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D K Kalousek

Publications and source records attributed to D K Kalousek.

At least 73 records · Page 4Linked to original sources
PubMed1993

Cytogenetic analysis of 109 pediatric central nervous system tumors.

Reports of cytogenetic abnormalities in pediatric central nervous system (CNS) tumors are important for collection and comparison of large numbers of karyotypes of primary CNS neoplasms to produce statistically significant correlations. We report cytogenetic results of 119 samples of pediatric CNS tumors from 109 patients. Tumors included 33 low-grade astrocytomas, 18 high-grade astrocytomas, 14 gangliogliomas, 13 ependymomas, 17 primitive neuroectodermal tumors (PNET), three choroid plexus papillomas and carcinomas, and a miscellaneous group of 20 rare primary CNS tumors and metastases. In each group, cytogenetic results were correlated with histologic subtype and survival. The study indicated specific chromosome abnormalities in different groups of tumors. Low-grade astrocytomas showed mostly numeric abnormalities with gains of chromosome 7, high-grade astrocytomas showed differences from karyotypic changes observed in adults in lacking double minutes (dmin) and monosomy 10. The ependymoma group showed the largest proportion of abnormal karyotypes with frequent involvement of chromosome 6 and 16. Chromosome 6 was the single most common abnormal chromosome in this study, closely followed by chromosomes 1 and 11. Pediatric CNS neoplasms differ from adult tumors cytogenetically as well as histologically and biologically.

Adolescent↗
PubMed1993

The effect of confined placental mosaicism on development of the human aneuploid conceptus.

The rate of meiotic errors in gametogenesis is high, resulting in approximately 30% of cleaving embryos with chromosomal defect. In addition, mitotic errors occur commonly in chromosomally normal and abnormal embryos. The most likely outcome of the mitotic error is CPM. Mitotic mutation in trisomic blastocysts may lead to diploid/trisomic trophoblast with intrauterine survival of the trisomic fetus or may result in a diploid fetus supported by a trisomic placenta. The outcome of pregnancies with a trisomic placenta and diploid fetus largely depends on the specific chromosome involved and on the presence or absence of uniparental disomy in the fetus.

Aneuploidy↗
PubMed1993

Partial molar pregnancy with fetal survival: an unusual example of confined placental mosaicism.

BACKGROUND: A pregnancy with a partial molar placenta and a normal fetus is a rare condition. Few guidelines exist for antenatal evaluation and management, particularly with respect to selecting cases for conservative management. CASE: Cytogenetic analysis of chorionic villi showed a triploid placenta, and both amniotic fluid and blood indicated a diploid fetus. The pregnancy resulted in a normal newborn. CONCLUSION: This disorder appears to be due to confined placental mosaicism.

Adult↗
PubMed1993

Uniparental disomy for chromosome 16 in humans.

The association between chromosomal mosaicism observed on chorionic villus sampling (CVS) and poor pregnancy outcome has been well documented. CVS mosaicism usually represents abnormal cell lines confined to the placenta and often involves chromosomal trisomy. Such confined placental mosaicism (CPM) may occur when there is complete dichotomy between a trisomic karyotype in the placenta and a normal diploid fetus or when both diploid and trisomic components are present within the placenta. Gestations involving pure or significant trisomy in placental lineages associated with a diploid fetal karyotype probably result from a trisomic zygote which has lost one copy of the trisomic chromosome in the embryonic progenitor cells during cleavage. Uniparental disomy would be expected to occur in one-third of such cases. Trisomy of chromosome 7, 9, 15, or 16 is most common among the gestations with these dichotomic CPMs. Nine pregnancies with trisomy 16 confined to the placenta were prenatally diagnosed. Pregnancy outcome, levels of trisomic cells in term placentas, and fetal uniparental disomy were studied. Intrauterine growth retardation (IUGR), low birthweight, or fetal death was observed in six of these pregnancies and correlated with high levels of trisomic cells in the term placentas. Four of the five cases of IUGR or fetal death showed fetal uniparental disomy for chromosome 16. One of the infants with maternal uniparental disomy 16 had a significant malformation (imperforate anus). All infants with normal intrauterine growth showed term placentas with low levels of trisomic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Canadian multicenter randomized clinical trial of chorion villus sampling and amniocentesis. chromosome mosaicism in CVS and amniocentesis samples.

