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Biomedical subjects

U Friedrich

Publications and source records attributed to U Friedrich.

At least 37 records · Page 2Linked to original sources
PubMed2000

Telomere length in different tissues of elderly patients.

Telomeres are supposed to play a role in cellular aging and might contribute to the genetic background of human aging and longevity. During the past few years telomere length has been measured in various human tissues. However, very little is known about the individual telomere loss in different tissues from the same donor. Therefore we have measured telomere restriction fragment (TRF) length in three unrelated tissues (leukocytes, skin and synovial tissue) of nine elderly patients (age range 73-95 years old). Dependent on the tissue specific proliferation rate we have found significantly shorter telomeres (6546+/-519 bp, mean +/- S.D.) in leukocytes compared to skin (7792+/-596 bp, P<0.01) and synovial tissue (7910+/-420 bp, P<0.001). In general, we have observed an inverse relationship between donor age and TRF length which becomes significant in leukocytes (P=0.04, R(2)=0.49) and skin specimens (P=0.006, R(2)=0.81). Interestingly, linear correlations (P values between 0.017 and 0.038, R(2) values between 0.54 and 0.79) were also obtained on comparison of telomere length in each pair of two different tissues from the same donor without taking donor age into account. This suggests that genetic determination of the regulation of telomere length is tissue-independent. Furthermore, our results indicate that TRF measurement in easily accessible tissues such as blood could serve as a surrogate parameter for the relative telomere length in other tissues.

Aged↗
PubMed2000

Microdissection of chromosome 2--between-arm intrachromosomal insertion.

This report describes a mother with a balanced intrachromosomal insertion of band q22 on chromosome number 2 into band p24 on the same chromosome. She had had four spontaneous abortions and two induced abortions. One foetus had a suspected obstruction of the uretero-pelvic part of the urinary tract and monosomy of band 2q22, the other foetus had anencephaly and trisomy of band 2q22. By microdissection we have generated a painting probe from the mother's abnormal short arm of chromosome 2 (der2p probe). This family specific probe will be used in future pregnancies for precise diagnosis.

Abortion, Induced↗
PubMed2000

Disease associated balanced chromosome rearrangements: a resource for large scale genotype-phenotype delineation in man.

Disease associated balanced chromosomal rearrangements (DBCRs), which truncate, delete, or otherwise inactivate specific genes, have been instrumental for positional cloning of many disease genes. A network of cytogenetic laboratories, Mendelian Cytogenetics Network (MCN), has been established to facilitate the identification and mapping of DBCRs. To get an estimate of the potential of this approach, we surveyed all cytogenetic archives in Denmark and southern Sweden, with a population of approximately 6.6 million. The nine laboratories have performed 71 739 postnatal cytogenetic tests. Excluding Robertsonian translocations and chromosome 9 inversions, we identified 216 DBCRs ( approximately 0.3%), including a minimum estimate of 114 de novo reciprocal translocations (0.16%) and eight de novo inversions (0.01%). Altogether, this is six times more frequent than in the general population, suggesting a causal relationship with the traits involved in most of these cases. Of the identified cases, only 25 (12%) have been published, including 12 cases with known syndromes and 13 cases with unspecified mental retardation/congenital malformations. The remaining DBCRs were associated with a plethora of traits including mental retardation, dysmorphic features, major congenital malformations, autism, and male and female infertility. Several of the unpublished DBCRs defined candidate breakpoints for nail-patella, Prader-Willi, and Schmidt syndromes, ataxia, and ulna aplasia. The implication of the survey is apparent when compared with MCN; altogether, the 292 participating laboratories have performed >2.5 million postnatal analyses, with an estimated approximately 7500 DBCRs stored in their archives, of which more than half might be causative mutations. In addition, an estimated 450-500 novel cases should be detected each year. Our data illustrate that DBCRs and MCN are resources for large scale establishment of phenotype-genotype relationships in man.

Chromosome Aberrations↗
PubMed1999

Pelagic Bacteria-Particle Interactions and Community-Specific Growth Rates in Four Lakes along a Trophic Gradient.

