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D K Kalousek

Publications and source records attributed to D K Kalousek.

At least 55 records · Page 3Linked to original sources
PubMed1996

Distribution of mosaicism in human placentae.

Traditional first trimester chorionic villus sampling (CVS) for prenatal diagnosis can be performed by cytogenetic analysis of cytotrophoblast or chorionic villous stroma. Approximately 2% of pregnancies studied by CVS show confined placental mosaicism (CPM) involving either cytotrophoblast, stroma or both. We present the results of a cytogenetic study of nine term placentae from pregnancies with prenatally diagnosed CPM. The aneuploid++ cell lines involved trisomies for chromosomes 7,9,16, and X. The cytotrophoblast and villous stroma from multiple biopsies of these placentae were examined using a combination of interphase and metaphase cytogenetic analysis. CPM was detected in all nine of the term placentae and both tissue-specific and site-specific patterns of mosaicism could be discerned. These results indicate that the analysis of villous stroma and cytotrophoblast from multiple placental biopsies is necessary to improve our understanding of the evolution of CPM during pregnancy and its effect on the fetus.

Biopsy↗
PubMed1996

Confined placental mosaicism.

In most pregnancies the chromosomal complement detected in the fetus is also present in the placenta. The detection of an identical chromosomal complement in both the fetus and its placenta has always been expected as both develop from the same zygote. However, in approximately 2% of viable pregnancies studied by chorionic villus sampling (CVS) at 9 to 11 weeks of gestation, the cytogenetic abnormality, most often trisomy, is confined to the placenta. This phenomenon is known as confined placental mosaicism (CPM). It was first described by Kalousek and Dill in term placentas of infants born with unexplained intrauterine growth restriction (IUGR). Contrary to generalised mosaicism, which is characterised by the presence of two or more karyotypically different cell lines within both the fetus and its placenta, CPM represents tissue specific chromosomal mosaicism affecting the placenta only. The diagnosis of CPM is most commonly made when, after the diagnosis of chromosomal mosaicism in a CVS sample, the second prenatal testing (amniotic fluid culture or fetal blood culture analysis) shows a normal diploid karyotype.

Chorionic Villi Sampling↗
PubMed1996

Morphologic, immunologic, and cytogenetic classification of acute myeloid leukemia and myelodysplastic syndrome in childhood: a report from the Childrens Cancer Group.

The purposes of this report are to reaffirm concordance difficulties with the acute myeloid leukemia (AML) French-American-British (FAB) classification, to present the frequency of previously delineated AML syndromes in pediatric patients and to describe additional characteristic AML profiles utilizing composite morphologic, cytogenetic and immunophenotypic data. Profiles of 124 children with acute myeloid leukemia (AML) and 13 children with myelodysplastic syndrome entered on the Childrens Cancer Group (CCG) pilot study CCG-2861 were examined. Concordance between institutions and reviewers for FAB designation was 65%. Discordance was found principally between M1 and M2, M2 and M4, and M4 and M5. In 49% of marrow specimens, leukemic blasts expressed at least one T lineage-related antigen; 24% expressed the B lineage-related antigen CD19. CDw14 correlated with FAB M4 or M5 morphology and was the only surface antigen associated with a specific FAB subtype. Normal karyotypes were found for 15% of the 75 children with satisfactory karyotype preparations. Recurring aberrations, found in 76% of children, included t(15;17)(q22;q11), t(8;21)(q22;q22), inv(16)(p13q22), rearrangements of band 11q23, t(6;9) (p23;q34), trisomy 8 and monosomy 7. Results from this pilot study and from the current CCG randomized trial correlating morphology, immunophenotyping and cytogenetics, will help to classify AML into unique subgroups with differing clinical consequences or therapy requirements.

Adolescent↗
PubMed1996

An improved technique for molecular cytogenetic analysis of human preimplantation embryos with fluorescence in situ hybridization.

