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Biomedical subjects

H von Koskull

Publications and source records attributed to H von Koskull.

At least 19 recordsLinked to original sources
PubMed1994

FRAXA locus in fragile X diagnosis: family studies, prenatal diagnosis, and diagnosis of sporadic cases of mental retardation.

Three hundred eighty-seven individuals from 32 Finnish fragile X families were studied, using the probe StB12.3 [Oberlé et al., 1991: Science 252:1097-1102] for the FRAXA locus, to reveal length variations in the FMR-1 gene. As expected, the affected individuals (with few exceptions) showed a full mutation; a few affected individuals with a premutation only were found. Seventy percent of the females with a full mutation were affected. The size of the mutation remained unchanged in 6, increased in 73, and decreased in 6 female meioses. In male meioses the size was unchanged in 15 cases, increased in 2 cases, and decreased in 1 case. Prenatal diagnosis was performed in 20 cases. In 7 of these the mutation was inherited by the fetus. Four hundred sixty-four mentally retarded patients were referred to us for FRAXA analysis. In 5% of these the fragile X mutation was found. In addition to the clear cut negative or positive results there were 6 cases in which an increase of 50-80 bp was detected. These findings may represent either large normal alleles or small premutations suggesting a possible tissue mosaicism which could explain the retardation of the patients.

Amniocentesis↗
PubMed1994

Isoforms of cellular fibronectin and tenascin in amniotic fluid.

Amniotic fluid (AF) obtained from second trimester pregnancies presented extradomain (ED) A, B and an oncofetal (onc-f) domain containing isoforms of cellular fibronectin (cFn) in Western blotting of gelatin-bound polypeptides and directly of AF. Western blotting after sequential immunoprecipitation suggested at least three Fn molecules: one containing EDA and the onc-f domain and another minor component distinctly containing all the domains, and a third one only containing EDA. The immunoblotting results for EDA-cFn and onc-f-cFn were closely similar to that for total Fn, whereas in plasma samples of normal and pregnant women only traces of EDA-cFn and onc-f-cFn, but no EDB-cFn, were found. Western blotting of AF also indicated the presence of three isoforms of tenascin (Tn), M(r) 190,000 and 280,000 polypeptides earlier found in many cells, and a M(r) 200,000 polypeptide, novel for AF and not present in plasma. The results suggest a novel extracellular matrix polypeptide composition for AF.

Amniocentesis↗
PubMed1993

Randomized trial comparing first-trimester transcervical chorionic villus sampling and second-trimester amniocentesis.

A total of 800 patients were randomized at the 9th to 11th week of pregnancy either for transcervical chorionic villus sampling (CVS) on the day of trial entry or for amniocentesis (AC) at the 16th week. The indication for fetal karyotyping was maternal age in 94 per cent of the cases; the mean maternal age was 39.2 years. An adequate sample was obtained in 98.3 per cent of the cases in the CVS group and in all cases in the AC group. Retesting was indicated in 3.3 per cent of the CVS cases. An abnormal karyotype was found in 6.1 per cent of the CV samples and in 4.5 per cent of the amniotic fluid samples. There was one false-positive chromosome result in both groups. Twelve (3.1 per cent) miscarriages occurred by the 22nd week of pregnancy in the CVS group in pregnancies intended to continue. No difference was seen between the groups for total fetal loss rates. The number of surviving infants in the CVS group was 92.2 per cent and in the AC group 91.7 per cent (rate difference 0.5 per cent (95 per cent confidence interval -3.3 to 4.3)). In our study, both the diagnostic accuracy and the risk of fetal loss were equal in the CVS and AC groups.

Abortion, Spontaneous↗
PubMed1993

Molecular cytogenetic study of patients with Pallister-Killian syndrome.

The Pallister-Killian syndrome (PKS) is characterized by tissue limited chromosomal mosaicism, i.e. the presence of a supernumerary metacentric chromosome [i(12p)] often confined to skin fibroblasts while the karyotype of cultured lymphocytes is normal. In the present study, chromosome painting by chromosomal in situ suppression (CISS) hybridization and interphase cytogenetic procedures employing biotinylated or digoxigenin labelled probes was carried out. These probes comprised a chromosome 12 specific library (LA 12NS01) and chromosome 12 centromere specific alpha-satellite (pSP12-1). They were used to analyse and quantify the presence of i(12p) in lymphocytes, granulocytes/monocytes, skin fibroblasts and buccal mucosal cells from five patients and one aborted fetus with PKS, and ten normal donors. CISS hybridization on mitotic skin fibroblasts reliably indicated the presence of i(12p) cells, even when metaphases of poor quality were included in the analysis. Two of the five patients showed i(12p) in a small proportion (< or = 0.5%) of the cultured lymphocytes too. The interphase cytogenetics procedure did not reveal the isochromosome in lymphocytes or granulocytes/monocytes in any of the patients. Two of the six patients had a twofold increase in the number of buccal mucosal cells with three hybridization signals over control values. However, for mucosal cells, methodological improvements are required. For cytogenetic diagnosis of PKS, cultured fibroblasts subjected to chromosome painting by CISS hybridization with a chromosome 12 specific library probe are recommended.