Abstract The relationships between bacterial concentration, bacterial production, and cell-specific activity of both free and attached bacteria and environmental factors such as suspended solids, nutrients, and temperature were examined in four lakes, two in New Zealand and two in Switzerland. Estimates of cell-specific production were obtained by microautoradiographic counts of [3H]thymidine-labeled cells. Bacteria attached to particles accounted for only 1.3 to 11.6% of the total bacterial abundance, but showed overall 20-fold higher specific growth rates and were relatively more active than their free counterparts. On average, 80 to 100% of epibacteria were attached to organic particles. The abundance and production of free and attached bacteria were positively correlated; however, relationships between these fractions and some environmental variables differed. Cell-specific activities of active bacteria were not equivalent to mean cellular activities of the entire bacterial community and differed in their relationship to trophic state. [3H]Thymidine-positive bacteria were more tightly linked to chlorophyll a than were total bacteria. Our findings indicate that production by attached bacteria, fueled by phytoplankton carbon, supplies "new" free bacteria to the bacterial community. Our results support the idea that particulate organic matter acts as a source of dissolved nutrients to free bacteria. Bottom-up control of bacterial biomass, as shown by regressions of biomass vs production, appeared to be stronger in two ultraoligotrophic lakes than in two more eutrophic ones.

Journal Article↗
PubMed1999

Community analysis of biofilters using fluorescence in situ hybridization including a new probe for the Xanthomonas branch of the class Proteobacteria.

Domain-, class-, and subclass-specific rRNA-targeted probes were applied to investigate the microbial communities of three industrial and three laboratory-scale biofilters. The set of probes also included a new probe (named XAN818) specific for the Xanthomonas branch of the class Proteobacteria; this probe is described in this study. The members of the Xanthomonas branch do not hybridize with previously developed rRNA-targeted oligonucleotide probes for the alpha-, beta-, and gamma-Proteobacteria. Bacteria of the Xanthomonas branch accounted for up to 4.5% of total direct counts obtained with 4',6-diamidino-2-phenylindole. In biofilter samples, the relative abundance of these bacteria was similar to that of the gamma-Proteobacteria. Actinobacteria (gram-positive bacteria with a high G+C DNA content) and alpha-Proteobacteria were the most dominant groups. Detection rates obtained with probe EUB338 varied between about 40 and 70%. For samples with high contents of gram-positive bacteria, these percentages were substantially improved when the calculations were corrected for the reduced permeability of gram-positive bacteria when formaldehyde was used as a fixative. The set of applied bacterial class- and subclass-specific probes yielded, on average, 58.5% (+/- a standard deviation of 23.0%) of the corrected eubacterial detection rates, thus indicating the necessity of additional probes for studies of biofilter communities. The Xanthomonas-specific probe presented here may serve as an efficient tool for identifying potential phytopathogens. In situ hybridization proved to be a practical tool for microbiological studies of biofiltration systems.

Air Pollutants↗
PubMed1999

Herpesvirus ateles gene product Tio interacts with nonreceptor protein tyrosine kinases.

Herpesvirus ateles is a gamma-2-herpesvirus which naturally infects spider monkeys (Ateles spp.) and causes malignant lymphoproliferative disorders in various other New World primates. The genomic sequence of herpesvirus ateles strain 73 revealed a close relationship to herpesvirus saimiri, with a high degree of variability within the left terminus of the coding region. A spliced mRNA transcribed from this region was detected in New World monkey T-cell lines transformed by herpesvirus ateles in vitro or derived from T cells of infected Saguinus oedipus. The encoded viral protein, termed Tio, shows restricted homology to the oncoprotein StpC and to the tyrosine kinase-interacting protein Tip, two gene products responsible for the T-cell-transforming and oncogenic phenotype of herpesvirus saimiri group C strains. Tio was detectable in lysates of the transformed T lymphocytes. Dimer formation was observed after expression of recombinant Tio. After cotransfection, Tio was phosphorylated in vivo by the protein tyrosine kinases Lck and Src and less efficiently by Fyn. Stable complexes of these Src family kinases with the viral protein were detected in lysates of the transfected cells. Binding analyses indicated a direct interaction of Tio with the SH3 domains of Lyn, Hck, Lck, Src, Fyn, and Yes. In addition, tyrosine-phosphorylated Tio bound to the SH2 domains of Lck, Src, or Fyn. Thus, herpesvirus ateles-encoded Tio may contribute to viral T-cell transformation by influencing the function of Src family kinases.

