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D K Kalousek

Publications and source records attributed to D K Kalousek.

At least 109 records · Page 6Linked to original sources
PubMed1988

Interstitial 7q deletion [46,XX,del(7)(pter----q21.1::q22----qter)] and the location of genes for beta-glucuronidase and cystic fibrosis.

We report on a patient with a de novo chromosome abnormality del(7)(q21.1q22). The cells of this patient were used to determine the assignment of the gene for the enzyme beta-glucuronidase and the DNA probes around the cystic fibrosis gene--pJ3.11 and metH. Both the beta-glucuronidase gene and the DNA probes pJ3.11 and metH were found in 2 copies in our patient, indicating that neither locus lies in the deleted segment.

Chromosome Deletion↗
PubMed1988

Trisomy 4 in acute nonlymphocytic leukemia.

Trisomy 4 has recently been identified as a nonrandom chromosomal abnormality associated with acute nonlymphocytic leukemia with myelomonocytic morphology (AML M4). It has been suggested that it may be related to a new type of environmental toxin exposure. During the 1975-1987 period we have detected only one case of simple trisomy 4 in over 1200 patients successfully investigated for hematologic malignancy; this patient was diagnosed as having AML M2 and did not have a history of toxic chemical or drug exposure.

Chromosomes, Human, Pair 4↗
PubMed1988

Cytogenetic studies of haemopoietic colonies from patients with an initial diagnosis of acute lymphoblastic leukaemia.

For patients with an initial diagnosis of Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukaemia (ALL) and no documented history of Ph1-positive chronic myeloid leukaemia (CML), the cell of origin and extent of lineage involvement of the disease is often unclear. This is largely due to the fact that cytogenetic analysis of direct marrow preparations cannot distinguish between the presence of Ph1-positive myeloid metaphases and infiltration of the marrow with dividing Ph1-positive blasts. Cytogenetic analysis of cultured haemopoietic colonies allows more precise lineage assignment. We have used this approach to study five adult patients who presented with Ph1-positive ALL and subsequently showed a significant increase in normal metaphases (to 18-100% of all metaphases examined) following remission induction. In four of these five patients, some Ph1-positive erythroid and granulopoietic cells could be demonstrated. In the other, as in three patients with childhood ALL who presented with a Ph1-negative but cytogenetically abnormal clone, only chromosomally normal erythroid and granulopoietic progenitors were detected. Two Ph1-positive CML patients who entered a lymphoid blast crisis following a recognized chronic phase were also studied. In both of these latter two patients all erythroid and granulocyte-macrophage colonies analysed were Ph1-positive. These findings support the concept that patients presenting with Ph1-positive ALL comprise a heterogeneous group. In some cases the disease may arise in a restricted lymphopoietic cell not capable of myelopoietic differentiation. However, in others involvement of myeloid cells suggests these may be variant forms of CML in spite of an unusual initial response of the Ph1-positive clone to therapy.

Adult↗
PubMed1988

So-called primitive neuroectodermal tumor in aborted previable fetuses.

We have described the gross anatomic and histopathologic characteristics of 36 tumorlike lesions found in previable fetuses. Although these lesions appear to be invasive, metastasizing, and likely contributing to the death of the fetus, they represent a frequent finding only among severely macerated retained fetuses of 9-16 developmental weeks and have never been found in fresh nonretained fetuses. No family history of neurofibromatosis could be elicited in any of these cases to support the suggestion in the literature that these tumors may represent fetal manifestations of neurofibromatosis. The most likely explanation is that they represent an artifact owing to squeezing of brain tissue into the spinal canal and along the spinal nerves into retroperitoneal and retropleural spaces or the neck area. As this artifact appears to be confined to a specific developmental period (9-16 weeks), it may be related to certain developmental characteristics such as a very soft consistency of brain tissue or incomplete development of vertebral foramina. A higher incidence of these lesions among heteroploid fetuses remains unexplained.

Aneuploidy↗
PubMed1988

Molecular analysis of clonality and bcr rearrangements in Philadelphia chromosome-positive acute lymphoblastic leukemia.

Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) patients consistently show a rearrangement in a 5.8-kilobase length of chromosome 22, referred to as the breakpoint cluster region (bcr). In Ph1-positive acute lymphoblastic leukemia (ALL), the breakpoint in chromosome 22 is more heterogeneous and, in some instances, does not occur within this region. In such cases the cell of origin of the neoplastic clone and the relationship of the disease to CML has remained obscure. We have analyzed the bcr rearrangement in the malignant cells from three patients who presented with Ph1-positive ALL and who in cytogenetic studies had shown evidence of variable involvement of myeloid cells in the Ph1-positive clone. Rearrangements in bcr typical of most cases of CML were detected in purified granulocyte preparations from two of the ALL patients (nos. 1 and 2) and in the blasts from patient 3 at the time of her terminal relapse. In the same analysis the simultaneously obtained granulocytes from patient 3, however, did not show any evidence of bcr rearrangement. Patient 3 was also heterozygous for the BamHI polymorphism in the X-linked hypoxanthine phosphoribosyltransferase (HPRT) gene, thus permitting a different method of clonal analysis based on methylation differences in active and inactive alleles. When DNA from her granulocytes that had shown no bcr rearrangement was hybridized to an HPRT probe, a pattern typical of a polyclonal population was seen. A similar pattern was exhibited by her marrow fibroblasts. In marked contrast, her simultaneously isolated blasts showed an unambiguous monoclonal pattern. These findings demonstrate the origin of the disease in the first two patients in a cell with myelopoietic as well as lymphopoietic potential and confirm the restricted lymphoid cell origin of the neoplastic clone in the third Ph1-positive ALL patient. Furthermore, they indicate that different target cells for transformation within the hematopoietic system may be affected by very similar bcr rearrangements.

Blast Crisis↗
PubMed1987

Nonclonal hemopoietic progenitors in a G6PD heterozygote with chronic myelogenous leukemia revealed after long-term marrow culture.

When marrow cells from Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) patients are placed into long-term culture, Ph-positive progenitor numbers typically decline rapidly. Karyotypically normal cells derived from persisting, but previously undetectable, precursors can then frequently be demonstrated. To investigate the origin of these cytogenetically normal progenitors, long-term cultures were established with marrow from a girl with CML who was also heterozygous for the glucose-6-phosphate dehydrogenase (G6PD) enzyme variants A and B as shown by studies of her skin fibroblasts. Erythroid and granulocytic colonies generated in methylcellulose assays of fresh marrow from this patient were all Ph-positive and expressed the enzyme G6PD-A as found in the mature blood cells. In assays of 4- and 6-week-old long-term cultures, numbers of progenitors present were low and most were Ph-positive, but some (2/11) were Ph-negative. G6PD analysis showed that a similar proportion was not part of the neoplastic clone (4/30 were G6PD-B and 26/30 were G6PD-A). Thus, long-term marrow culture in conjunction with G6PD analysis was able to reveal the presence of a nonclonal hemopoietic progenitor population in a CML patient where such cells would not otherwise have been detected. This approach may offer a novel strategy for the demonstration and selection of populations of normal hemopoietic progenitors in other patients where the malignant cells cannot be distinguished by chromosome analysis.

Bone Marrow↗
PubMed1987

Acute myelomonocytic leukemia (AML-M4) and translocation t(6;9)(p23);q34): two additional patients with prominent myelodysplasia.

Two patients with acute myelomonocytic leukemia (AML-M4) and a specific chromosomal translocation t(6;9)(p23;q34) are reported and compared to 21 AML patients with the same translocation collected from the literature. Our observation suggest that AML with t(6;9)(p23;q34) is characterized by myelodysplasia, basophilia, and a variety of blast cell morphologies (M1, M2, M4) with a greater proportion of the cases than previously appreciated being examples of acute myelomonocytic leukemia (AML-M4). The consistent association of myelodysplasia provokes the proposal that this subtype of de novo AML is a result of an acute stem cell disorder. The poor outcome with standard AML chemotherapy experienced in this group of relatively young patients necessitates consideration of alternative therapeutic strategies such as early bone marrow transplantation.

Adult↗
PubMed1987

X chromosome aneuploidy in lymphocyte cultures from women with recurrent spontaneous abortions.

Occasional metaphases with X chromosome aneuploidy can be detected in short-term lymphocyte cultures from women with recurrent abortions. The significance of this finding is unknown. It has been suggested that it may reflect a genetic tendency to nondisjunction that predisposes these women to an increased risk of producing aneuploid offspring. We have investigated prospectively the frequency of X chromosome aneuploidy in lymphocyte cultures from 104 women with a normal chromosome constitution and a history of recurrent pregnancy loss defined as 2 or more spontaneous abortions. Seventeen women (16%) had a significant number (2-10%) of X aneuploid cells in cultured lymphocytes but no evidence of constitutional chromosome mosaicism, based on analysis of fibroblast cultures. A control group of age-matched fertile women without a history of recurrent abortions showed a similar level of X chromosome aneuploidy in lymphocyte cultures. No increased risk for production of liveborn children with aneuploidy was found on retrospective analysis of the reproductive histories of these women. A significant effect of culture conditions on X chromosome gain or loss has been demonstrated by comparison of medium 199 with Dulbecco's modified Eagle medium.

