Biomedical subjects

G W Dewald

Publications and source records attributed to G W Dewald.

At least 91 records · Page 5Linked to original sources

PubMed1991

Normal cytogenetic values for bone marrow based on studies of bone marrow transplant donors.

For individuals suspected of having hematologic neoplasms, interpretation of the clinical significance of sporadic cells with chromosome breakage, structural anomalies, aneuploidy, or polyploidy is often difficult. To help resolve this problem, we established normal cytogenetic values for bone marrow (BM) by investigating 219 BM transplant (BMT) donors using standard techniques for chromosome analysis. The donors ranged in age from 2 to 58 years and were studied for 7 years. The constitutional karyotype for two individuals was 47,XXY; one was mos45,X/46,XX, one was mos46,XX/47,XX, + mar, and 215 were normal. Among other statistics, the median and normal ranges (95th percentile) were determined for any kind of chromosome abnormality, autosomal loss, autosomal gain, sex chromosome loss, sex chromosome gain, chromosome breaks or gaps, major structural abnormalities, and polyploidy. The results suggest that random loss of chromosomes is common in cytogenetic preparations of BM, appears to be largely technical and is inversely proportional to chromosome size. Cells with extra chromosomes or with structural abnormalities are rare in normal BM. No specific sporadic structural abnormalities of chromosomes are associated with normal BM. The widely accepted cytogenetic definition for an abnormal clone appears to be valid, with the possible exception of occasional studies involving loss of smaller autosomes. There may be a correlation between loss of the Y chromosome and age of the patient.

Adolescent↗

PubMed1991

Chromosome studies in 104 patients with polycythemia vera.

Chromosome studies were done in 104 patients with various stages of polycythemia vera (PV): 10 had leukemia-myelodysplastic syndrome, 28 had post-PV with myeloid metaplasia (PPVMM), 12 had PV with myelofibrosis, and 54 had PV. Chromosome studies were successful in 86 patients, 37 (43%) of whom had a chromosome abnormality. At diagnosis, 4 of 28 patients (14%) had an abnormal clone; the incidence was 78% in PPVMM and 100% in leukemia-myelodysplastic syndrome. Among the 63 patients with successful chromosome studies during the first 10 years of disease, 27% had an abnormal clone. In contrast, of the 23 patients who had the disease for more than 10 years, 87% had an abnormal clone. Chromosome abnormalities were found in 11 of the 60 patients who either were untreated or underwent only phlebotomy and in 26 of the 44 patients who were treated with myelosuppressive agents. Trisomy 8, +9, and 20q- were found in some patients early during the course of their disease and also among untreated patients. These chromosome abnormalities seem to be related to the natural course of PV rather than to therapy. Patients with a chromosomally abnormal clone at the time of diagnosis of PV had a poorer survival than did those with only normal metaphases. Cytogenetic results did not predict evolution of the disease, but they did provide clues to hematologic phenotype, duration of the disease, and consequences of myelosuppressive therapy.

Acute Disease↗

PubMed1990

Frequent occurrence of cytogenetic abnormalities in sporadic nonmedullary thyroid carcinoma.

Cytogenetic studies may provide important clues to the molecular pathogenesis of thyroid neoplasia. Thus, the authors attempted cytogenetic studies on 12 thyroid carcinomas: seven papillary, three follicular, and two anaplastic. Successful cytogenetic results were obtained on all 12 tumors; nine (75%) had one or more chromosomally abnormal clones. Four of the papillary carcinomas had a simple clonal karyotype, and three had no apparent chromosome abnormality. All four abnormal papillary tumors contained an anomaly of a chromosome 10q arm. In one instance, an inv(10)(q11.2q21.2) was observed in a Grade 2 papillary carcinoma as the sole acquired abnormality. In another case, an inversion or insertion involving 10q21.2 was found in a Grade 1 papillary tumor. The karyotype of a third tumor, a Grade 1 papillary carcinoma, was 46,XX,der(5)t(5;10)(p15.3;q11),der(9)t(9;?)(q11;?). A fourth abnormal papillary carcinoma, a Grade 1 tumor, had a t(6;10)(q21;q26.1) as the sole abnormality. Each of the five follicular or anaplastic carcinomas had a complex clonal karyotype. The three follicular carcinomas contained an abnormality of 3p25-p21, along with several other chromosome abnormalities.

