Search PubMed⌕ Search

Biomedical subjects

G Dewald

Publications and source records attributed to G Dewald.

At least 37 records · Page 2Linked to original sources
PubMed1994

Long-term survival in acute myelogenous leukemia: a second follow-up of the Fourth International Workshop on Chromosomes in Leukemia.

Patients with acute myeloid leukemia (AML, equivalent to acute non-lymphoblastic leukemia [ANLL]) who were studied at the Fourth and Sixth International Workshops on Chromosomes in Leukemia and who have long survival have been re-assessed to identify factors which may be associated with good prognosis in AML. In a long-term survivor (LTS) group, there were more cases than expected in each age decade below 50, more cases than expected with FAB type M3, and fewer cases than expected of secondary leukemia. Of the distribution of chromosome abnormalities, t(15;17), t(8;21), and inv/del(16) were over-represented, and -5, -7, and rearrangements of 11q were under-represented. Multivariate analysis of all patients showed that age group, cytogenetic classification, FAB type, and sex all had independent, significant effects on survival. A new observation from a very small subgroup of patients was that deletion of 7q without concurrent abnormality of chromosome 5 appeared to be associated with a good prognosis.

Adolescent↗
PubMed1993

Polymorphism of human complement component C6: an amino acid substitution (Glu/Ala) within the second thrombospondin repeat differentiates between the two common allotypes C6 A and C6 B.

Component C6 of the human complement system exhibits a genetic polymorphism in all populations tested so far. Using isoelectric focusing two common allotypes, C6 A ('acidic') and C6 B ('basic') and a number of rare variants have been described. A comparison of the two published cDNA sequences of C6 suggests a polymorphism in codon 98. Using polymerase chain reaction (PCR) we amplified a segment of the human C6 gene encompassing the presumably polymorphic codon. According to the restriction fragment patterns obtained after DdeI digestion of the PCR product, three genotypes were distinguished. The polymorphism is caused by a nucleotide substitution (C-->A) in the second position of codon 98; allele 1 (GCG) codes for Ala, allele 2 (GAG) for Glu. Sequencing of PCR products confirmed the mutation. For 46 unrelated individuals genotyped by this PCR-based method we also determined C6 protein phenotype. Three phenotypes were observed (C6 A, C6 AB, C6 B). There was an absolute concordance between C6 protein typing and DNA typing. We thus conclude that the C6 A allotype is characterized by a Glu and the C6 B allotype by an Ala residue in position 98 of the C6 polypeptide chain.

Alanine↗
PubMed1993

Proficiency testing in clinical cytogenetics. A 6-year experience with photographs, fixed cells, and fresh blood.

The College of American Pathologists and the American Society of Human Genetics offer a proficiency testing program in clinical cytogenetics. Two hundred twenty-five laboratories now provide data for this survey, which was begun in 1986. Challenges have consisted of photographed metaphases, fixed lymphoblastoid cell suspensions, fresh peripheral blood, and disarranged karyotypes. The "correct" response was based on 80% or greater consensus among either the referees or the participants. Referee laboratories performed better than participants. More laboratories were able to report accurate recognition of abnormalities by using a coded list than could write the interpretation in standardized nomenclature. Deletions, unbalanced translocations, and inversions were more difficult challenges than balanced translocations or trisomies. Prenatal and lymphocyte challenges were more likely to result in consensus than were bone marrow challenges. Participants performed best on whole-blood challenges. Fixed cell suspensions were less satisfactory. Excellent quality case material is essential for a successful challenge. A grading system has been devised to separate artifacts of the survey process from proficiency variables.

Chromosome Aberrations↗
PubMed1991

Recombinational biases in the rearranged C1-inhibitor genes of hereditary angioedema patients.

DNA structural changes responsible for hereditary angioedema were sought in the C1-inhibitor gene, which contains unusually dense clusters of Alu repeats in various orientations. Among patients belonging to 45 unrelated families, eight partial C1-inhibitor gene deletions and a partial duplication were found. Four deletions had one of the boundaries within the gene and the other in extragenic regions--in three cases 5' of the gene and in one case 3' of the gene. The boundaries of the partial duplication and of the remaining four deletions mapped instead within a few kilobases of exon 4. The same element--Alu 1--the first of three tandem Alu repeats preceding exon 4, contained one of the breakpoints of each of these five rearrangements. Moreover, these recombination breakpoints spread over the entire length of Alu 1, in contrast with the tight clustering observed near the 5' end of Alu sequences rearranged in other human genes. Thus, two uncommon recombinational biases are observed in the Alu rearrangements of hereditary angioedema patients; one promotes the occurrence of intragenic breakpoints in a single Alu repeat, and the other allows the breaks to be distributed over the entire Alu structure rather than within the hot spot of the left Alu monomer. A region of potential Z-DNA structure, located 1.7 kb upstream of Alu 1, may contribute to both peculiarities.

Angioedema↗
PubMed1989

Characterization of a translocation within the von Recklinghausen neurofibromatosis region of chromosome 17.