Amino Acid Sequence↗
PubMed1998

Occurrence of cancer in a cohort of 183 persons with constitutional chromosome 7 abnormalities.

Cytogenetic abnormalities in human malignancies frequently involve chromosome 7. The existence of several tumor suppressor genes on the long arm of chromosome 7 has been suggested in both epithelial and hematologic malignancies. From the Danish Cytogenetic Register, we identified 183 persons with constitutional abnormalities involving chromosome 7, including 16 patients with Williams syndrome. By linkage to the Danish Cancer Registry, we found five persons with cancer, including one thyroid carcinoma, three carcinomas of the digestive tract, and one malignant melanoma. There were no cases of leukemia. The overall risk of developing cancer was not increased.

Adult↗
PubMed1997

A de nevo complex t(7;13;8) translocation with a deletion in the TRPS gene region.

Molecular cytogenetic analyses have resolved the pathogenetic aberration of an 8-year-old girl with tricho-rhino-phalangeal syndrome type I (TRPS I), normal intelligence, and a karyotype originally described as 46,XX,t(8;13)(q24;q21). R- and Q-banding and high resolution R-banding analyses have also disclosed a seemingly mosaic abnormality of the distal short arm of chromosome 7 but have not fully characterized this abnormality. Combined primed in situ labelling and chromosome painting, and three-colour chromosome painting have revealed a complex, apparently balanced translocation t(7;13;8). Fluorescence in situ hybridization with yeast artificial chromosome and cosmid clones from 8q24.1 has shown an interstitial deletion of at least 3 Mb covering most of the TRPS I critical region.

Child↗
PubMed1997

Fre2, a proviral integration site of Friend murine leukemia virus that is closely linked to Fv2.

Friend murine leukemia virus (F-MuLV) induces leukemia by integration into the cellular genome, thereby changing the structure or expression of cellular oncogenes. In this report we describe a new F-MuLV integration site Fre2 isolated from splenic DNA of an erythroleukemic animal. This site was found to be rearranged in six out of 64 tumors tested; however, in five out of these six cases no F-MuLV proviruses could be detected in the vicinity of the rearrangement sites. The rearrangements represented closely clustered chromosomal breakpoints, presumably chromosomal translocations. Exons transcribed into differentially spliced mRNAs of 1.9 and 3.7 kb have been found near the breakpoint. Fre2 is closely linked to Fv2, a locus on mouse chromosome 9 involved in erythropoiesis. Sequences homologous to Fre2 could not be found in the gene databases.

Alternative Splicing↗
PubMed1997

Experimental and clinical experience with new pyeloureteral stents in pediatric urology.

In light of the many problems with the use of conventional external stents in supravesical reconstructive urinary tract surgery in children; e.g. the risk of infection, urodynamic malfunction, and lack of flexibility insertion methods, the return to internal pyeloureteral stenting is a much discussed topic in pediatric urology. In order to improve the generally unsatisfactory situation, we developed, together with the Rüsch Co., a new type of directable and deconnectable ureteral stent. This polyurethane catheter features a membrane valve made of soft Wiruthan at the bladder end, which closes automatically with increasing bladder pressure. Thus, urinary backflow from the urinary bladder into the renal pelvis is prevented. Experimental data from antireflux stenting justify the clinical use of such a stent in children, as the urodynamic in vivo criteria and requirements were fulfilled completely. We now have clinical experience with the application of 340 pyeloureteral DD stents in 241 children from 1993 through 1996; 259 stents were inserted intraoperatively, and 81 stents were applied by endoscope. It was impressive that secondarily, renal function that had been considerably reduced could be regained and stabilized by long-term stenting, even in some older children with chronic supravesical ureteral obstruction. Although small technical details have to be clarified, such as simplification of stent retrieval and an antireflux valve that can be applied using an anterograde approach, the DD valve stent used in this patient population after reconstruction of a malformed supravesical urinary tract can be recommended without any reservations.

Animals↗
PubMed1997

Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations.

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.

Child↗
PubMed1997

Prenatal diagnosis of a half-cryptic translocation using chromosome microdissection.

