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Biomedical subjects

H Hoehn

Publications and source records attributed to H Hoehn.

At least 91 records · Page 5Linked to original sources
PubMed1981

Cytogenetics of Werner's syndrome cultured skin fibroblasts: variegated translocation mosaicism.

Skin fibroblast-like (FL) cells from patients with Werner's syndrome (adult progeria) regularly demonstrate frequent pseudodiploidy involving variable structural rearrangements that are clonal: variegated translocation mosaicism (VTM). Ninety-two percent of 1,538 metaphases from 29 independent strains derived from five patients with Werner's syndrome demonstrated this cytogenetic abnormality. In contrast, only eight (8.4%) of 95 non-Werner's syndrome FL cell cultures demonstrated VTM: seven with low-grade VTM (approximately 5% of 300 metaphases), and one with VTM affecting 90-100% of metaphases. Unlike the cytogenetic abnormalities observed in the terminal stages of normal FL cell cultures, VTM occurs throughout the entire lifespan of Werner's syndrome cultures. Ten of the identifiable break points in 1,005 banded metaphases accounted for 27% of all definable rearrangements. Baseline sister chromatid exchanges were not increased. Cocultivation of Werner's syndrome and normal strains did not induce VTM in the normal strain. The relationship between VTM and the reduced growth potential of Werner's syndrome FL cells is not yet understood, nor is the relationship between these in vitro abnormalities and the presumptive single gene defect that causes the progeroid clinical manifestations of Werner's syndrome.

Adolescent↗
PubMed1981

Evidence of clonal attenuation, clonal succession, and clonal expansion in mass cultures of aging Werner's syndrome skin fibroblasts.

Skin fibroblast-like (FL) cells from patients with Werner's syndrome (adult progeria) demonstrate multiple, stable, structural chromosome rearrangements (variegated translocation mosaicism) which can be used to identify cytogenetically marked clones of cells within a mass culture. We have cytogenetically followed eight FL cell strains (from two patients) throughout their entire in vitro replicative lifespans, and we show a correlation between the expansion and attenuation of individual clones and the growth of the mass cultures. One strain, which was aged several times, demonstrated a generally reproducible pattern of clonal succession but, surprisingly, also demonstrated, in two parallel derivative cultures, the late emergence of two relatively rapidly growing clones that had not been observed in the parental culture. These observations suggest that clonal succession and clonal attenuation occur in mass cultures, as had been predicted on the basis of dilute-plating cloning experiments. Our results may have implications for models of in vitro cellular senescence. In addition, there are interesting parallels with the tissue hyperplasia associated with in vivo aging, and this observation is compatible with the suggestion that skin FL cells in vitro provide a model for hyperplasia in vivo.

Cell Cycle↗
PubMed1981

Diploid-triploid mixoploidy: clinical and cytogenetic aspects.

A patient with 46, XY/69,XXY mixoploidy (a mixture of cell populations whose component cells differ in their chromosome numbers, irrespective of whether these numbers are euploid or aneuploid) who had some clinical manifestations of the Russell-Silver syndrome is reported. Triploidy results in a clinically recognizable lethal syndrome with hydatidiform placental changes, severe intrauterine growth deficiency, dysplastic cranial bones, eye defects, cleft lip and/or, palate malformed ears, micrognathia, syndactyly, genital anomalies and, rarely, spina bifida. Less severe are instances of diploid-triploid mixoploidy and patients are more likely to survive; one of these patients was detected at birth because of asymmetric growth deficiency with syndactyly. Cytogenetic and flow cytometric studies demonstrated absence of triploid cells in peripheral lymphocytes while varying proportions of triploid cells were found in fibroblast cultures derived from each limb. The triploid cell population disappeared with prolonged cell culture. Replication studies with 5-bromodeoxyuridine-DAPI fluorescence revealed two active X chromosomes, and marker chromosomes suggested a paternal origin for the extra haploid set. The following points are emphasized: (1) diploid-triploid mixoploidy can be suspected clinically; (2) the triploid cell population may not be detectable on examination of peripheral blood (3) the relative degree of asymmetry in the growth deficiency does not appear to relate to the proportion of triploid cells; and (4) both X chromosomes may remain active in the presence of an extra haploid set of chromosomes.

Abnormalities, Multiple↗
PubMed1980

Utility and limitations of chromosome banding in pre- and postnatal service cytogenetics.