The genetic defect causing von Recklinghausen neurofibromatosis (NF1) has been mapped to the proximal long arm of chromosome 17 by linkage analysis. Flanking markers have been identified, bracketing NF1 in 17q11.2 and laying the foundation for isolating the disease gene. Recently, a family in which a mother and her two children show both the symptoms of NF1 and the presence of a balanced translocation, t(1;17)(p34.3;q11.2), has been identified. We have examined the possibility that the translocation has occurred in or near the NF1 gene by constructing a somatic cell hybrid line containing the derivative chromosome 1 (1qter-p34.3::17q11-qter). On chromosome 1, the breakpoint occurred between SRC2 and D1S57, which are separated by 14 cM. The translocation breakpoint was localized on chromosome 17 between D17S33 and D17S57, markers that also flank NF1 within a region of 4 cM. These data are consistent with the possibility that the translocation event is the cause of NF1 in this pedigree. Consequently, the isolation of the translocation breakpoint, by approach from either the chromosome 1 or the chromosome 17 side, may facilitate the identification of the NF1 gene.

Animals↗
PubMed1989

[Genetic variants of the complement components and HLA-antigens associated in patients with psoriasis vulgaris in Japanese].

Genetic polymorphisms of the serum complement components (C2, C4, C6, and C7) and HLA-antigens were studied in Japanese patients with psoriasis vulgaris. Among these complement components, positive associations with C4A4 and C4B2 were obtained. In addition to the previously reported haplotypes HLA-Cw6-B13 and Cw6-Bw57-DR7, the extended haplotype HLA-Cw11-Bw46-C4A4. 4B2-BFS-C2C-DRw8 may be a high risk haplotype in Japanese patients with psoriasis vulgaris.

Asian People↗
PubMed1988

Establishment of an immature mast cell line from a patient with mast cell leukemia.

A cell line showing many characteristics of immature mast cells has been established from the peripheral blood of a patient with mast cell leukemia. Cultured cells contain low levels of histamine, are stained metachromatically by toluidine blue, and contain chloroacetate esterase, aminocaproate esterase and tryptase activities. The cells lack T and B lymphocyte, as well as myeloid cell markers, and do not possess IgE receptors. Solid tumors of metachromatically positive cells have been successfully induced and serially passed in nude mice using 5-azacytidine transformed cells. This cell line may be useful for future studies of mast cells and their constituents.

Animals↗
PubMed1988

Proficiency testing in clinical cytogenetics. The 1986 experience of the College of American Pathologists.

In 1986, the College of American Pathologists introduced a proficiency testing program in cytogenetics entitled "survey CY." Approximately 140 laboratories actively participated. The survey consisted of 20 cytogenetic cases sent to the participants in quarterly shipments of five challenges each. Photographic negatives of metaphases were the primary medium studied. The results reported by the participants were highly concordant for the determination of modal chromosome count and sex chromosome designation. More than 90% of the participants correctly identified the following abnormalities: trisomies 8, 13, 18, 21, and X; monosomy X; t(9;22); t(8;21); der(2) t(2;?); and 5p-. Abnormalities A fra(X)(q27), t(5;11), inv(16), and t(15;17) were correctly identified by more than 80%, 70%, 70%, and 60% of the participants, respectively. The participants had the most difficulty with diagnoses that involved photographs of high-resolution chromosome banding. The 1986 survey was not graded, but the 1987 cytogenetics survey will be scored on those challenges where there is at least 80% consensus among the participants.

Chromosome Aberrations↗
PubMed1987

Effect of recombinant gamma interferon on chronic myelogenous leukemia bone marrow progenitors.

In order to understand its mechanism of action and explore its potential as a therapeutic agent, we studied the effect of recombinant gamma interferon (IFN) on in vitro proliferation and on karyotype of bone marrow-derived hematopoietic stem cell progenitors (BFUe, CFUmix) obtained from patients with Ph1-positive chronic myelogenous leukemia (CML). Addition of IFN to culture resulted in a dose-dependent inhibition of both normal and CML BFUe and CFUmix. The maximum dose-dependent suppression of CML BFUe (92% +/- 4%) and CML CFUmix (100%) exceeded the maximum suppression of normal BFUe (40% +/- 4%) and normal CFU mix (68% +/- 6%) (p less than 0.001 and p = 0.008). In parallel studies, CML BFUe and CFUmix were cultured with and without IFN, and cells recovered from culture were examined cytogenetically. Treatment of CML bone marrow cells (BMC) with IFN resulted in an increase in the proportion (p less than 0.001) of Ph1-negative metaphases when compared to control cells grown in the absence of IFN. Recombinant gamma interferon has a significant antiproliferative effect against CML bone marrow-derived stem cell progenitors in vitro, and the addition of this agent to culture increases our ability to identify a cell population derived from a Ph1-negative progenitor pool. Recombinant gamma interferon may selectively spare Ph1-negative hematopoietic progenitors, and may be an active agent in the treatment of CML.

Cell Division↗
PubMed1986

Family study on the polymorphisms of the sixth and seventh components (C6 and C7) of human complement: linkage and haplotype analyses.