Data on 1040 chorionic villus and 969 amniotic fluid samples were collected from women studied in the Canadian Multicentre Randomized Clinical Trial of Chorion Villus Sampling and Amniocentesis. Cytogenetic results were obtained from 98.0 per cent of chorionic villus samples and from 99.9 per cent of amniotic fluid samples. Level I mosaicism (a single cell with an abnormal karyotype) occurred frequently in both chorionic villus and amniotic fluid samples and appeared to have no clinical significance. Level II mosaicism occurred in 0.9 per cent of CVS mesenchyme and 1.5 per cent of amniotic fluid cultures and in general was not perceived to be of sufficient concern to warrant cytogenetic follow-up studies. Level III mosaicism was reported in 18 CVS cases (15 cytotrophoblast, 1 mesenchyme, and 2 with both cell methods) and in one amniotic fluid case. In all cases but one (fetus with trisomy 18), level III mosaicism was confined to the placenta. Maternal cell contamination occurring with a frequency of 6.4 per cent in the mesenchyme analyses was a concern. This study supports the final report of the Canadian Multicentre Randomized Clinical Trial of Chorion Villus Sampling and Amniocentesis. Cytogenetic analysis of chorionic villus samples appears to be an acceptable alternative to the analysis of amniotic fluid samples. However, because of mosaicism and maternal cell contamination concerns, the examination of both cytotrophoblast preparations and mesenchyme cultures from chorionic villus samples is recommended.

Adult↗
PubMed1992

Spontaneous abortion and confined chromosomal mosaicism.

Confined placental chorionic mosaicism is reported in 2% of viable pregnancies cytogenetically analyzed on chorionic villi samplings (CVS) at 9-12 weeks of gestation. In follow-up studies this mosaicism has been shown to be associated with increased frequency of second and third trimester pregnancy loss or intrauterine fetal growth retardation. We have studied 54 spontaneous abortions (SA) for the detection of confined placental mosaicism and found 11 of them to be mosaic. All mosaic cases were identified among first trimester spontaneous abortions, and the mosaicism was confined to specific placental or embryonic/fetal cell lineages. These results indicate that the previously reported mosaicism in SA represents both confined and generalized types of mosaicism and that its accepted frequency of 5%-10% in SA will likely be higher. Over the whole gestational period, the confined placental mosaicism is more common than the reported rate of 1%-2% seen in viable pregnancies at CVS, and a higher proportion of pregnancy complications than previously suspected may be associated with confined placental mosaicism.

Abortion, Spontaneous↗
PubMed1992

Simultaneous appearance of a unique common epitope in fetal colon, skin, and biliary epithelial cells. A possible link for extracolonic manifestations in ulcerative colitis.

The tissue distribution of a previously identified M(r) 40 K epithelial autoantigen in ulcerative colitis was examined in situ in the fetal tissue by immunocytochemical method, using an immunoglobulin M (IgM) monoclonal antibody (7E12H12). Fetal-autopsy tissue from 9 to 19 weeks of development (11-21 gestational weeks) gestations, including specimens of colon (20 specimens), skin (19), small intestine (12), gallbladder (15), liver (20), spleen (20), kidney (3), urinary bladder (3), and umbilical cord/placenta (25) were examined. 7E12H12 reactive epitope appeared first in a few colonic epithelial cells at 10 weeks of gestation. By 11 weeks, 7E12H12 reactivity was clearly evident in most of the colonic epithelial cells. Goblet-cell reactivity was evident from 15 weeks of gestation. Enterocytes lining the small intestine from all the specimens were negative. In the skin, earliest immunoreactivity was evident in the basal layer of epidermis at 10 weeks of development, and by 11 weeks, the staining was intense and localized exclusively to squamous epithelial cells of the epidermis. The immunoreactivity in the fetal gallbladder mucosa was also evident earliest at 11 weeks of development. The staining was distinct in the mucosal epithelial cells, and localized along the periphery of the cells and in the apical areas. None of the other tissue specimens reacted with 7E12H12. These results demonstrate that the 7E12H12 reactive epitope is novel, is shared by colon, skin, and biliary epithelium, and appears more or less simultaneously in the three organs at 10 to 11 weeks of development of the fetus. A possible link of this crossreactive protein or proteins in the immunopathogenesis of ulcerative colitis, sclerosing cholangitis, and pyoderma gangrenosum is discussed.

