PubMed Health⌕ Search

Biomedical subjects

J M Scheres

Publications and source records attributed to J M Scheres.

At least 19 recordsLinked to original sources
PubMed2001

Variegated aneuploidy related to premature centromere division (PCD) is expressed in vivo and is a cancer-prone disease.

We present three patients with variegated aneuploidy and premature centromere division (PCD), a rare chromosomal abnormality in humans. Comparison of these three and eight other patients with variegated aneuploidy related to PCD demonstrates a phenotype comprising most frequently microcephaly, CNS anomalies (with cerebellar affection and migration defects), mental retardation, pre-and postnatal growth retardation, flat and broad nasal bridge, apparently low-set ears, eye and skin abnormalities, and ambiguous genitalia in male patients. The occurrence of Wilms tumor in three patients, rhabdomyosarcoma in two others and acute leukemia in a fifth characterizes this condition as a chromosome or genome instability disorder with a high risk of malignancy. FISH studies in uncultured blood and buccal smear cells demonstrate that the random aneuploidies are not limited to cultured cells, but also occur in vivo.

Abnormalities, Multiple↗
PubMed2000

Precarious acrocentric short arm in prenatal diagnosis: no chromosome 14 polymorphism, but trisomy 17p.

Precarious acrocentric short arm in prenatal diagnosis: no chromosome 14 polymorphism, but trisomy 17p: We report on a girl with multiple congenital abnormalities and a prenatally diagnosed 46,XX,14p+ de novo karyotype. Fluorescence in situ hybridization (FISH) demonstrated that the extra material on the short arm of chromosome 14 was not just a polymorphism, but that it originated from chromosome 17. The phenotypic findings of this patient with pure trisomy 17p are compared with those of ten previously published cases.

Abnormalities, Multiple↗
PubMed1999

Isochromosome 1q as the sole chromosomal abnormality in two fetal teratomas. Possible trisomic or tetrasomic zygote rescue in fetal teratoma with an additional isochromosome 1q.

An isochromosome of the long arm of chromosome 1 leading to tetrasomy 1q was detected as the sole chromosomal aberration in two cases of fetal teratoma arising from the oral cavity. This type of teratoma is extremely rare and has seldom been investigated cytogenetically. Studies of DNA markers in the tumor, normal fetal skin, and parental cells demonstrated that in both cases the additional 1q material was of maternal origin. In one of the patients, the teratoma had maternal 1q marker alleles that were not found in the fetal body cells. This implies that the tumor was not derived in a direct way from the fetal body tissue; instead, the chromosomally-normal fetus might be the result of some trisomic or tetrasomic zygote rescue mechanism.

Alleles↗
PubMed1999

Subfertile men with constitutive chromosome abnormalities do not necessarily refrain from intracytoplasmic sperm injection treatment: a follow-up study on 75 Dutch patients.

A follow-up study was performed to investigate the impact of the detection of a chromosome abnormality in infertile men who are candidates for intracytoplasmic sperm injection (ICSI) treatment. In this collaborative study between clinical genetics centres and fertility clinics in the Netherlands, 75 ICSI couples of which the male partners had a chromosome abnormality were included. All couples were extensively counselled on the risk of having a chromosomally unbalanced child. Forty-two out of 75 couples chose to proceed with the ICSI treatment. So far, treatment has resulted in a pregnancy in 11 cases. Four of them opted to have invasive prenatal diagnosis. Despite the genetic risks related to a chromosome abnormality in infertile men, a small majority (56%) of the couples did not refrain from the ICSI treatment.

Adult↗
PubMed1999

Sperm analysis in a subfertile male with a Y;16 translocation, using four-color FISH.