OBJECTIVE: To develop a method for the cytogenetic evaluation of preimplantation embryos using nonradioactive centromeric probes for chromosomes 1, 16 and X. STUDY DESIGN: The embryos used for this study were either fragmented or polyploid embryos rejected from an in vitro fertilization program. Prior to in situ hybridization, the embryos were treated with 0.5% protease. After application of gradual fixation, conventional hybridization protocol was followed. RESULTS: Ten of 11 embryos showed hybridization signals suggesting that the success rate of in situ hybridization of human embryos is improved when a modified method of digesting the zona pellucida and gradual fixation with removal of the cytoplasm are used. CONCLUSION: The method described in this study demonstrates that the zona pellucida is the key to successful in situ hybridization of whole human embryos. When the zona pellucida is removed, penetration by a probe becomes possible.

Chromosome Aberrations↗
PubMed1995

Molecular cytogenetic analysis of monosomy 7 in pediatric patients with myelodysplastic syndrome.

Monosomy 7 is a non-random cytogenetic abnormality that is frequently associated with myelodysplastic syndromes (MDS). Twenty-four bone marrow samples from five pediatric patients with MDS were analysed using both traditional and interphase cytogenetic analysis. The majority of the metaphases were monosomic for chromosome 7 while interphase cytogenetic analysis consistently detected a disomic cell population in nondividing cell populations. This suggests that the monosomy 7 cells have a distinct proliferative advantage compared to the disomic cell population. The results demonstrate that interphase cytogenetic analysis provides important cytogenetic information about non-dividing cell subpopulations, enhancing our understanding of the cell dynamics of normal and monosomy 7 cells in MDS.

Adolescent↗
PubMed1995

Prenatal and postnatal growth failure associated with maternal heterodisomy for chromosome 7.

The association of maternal uniparental disomy for chromosome 7 and postnatal growth failure has been reported in four cases and suggests the presence of genomic imprinting of one or more growth related genes on chromosome 7. However, in the reported cases, the possibility of homozygosity for a recessive mutation could not be excluded as the cause of the growth failure as in all cases isodisomy rather than heterodisomy for chromosome 7 was present. We report a case of prenatal and postnatal growth retardation associated with a prenatal diagnosis of mosaicism for trisomy 7 confined to the placenta. DNA typing of polymorphic markers on chromosome 7 has established that the zygote originated as a trisomy 7 with two maternal and one paternal chromosomes 7 with subsequent loss of the paternal chromosome resulting in a disomic child with maternal heterodisomy for chromosome 7. The growth failure seen in this child with heterodisomy 7 lends strong support to the hypothesis of imprinted gene(s) on chromosome 7.

Adult↗
PubMed1995

The chromosome pattern of embryos derived from tripronuclear zygotes studied by cytogenetic analysis and fluorescence in situ hybridization.

OBJECTIVE: To detect the chromosomal complement of embryos, which developed from tripronuclear zygote, using nonradioactive centromeric probes. DESIGN: The chromosome pattern of embryos developing from tripronuclear zygote, studied by fluorescence in situ hybridization, was compared with that of embryos studied by standard cytogenetic methods. SETTING: These embryos were obtained from superovulated patients undergoing IVF treatment. RESULTS: We have attempted to examine the chromosomal complement of 72 embryos derived from tripronuclear zygotes using both traditional cytogenetic analysis and fluorescence in situ hybridization. Of these 72 embryos, 22 were analyzed with fluorescence in situ hybridization and 50 were analyzed with traditional cytogenetic analysis. For fluorescence in situ hybridization analysis, probes specific for the centromeric regions of chromosomes 1, 16, and X were used, with results being obtained from 18 embryos. One embryo was haploid (5.6%), five were triploid (27.8%), and one was hexaploid (5.6%). Eleven (61%) embryos were mosaic. Traditional cytogenetic analysis could be performed on 25 of 50 embryos. Five (20%) were haploid, one (4%) was diploid, seven (28%) were triploid, one (4%) were tetraploid, and two were hexaploid. Nine (36%) were mosaic. CONCLUSION: These findings indicate that not all tripronuclear human zygotes develop into triploid embryos. This study also demonstrates the usefulness of fluorescence in situ hybridization for preimplantation diagnosis and screening for chromosome abnormalities.

Cell Nucleus↗
PubMed1995

Interphase cytogenetic analysis of single cell suspensions prepared from previously formalin-fixed and paraffin-embedded tissues.