Adenocarcinoma↗

PubMed1990

Cytogenetic findings in 21 cases of peripheral T-cell lymphoma.

Although numerous publications have described the chromosome abnormalities in B-cell non-Hodgkin lymphoma and their significance, sparse literature exists pertaining to the chromosome abnormalities in T-cell lymphoma. We did cytogenetic analyses in 21 cases of peripheral T-cell lymphoma (PTCL). Chromosomally abnormal clones were identified in 15 (71%) of the cases, including 7 of the 10 cases in which the histologic distinction between a malignant and benign process was difficult. Abnormalities of chromosome 1 were observed in 10 cases; a breakpoint at 1p36 was demonstrated in 5 of these cases. Chromosome abnormalities previously attributed to B-cell malignancies were infrequent. These results suggest an association between 1p36 breakpoints and PTCL and emphasize the utility of cytogenetic analysis for documenting clonality among the histologically diverse groupings of PTCL.

Adolescent↗

PubMed1990

Hematologic disorders in 13 patients with acquired trisomy 21 and 13 individuals with Down syndrome.

To study the role of trisomy 21 in hematologic malignancies, we investigated the hematologic disorders of 13 patients with acquired trisomy 21 and 13 individuals with Down syndrome (DS). The most common hematologic malignancy among the patients with acquired trisomy 21 involved both granulocytic and monocytic lineages. By comparison, the hematologic disorders among the DS patients were predominantly acute lymphocytic leukemia and acute megakaryocytic leukemia. Although our sample was small, our results suggest that most patients with acquired trisomy 21 have different hematologic disorders than individuals with DS. Perhaps the role of trisomy 21 in the development of hematologic malignancy is different in constitutional trisomy 21 than it is in acquired trisomy 21.

Aged↗

PubMed1990

Chromosome analysis of cryopreserved cells.

We describe a technique for freezing and thawing human leukemic cells for cytogenetic studies. We studied 64 harvests on 26 cryopreserved samples from 20 individuals. Chromosome quality was best in the samples from patients with myeloid disturbances. Successful chromosome studies of approximately 50% of the samples were accomplished. Cryopreservation of leukemic cells is not a substitute for fresh material because the method produces relatively few metaphases and mediocre chromosome spreading and banding. However, when rigid and appropriate research objectives are applied, chromosome analysis of cryopreserved leukemic cells can be a viable alternative to analysis of fresh cells.

Adolescent↗

PubMed1989

Twenty-six patients with hematologic disorders and X chromosome abnormalities. Frequent idic(X)(q13) chromosomes and Xq13 anomalies associated with pathologic ringed sideroblasts.

In our experience, acquired structurally abnormal X chromosomes are found in about 1% of patients with hematologic disorders who have a chromosomally abnormal clone. Over a 10-year period, we identified 26 patients with hematologic disorders who had an acquired X chromosome abnormality. In 13 of these patients, the breakpoints were at Xq13, and in 13 the had idic(X)(q13) chromosomes. The 13 patients with Xq13 breakpoints were all older females, and 12 had pathologic ringed sideroblasts with dysmyelopoietic syndromes or a history of these syndromes. Among the 13 patients with breakpoints other than Xq13, seven were male and six were female; only one of these patients had pathologic ringed sideroblasts, and all of these patients had a variety of hematologic disorders. Xq13 may contain genes that, when altered by the formation of chromosome abnormalities, may be associated with neoplastic disorders involving pathologic ringed sideroblasts.

Anemia, Sideroblastic↗

PubMed1989

Clinical-cytogenetic correlations in myelodysplasia (preleukemia).

