheral blood or bone marrow were performed in 19 patients with myelofibrosis with myeloid metaplasia (group 1), nine patients with other myeloproliferative syndromes without myelofibrosis (group 2), and 12 patients with anaemia secondary to iron deficiency or chronic inflammatory disease (group 3). Clonal cell populations with abnormal karyotypes were seen in the bone marrow or blood in five of 14 (36%) group 1 patients, one of nine (11%) group 2 patients and none (0%) of the group 3 patients. Abnormal karyotypes of bone marrow fibroblasts were found in three of 16 (19%) of patients of group 1, and in two of nine (22%) and two of 12 (17%) patients each of groups 2 and 3, respectively. Since abnormal karyotypes can be found in bone marrow fibroblasts cultured from normal subjects, and since the abnormalities seen in the bone marrow fibroblasts differed from those found in bone marrow or blood cells, it is suggested that abnormal karyotypes found in bone marrow fibroblasts cultured from patients with primary myelofibrosis do not necessarily reflect neoplasia. The results of this study are compatible with the widely accepted hypothesis that in patients presenting with 'primary' myelofibrosis, the fibrosis is a secondary reactive process.

Aged↗
PubMed1990

Highly complex genetic rearrangement involving at least seven breakpoints in a case of chronic myeloid leukemia.

Cytogenetic analysis for an atypical case of chronic myeloid leukemia (CML) showed a complex karyotype with four chromosome breakpoints (5q12, 12q21, 12q24, and 22q11) and translocation products that included a typical Philadelphia chromosome but apparently normal chromosomes 9. Molecular genetic analyses using four breakpoint cluster region (bcr) probes indicated that three breaks were probably present on chromosome 22. Two apparently independent breaks appeared to exist within the bcr, one of which was probably associated with a deletion of some bcr sequences. By combining the molecular and cytogenetic data, we could infer a total of seven breaks. This case illustrates the extensive and complex types of genetic alteration that may be associated with a c-abl and bcr fusion.

Chromosome Aberrations↗
PubMed1990

Recombinant gamma-interferon has activity in chronic myeloid leukemia.

We demonstrated the clinical effectiveness of recombinant interferon-gamma (rIFN gamma) (Biogen) in 18 patients with Philadelphia-positive chronic myeloid leukemia. Sequential cytogenetic studies and molecular analyses of the breakpoint cluster region and for immunoglobulin and T cell rearrangements were performed every 3-4 months. In 13 patients who received treatment for a minimum of 3 months, the majority were treated with 1.5 mg/m2, t.i.w., i.v. Nonhematologic effects--particularly chills, rigors, myalgia, fatigue, headaches, and nausea--were significant. Complete or partial hematologic responses were observed in six patients, two of whom had approximately 20% normal metaphases after an average of 74 weeks of treatment. However, reversion to 100% Ph+ cells occurred 30 weeks later. In these two patients, in whom normal metaphases were found, no changes were observed in the presence of rearrangements of the breakpoint cluster region. In addition, the marrows remained hypercellular, and the leukocyte alkaline phosphatase score and B12 levels remained abnormal. No immunoglobulin or T cell beta-chain gene rearrangements were found. These data indicate the clinical effectiveness of rIFN gamma in some patients with chronic myeloid leukemia, although the fundamental nature of the disease is unaltered by this form of treatment.

Bone Marrow↗
PubMed1989

Location of breakpoints within the major breakpoint cluster region (bcr) in 33 patients with bcr rearrangement-positive chronic myeloid leukemia (CML) with complex or absent Philadelphia chromosomes.

We report the sublocalization of the breakpoint in chromosome 22 in 33 patients with chronic myeloid leukemia (CML) who also had unusual marrow cytogenetics. In 23 patients, the leukemic clones were characterized by Philadelphia (Ph1) chromosomes that arose through complex translocations that involved three or more chromosomes. In the remaining ten patients, there were no detectable Ph1 chromosomes despite molecular evidence for the presence of rearrangements in the major breakpoint cluster region (bcr) of chromosome 22 in all cases. There was no significant difference between the two groups with respect to location of the breakpoints within the bcr. When these two groups of patients were combined, there was a significant excess of breakpoints in one segment of the bcr when compared to the distribution of breakpoints seen in 119 patients with simple 9;22 translocations. The difference in breakpoint distributions did not appear to be entirely attributable to differences between groups in disease duration at the time of study. These data support the notion that the unusual genetic recombinations that give rise to BCR/ABL fusion genes in CML involve specific DNA sequences of BCR (and possibly ABL) and additional, recombinogenic sequences, at least some of which are present in loci known to be nonrandomly involved in complex Ph1 translocations.

Adult↗
PubMed1989

Comparison of phenotyping and genotyping of lymphoid neoplasms.