Adolescent↗
PubMed1993

Three Finnish incontinentia pigmenti (IP) families with recombinations with the IP loci at Xq28 and Xp11.

The locus (IP2) for the hereditary form of incontinentia pigmenti (IP) has been mapped to Xq28 by linkage analysis. We studied three IP families with polymorphic markers in the Xq28 region. In two families we observed recombination between the marker loci and IP. In the third family no crossing overs were seen and linkage to the Xq28 region could not be excluded. The other IP locus (IP1) has been mapped to Xp11.21, because of sporadic cases of IP with X-chromosomal alterations involving Xp11.21. To check whether this locus is linked to IP in these families, we used polymorphic markers in the Xp11 region. In all three families recombinations were observed, thus excluding linkage to this locus in these IP families.

Chromosome Mapping↗
PubMed1993

Striking founder effect for the fragile X syndrome in Finland.

The fragile X mental retardation syndrome is caused by the expansion of an unstable CGG repeat in a 5' exon of the FMR1 gene. Significant linkage disequilibrium between this mutation and flanking microsatellite markers has been observed previously in Caucasian populations, a very unusual finding for an X-linked disease which severely impairs reproduction fitness in affected males. This reflects the multistep process at the origin of the full mutation. We have analyzed the FRAXAC2 and DXS548 microsatellites in 26 fragile X families originating from various parts of Finland, and report a striking founder effect much stronger than the linkage disequilibrium observed previously in other more heterogeneous populations. One DXS548 allele was present on 92% of fragile X chromosomes and on 17% of normal chromosomes. A single haplotype accounted for 73% of fragile X chromosomes, and was found only once in 34 normal chromosomes, corresponding to a relative risk of about 90 compared to its absence. The broad geographic origin of the high-risk haplotype and its expected frequency suggest that it was present in initial settlers of Finland, and could thus have been carried silently through 100 generations.

Child↗
PubMed1992

Linkage to Xq28 in a family with nonspecific X-linked mental retardation.

Linkage analysis was performed in a family with nonspecific X-linked mental retardation (MRX). Affected individuals had no clinical characteristics other than mental retardation. Linkage was detected to the marker loci DXS477, DXS465, DXS52, DXS15 and F8C with maximum lod scores of 1.70, 1.32, 2.52, 1.70, and 1.09, respectively (theta = 0.0). The results strongly indicate that the gene for mental retardation in the family studied maps close to DXS52.

Female↗
PubMed1989

Trisomy 12 mosaicism in amniocytes and dysmorphic child despite normal chromosomes in fetal blood sample.

Trisomy 12 mosaicism (44 per cent) was detected prenatally in cultured amniocytes. A cordocentesis was performed to confirm the result. Only normal cells were found in the fetal blood sample. The fetus was estimated to be at a low risk of having a chromosomal abnormality and the pregnancy continued. Eight days after birth, a congenital heart defect was detected in the child. Several dysmorphic features were also evident. Further karyotyping of different tissues revealed normal blood and urinary cells but trisomic cells in the placenta (100 per cent) and in skin fibroblasts (25 per cent). The child died at 5 weeks of age. In this case, the fetal blood sample failed to reveal the real chromosome constitution of the fetus.

Amniocentesis↗
PubMed1988

First trimester diagnosis of Wolman's disease.

Wolman's disease was diagnosed in the first trimester of pregnancy by the direct demonstration of acid lipase deficiency in chorionic villi. The diagnosis was confirmed by studies on cultured chorionic villus cells and fetal skin fibroblasts. Acid lipase activity was assayed with both 4-methylumbelliferyl-palmitate and radiolabelled cholesterol oleate as substrates. The higher specificity of the enzyme for the latter, natural, substrate makes it superior in prenatal diagnosis.

Chorionic Villi Sampling↗
PubMed1987

Induction of cytokeratin expression in human mesenchymal cells.