Abortion, Habitual↗
PubMed1987

Differential diagnosis of posterior cervical hygroma in previable fetuses.

Posterior cervical hygroma, once considered diagnostic of fetal Ullrich-Turner syndrome, is now recognized as being a nonspecific malformation found in a number of unrelated conditions. We have studied 61 fetuses of 10-23 developmental weeks from therapeutic and spontaneous abortions who had posterior cervical hygroma. We found that the group was indeed markedly heterogeneous, for both sexes were represented, and a variety of genetic and nongenetic disorders were present, such as trisomy 18, 21, and probably also 13; lethal multiple pterygium syndrome; Noonan syndrome; isolated congenital heart defect, isolated pterygium colli; and monosomy X (45,X). Unlike any of the other conditions, 45,X fetuses had a constant association of 3 defects--posterior cervical cystic hygroma, generalized subcutaneous oedema, and preductal aortic coarctation. Therefore, we suggest that this triad is diagnostic of lethal Ullrich-Turner syndrome in the fetal period and that it may be used reliably to diagnose the syndrome in fetuses when chromosome analysis is impossible. Further, since preductal coarctation of the aorta is found in only a small proportion of liveborn girls with Ullrich-Turner syndrome, but occurred in all aborted fetuses in our study, we suggest that this abnormality is related to the lethality of the 45,X chromosome constitution during fetal development.

Aortic Coarctation↗
PubMed1987

Cytogenetic abnormalities among spontaneously aborted previable fetuses.

We have reviewed spontaneously aborted fetuses of 9 to 20 developmental weeks. All fetuses with either external or internal developmental defects and those with maternal history of repeated spontaneous abortion were studied cytogenetically. Among 723 fetuses the cytogenetically proven prevalence of chromosome abnormalities was 5.8%. Inclusion of suspected chromosome abnormality based on morphologic findings resulted in an overall prevalence of only 7.1%. This prevalence and restricted spectrum of chromosome abnormalities, which included monosomy X, triploidy, gonosomal aneuploidy, trisomies 13, 18, and 21, resembled the prevalence and spectrum found among perinatal deaths and differed both in prevalence and type from those chromosome abnormalities found in spontaneous abortions occurring during the embryonic period. Monosomy X was the most common chromosome abnormality among previable fetuses. Both monosomy X and triploidy were more frequently detected in the early fetal period than in perinatal deaths. The combined prevalence of autosomal trisomies was equal to that which has been reported in the perinatal deaths. Chromosomal structural abnormalities, seen in perinatal deaths, were not found in our study.

Abortion, Spontaneous↗
PubMed1987

Transient myeloproliferative disorder in chromosomally normal newborn infant.

Transient myeloproliferative disorder is a condition clinically resembling congenital acute myelogenous leukemia. As in acute leukemias the blast cell population in this disorder may have either normal or abnormal chromosomal complement. Transient myeloproliferative disorder is well recognized in neonates with a complete or mosaic trisomy 21 (Down's syndrome). We report a phenotypically and cytogenetically normal infant with this syndrome in whom only blast cells showed trisomy 21. We postulate that the pathogenesis of the transient myeloproliferative disorder in both Down's syndrome infants and those with a normal chromosomal complement is related to abnormal prenatal production of placental regulatory hemopoietic factors caused by chromosomal defect(s) confined to placental tissues.

Bone Marrow↗
PubMed1987

Confined chorionic mosaicism in prenatal diagnosis.

Confined chorionic mosaicism, detected commonly on chorionic villus sampling (CVS) and occasionally in cultured amniotic fluid cells, is described in five pregnancies that showed confined chorionic mosaicism for trisomies 12, 13, 14, 17 and a marker chromosome. Cytogenetic findings in these pregnancies support the conclusion that within chorion some chromosomal mosaicism are confined to the trophectoderm derivatives while others to the extra-embryonic mesoderm. The etiology of confined chorionic mosaicism is discussed in relation to a significant role of multiple cell lineages contributing to the early development of placenta. The need is indicated for the use of both direct and long-term cultures in CVS prenatal diagnosis, and for the confirmatory testing of fetal blood or amniotic fluid in cases where mosaicism is detected in chorionic villi.

Adult↗
PubMed1987

Juvenile monosomy 7 syndrome: evidence that the disease originates in a pluripotent hemopoietic stem cell.