This report describes a case of a paternal balanced, but apparently non-reciprocal, insertion of chromosome 15 material into the short arm of chromosome 17 with difficulties in distinguishing between the normal and the deleted chromosome 15 in prenatal karyotype analysis. Microdissection and degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR) of the paternal 17p+ chromosome was performed to generate a painting probe specific for the small region inserted from chromosome 15 into chromosome 17. Fluorescence in situ hybridization (FISH) of this probe simultaneously with a differentially labelled 15q microdissection probe enabled the identification of a balanced karyotype in the fetus. In this case, microdissection combined with FISH was the only method for obtaining a reliable result within the short time available for prenatal diagnosis. In addition, it was possible to identify with certainty the originally suspected reciprocal translocation as an insertion of the region 15q22.3-->q23 or 24 into the sub-telomeric region of 17p [ins(17;15)(p13;q22.3q23 or 24)]. Thus, the chromosomal defect of two family members with a partial trisomy of chromosome 15 having severe mental retardation and dysmorphic features was identified precisely.

Adult↗
PubMed1997

Fre-2, a locus closely linked to Fv-2, is rearranged in some erythroleukemias induced by Friend murine leukemia virus.

Friend murine leukemia virus (F-MuLV) induces leukemia by integration into the cellular genome, thereby changing the structure of expression of cellular oncogenes. Here we describe a new F-MuLV integration site Fre-2 isolated from splenic DNA of an erythroleukemic animal. This site has been found rearranged in 5 out of 63 additional tumors; however, no F-MuLV proviruses could be detected in the vicinity of the rearrangement sites in these 5 cases. The rearrangements represented closely clustered chromosomal breakpoints, presumably chromosomal translocations. Exons transcribed into differentially spliced mRNAs of 1.9 and 3.7 kb have been found near the breakpoint. No sequences that are homologous to Fre-2 could be found in databases.

Animals↗
PubMed1996

Systematic chromosome examination of two families with schizophrenia and two families with manic depressive illness.

Systematic and detailed chromosome analysis, combined with a semistructured interview, was performed in 2 families with schizophrenia and in 2 families with manic depressive illness. Prometaphase technique did not reveal any subtle structural chromosome abnormalities. However, in standard techniques, gain and loss of sex chromosomes were observed. This occurred in patients at a younger age than in unaffected persons. This gives rise to the suspicion that sex chromosome aneuploidy may somehow be related to the development of psychosis. But since the data set is small, especially with respect to schizophrenia, further studies are needed to elucidate this observation. In one family, cosegregation of the disease locus with a marker on chromosome 21 was seen. Therefore, further research should determine if chromosome 21 contains a gene for manic depressive illness.

Adult↗
PubMed1996

Extreme variant of the short arm of chromosome 15.

Using fluorescence in situ hybridization, primed in situ labelling, and conventional cytogenetic staining we have characterized an excessively enlarged short arm of chromosome 15. The likely mechanism explaining this variant chromosome involves amplification of rDNA sequences followed by inverted insertional translocation between the enlarged sister chromatids of the short arm of chromosome 15.

Chromatids↗
PubMed1996

Occurrence of cancer in women with Turner syndrome.

A study of cancer incidence in a cohort of 597 women with Turner syndrome (TS) and a virtually complete follow-up is presented. The cohort was established from the Danish Cytogenetic Register. Information on cancer incidence was obtained from the Danish Cancer Registry and compared with the expected number calculated from the age-, period- and site-specific cancer rates for Danish women. A total of 21 neoplasms was observed, of which 13 occurred more than 1 year after diagnosis of TS, corresponding to a relative risk of cancer of 1.1. Wilms' tumour was the only identified childhood cancer. No case of gonadoblastoma or dysgerminoma was identified in the 29 women with a Y chromosome or in the women in whom no Y chromosome material was detected by standard cytogenetic methods, suggesting that the risk of ovarian germ cell tumours may be lower than previously estimated. Colon cancer was observed in five patients (relative risk 6.9, 95% confidence interval 2.2-16.2). Further studies are needed to assess whether colon cancer in TS is related to Turner-associated genes on the sex chromosome(s).

Adolescent↗