Cytogenetic studies detected abnormalities in 107 (43%) of the 247 patients in this series. Some degree of overt clinical progression occurred in 55 patients (22%), this being 29% of those patients with cytogenetic abnormalities and 17% of those with normal chromosomes. The presence and complexity of a clonal cytogenetic abnormality correlated with shorter survival. In each clone category of a complexity classification (simple, complex, very complex), patients with some normal cells appeared to have better survival than those with none. In multiple regression analyses, the prognostic value of chromosomes was independent of (and second in importance to) the FAB type of myelodysplastic syndrome (MDS) whichever chromosome classification was used. Patients with refractory anemia (RA) had the lowest incidence of chromosome abnormalities and no cases were found to have only abnormal cells (AA). A greater proportion of patients with refractory anemia with an excess of blasts (RAEB) and RAEB in transformation (RAEB-t) had clonal abnormalities. Morphology alone is not at present able to distinguish between RA or refractory anemia with ringed sideroblasts and similar disorders that may not be MDS in the strict sense. Demonstration of a clonal cytogenetic abnormality remains a positive indication of the presence of the neoplastic nature of the disease.

Adult↗

PubMed1989

The clinical significance of karyotype in acute myelogenous leukemia.

To evaluate further the prognostic significance of karyotype at diagnosis of acute myelogenous leukemia (AML), we have made a follow-up study of 711 patients who were diagnosed between January 1, 1980, and March 31, 1982, and who were originally reported by the Fourth International Workshop on Chromosomes in Leukemia (4IWCL). Three different chromosomal classifications were evaluated, including presence of normal and abnormal metaphases (NN-AN-AA classification), a modification of the Chicago classification, and a complexity classification. All three chromosomal classifications were shown to correlate significantly with outcome in patients with de novo AML. Furthermore, the NN-AN-AA classification and the complexity classification had independent prognostic significance when age, sex, and FAB morphology were also considered in multivariate analyses of survival. These data provide further evidence that karyotype is an important factor in predicting the outcome of patients with AML.

Adolescent↗

PubMed1989

Physical mapping of a translocation breakpoint in neurofibromatosis.

The gene for von Recklinghausen neurofibromatosis (NF1), one of the most common autosomal-dominant disorders of humans, was recently mapped to chromosome 17 by linkage analysis. The identification of two NF1 patients with balanced translocations that involved chromosome 17q11.2 suggests that the disease can arise by gross rearrangement of the NF1 locus, and that the NF1 gene might be identified by cloning the region around these translocation breakpoints. To further define the region of these translocations, a series of chromosome 17 Not I-linking clones has been mapped to proximal 17q and studied by pulsed-field gel electrophoresis. One clone, 17L1 (D17S133), clearly identifies the breakpoint in an NF1 patient with a t(1;17) translocation. A 2.3-megabase pulsed-field map of this region was constructed and indicates that the NF1 breakpoint is only 10 to 240 kilobases away from 17L1. This finding prepares the way for the cloning of NF1.

Chromosome Mapping↗

PubMed1989

Acute leukemia with abnormal thrombopoiesis and inversions of chromosome 3.

Abnormal thrombopoiesis has been described in acute leukemias associated with inv(3) (q21q26.2) or t(3;3)(q21;q26.2). We reviewed 13 patients seen at the Mayo Clinic since 1979 with inversions of chromosome 3 or related abnormalities; 12 acquired and one constitutional. The patient with the constitutional abnormality had an inv(3)(p21q29) and mild leukocytosis and thrombocytosis. Among the 12 patients with acquired abnormalities, five had inv(3) (q21q26.2), three had t(3;3)(q21;q26.2), one had del(3)(q12q21), one had ins(6;3) (p21;q21q26.2), one had inv(3)(p21q12), and one had r(3)(p?21q?21). Each of these patients developed acute leukemia; eight had antecedent myelodysplastic syndrome, eight presented with platelet counts greater than 100 x 10(3)/microliters, and six had atypical megakaryocytic hyperplasia. Five patients had ringed sideroblasts in their marrow, an antecedent refractory anemia with ringed sideroblasts, or erythroleukemia. Seven patients received chemotherapy but showed no response. From the time of chromosome study, the median duration of survival was 4 months. Our results suggest that 1) although abnormal megakaryocytopoiesis is observed in patients with inv(3)(q21q26.2), multiple hematopoietic lineages are also involved in the neoplastic process; 2) an antecedent myelodysplastic syndrome is common in acute leukemia with inv(3) or related abnormalities; 3) affected patients have a poor survival and are resistant to conventional chemotherapy; and 4) abnormal megakaryocytopoiesis in acute leukemia may also be associated with pericentric inversions of chromosome 3.