We studied the phenotypic features of some typical human mesenchymal cells, including decidual stromal cells and adult and fetal fibroblasts under different cell culture conditions by using antibodies to intermediate filament proteins and desmoplakins. In cell culture, the decidual stromal cells rapidly acquired typical fibroblastoid appearance with abundant arrays of vimentin filaments while the cytokeratin-positive epithelial cells, occasionally found in typical epithelioid colonies, lacked vimentin positivity and showed desmoplakin positivity. Within a few days, many of the stromal cells started to present cytokeratin positivity when cultured either in Condimed or in Chang medium. The cytokeratin positivity was first detected in small, scattered cytoplasmic dotted fibrils or in perinuclear dotlike aggregates with fibrillar projections. Later, denser cytokeratin-positive fibrillar arrays could also be seen in stromal cells, which lacked desmoplakin positivity as judged by two monoclonal antibodies. Decidual stromal cells were also cloned and in five out of ten clones some of the cells acquired a similar cytokeratin positivity when transferred into Chang or Condimed medium. Immunoblotting results indicated that cytokeratins 8, 18, and 19 can be found in these cultures. Similar cytokeratin positivity could also be seen in the same culture conditions in cultured fetal fibroblasts from skin, chorionic villi, and lung but not in young or adult skin fibroblast cultures. The present results suggest that decidual stromal cells as well as some embryonal mesenchymal cells can acquire epithelial differentiation in vitro as judged by the emergence of cytokeratin proteins. This ability appears to be lost in the corresponding adult cell. The results furthermore suggest that cytokeratin fibrils can be organized in the cytoplasm without an apparent organization center and that neither the appearance of desmoplakins nor the formation of cell-to-cell contacts are required for cytokeratin filament assembly.

Adult↗
PubMed1987

Prenatal diagnosis of X-linked chronic granulomatous disease using restriction fragment length polymorphism analysis.

Prenatal diagnosis of X-linked chronic granulomatous disease (CGD) was performed with restriction fragment length polymorphism (RFLP) analysis using probes flanking the gene. The male fetus and an affected male displayed the same haplotype for RFLPs belonging to six linked loci extending from DXS164 to DXS7, which encompass the CGD locus, and for which the mother was heterozygous. Diagnosis of an affected fetus was confirmed after termination of the pregnancy by the study of fetal granulocytes using the nitroblue tetrazolium reduction test. In informative families prenatal diagnosis of CGD can be made earlier by RFLP analysis than by fetal blood sampling.

DNA↗
PubMed1987

Localization of insulin-like growth factor-binding protein and endometrial beta-lactoglobulin in cultured decidual and chorionic villus cells.

Immunofluorescence staining was used to localize two 'endometrial' proteins, insulin-like growth factor-binding protein and human beta-lactoglobulin homologue, in cultured cells of chorionic villi and decidua. Both cultured cell types were positive for each protein. These results indicate that immunohistochemical detection of these two proteins cannot be used to distinguish between cultured chorionic villus and decidual cells.

Carrier Proteins↗
PubMed1986

Cytoskeletal markers and specific protein production in cells cultured from human first and third trimester placentae.

In primary, short-term cultures derived from first and third trimester placentae, 60 to 90 and 70 to 95%, respectively, of the total cell population positively stain for cytokeratin intermediate filaments, typical of epithelial, i.e. trophoblastic cells. The rest of the cells express only vimentin intermediate filaments and thus are of mesenchymal origin. Only the cytokeratin-positive cells express human chorionic gonadotropin (hCG), whereas both the epithelial and the mesenchymal cells stain positively for pregnancy-specific beta-1-glycoprotein (SP1). Cytokeratin-negative and vimentin-positive cell overgrowth is observed in cultures derived from first and early third trimester placentae. The cells constituting the monolayer thus formed are of fetal origin as evidenced by the expression of Y-body in over 80% of them. The cultured cells synthesize and secrete hCG and SP1. The activity of these trophoblast-specific functions is inversely proportional to the gestational age of the placenta. Production of specific proteins and expression of intermediate filaments are proposed as criteria for defining the nature and origin of placental cells in primary, short-term cultures.

Chorionic Gonadotropin↗
PubMed1985

Zinc and alpha-fetoprotein in amniotic fluid from early pregnancies with fetal malformations.

Zinc and alpha-fetoprotein concentrations were quantitated in second-trimester amniotic fluid from 111 normal pregnancies and 29 pregnancies with various fetal malformations. The zinc level varied between 0.3 and 4.0 mumol/L (median 1.3) in the normal samples and between 1.8 and 17.9 mumol/L (median 5.0) in cases with malformations. The level was above 2.5 times the normal median in 23 of the 29 (79%) gestations with the malformations. Amniotic fluid zinc and alpha-fetoprotein levels showed a positive correlation (r = 0.78), and the alpha-fetoprotein level was elevated in all gestations with fetal disorders and elevated zinc levels, as well as in five of the six cases with fetal defects but normal zinc concentrations. The elevation of zinc was more marked than that of alpha-fetoprotein in three cases of fetal malformations. Five samples were false positive on alpha-fetoprotein assay but contained normal zinc levels. Removal of alpha-fetoprotein from amniotic fluid had no effect on the zinc concentration, indicating that zinc is not bound to amniotic fluid alpha-fetoprotein.

Adult↗