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A Beishuizen

Publications and source records attributed to A Beishuizen.

35 records · Page 2Linked to original sources
PubMed1995

Immunophenotypic changes between diagnosis and relapse in childhood acute lymphoblastic leukemia.

To get more insight into the phenotypic changes of childhood acute lymphoblastic leukemia (ALL) at relapse, a detailed morphological and immunophenotypic study in 40 childhood ALL cases (32 precursor B-ALL and 8 T-ALL) was performed. Expression patterns of non-lineage specific markers (terminal deoxynucleotidyl transferase (TdT), CD34, and HLA-DR), B-lineage markers (CD10, CD19, CD20, and CD22), T-lineage markers (CD1, CD2, CD3, CD4, CD5, CD7, and CD8), and cross-lineage myeloid markers (CD14, CD15, and CD33) were compared at diagnosis and relapse. In case of low blast counts (< or = 70%) at relapse, double labeling for membrane markers and TdT was used in order to define the precise immunophenotype of the TdT+ leukemic cells. An immunological marker-shift was defined as either a conversion from positive to negative and vice versa or a difference in positivity of > or = 50%. Morphological differences between diagnosis and relapse were detected in 34% of precursor B-ALL and 14% of T-ALL. Differences in immunological marker expression were found in 72% of precursor B-ALL and in 75% of T-ALL, and generally concerned minor shifts with loss or acquisition of a few markers. The morphological shifts and immunophenotypic shifts were not correlated. Immunophenotypic shifts were found for all markers tested in precursor B-ALL, except for HLA-DR. Shifts in CD10 expression (16% of cases) were only observed in relapses occurring 30 months or more after diagnosis. In four precursor B-ALL an intra-lineage shift was found at relapse (one common ALL to null ALL and three pre-B-ALL to common ALL or null ALL) and two precursor B-ALL cases were diagnosed as acute non-lymphocytic leukemia at relapse based on morphology and immunophenotype. In T-ALL, neither intra-lineage nor inter-lineage shifts were observed, although shifts were detected in all T cell markers tested, except for the lineage specific CD3 and T cell receptor (TcR) markers. In conclusion, immunophenotypic shifts at relapse frequently occur in precursor B-ALL and T-ALL, in a small percentage leading to an intra-lineage shift (10%) or inter-lineage shift (5%). Therefore immunophenotypic monitoring of minimal residual disease in ALL patients should be based on multiple marker combinations, preferably together with polymerase chain reaction analysis of rearranged immunoglobulin and/or TcR genes or chromosome aberrations.

Adolescent↗
PubMed1994

Analysis of Ig and T-cell receptor genes in 40 childhood acute lymphoblastic leukemias at diagnosis and subsequent relapse: implications for the detection of minimal residual disease by polymerase chain reaction analysis.