Genetic polymorphisms of the sixth and seventh complement components (C6 and C7) have been studied in Japanese family material using polyacrylamide gel isoelectric focusing followed by immunoblotting. Three common and four rare alleles were observed at the locus for C6. Inheritance of the two rare C6 variants, M11 and B3, was first confirmed. Three common C7 allotypes were classified as C7 1, C7 2, and C7 4, respectively. Linkage analysis confirmed the close linkage between the loci for C6 and C7. The maximum lod score was 8.43 at phi = 0 (95% confidence limits: phi = 0 and phi = .07). No significant linkage disequilibrium was found between C6 and C7 in directly determined haplotypes of unrelated parents.

Alleles↗
PubMed1984

Duplication of part of chromosome 1q: clinical report and review of literature.

We report a male infant with a 47,XY, + der(22),t(1;22)(q32;q11)pat karyotype. Thus, he has duplication of chromosomes 1(q32----qter) and 22(pter----q11). Six patients with dup 1(q32----qter) and eight with dup 1(q42----qter) have been described. These two groups of patients share several manifestations, including postnatal growth retardation; relative macrocephaly with widely separated sutures or large fontanelles; prominent forehead; highly arched palate; micrognathia; downward slant of the palpebral fissures; broad, flat nasal bridge; and apparently low-set, malformed ears. Although many of these abnormalities are nonspecific, partial duplication of 1q should be considered in infants with relative macrocephaly, large fontanelles, and downward slant of the palpebral fissures. Our patient had duplication of the part of chromosome 22 that may be associated with the clinically variable cat-eye syndrome. Patients with dup 22(pter----q11) may also have downward slant of the palpebral fissures, micrognathia, and apparently low-set, malformed ears. The structural gene locus for beta-glucosidase has been mapped to chromosome 1. beta-Glucosidase activity in fibroblasts from our patient was normal, and his parents' activities were not significantly different from those of control individuals. Therefore, either the locus for this enzyme is not present on 1(q32----qter) or the enzyme does not consistently show a substantial gene-dose effect.

Abnormalities, Multiple↗
PubMed1983

HLA-linked complement polymorphisms (C2, BF) in psoriasis.

Starting from the known association between psoriasis and several HLA antigens and from the fact that the HLA chromosomal region contains the structural genes for at least three complement components, the authors have looked for an association between psoriasis and allotypes of C2 and BF. C2 and BF polymorphism were examined in 230 psoriatic patients. Two rare complement genes were found to be significantly increased when compared with controls: the frequency of the C2*2 gene was 0.061 among patients and 0.035 among controls (P less than 0.05); for BF*SO7, the frequencies were 0.0304 in patients and 0.0092 in controls (P less than 0.0005). The BF*F gene frequency, however, was significantly decreased among patients: 0.1196 vs. 0.1743 (P less than 0.01). The relative risks were 1.79 for the C2 2, 3.44 for the BF SO7, and 0.6 for the BF F gene product. From previous studies, it is known that these three complement alleles (C2*2, BF*SO7, BF*F) are in linkage disequilibrium with HLA alleles that have also been found increased or decreased, respectively, in psoriasis.

Alleles↗
PubMed1980

Origin of chi46,XX/46,XY chimerism in a human true hermaphrodite.

Using chromosome heteromorphisms and blood cell types as genetic markers, we demonstrated chimerism in a chi46,XX/46,XY true hermaphrodite. The pattern of inheritance of the chromosome heteromorphisms indicates that this individual was probably conceived by the fertilization, by two different spermatozoa, of an ovum and the second meiotic division polar body derived from the ovum and subsequent fusion of the two zygotes. This conclusion is based on the identification of the same maternal chromosomes 13, 16, and 21 in both the 46,XX and 46,XY cells of the patient. In the two cell lines of the chimera, chromosomal markers showed different paternal No. 9 chromosomes and sex chromosomes, as well as the same paternal chromosome 22.

Chimera↗
PubMed1980

Female phenotype and multiple abnormalities in sibs with a Y chromosome and partial X chromosome duplication: H--Y antigen and Xg blood group findings.

A mentally retarded female child with multiple congenital abnormalities had an abnormal X chromosome and a Y chromosome; the karyotype was interpreted as 46,dup(X)(p21 leads to pter)Y. Prenatal chromosome studies in a later pregnancy indicated the same chromosomal abnormality in the fetus. The fetus and proband had normal female genitalia and ovarian tissue. H--Y antigen was virtually absent in both sibs, a finding consistent with the view that testis-determining genes of the Y chromosome may be suppressed by regulatory elements of the X. The abnormal X chromosome was present in the mother, the maternal grandmother, and a female sib: all were phenotypically normal and showed the karyotype 46,Xdup(X)(p21 leads to pter) with non-random inactivation of the abnormal X. Anomalous segregation of the Xga allele suggests that the Xg locus was involved in the inactivation process or that crossing-over at meiosis occurred.

Abnormalities, Multiple↗