Acute Disease↗

PubMed1989

A cytogenetic study of 53 human gliomas.

Cytogenetic studies were performed on human glioma samples obtained by stereotactic biopsy, stereotactic craniotomy, or routine craniotomy. Using in situ culture and robotic harvesting techniques, we obtained suitable metaphases in 50 (94%) of 53 tumors, including 28 diffuse astrocytomas, four juvenile pilocytic astrocytomas, two gliosarcomas, three other miscellaneous astrocytomas, eight oligodendrogliomas, four mixed oligodendroglioma-astrocytomas, and four ependymomas. Cytogenetic studies were performed only on primary cultures; the mean culture time was 9.6 days (range 1-31 days). One or more chromosomally abnormal clones were observed in 35 (66%) tumors. Eleven (21%) other specimens had random nonclonal chromosome abnormalities. In four (8%) specimens, no chromosome abnormalities were noted. The results of this study suggest that grade 3 and 4 tumors are more likely to contain an abnormal clone than tumors of grade 1 or 2 (p less than 0.01). The most common numeric chromosome abnormalities were -6, +7, -10, -13, -14, -15, -18, and -Y. The most common structural abnormalities involved 1p, 6q, 7q, 8p, 9p, 11p, 11q, 13q, and 19q. Four tumors had two or more independent clones and ten contained subclones demonstrating karyotype evolution. With in situ culture and robotic harvesting techniques, cytogenetic studies can be successful on nearly all human gliomas, including those derived from small stereotactic biopsies.

Adolescent↗

PubMed1989

Cytogenetic studies in 11 patients with small cell carcinoma of the lung.

Small cell carcinoma of the lung has reportedly been associated with structural abnormalities of the short arm of chromosome 3, but most of the previous studies were done on long-term cultures that involved cell lines. In the current study, we investigated the chromosome abnormalities in specimens from primary lung tumors grown in short-term cultures. Cytogenetic studies were done in 11 patients with small cell carcinoma of the lung, and a chromosomally abnormal clone was observed in each tumor. An abnormality of chromosome 3 was observed in six of these tumors.

Aged↗

PubMed1989

Cytogenetic analyses on giant-cell tumors of bone.

Giant-cell bone tumors are considered to be benign proliferations composed of poorly differentiated mononuclear cells and large multinucleated giant cells with the appearance of osteoclasts. Treatment is usually surgical resection, but there is a small risk of local recurrence and metastasis. Cytogenetic analyses were performed on giant-cell bone tumors of six consecutive patients. Chromosomally abnormal clones were found in three of the tumors, but no two patients had the same chromosome abnormality. Thus, there was no correlation between any specific chromosome change and the clinical behavior or histology of giant-cell bone tumors. However, all of the tumors had a significantly higher incidence of nonclonal chromosome abnormalities than is encountered in cultures of normal cells. The most common nonclonal abnormalities involved unusual telomere-to-telomere chromosome translocations. These findings suggest that the cells in these tumors are chromosomally unstable. The telomeres most frequently involved were on the long arm of chromosomes 19 and 20.

Adult↗

PubMed1988

Possible cytogenetic distinction between lymphoid and myeloid blast crisis in chronic granulocytic leukemia.