Fluorescence in situ hybridization (FISH) provides a rapid and accurate method for the detection of chromosomal aneuploidy. We have developed a technique for the use of FISH on single cell suspensions produced from either formalin-fixed or paraffin-embedded tissues. Preparation of such tissues involves sequential rehydration, enzymatic digestion to release single nuclei, and hybridization with a fluorescently labeled chromosome-specific centromeric probe. In a clinical setting formalin-fixed tissue from many tissue types is readily available for additional retrospective study. FISH on formalin-fixed tissues is especially beneficial in follow-up studies of cases involving termination after prenatal diagnosis or patients with a malignant disease where previous routine cytogenetics established the chromosomal aneuploidy. The use of this technique eliminates the biases of cytogenetic analysis due to clonal selection in tissue culture, the low number of cells analyzed, and the restriction to only dividing cell populations. We have demonstrated that this application of interphase cytogenetics to the study of various formalin-fixed tissues is amenable to the detection of chromosomal aneuploidies and has specific advantages over cytogenetic analysis.

Aneuploidy↗
PubMed1994

The utilization of interphase cytogenetic analysis for the detection of mosaicism.

This study describes a method for defining mosaic aneuploidy by interphase cytogenetics based on statistical limits established from control specimens. Fluorescence in situ hybridization (FISH) has been used to detect the number of copies of specific chromosomes in interphase nuclei from placental tissues of diploid controls and mosaic placentas. FISH was performed using probes D7Z1/D7Z2, D9Z1, D10Z1, and D18Z1, all purchased from Oncor, Inc. Statistical analysis of data obtained from diploid controls was used to determine the one-sided upper reference limit and corresponding 95% confidence interval for the proportion of cells with one and three signals for each of the probes used. The one-sided upper reference limits established the lower levels of monosomy and trisomy detectable using each of the four probes. These statistical parameters were then used to interpret the results obtained by FISH applied to the study of term placentas for the confirmation of prenatally diagnosed chromosomal mosaicism.

Aneuploidy↗
PubMed1994

Chromosome investigation in in vitro fertilization failure.

PURPOSE: A chromosomal complement of 227 human oocytes was studied to provide information on the frequency and type of chromosomal abnormalities in oocytes failing in vitro fertilization. RESULTS: Normal haploid chromosome complement was found in 54.6%; chromosomal abnormalities consisting of diploid sets were identified in 16.7% and aneuploidy was observed in 26%. Premature condensation of sperm chromosomes of the GI-phase was observed in 22.9% oocytes. Male infertility was correlated with an increase in the rate of aneuploidy when compared with tubal infertility. The rate of chromosome abnormalities for the oocytes recovered from women who had no fertilized oocytes was significantly higher compared to those with at least one oocyte fertilized. CONCLUSION: A high frequency of chromosome abnormalities in unfertilized oocytes suggests that natural selection against chromosome abnormalities may occur even prior to fertilization.

Adult↗
PubMed1994

Current topic: confined placental mosaicism and intrauterine fetal development.

Chromosomal mosaicism is the presence of two or more cell lines with different chromosomal complements in an individual derived from a single zygote (which is distinguishable from chimaerism in which an individual is derived from more than one zygote). Mosaicism may involve a number of different karyotypic abnormalities including those for whole sets of chromosomes (polyploidy, including triploidy and tetraploidy), trisomies, sex chromosomal anomalies and chromosomal rearrangements. Mosaicism itself may be present in all the tissues of the body and placenta, or it may only be seen in certain tissues or may be restricted to only the placenta and extraembryonic membranes. The type of mosaicism seen depends upon the stage of development at which it originated, the tissue types to which the abnormal cell lines were distributed and the cell cycle times of both the normal and abnormal cells. The phenotypic effects or consequences of chromosomal mosaicism may be dramatic. During the pregnancy, high levels of mosaicism are seen in early abnormal preimplantation embryos, spontaneous abortions, intrauterine growth restriction and intrauterine fetal death. However, not all cases of mosaicism are serious and the presence of a normal cell line may dilute the effects of an abnormal cell line to such an extent that in many cases mosaicism will remain undetected because the consequences are not severe. Investigations of chromosomal mosaicism were, until recently, restricted to those cells which could be induced to divide and be karyotyped from metaphase analysis. Advances in molecular genetics and cytogenetics have made possible the identification of chromosomal abnormalities, specifically mosaicism in interphase cells. The identification of abnormalities such as confined placental mosaicism and its association with uniparental disomy has led to the recognition that chromosomal mosaicism plays a major role in abnormal human development and dysmorphology (Hall, 1990). An understanding of mosaicism and the role of the placenta during development, including the phenomenon of trisomic zygote rescue, is helping to cast light on problems in prenatal diagnosis, many of which involve confined placental mosaicism.