Antibodies, Monoclonal↗
PubMed1991

Two different phenotypes of fetuses with chromosomal triploidy: correlation with parental origin of the extra haploid set.

Triploidy is a condition in which there is over-representation of one parental genome. Recent work in experimental mouse embryo-genesis suggests that the parental origin of the extra genome in triploidy may have specific effects on both embryonic/fetal phenotype and placental development due to an "imprinting" effect. We studied 19 human triploid fetuses and discerned 2 distinct fetal phenotypes, as well as the previously described placental phenotypes, which correlate with the parental origin of the extra haploid set. Although these findings suggest that in human triploids the parental origin of the extra haploid set is important in determination of both fetal and placental phenotype it is not clear to what degree placental development and function affect the resultant fetal phenotype.

Aneuploidy↗
PubMed1991

Confirmation of CVS mosaicism in term placentae and high frequency of intrauterine growth retardation association with confined placental mosaicism.

About 2 per cent of specimens from chorionic villus sampling (CVS) analysed either on direct preparation of cytotrophoblast cells or after culture of mesenchymal stroma reveal confined placental mosaicism (CPM), most commonly involving chromosomal trisomy. A significantly higher rate of prenatal loss (22 per cent) as well as the presence of intrauterine growth retardation (IUGR) has been reported among pregnancies with CPM. To evaluate more precisely the effect of these aneuploid cell lines confined to the placenta on intrauterine fetal growth and fetal survival, we have studied 34 term placentae from pregnancies with CPM diagnosed on CVS and confirmed identical mosaicism in 17 of these placentae. There was a direct correlation between a high number of aneuploid cells present at CVS and a high likelihood of their detection in term placenta. Also, the proportion of aneuploid cells in the mosaic term placentae correlated with that observed in CVS specimens. Among 17 gestations with confirmed CPM at delivery, there were six cases of IUGR identified, five in liveborns and one associated with intrauterine death.

Amnion↗
PubMed1991

Deletion of chromosome 21 and normal intelligence: molecular definition of the lesion.

Application of a method for the fine structure analysis of unbalanced chromosomal rearrangements using quantitative Southern blot analysis has established that an individual of normal intelligence and largely normal appearance has a significant interstitial deletion of chromosome 21. Using high resolution cytogenetic analysis and molecular analysis with five single copy DNA sequences unique to chromosome 21 and a probe for human SOD1 (CuZn, superoxide dismutase), we find that the deletion extends to the border of bands 21q11.1-11.2. and extends to the border of bands 21q21.2-q21.3. The latter border is established molecularly by the presence of two copies of SOD1, previously mapped to band 21q22.1, and of four single copy sequences known to be located distal to this region. The presence of SOD1 was confirmed by enzyme dosage analysis. These findings demonstrate that deletion of close to 20,000 kb of autosomal material is compatible with normal intelligence. Further, they suggest that chromosome 21 may include a large region of relative developmental neutrality whose molecular basis may now be investigated. Because of the limits of even high resolution cytogenetic analysis, fine structure molecular analyses of this type will be necessary to reliably detect and define similar small chromosomal deletions or insertions. The molecular definition of such aneuploidy provides the basis for increasing the resolution of the human physical genetic map.

Blotting, Southern↗
PubMed1991

Pathology of abortion: chromosomal and genetic correlations.

The examination of spontaneous abortion specimens is as important as doing perinatal autopsies or surgicals in today's practice of medicine. The results of the pathologist's examination assist obstetricians in specific follow-up of future pregnancies and geneticists in predicting the chances of specific developmental defects or repeat pregnancy loss. Without the information provided by the pathologist, the other specialists can offer no real assistance. More extensive use of cytogenetic analysis of placentas may help explain intrauterine fetal death in pregnancies with confined placental mosaicism, which complicates one to two percent of pregnancies. A brief review of morphologic and genetic differences between partial and complete moles emphasizes the disparate origins of these distantly related conditions.

Abortion, Spontaneous↗
PubMed1990

Detection of breakpoint cluster region- negative and nonclonal hematopoiesis in vitro and in vivo after transplantation of cells selected in cultures of chronic myeloid leukemia marrow.