The rearrangement patterns of Ig and T-cell receptor (TcR) genes were studied by Southern blot analysis in 30 precursor B-cell acute lymphoblastic leukemias (B-ALLs) and 10 T-ALLs at diagnosis and subsequent relapse. Eight precursor B-ALLs appeared to contain biclonal/oligoclonal Ig heavy-chain (IgH) gene rearrangements at diagnosis. Differences in rearrangement patterns between diagnosis and relapse were found in 67% (20 cases) of precursor B-ALLs (including all eight biclonal/oligoclonal cases) and 50% (five cases) of T-ALLs. In precursor B-ALLs, especially changes in IgH and/or TcR-delta gene rearrangements were found (17 cases), but also changes in TcR-beta, TcR-gamma, Ig kappa, and/or Ig lambda genes (11 cases) occurred. The changes in T-ALLs concerned the TcR-beta, TcR-gamma, TcR-delta, and/or IgH genes. Two precursor B-ALLs showed completely different Ig and TcR gene rearrangement patterns at relapse, suggesting the absence of a clonal relation between the leukemic cells at diagnosis and relapse and the development of a secondary leukemia. The clonal evolution in the other 23 ALL patients was based on continuing rearrangement processes and selection of subclones. The development of changes in Ig and TcR gene rearrangement patterns was related to remission duration, suggesting an increasing chance of continuing rearrangement processes with time. These immunogenotypic changes at relapse occurred in a hierarchical order, with changes in IgH and TcR-delta genes occurring after only 6 months of remission duration, whereas changes in other Ig and TcR genes were generally detectable after 1 to 2 years of remission duration. The heterogeneity reported here in Ig and/or TcR gene rearrangement patterns at diagnosis and relapse might hamper polymerase chain reaction (PCR)-mediated detection of minimal residual disease (MRD) using junctional regions of rearranged Ig or TcR genes as PCR targets. However, our data also indicate that in 75% to 90% of ALLs, at least one major rearranged IgH, TcR-gamma, or TcR-delta band (allele) remained stable at relapse. We conclude that two or more junctional regions of different genes (IgH, TcR-gamma, and/or TcR-delta) should be monitored during follow-up of ALL patients for MRD detection by use of PCR techniques. Especially in biclonal/oligoclonal precursor B-ALL cases, the monitoring should not be restricted to rearranged IgH genes, but TcR-gamma and/or TcR-delta genes should be monitored as well, because of the extensive changes in IgH gene rearrangement patterns in this ALL subgroup.

Adolescent↗
PubMed1994

A new B-cell line showing a complex translocation (8;14;18) and BCL2 rearrangement.

A cell line named ROS-50 (Rotterdam suspension cell line no. 50) has been established from peripheral blood of a 69-year-old male with acute lymphoblastic leukemia (FAB type L3). Among the aberrations, cytogenetic analysis showed the presence of 14q+, 18q-, and two 8q- marker chromosomes. With fluorescence in situ hybridization (FISH) we characterized the chromosomal translocations, t(8;14) and t(14;18), in which the same chromosome 14 is involved. PCR analysis demonstrated the presence of on IGH-BCL2 rearrangement with a breakpoint in the minor cluster region (mcr) confirming the t(14;18) characteristic for follicular lymphoma. Additional studies showed high expression of BCL2 protein, an early B-cell immunophenotype, and an unusual pattern of IGH gene rearrangement.

Aged↗
PubMed1994

Detection of immunoglobulin kappa light-chain gene rearrangement patterns by Southern blot analysis.

Immunoglobulin light-chain (IgL) gene rearrangements occur in a sequential order during normal B-cell differentiation with Ig kappa gene rearrangements prior to Ig lambda gene rearrangements. Therefore, Ig kappa producing B-cells usually retain Ig lambda genes in germline configuration, whereas the Ig kappa genes are generally deleted on one or both alleles in most Ig lambda producing B-cells. The deletion processes in the Ig kappa locus are mediated via rearrangement of the kappa deleting element (Kde), which is located approximately 24 kb downstream of the constant (C) kappa gene segment. Kde rearrangements can delete the C kappa region (including the Ig kappa enhancer) or the complete joining (J) kappa-C kappa region via rearrangements to a heptamer recombination signal sequence in the J kappa-C kappa intron (intron RSS), or via rearrangement to a variable (V) kappa gene segment, respectively. To improve the Southern blot detection of clonal Ig kappa gene rearrangements and deletions in B-lineage malignancies, we developed a new set of optimal J kappa, C kappa, and Kde probes, and made a detailed restriction map of the J kappa, C kappa, and Kde region. Extensive Southern blot studies revealed that rearrangements in the J kappa gene region are optimally detectable by use of a J kappa probe in combination with at least two appropriate restriction enzymes, i.e. BamHI, BglII, EcoRI, HindIII, and/or SacI. J kappa gene rearrangements are also detectable with the C kappa probe in BglII and BamHI digests, if no deletion of the C kappa region has occurred. The two different types of Kde-mediated J kappa and/or C kappa gene deletions are easily detectable with the Kde probe in BglII, HindIII and/or EcoRI digests. This is in contrast to the inaccurate information obtained with the J kappa and C kappa probes, because these probes can detect deletions only in the form of decreased densities of J kappa and/or C kappa germline bands in the absence of rearranged bands. Our detailed analysis of 217 B-lineage leukemias revealed that 62% (69/111) of precursor B-cell acute lymphoblastic leukemias had rearranged and/or deleted Ig kappa genes. All 53 Ig lambda+ chronic B-cell leukemias contained Ig kappa gene deletions; in 75% this concerned biallelic J kappa and/or C kappa gene deletions. Virtually all Ig kappa gene deletions appeared to be mediated via Kde rearrangements, while only 1.5% of the Ig kappa gene deletions were mediated via an alternative deletion mechanism which involved the J kappa region.