Comparison of phenotyping (PT) and genotyping (GT) of lymphoid neoplasms was performed on 51 specimens including lymph nodes, bone marrows, and body fluids. PT was performed with a flow cytometer using a large monoclonal antibody panel. GT included the testing for gene rearrangements of heavy chain, kappa and lambda light chains, and T-cell receptor beta-chain genes with DNA probes. The results obtained from these two techniques were generally compatible in terms of clonality and cell lineage. Only one case of B-cell lymphoma was not diagnosed by PT but showed gene rearrangement. For T-cell lymphoma, GT offers a more definitive diagnosis than does PT. Biclonality was demonstrated in one case of hairy cell leukemia by GT only. The rearranged band also offers a definitive clonal identification based on electrophoretic mobility. GT can detect a monoclonal population as small as 5% and can be performed on old or fresh specimens. PT requires 20% abnormal cells and a fresh specimen. It is concluded that GT is superior to PT for lymphoid tumor diagnosis, but it should be reserved as a supplementary test at this stage because of its technical complexity.

Antibodies, Monoclonal↗
PubMed1989

Molecular characterization of variant translocations in chronic myelogenous leukemia.

Five to ten percent of the Ph-positive cases of chronic myelogenous leukemia (CML), termed variant translocations, involve at least one chromosome in addition to 9 and 22 in the abnormality. The involvement of chromosome 9 band q34, where the c-abl oncogene has been localized, is not always cytogenetically detectable in so called variant translocations due to complex rearrangements. We present two cases having the most frequently involved chromosomes (#3 and #17) in such translocations. In one case, both chromosome 9's were cytogenetically normal while in the other, band 9q34 was so called 'masked' or 'hidden'. After molecular evaluation using in situ hybridization and Southern blotting techniques, the involvement of the altered bcr/abl gene was demonstrated and the cytogenetic analysis was revised. Utilization of molecular probes in the evaluation of such cases should become a routine diagnostic procedure in detecting the exchange of bcr and c-abl sequences.

Adult↗
PubMed1988

A new translocation involving chromosomes 8 and 9 in a Philadelphia-negative chronic myelogenous leukemia.

A new case is presented displaying typical features of the stable phase of chronic myelogenous leukemia (CML), with a complex translocation involving chromosomes 8q and 9q. Cytogenetic evaluation revealed an abnormal karyotype, 46,XY,t(8;9)(q22;q34). Both chromosomes 22 were found to be cytogenetically normal. After molecular evaluation the cytogenetic diagnosis was revised to 46,XY,t(8;9;22)(q22;q34;q11). The importance of the chimeric abl/bcr gene fusion product in the pathogenesis of CML is suggested as a characteristic feature, even in some patients with a so-called Philadelphia (Ph) negative CML. Utilization of molecular probes in the evaluation of such cases must become a routine diagnostic procedure. Our patient received the potential benefit of Ph-positive directed therapy because of the present approach.

Adult↗
PubMed1988

Clonal immunoglobulin gene rearrangements in chronic lymphocytic leukemia: a correlative study.

Forty-two patients with chronic lymphocytic leukemia (CLL) were studied for immunoglobulin gene and T-cell receptor gene rearrangements. Immunoglobulin heavy chain gene rearrangements were demonstrable in 41 cases. One rearrangement of the T-cell receptor beta chain gene was detected. Quantification of the relative intensities of germline and rearranged DNA bands suggests that a significant component of the lymphocytosis may be due to cell populations other than the malignant clonal population, particularly in earlier stages of the disease. A direct relationship was found between severity of disease and the relative amount of clonal immunoglobulin heavy chain gene rearrangement. Preliminary data for 12 patients followed sequentially indicated that clinical deteriorations or improvements are reflected in an increase or decrease, respectively, in the proportion of cells with rearranged immunoglobulin genes. Change in the relative proportion of cells with germline versus rearranged genes may provide an additional useful criterion for staging CLL, for more precisely defining the abnormal lymphocyte population, and for monitoring progression of the disease and efficacy of treatment.

Adult↗
PubMed1988

A rare restriction enzyme site polymorphism in the breakpoint cluster region (bcr) of chromosome 22.

Detection of rearrangement of the breakpoint cluster region (bcr) of chromosome 22 by Southern blot analysis can be used for the routine diagnosis of CML. Restriction fragment length polymorphisms (RFLPs) in the bcr can potentially be confused with translocation since both alter the size of DNA fragments obtained. By digesting DNA with the restriction enzyme BamHl and analyzing with probes commonly used for identifying rearrangement of the bcr, we have observed a RFLP within the bcr. For one CML patient studied in detail, the presence of the polymorphism was confirmed by comparing the results of analyses of granulocytes and a T cell-enriched population. The same polymorphism was detected in three additional CML patients and a patient with thrombocytosis. For the diagnosis of CML, verification of rearrangement with multiple probes and/or restriction enzyme combinations is necessary to rule out false positives, as well as to reduce the chance of false negatives due to co-migration of DNA fragments.