Sperm analysis was performed in a male with oligoasthenoteratozoospermia (OAT) and a reciprocal t(Y;16) (q11. 21;q24), using four-color FISH. Intracytoplasmic sperm injection (ICSI) treatment in this patient had resulted in the birth of one chromosomally balanced and two chromosomally normal children. To assess the risk of having a chromosomally unbalanced conception after ICSI, morphologically normal spermatozoa were studied with a set of probes allowing detection of all segregation variants. There were 51% normal or balanced sperm cells. The fraction of sperm products resulting from alternate and adjacent I segregation was 87%, 12% were products of 3:1 disjunction, and the other 1% had other types of aneuploidy. If morphologically abnormal cells were also included in the FISH analysis, nearly 90% of all the spermatozoa were unbalanced. We conclude that although the majority of males with a Y/autosome translocation are infertile due to azoospermia, our patient produces sufficient morphologically and chromosomally normal spermatozoa to have chromosomally normal or balanced offspring after ICSI. Assuming that ICSI with an unbalanced spermatozoon from this patient would result in a nonviable embryo in many cases, the combination of in vitro and subsequent in vivo selection probably results in a risk of unbalanced offspring of much less than 50%. Hence, FISH studies on the sperm of translocation carriers are useful for estimating the risk of having unbalanced offspring after ICSI and in understanding the mechanisms underlying infertility in such carriers.

Adult↗
PubMed1998

One normal child and a chromosomally balanced/normal twin after intracytoplasmic sperm injection in a male with a de-novo t(Y;16) translocation.

A balanced translocation t(Y;16)(q11.21;q24) is described in a male with severe oligoasthenoteratozoospermia (OAT). Before having a chromosome investigation, the patient and his partner had undergone intracytoplasmic sperm injection (ICSI) treatment resulting in the birth of a healthy 46,XX child. After detection of the t(Y;16) translocation, the couple opted for further ICSI treatment, although they were extensively counselled on the risk of having chromosomally unbalanced offspring. This treatment resulted in a twin pregnancy, one with a 46,XX karyotype and the other a 46,X,t(Y;16) (q11.21;q24) karyotype, the same as the father. After an uncomplicated pregnancy two healthy children were born. We conclude that patients with a Y/autosome translocation as a cause of OAT can have chromosomally normal children after ICSI treatment.

Adult↗
PubMed1992

Absence of Turner stigmata in a 46,XYp-female.

A 46,XY female patient with streak gonads and a large deletion of Yp is described. The deletion included the Y chromosomal genes SRY, ZFY, and RPS4Y. The patient did not display any Turner stigmata, such as webbing of the neck, cardiac or other abnormalities. The findings argue against an important role of RPS4Y in the prevention of Turner stigmata in males and are consistent with a role of SRY in testis differentiation in humans.

Adult↗
PubMed1992

Simultaneous measurement, using flow cytometry, of radiosensitivity and defective mitogen response in ataxia telangiectasia and related syndromes.

In a retrospective study, peripheral blood mononuclear cells from 13 patients with known ataxia telangiectasia (AT) (Louis Bar syndrome, McKusick #20890) were irradiated with different doses of X-rays prior to stimulation with phytohaemagglutinin. Mitogen response and cell cycle progression were assessed by two-parameter 5-bromo-2'-deoxyuridine/Hoechst--ethidium bromide flow cytometry. Compared to age-matched controls, AT cells show a severely defective mitogen response in both unirradiated and irradiated cells. Following irradiation with 1.5 Gy, AT cells exhibit significantly greater accumulations of cells in the G2 phase of the first cell cycle than controls. The ratio between the number of cells accumulated in the first cycle G2 phase and the growth fraction provides a clear distinction between AT and control cultures. In addition, two patients with microcephaly, normal intelligence, immunodeficiency, chromosomal instability and risk for lymphoreticular malignancies (Seemanová syndrome) and two patients with the Nijmegen breakage syndrome (both syndromes are listed as McKusick #25126) also exhibit very poor mitogen response and moderately increased G2 phase accumulations after X-irradiation. The simultaneous assessment of radiosensitivity and mitogen response in a single cell kinetic assay provides a speedy and accurate classification of cells of AT and AT-related syndromes.