Philadelphia (Ph1) chromosome-positive clonogenic progenitors usually disappear within 4 to 6 weeks in long-term cultures established from the marrow of patients with chronic myeloid leukemia (CML). In contrast, coexisting chromosomally normal hematopoietic cells are relatively well maintained. Thus, even though normal cells are initially undetectable, they may become the predominant population. Recently, we have begun to explore the potential of such cultures as a strategy for preparing CML marrow for autografting, and based on cytogenetic studies of the differential kinetics of Ph1-positive and Ph1-negative clonogenic cells, have chosen a 10-day period in culture to obtain maximal numbers of selectively enriched normal stem cells. Here we present the results of molecular analyses of the cells regenerated in vivo for the initial three CML patients to be treated using this approach by comparison with the differentiated cells generated by continued maintenance of an aliquot of the autograft in vitro (using a slightly modified culture feeding procedure to enhance the production and release of cells into the nonadherent fraction after 4 weeks) for the one patient whose genotype made molecular analysis of clonality status also possible. These analyses showed that cells with a rearranged breakpoint cluster region (BCR) gene were not detectable by Southern blotting in either in vitro or in vivo populations of mature cells that might be assumed to represent the progeny of primitive cells present at the end of the initial 10 days in culture. Production of BCR-negative cells was also shown to be temporally correlated with the appearance of nonclonal hematopoietic cells both in culture and in vivo. These findings provide support for the view that prolonged maintenance of CML marrow cells in long-term culture may allow molecular characterization of both the BCR-genotype and clonality status of cells with in vivo regenerative potential.

Bone Marrow↗
PubMed1990

Mild phenotypic abnormalities in combined del 9p2 and dup 3p2.

Clinically recognizable syndromes have been reported in association with both del 9p2 and dup 3p2. We report on a girl with combined del 9p2 and dup 3p2 with manifestations of both syndromes but who is less severely affected than one would expect.

Abnormalities, Multiple↗
PubMed1990

Detection and enumeration of colonic mucosal cells in amniotic fluid using a colon epithelial-specific monoclonal antibody.

Since its introduction, prenatal diagnosis of chromosomal and metabolic disorder by midtrimester amniocentesis has relied upon the use of a mixture of fetal cells obtained from amniotic fluid. Little knowledge has been gained in the sorting of these cells for diagnosis of tissue-specific disorders. In an attempt to determine the contribution of fetal colonic mucosal cells to the overall amniocyte population, we used the colonic epithelial-specific monoclonal antibody (MC-Ab) 7E12H12, IgM isotype. Specimens of the small intestine, colon, buccal mucosa, kidney, urinary bladder, and umbilical cord were obtained from electively aborted normal fetuses of 12-28 weeks' gestation. All of these specimens were examined with 7E12H12 by the immunoperoxidase technique. The MC-Ab reacted with the colonic epithelial cells but not with any of the other tissues. In addition, 40 amniotic fluid samples obtained from women between 16 and 18 weeks of gestation, who underwent amniocentesis because of advanced maternal age, were tested using a fluorescent activated cell sorter. Among the amniotic fluid specimens examined, 18.4 +/- 10.3 per cent cells reacted with 7E12H12. Double immunofluorescence studies revealed that all Mc-Ab-stained cells contained secretory component, confirming that they were epithelial in origin. All fetuses whose amniotic fluid was analysed had normal karyotypes and amniotic fluid alpha-fetoprotein levels that were also normal. This study demonstrates that cell-specific Mc-Ab can be used to detect colon cells in the amniotic fluid and that colon cells contribute significant numbers in the mixture of amniotic fluid cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniotic Fluid↗
PubMed1990

The chromosomal complements of cleaved human embryos resulting from in vitro fertilization.

Chromosome preparations were made from 25 cleaved abnormal human embryos at the two- to eight-cell stage after in vitro fertilization. Morphologically, these embryos showed either variable degrees of degeneration or an abnormal number of pronuclei before first cleavage. Among 14 successfully karyotyped embryos, only 3 had a normal chromosomal complement. Eleven showed chromosomal abnormalities, including triploidy, haploidy, and mosaicism. This finding documents a high incidence of chromosomal errors in morphologically abnormal early preimplantation embryos.

Chromosome Aberrations↗