Adult↗
PubMed1988

The location of breakpoints within the breakpoint cluster region (bcr) of chromosome 22 in chronic myeloid leukemia.

Rearrangement of the breakpoint cluster region (bcr) was demonstrated by Southern blot analysis in the DNA in each of 68 patients with Ph chromosome-positive CML and in 3 of 7 patients with apparent Ph chromosome-negative CML. In contrast, no bcr rearrangement could be found in DNA from 17 normal individuals and 28 patients with various hematologic disorders other than CML or ALL. An analysis of the location of the breakpoints within the bcr indicated that 3' breakpoints were significantly more common in patients in blast crisis or accelerated phase disease compared to those with chronic phase disease. Patients with chronic phase disease and 3' breakpoints had shorter average disease duration than that for chronic phase patients with 5' breakpoints, although the difference between these two groups of patients was not statistically significant. For patients who had progressed to accelerated disease or blast crisis, a statistically significant difference in chronic phase disease duration could be demonstrated between 11 patients with 3' breakpoints (average chronic phase 30.2 months) and 15 patients with 5' breakpoints (average chronic phase 50.6 months). For 8 patients studied in both chronic phase and accelerated or blast crisis, the location of the breakpoint did not change. We suggest that the bcr-abl fusion protein associated with a 3' breakpoint could result in more rapid progression to acute disease, and this may account for differences in the relative frequency of 3' and 5' breakpoints at different disease stages. Although more studies are required, identifying CML patients with a higher propensity for early blast transformation may eventually prove to be of some clinical value.

Blast Crisis↗
PubMed1988

Marker discrepancy as a diagnostic criterion for lymphoid neoplasms.

Multimarker studies were conducted on 195 lymph node, 59 bone marrow, 44 peripheral blood, eight body fluid, and eight internal organ specimens. The markers were identified by fluorochrome-labeled antibodies quantified with flow cytometry. T-cell receptor gene rearrangements were used for the determination of T-cell clonality. These studies confirmed that CD 19 (B4, Leu 12) is highly sensitive for B-lymphoblastic leukemia, CD 7 (Leu 9) is highly sensitive for T-lymphoblastic leukemia, and CD 5 (Leu 1) is highly sensitive for chronic lymphocytic leukemia. When these markers were compared to antigens of the same cell lineage (e.g., CD 19 to CD 20 [Leu 16] or to surface immunoglobulin, CD 7 to CD 3 [Leu 4], and CD 5 to CD 3), a marked discrepancy between them was diagnostic of the corresponding tumor. T-cell marker discrepancy (CD3 vs. CD 7) was demonstrated in T-cell lymphomas, but it was also shown occasionally in polyclonal T-cell populations. On the other hand, a marked discrepancy between the percentages of a B-lineage (CD 19 or CD 20)-positive and a surface-immunoglobulin-positive population is a reliable phenotype for the diagnosis of a surface-immunoglobulin-negative B-cell lymphoma.

Antigens, Surface↗
PubMed1987

Utility of molecular genetic analysis of bcr rearrangement in the diagnosis of chronic myeloid leukemia.

Two DNA probes for the breakpoint cluster region (bcr) of chromosome # 22 have been used to determine the proportion of Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML) cases that can be diagnosed by Southern blot analysis. Studies on 17 normal individuals and 17 patients with lymphomas and leukemias (other than CML) indicated that for the restriction enzymes chosen, only expected germ line DNA bands were obtained. In contrast, novel DNA bands interpreted as being the product of translocation within the bcr region could be demonstrated in 31 of 31 cases of Ph-positive CML. One commercially available 1.2 kb bcr probe detected most cases of CML. Because of the frequent presence of deletion of part of the bcr region, however, a probe from the 5' end of bcr is essential to detect some cases. An analysis of the bcr breakpoints occurring in CML patients suggested a difference in the location of the breakpoints for the blast crisis patients versus chronic phase patients although the difference between these two groups was not statistically significant. It is concluded that bcr analysis provides a powerful aid in the diagnosis of CML. This technique is of particular merit in cases when cytogenetic analysis is inconclusive and has considerable potential for improved speed and sensitivity of diagnosis.

Chromosome Banding↗
PubMed1983

Semi-independent living for the long-term mentally ill.

This article describes a program developed in Burnaby, British Columbia in early 1981 to provide former boarding home clients with placements in unsupervised group home settings. The article also demonstrates how the mentally ill can foster solutions to their housing problems by means of participation in a special needs housing society.

Activities of Daily Living↗