Adolescent↗
PubMed1991

Chromosome instability and X-ray hypersensitivity in a microcephalic and growth-retarded child.

We report on a microcephalic, growth-retarded newborn girl without major anomalies who has chromosome instability in lymphocytes and fibroblasts. Frequent involvement of bands 7p13, 7q34, 14q11, and 14q32 suggested the diagnosis of ataxia telangiectasia (AT) or a related disorder. Supportive evidence was radioresistant DNA synthesis in fibroblasts and radiation hypersensitivity of short-term lymphocyte cultures. Follow-up for nearly 4 years showed largely normal development, and no signs of telangiectasia, ataxia, or immunodeficiency. Serum AFP levels turned from elevated at age 5 months to normal at age 2 years. We propose that our patient belongs to the expanding category of "AT-related" genetic disorders, probably to the Nijmegen breakage syndrome.

Cell Cycle↗
PubMed1989

Further delineation of the Nijmegen breakage syndrome.

We report on five independent families with a chromosome instability disorder that earlier had been called the Nijmegen breakage syndrome (NBS). These families, two from the Netherlands and three from Czechoslovakia, had a total of eight patients, five of whom are still alive. The main clinical manifestations were microcephaly, short stature, a "bird-like" face, immunological defects involving both the humoral and cellular system. In four of the five living patients it has been possible to study the chromosomes of cultured lymphocytes. The basic karyotype in these patients were normal, but in 17% to 35% of the metaphases rearrangements were found, preferentially involving chromosomes 7 and/or 14 at the sites 7p13, 7q34, and 14q11. The chromosomes of all five living patients were very sensitive to ionizing radiation. In addition, the DNA synthesis in their cultured lymphocytes and fibroblasts was more resistant to X-rays than in cells from controls. The NBS shares a number of important features with ataxia telangiectasia (AT). Both syndromes are characterized by the occurrence of typical rearrangements of chromosomes 7 and/or 14, cellular and chromosomal hypersensitivity to X-irradiation, radioresistance of DNA replication and immunodeficiency. However, there are also obvious differences: NBS patients have microcephaly but neither ataxia nor telangiectasia, and in contrast to the situation in AT the alpha-fetoprotein level in their serum is normal.

Abnormalities, Multiple↗
PubMed1989

Characterization of a hormone-producing ovarian carcinoma cell line.

An ovarian carcinoma cell line (OTN 11) was produced from the ascitic fluid of a patient with a moderately to well differentiated papilliferous cystadenocarcinoma of the ovary. The cell line was characterized using electron microscopy karyotyping, immunohistochemical techniques with monoclonal antibodies against keratins as epithelial markers, and the monoclonal antibodies OV-TL 3 and OC 125 as ovarian carcinoma markers. These techniques revealed the epithelial and adenocarcinomatous nature of the cell line and the presence of ovarian carcinoma-related surface markers. The adenocarcinomatous nature of the cell line also became apparent after heterotransplantation of cell suspensions into nude mice and nude rats, in which adenomatous tumor structures were formed. These xenografts had the same ultrastructural and immunohistochemical properties as the cell line. Despite the adenocarcinomatous character of the tumor the cultured cells release estradiol into the culture medium. We may conclude that OTN 11 is an ovarian carcinoma cell line which has retained highly differentiated functions, such as the production of an ovarian hormone.

Adult↗
PubMed1988

[Immunodeficiency and chromosome instability].

In this paper, a survey is given of the immunological disturbances in some chromosome instability disorders (e.g. Bloom syndrome, ataxia teleangiectasia and Nijmegen Breakage syndrome). Further, the clinical symptoms and the diagnostic approach will be discussed.

Antibody Formation↗
PubMed1987

Epidermodysplasia verruciformis: Langerhans cells, immunologic effect of retinoid treatment and cytogenetics.