Base Sequence↗
PubMed1993

Southern blot patterns, frequencies, and junctional diversity of T-cell receptor-delta gene rearrangements in acute lymphoblastic leukemia.

Southern blot analysis of T-cell receptor (TCR)-delta gene rearrangements is useful for diagnostic studies on the clonality of lymphoproliferative diseases. We have developed 18 new TCR-delta gene probes by use of the polymerase chain reaction (PCR) techniques. Application of these probes for detailed analysis of the TCR-delta genes in normal control samples, 138 T-cell acute lymphoblastic leukemias (T-ALL), and 91 precursor B-ALL allowed us to determine the TCR-delta gene restriction map for five restriction enzymes, as well as the Southern blot restriction enzyme patterns of all theoretically possible TCR-delta gene rearrangements. Based on this information, it appeared that 97% of all 213 detected TCR-delta gene rearrangements in our series of ALL could be detected by use of the TCRDJ1 probe and that the majority (76%) of the 213 rearrangements could be identified precisely. In T-ALL, we found a strong preference for the complete rearrangements V delta 1-J delta 1 (33%), V delta 2-J delta 1 (10%), and V delta 3-J delta 1 (7%) and the incomplete rearrangement D delta 2-J delta 1 (11%). In precursor B-ALL, the majority of rearrangements consisted of V delta 2-D delta 3 (72%) and D delta 2-D delta 3 (10%). The junctional diversity of these 6 preferential TCR-delta rearrangements was analyzed and showed an extensive junctional insertion (approximately 30 nucleotides) for complete V delta-J delta rearrangements, whereas incomplete rearrangements had correspondingly smaller junctional regions. The detailed TCR-delta gene restriction map and probes presented here, in combination with the Southern blot patterns of TCR-delta gene rearrangements, are important for TCR-delta gene studies in ALL; all TCR-delta gene rearrangements can be detected and the majority can be identified precisely. Identification of rearrangements is a prerequisite for subsequent PCR analysis of TCR-delta gene junctional regions, eg, for detection of minimal residual disease during follow-up of ALL patients.

Alleles↗
PubMed1993

Detection of immunoglobulin heavy-chain gene rearrangements by Southern blot analysis: recommendations for optimal results.

Southern blot analysis of immunoglobulin (Ig) and T-cell receptor genes has proven to be important for detection of clonal rearrangements in patients with lymphoproliferative diseases. To improve the detection of clonal Ig heavy-chain (IgH) gene rearrangements, we carefully determined the precise restriction map of the joining (J)H and constant (C)mu region of the IgH locus, and evaluated relevant combinations of restriction enzymes with JH and C mu probes. Our extensive Southern blot analyses revealed that rearrangements in the JH region are optimally detectable by use of a JH probe in combination with at least two restriction enzyme digests which are not affected by polymorphisms, and which produce small germline bands (e.g. BglII and BamHI/HindIII), thereby reducing the chance of comigration of germline and/or rearranged bands. Application of a JH or a C mu probe in combination with BamHI or EcoRI digests should be avoided, because of the large size of the restriction fragments and the occurrence of polymorphisms. Comparison of different types of JH probes demonstrated that optimally reproducible signals, independent of the rearranged JH gene segment, are only obtained if the JH probe is complementary to the 3' flanking sequences of the JH gene region, such as our IGHJ6 probe.