The present study was undertaken to investigate the hemopoietic cell from which malignant change evolves in juvenile dyshemopoiesis with monosomy 7. Two male patients, aged 18 and 5 months, were studied using progenitor assays combined with cytogenetics. Both had hepatosplenomegaly, cytopenias and a cellular marrow. The karyotype in direct marrow was 45,XY-7/47,XY,+8/46,XY in patient 1 and 45,XY,-7/46,XY in patient 2. Patient 1 received chemotherapy but developed acute nonlymphocytic leukemia after 17 months and died 20 months after diagnosis. During this time marrow metaphases with 45,XY,-7 increased to 100% (25/25). Patient 2 received an allogeneic marrow transplant 4 months after diagnosis which did not engraft. In both patients progenitors of both small (CFU-E) and large (BFU-E) erythroid colonies were present at normal frequencies. However, the colonies produced were small and poorly hemoglobinized with some erythropoietin-independent maturation. Progenitors of large granulocyte/macrophage colonies (CFU-GM) were present at an elevated frequency in the marrow of patient 1 and in the blood all progenitor classes were markedly increased. Cytogenetic analysis of colonies from this patient showed BFU-E to be 45,XY,-7 or 47,XY,+8 and CFU-GM to be 45,XY,-7 or 47,XY,+8 or 46,XY. In patient 2, most BFU-E were 45,XY,-7, although a few were 46,XY. These data indicate that malignant change in this disease involves hemopoietic stem cells capable of erythroid and in at least some cases, myeloid differentiation.

Acute Disease↗
PubMed1987

A routine method for cytogenetic analysis of small urinary bladder tumor biopsies.

A method that allows routine cytogenetic analysis of small cystoscopic biopsies from urothelial tumors is described. This method is based on prolonged mild collagenase disaggregation, a 12-16 hour culture, and harvesting procedures adapted to give maximal metaphase recovery. In addition to providing a means for cytogenetic studies of small biopsies from urinary bladder tumors, this method provides the advantages of direct preparations, with chromosome morphology and banding sufficient for karyotypic analysis. Conventional cell synchronization techniques, applied to this system, should enable high-resolution banding and optimize analysis.

Carcinoma, Transitional Cell↗
PubMed1987

Klinefelter's syndrome and acute leukemia.

Klinefelter's syndrome is associated with an increased risk of certain types of cancer. A small number of reports have documented the occurrence of acute leukemia in these patients. Our review of 1200 consecutive patients investigated cytogenetically for actual or suspected hematologic malignancy revealed only one patient with acute leukemia and the 47,XXY syndrome. This finding suggests that the risk of acute leukemia in Klinefelter's patients is no greater than that of the general population.

Acute Disease↗
PubMed1987

Fluorodeoxyuridine synchronization of hemopoietic colonies.

A method that allows the routine cytogenetic analysis of colonies growing in semisolid medium and containing as few as 50 cells is described. This method is based on the sequential addition of fluorodeoxyuridine and then thymidine to achieve higher mitotic yields by the synchronization of colony cells. In this study the schedule outlined was specifically optimized for application to small granulopoietic colonies from patients with Philadelphia chromosome (Ph)-positive chronic myeloid leukemia. In addition to increasing the spectrum of colony sizes yielding analyzable metaphases, this method significantly improved the general quality of the chromosome preparations obtained. Minor changes should enable this method to be applied to the analysis of colonies derived from a variety of other normal or malignant clonogenic cell types.

Cells, Cultured↗
PubMed1987

Flow cytometric and karyotypic analyses of androgen-responsive and androgen-independent Shionogi mouse mammary tumours.

The androgen-responsive (AR) Shionogi mouse mammary carcinoma is a heterogeneous tumour composed of AR and androgen-independent (AI) cells. We characterized the cells of the AR tumour and those of its AI derivative by flow cytometric analysis of DNA content and karyotypic analysis of metaphase spreads. Both tumours had diploid and near tetraploid populations of cells. However, the AR and AI malignant cells of these tumours both appeared to be polyploid. A decrease in the polyploid population of the AR tumour accompanied tumour regression following castration, but this population was restored when tumour growth resumed. Although karyotypic analysis of metaphase spreads showed wide variations in chromosome numbers among the polyploid population, the range, 55-88 chromosomes, was found in both AR and AI tumours. In addition, the same chromosome anomalies, including a marker chromosome, were identified in both tumours. Since the AR and AI malignant cells could not be distinguished on the basis of their DNA content or karyotype, the cell types may not represent genetically distinct populations of cells. The AR cells may undergo alterations in gene expression in adapting to their androgen-free environment.

Androgens↗