This report analyzes detection rates of chromosome aberrations as a function of stainig technique. Of 1,717 peripheral lymphocyte cultures processed by a midsize service cytogenetics laboratory, 23 chromosomal aberrations (1.3%) would not have been detected without the use of either R-banding or G-banding. These 23 cases comprise 21 of 64 non-Robertsonian structural autosomal changes and two of 68 gonosomal aberrations. In contrast, in 1,634 amniotic fluid cell cultures only one balanced rearrangement (0.06% of all cases) would not have been detected without banding. Combined with incidence rates from newborn cytogenetic screenings, these figures suggest that among 10,000 prenatal diagnoses for advanced maternal age, at most one chromosomally unbalanced fetus would be missed if banding were not routinely applied. Because of savings in time and possible automation, it is estimated that discretionary rather than routine use of chromosome banding in prenatal cytogenetics would allow for detection of at least twice as many age-related aneuploidies. In view of sharply rising demand for prenatal cytogenetic services, a discretionary approach might therefore assure a more equitable distribution of limited cytogenetic resources.

Adult↗
PubMed1980

Effects of chromosome constitution on growth and longevity of human skin fibroblast cultures.

Employing standardized cell-culture methods, 10 euploid and 22 constitutionally aneuploid human skin fibroblast strains were assessed in triplicate for total growth potential, growth rates, population-doubling times, and cloning. In addition, longitudinal growth rate studies were carried out with otherwise isogenic 45,X and 47,XXX clonal cultures derived from a mosaic parental strain. Growth rates and longevities were cell-strain specific and highly reproducible among sister cultures of a given strain. There was no systematic correlation between chromosome constitution and any of the measured growth parameters. Trisomic as well as monosomic strains showed the same degree of variability with respect to these parameters as did euploid cultures. In particular, 4 trisomy 21 strains were not unusually short-lived, nor were clones with the 47,XXX constitution compared to those with 45,X karyotypes. We therefore conclude that the cumulative number of in vitro doublings preceding senescence of fibroblast-like cells cultured from skin does not differ significantly among cultures derived from humans who have a normal karyotype, trisomy 13, 18, or 21, the 45,X constitution, or various combinations of extra X and Y chromosomes.

Aneuploidy↗
PubMed1980

Prenatal genetic diagnosis and elective abortion in women over 35: utilization and relative impact on the birth prevalence of Down syndrome in Washington State.

We have examined the relative contributions of a population-based antenatal detection program and unrestricted elective abortion used by women 35 years old and over in Washington State and King County for 1976--1977 to the declining birth prevalence of Down syndrome (DS). The amniocentesis/live birth (LB) ratio for women 35 years old and over was 20.5/100 LBs for King County and 11.7/100 LBs for Washington State in 1977. For the state in 1976, abortion ratios/1,000 LBs were 571 for women 35 to 39 years old and 1,096 for women 40 years old and over. Based on the total Washington State data, elective abortion has a greater impact on averting DS births than does the antenatal detection program. The impact of elective abortion appears to be related to its disproportionate use by women 35 years old and over compared to their contribution to the population of of LBs.

Abortion, Legal↗
PubMed1980

Significance of phenotypic and chromosomal abnormalities in X-linked mental retardation (Martin-Bell or Renpenning syndrome).

With the exception of macro-orchidism, three families with X-linked mental retardation showed diagnostic concordance of clinical features among the affected males. Since macro-orchidism was a variable feature among the otherwise identically affected males in one family, we question the existence of a separate entity of X-linked mental retardation characterized only be testicular enlargement. The X chromosome marker of Lubs was expressed, under the culture conditions of Sutherland, in lymphocytes of the affected males of two families, one with and the other without megalotestes. Two affected members of the third family, with megalotestes, did not show the marker. Telomeric structural changes similar to the mar(X) (qter) formation were found on certain autosomes, notably, chromosome 6 in some of the affected males, potential and obligate carrier females, and in both related and unrelated normal males. These autosomal markers appear to represent a nonspecific response to either in vivo or in vitro folate deficiency. Caution against premature introduction of this test for prenatal diagnosis, in the face of current ignorance regarding diagnostic specificity, is urged.

Female↗
PubMed1979

Cellular aging in Werner's syndrome: a unique phenotype?

Werner's syndrome is commonly regarded as a model for the study of premature aging. There are, however, a variety of clinical and pathologic anatomical features that clearly distinguish it from aging in normal individuals. In this paper we report on in vitro cytogenetic and cell fusion studies that indicate cultured fibroblast-like cells derived from Werner patients differ from cells of normal donors. Despite these discordances with "natural" aging, however, Werner's syndrome, like several other "segmental progeroid syndromes," may prove useful for the investigation of selected aspects of the aging process and of age-related diseases.