Base Sequence↗
PubMed1993

tal-1 deletions in T-cell acute lymphoblastic leukemia as PCR target for detection of minimal residual disease.

Polymerase chain reaction (PCR) techniques based on amplification and identification of leukemia-specific DNA sequences provide a sensitive diagnostic method for detection of minimal residual disease (MRD) with a detection limit of 10(-5) to 10(-6) (1-10 malignant cells in 10(6) normal cells). To date, the main leukemia-specific DNA sequences used as PCR targets in detection of MRD are breakpoint fusion regions of chromosome translocations and junctional regions of rearranged immunoglobulin (Ig) or T-cell receptor (TcR) genes. The recently identified tal-1 deletions involving the sil and tal-1 genes, provide a potential MRD-PCR target. tal-1 deletions are site-specific because they are mediated via recombination signal sequences homologous to Ig/TcR genes. In line with this homology, tal-1 deletions also show random insertion and deletion of nucleotides at their breakpoints, resulting in highly variable breakpoint fusion regions. The fusion region diversity can be applied to design patient-specific oligonucleotide probes. Our Southern blot analyses of a large series of 313 acute leukemias with a specific tal-1 deletion probe (SILDB) demonstrated that tal-1 deletions exclusively occur in T-cell acute lymphoblastic leukemia (T-ALL) and not in precursor B-ALL or acute non-lymphocytic leukemias. In addition, we did not detect tal-1 deletions in normal blood cells and normal thymocytes by PCR analysis. The diversity observed in tal-1 deletion fusion regions with an average insertion and deletion of approximately 7 and approximately 6 nucleotides, respectively, allowed us to design fusion-region-specific probes. The specificity of the fusion-region probes was proven and the detection limit of the MRD-PCR technique was tested in a series of dilution experiments. The observed detection limit of 10(-5) indicates that tal-1 deletions in T-ALL represent ideal leukemia-specific PCR targets for detection of MRD.

Base Sequence↗
PubMed1993

Differences in immunoglobulin heavy chain gene rearrangmeent patterns between bone marrow and blood samples in childhood precursor B-acute lymphoblastic leaukemia at diagnosis.

Bone marrow (BM) and corresponding peripheral blood (PB) samples from 30 patients with precursor B-acute lymphoblastic leukemia (precursor B-ALL) were analyzed for the configuration of their immunoglobulin (Ig) heavy chain (IgH) and Ig kappa chain (Ig kappa) genes. Rearrangements and/or delections of the IgH and Ig kappa genes were detected in 100 and 47% of patients in this series of precursor B-ALL, respectively. Multiple rearranged IgH gene bands, generally differing in density, were found in 10 precursor B-ALL samples. This multi-band pattern is most probably caused by subclone formation due to continuing rearrangement processes. In five of the 10 bi/oligoclonal cases (50%) differences in IgH gene rearrangement patterns between BM and PB samples were observed, which could be interpreted as the presence of an edeletections of the IgH and Ig kappa genestra subclone in two cases and differences in the size of the subclones in three cases. In the 20 monoclonal precursor B-ALL, no dissimilarities in IgH gene rearrangement patterns between BM and the corresponding PB samples were found. Differences in Ig kappa gene rearrangement patterns between BM and PB were not observed in this series of precursor B-ALL, which is in line with the finding that no multiple Ig kappa gene rearrangements were detectable. In all five cases, the edelections of the IgH and Ig kappa genestra subclones or the relatively larger sized subclones were found in the BM samples, suggesting that subclone formation in precursor B-ALL occurs in the tissue compartment from which the precursor B-ALL cells are thought to originate. This phenomenon will lead to underestimation of subclone formation, if only IgH gene analysis of PB samples is performed. In addition, it will hamper the detection of minimal residual disease by the polymerase chain reaction mediated amplification of 'leukemia-specific' IgH gene junctional regions, because it is unpredictable which subclone will cause minimal residual disease and/or relapse.

Bone Marrow Examination↗
PubMed1993

Eosinophilic gastroenteritis--a disease with a wide clinical spectrum.