A case study is presented of a 44-year-old negroid male with epidermodysplasia verruciformis (EV), cutaneous carcinomas, and impaired cell-mediated immunity (CMI), infected with human papillomavirus type 8 and 17. Analysis was made of (a) T6+ and HLA-DR+ Langerhans cells (LCs) by immunoperoxidase staining in lesional and clinically normal skin before and during retinoid treatment, (b) the effect of retinoid treatment on CMI in vivo and in vitro, and (c) cytogenetic aspects related to chromosomal instability. The results showed the virtual absence of T6+ and HLA-DR+ LCs in koilocytic areas of epidermis involved with EV. Light-exposed, clinically normal skin also demonstrated microscopic EV lesions largely devoid of T6+ and HLA-DR+ LCs. Retinoid treatment with etretinate (Ro 10-9359) appeared both to increase the CMI response in vitro to T-cell mitogens and to influence the in situ pattern of T6+ and HLA-DR+ LCs. The cytogenetic study did not show evidence of spontaneous or UV-induced chromosomal instability.

Adult↗
PubMed1987

Chromosome studies in IgA-deficient patients.

Chromosome analysis was performed in 17 children with IgA-deficiency. In two patients a constitutional structural chromosome abnormality was found. A ring chromosome 22 was seen in one, while in the other a mosaicism of ring chromosome 18/18p+ was observed. Both patients were mentally retarded and showed distinct congenital defects. From ten asymptomatic patients, spontaneous as well as X-ray-induced chromosome instability was investigated. There was no increased spontaneous instability, and also after irradiation the induced chromosome damage was within normal control levels. A relationship between IgA-deficiency and X-ray hypersensitivity, as might be suggested by the frequently occurring coincidence of radiosensitivity and IgA-deficiency in ataxia telangiectasia patients, is not established.

Adolescent↗
PubMed1986

Possible involvement of unstable sites on chromosomes 7 and 14 in human cancer.

Specific sites on human chromosomes appear to have a tendency to rearrange in so-called "sporadic translocations," which are found in approximately 1 of 1000 metaphases from peripheral blood lymphocyte cultures. We now present data that implicates four sites in the human genome as displaying this distinct type of chromosomal instability (7p13, 7q34, 14q11, and 14q32). Chromosome 14q11 was found to be involved in sporadic translocations most often, followed by 7p13 greater than 7q34 greater than 14q32. The 14q11 locus also shows the highest frequency of spontaneous sister chromatid exchange. It is proposed that these sporadic translocations involving chromosomes #7 and #14 arise following recombinational errors occurring at sites of T- and B-cell genes known to be located at these four sites. Evidence is presented that in some cases "fixation" of a sporadic translocation might be involved in malignancy of lymphoid origin.

Chromosome Banding↗
PubMed1986

The most common fragile site in man is 3p14.

In man a common fragile site is known to occur at 3p14. We studied the expression of this fragility in a group of 70 normal healthy subjects. Chromosome breaks, chromatid breaks and gaps at 3p14 could be observed in every examined individual, and in a total of 7000 metaphases they were seen in a mean of 4% of cells. Fluorescence studies in ten persons with chromosome No. 3 polymorphism showed that in all cases both Nos. 3 were about equally liable to breakage. A considerable variation in the fra 3p14 expression was found between individuals as well as in repeated cultures from the same person. Neither sex nor age influences could be detected. Cultures with a high percentage of lesions at 3p14 tended to have also a high number of lesions at other sites. Methotrexate and fluorodeoxyuridine markedly enhanced the expression of fra 3p14 and other fragilities. It is concluded that the chromosomal region at 3p14 represents man's most common fragile site, the expression of which seems to be influenced by environmental and heritable factors.

Adolescent↗
PubMed1986

Demonstration of X chromatin in drumstick-like nuclear appendages of leukocytes by in situ hybridization on blood smears.

An X chromosome specific nucleic acid probe was used to study the positions of the X chromosomes in leukocyte nuclei by in situ hybridization to smears of peripheral blood. This autoradiographic approach allowed the first direct demonstration of the presence of X chromosomal material in the drumstick-like structures of female polymorphonuclear leukocytes.

Cell Nucleus↗