Adult↗
PubMed1979

No evidence for chromosomal mosaicism in multiple tissues of 10 patients with 45, XO Turner syndrome.

Why the frequency of spontaneous abortions among monosomy X conceptuses is 98% while the postnatal course of Turner syndrome is relatively benign has not been understood. One explanation could be that mosaicism for a euploid cell line confers viability and that those 2% of 45,XO zygotes surviving in utero have some degree of mosaicism. We thus reasoned that if the non-mosaic 45,XO karyotype is lethal, a thorough study of living Turner syndrome patients might reveal a much higher frequency of mosaicism than the 30--40% reported. Ten adult women with a 45,XO leukocyte karyotype were investigated, looking at five tissue types from all three germ layers: buccal mucosa and hair from ectoderm, urinary epithelium from endoderm and ectoderm, and lymphocytes and skin fibroblasts from mesoderm. We were unable to confirm mosaicism in these patients, although in 2 out of 10 there was the suggestion of a small percentage of euploid cells in skin and blood karyotypes.

Abortion, Spontaneous↗
PubMed1978

Mosaicism in amniotic fluid cell cultures: classification and significance.

The last decade has witnessed increasing application of human cytogenetic technology to prenatal chromosome analysis. However, unlike the rather uniform peripheral blood T-lymphocyte system which has provided most of our experience in human cytogenetics, long-term amniotic-fluid cell cultures display extreme cellular heterogeneity and disproportionate growth of certain cell types as a consequence of clonal amplification. When they enter cell culture, many of these cells are approaching the terminal stages of their respective, life spans and may have accumulated chromosomal aberrations. Concern about the possibility of true fetal mosaicism seems warranted chiefly in situations were multiple colonies display potentially viable aberrations. Clonal analysis, preferably of multiple clonal types, and attention to details of clonal morphology are likely to minimize diagnostic errors and undue apprehension resulting from mosaicism in amniotic-fluid cell cultures.

Amniocentesis↗
PubMed1978

Amniotic fluid cell mosaicism for presumptive trisomy 20.

Trisomy for an F-like chromosome with banding characteristics of chromosome 20 was observed, respectively, in 25 and 8% of amniotic fluid cell clones in two cases of prenatal diagnosis for advanced maternal age. No such aneuploidy was found upon examination of fetal or postnatal tissues. In both instances there were no detectable malformation. It is suggested that propensity to nondisjunction for an F-like chromosome, not unlike tetraploidy, might be another characteristic of amniotic fluid cells in culture.

Abortion, Induced↗
PubMed1978

The replicative life spans of euploid hybrids derived from short-lived and long-lived human skin fibroblast cultures.

Two recent technical advances facilitate the derivation of proliferating hybrids from human diploid fibroblast strains without recourse to biochemical selection: (1) a new chemically-mediated method of somatic cell fusion (PEG-DMSO) yields hybrids at rates as high as 1 in 160 colonies after dilute plating of treated cell mixtures, and (2) a simple technology for assessment of DNA content (flow microfluorometry) permits rapid and highly sensitive monitoring of ploidy. Employing these techniques, we isolated 43 chromosomally stable hybrid clones from 12 crosses between seven different strains representing a wide range of longevities. Crosses between short-lived strains resulted in short-lived hybrid offspring, whereas hybrids derived from long-lived parents tended to be long-lived. Crosses between strains of contrasting longevities gave clones with intermediate growth potentials relative to the other types of hybrids. The failure to observe complementation (enhanced longevity) of hybrids argues against random recessive single-copy gene mutations as important determinants of clonal senescence.

Cell Fusion↗
PubMed1978

Trisomy 3 (p23-pter) resulting from maternal translocation, t (3 ; 4)(p23 ; q35).

We describe a patient with partial trisomy 3p resulting from maternal translocation, t(3:4)(p23;q35). The male newborn who died at the age of 22 hours presented with distinct facial features including a square-shaped face with prominent forehead and depressed temporal regions, prominent cheeks, short broad nose, left cleft lip and cleft palate, malformed ears, and a receding mandible. Further findings were flexion deformities of the fingers with finger-like thumbs and mild cutaneous syndactyly 2/3 and 4/5, hypoplastic penis and scrotum with no palpable testes. He probably had a congenital heart defect and situs inversus abdominalis. Many of these features have been reported in other patients with distal trisomy 3p.

Abnormalities, Multiple↗