Two patients with eosinophilic gastroenteritis are described. The predominant eosinophilic infiltration of the mucosal layer of the upper gastrointestinal tract resulted in severe protein-losing enteropathy and peripheral eosinophilia in one patient and a malabsorption syndrome due to saccharose and lactose intolerance in another patient. There was a wide range of abdominal symptoms, depending on the site and extent of the disease. The diagnosis was based upon typical biopsy findings. There was a marked lack of any biochemical abnormality. The course of the disease was chronic and relapsing. Symptoms were not controlled with corticosteroids alone; only after the addition of disodium chromoglycate per os was prolonged disease control achieved.

Adrenal Cortex Hormones↗
PubMed1992

Seizures and fever: can we rule out meningitis on clinical grounds alone?

A study was done of 309 children seen in two ERs with a first seizure and fever to assess whether meningitis could be recognized using readily available clinical information. Among these children, 23 (7%) cases of meningitis were diagnosed. A group of 69 children with seizures and fever but no meningitis served as controls. Signs from ER examinations that discriminated between children with and those without meningitis were: petechiae, nuchal rigidity, coma, persistent drowsiness, ongoing convulsions, and paresis or paralysis; 21 cases were thus identified. Two children with a suspicious history but none of these signs proved to have meningitis. Children whose seizures showed no complex features and whose febrile illness revealed no suspicious features did not have meningitis. Our results indicate that based on available clinical data, meningitis can be ruled out in children presenting with seizures and fever; thus, there is no need for routine investigation of cerebrospinal fluid.

Blood Sedimentation↗
PubMed1992

Detection of minimal residual disease in acute leukemia by immunological marker analysis and polymerase chain reaction.

Detection of minimal residual disease (MRD) can be useful for adaptation or stratification of treatment in acute leukemia patients and may finally result in individualization of treatment protocols. Although leukemic cells generally have immunophenotypes comparable to their normal counterparts, it is possible to use immunological marker analysis for the detection of MRD based on the assumption that the presence of positive cells outside their normal breeding sites and 'homing areas' is indicative of malignancy. This approach can be used for the detection of MRD in blood and bone marrow of patients with a terminal deoxynucleotidyl transferase (TdT) positive T-cell acute lymphoblastic leukemia (ALL) and patients with a TdT+ acute myeloid leukemia (AML) as well as in cerebrospinal fluid of patients with a TdT+ leukemia. In other types of acute leukemias, immunological marker analysis generally does not allow detection of low frequencies of malignant cells, but in a part of them the polymerase chain reaction (PCR) technique may be valuable. The PCR technique allows the amplification of tumor-specific DNA sequences or mRNA sequences (after reverse transcription into cDNA), if the flanking sequences are well-defined. This PCR-mediated amplification can detect specific sequences which are derived from only a few malignant cells between many normal cells. Well-defined chromosome translocations have been used as tumor-specific markers, such as t(9;22). An advantage of using specific chromosome aberrations as tumor-specific markers is their stability during the disease course. However, only 10-15% of ALL and 25-30% of AML have a specific chromosome translocation and in a large part of them the precise breakpoints are not (yet) known. Recent studies indicate that it is possible to detect MRD in acute leukemias by use of PCR-mediated amplification of the junctional regions of rearranged immunoglobulin (Ig) and T-cell receptor (TcR) genes, using variable (V) and joining (J) gene-specific oligonucleotides as primers. Major pitfalls of this application are the occurrence of multiple rearrangements at diagnosis (oligoclonality) and changes in rearrangement patterns at relapse (clonal evolution), which will lead to false negative results of this MRD-PCR technique. In conclusion, the technique of choice for the detection of MRD is dependent on the immunophenotype of the leukemia, the presence of a well-defined chromosome translocation and the presence of a rearranged Ig and/or TcR gene as well as the chance of immunophenotypic shifts and changes in Ig and TcR gene rearrangement patterns.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1991

[Hemobilia, a rare and difficult diagnosis].