Embryonic and Fetal Development↗
PubMed1994

Astrocytoma with a unique telomere association.

Many primary pediatric brain tumors are characterized by nonrandom cytogenetic abnormalities involving specific structural rearrangements and loss or gain of specific chromosomes. We describe a low-grade cerebellar astrocytoma with telomeric association of chromosomes 18 and 21 in a 7-year old girl. The nonrandom telomeric association of these chromosomes represents a unique cytogenetic finding in this type of pediatric brain tumor.

Astrocytoma↗
PubMed1993

Evidence for multi-site closure of the neural tube in humans.

Four separate initiation sites for neural tube (NT) fusion have been demonstrated recently in mice and other experimental animals. We evaluated the question of whether the multisite model vs. the traditional single-site model of NT closure provided the best explanation for neural tube defects (NTDs) in humans. Evidence for segmental vs. continuous NT closure was obtained by review of our recent clinical cases of NTDs and previous medical literature. With the multi-site NT closure model, we find that the majority of NTDs can be explained by failure of fusion of one of the closures or their contiguous neuropores. We hypothesize that: Anencephaly results from failure of closure 2 for meroacranium and closures 2 and 4 for holoacranium. Spina-bifida cystica results from failure of rostral and/or caudal closure 1 fusion. Craniorachischisis results from failure of closures 2, 4, and 1. Closure 3 non-fusion is rare, presenting as a midfacial cleft extending from the upper lip through the frontal area ("facioschisis"). Frontal and parietal cephaloceles occur at the sites of the junctions of the cranial closures 3-2 and 2-4 (the prosencephalic and mesencephalic neuropores). Occipital cephaloceles result from incomplete membrane fusion of closure 4. In humans, the most caudal NT may have a 5th closure site involving L2 to S2. Closure below S2 is by secondary neurulation. Evidence for multi-site NT closure is apparent in clinical cases of NTDs, as well as in previous epidemiological studies, empiric recurrence risk studies, and pathological studies. Genetic variations of NT closures sites occur in mice and are evident in humans, e.g., familial NTDs with Sikh heritage (closure 4 and rostral 1), Meckel-Gruber syndrome (closure 4), and Walker-Warburg syndrome (2-4 neuropore, closure 4). Environmental and teratogenic exposures frequently affect specific closure sites, e.g., folate deficiency (closures 2, 4, and caudal 1) and valproic acid (closure 5 and canalization). Classification of NTDs by closure site is recommended for all studies of NTDs in humans.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Detection of confined placental mosaicism in trisomy 18 conceptions using interphase cytogenetic analysis.

Fluorescence in situ hybridization provides a rapid and accurate technique for detecting chromosomal aneuploidy. It is an excellent method for identifying mosaicism in placental tissues following prenatal diagnosis. Mosaicism, in the form of confined placental mosaicism, occurs im approximately 1%-2% of viable pregnancies studied by chorionic villus sampling at 9-11 weeks of gestation. It has been detected in pregnancies with both diploid and trisomic fetuses and appears to have an important effect on the intrauterine fetal survival. Using both standard cytogenetic analysis and fluorescence in situ hybridization, we have studied 12 placentas from pregnancies with trisomy 18 for the presence of chromosomal mosaicism. These included 2 that were spontaneously aborted, 5 that were terminated after prenatal diagnosis, and 4 that were delivered as either stillborn or liveborn. Significant levels of mosaicism, confined exclusively to cytotrophoblast, were detected in 7 pregnancies. This study demonstrates the usefulness of interphase cytogenetic analysis of uncultured tissues as an alternative method for the detection of mosaicism.

Aneuploidy↗