This study consists of 25 patients with chronic granulocytic leukemia in blast crisis (BC) or with acute leukemia who had a Ph1 chromosome and one or more other chromosome abnormalities and who were investigated by cytochemistry and immunocytochemistry techniques to determine whether the predominant blasts were myeloid or lymphoid. The disorder was myeloid in 15 patients, lymphoid in 8, and mixed in 2. Among the 15 patients with myeloid disorders, 13 (86.6%) had an additional Ph1 chromosome, i(17q), +8, +19, or some combination of these abnormalities. None of the eight patients with a lymphoid disorder had +8, +19, or i(17q), but one had an additional Ph1 chromosome. Among the eight patients with lymphoid disorders, two had structural abnormalities of chromosome 7 and two were monosomy 7. None of the patients with myeloid disease had a structurally abnormal chromosome 7, but one was monosomy 7. Our findings suggest that the number of chromosomes in an abnormal clone may be unreliable for distinguishing between lymphoid and myeloid BC. Most patients with myeloid disease had only abnormal metaphases, whereas many patients with lymphoid disorders had both normal and abnormal metaphases. This finding may partially explain why many patients with lymphoid BC respond better to treatment than do those with myeloid BC.

Acute Disease↗

PubMed1988

Familial pericentric and paracentric inversions of chromosome 1.

We investigated 33 individuals (21 carriers) from one family with a pericentric inversion involving a large part of chromosome 1 (1p36.1----1q32). In addition, we investigated 15 individuals (10 carriers) from another family with a paracentric inversion of a small part of chromosome 1 (1p32----1p36.1). In each family, the index patient was ascertained because three miscarriages had occurred. Each carrier of these inversions was phenotypically normal. If the miscarriages of the index patients are excluded, the frequency of recognized miscarriages among the carriers of childbearing age was 9% (4 of 46) for the family with pericentric inversion and 17% (4 of 23) for the family with paracentric inversion. One of the pericentric inv(1) carriers had had a stillborn daughter. The carriers of the pericentric inversion who were of childbearing age had 41 children; carriers of the paracentric inversion who were of childbearing age had 19 children. No live-born children with birth defects were observed in either family. This evidence, together with the low frequency of miscarriages, suggests that crossover within the inversion loop occurs much less frequently than might be expected from the large size of this inversion. Our investigation suggests that the risk of recognized miscarriages, stilbirths, and live-born children with recombinant chromosomes who have birth defects may be much lower for inv(1) carriers than previously reported. The risk of having a malformed child because of a recombinant chromosome is probably less than 3% for carriers of the pericentric inversion and less than 6% for the carriers of the paracentric inversion.

Chromosome Banding↗

PubMed1988

Oncogene expression in T-cell lymphoproliferative disorders.

We have investigated the expression of oncogenes and other related genes in eleven patients with T-cell lymphoproliferative disorders and ten patients with other hematologic malignancies. The phenotypes of the T-cell disorders were determined using monoclonal antibodies specific for helper or suppressor subsets. RNA preparations were isolated from peripheral blood mononuclear cells and/or lymph node sections, 5'-end labeled with gamma-32P-ATP, and hybridized under stringent conditions to an excess of nitrocellulose-bound specific cloned DNA; autoradiographs were analysed by microdensitometry. Results revealed increased expression of K-ras, v-fps, transferrin receptor, alpha-tubulin and alpha-interferon in at least five of six helper T-cell lymphoproliferative disorders, while five of five suppressor T-cell disorders demonstrated levels of hybridization to these clones no higher than background. However, studies of T-suppressor disorders demonstrated enhanced levels of beta-interferon-specific RNA in five of five patients, an increase apparent in three of six T-helper chronic lymphoproliferative disorders. These results demonstrate different patterns of gene expression evident in T-helper and T-suppressor abnormalities.

Adult↗

PubMed1988

Culturing and robotic harvesting of bone marrow, lymph nodes, peripheral blood, fibroblasts, and solid tumors with in situ techniques.

We have modified our in situ method for culturing amniocytes and have successfully used this new procedure to culture cells from bone marrow, lymph nodes, peripheral blood, fibroblasts, and solid tumors. We have been so satisfied with this method that we have used it in our routine practice for the past 2.5 years. A convenient feature of the in situ method is that the cultures can be processed with a commercially available robotic harvesting system (modified Tecan Robotic Sample Processor Model 505). This system also works well for in situ cultures of amniotic fluids. Robotic harvesting of in situ cultures provides a consistent and accurate procedure that saves about 10-15 minutes of technologist time per case.

Blood Cells↗