Haemobilia, i.e. blood loss via the bile ducts, is a rare disorder, which may be caused by trauma, vascular disorders, gallstones, infection/inflammation, tumours and coagulation disorders. Haemobilia may cause grave morbidity and mortality. Important symptoms are: gastrointestinal bleeding, jaundice and colicky pains in the right upper abdominal quadrant. Gastroduodenoscopy, ultrasound, ERCP, CT-scan and MRI may be used to obtain additional information when haemobilia is suspected. Selective angiography may provide detailed information of the bleeding, but is less appropriate as an initial screening method. Haemobilia may be treated by selective embolisation of the involved artery or by operative treatment. Embolisation is the treatment of first choice in most situations. We present a case report of a patient with recurrent haemobilia caused by a ruptured aneurysm of a hepatic artery leaking intermittently into the bile ducts. Partly because of the rareness of this syndrome, the disorder was recognized with delay in our patient. After two embolisation attempts had failed, he was treated successfully by obliterative endoaneurysmorrhaphy.

Aneurysm↗
PubMed1991

Multiple rearranged immunoglobulin genes in childhood acute lymphoblastic leukemia of precursor B-cell origin.

Sixty precursor B-cell acute lymphoblastic leukemia (ALL) patients were analyzed for the configuration of their immunoglobulin (Ig) genes. Rearrangements and/or deletions of the Ig heavy chain (IgH), Ig kappa chain (Ig kappa), and Ig lambda chain (Ig lambda) genes were detected in 98, 48, and 23% of cases, respectively. Although these percentages suggest the presence of a hierarchical order in IgH and Ig light chain (IgL) gene rearrangements during B-cell differentiation, no correlation was found between the immunophenotype of the precursor B-ALL and the arrangement patterns of their IgH and IgL genes. Multiple rearranged IgH gene bands, generally differing in density, were found in 27 (45%) of the precursor B-ALL in various restriction enzyme digests. Cytogenetic data were used to determine whether the presence of more than two rearranged IgH gene bands was caused by hyperdiploidy of chromosome 14 or other chromosome 14 aberrations. The combined cytogenetic and IgH gene data allowed the precursor B-ALL to be divided into three groups: a monoclonal group (n = 36; 60%), a biclonal group (n = 16; 27%), and an oligoclonal group (n = 8; 13%). In five biclonal ALL biclonality at the Ig kappa gene level was also found. Such subclone formation was not detected at the Ig lambda gene level. As the detection limit of the Southern blot technique is 2-5%, it might well be that small subclones remained undetected, implying that the frequency of subclone formation at the IgH gene level in precursor B-ALL is probably higher than 40%. It has been suggested that precursor B-ALL with multiple IgH gene rearrangements have a higher tendency to relapse. Although higher relapse rates were found in the oligoclonal group (53%) and in the combined bi-oligoclonal group (33%) compared with the monoclonal group (20%), the log rank trend test showed no significance. The occurrence of multiple subclones in precursor B-ALL as found by IgH gene analyses will severely hamper the detection of minimal residual disease using the polymerase chain reaction (PCR) mediated amplification of 'tumor-specific' IgH gene junctional regions, because it cannot be predicted which detectable (or undetectable) subclone will cause minimal residual disease and/or relapse. Therefore it can be expected that the PCR technique will frequently produce false negative results during the follow-up of precursor B-ALL.

Antigens, CD↗
PubMed1989

[An infant with AIDS].

A four-month-old girl was hospitalized with pneumococcal sepsis from which she recovered. Subsequently she developed various other infectious diseases, including chronic diarrhoea caused by Cryptosporidium. After a period with neurological symptoms, later sagittal sinus thrombosis and cerebral atrophy, she died at age 13 months. It was found that the child suffered from AIDS. The mother was seropositive and the virus had probably been transmitted via the placenta. Rapid recognition of infants and young children with AIDS is necessary, for in the near future more cases of this disease will occur. Antiviral treatment may bring about improvement in children as well.

Acquired Immunodeficiency Syndrome↗