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Biomedical subjects

U Müller

Publications and source records attributed to U Müller.

At least 307 records · Page 17Linked to original sources
PubMed1993

Identification of the gene encoding the activator of (R)-2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans by gene expression in Escherichia coli.

(R)-2-Hydroxyglutaryl-CoA dehydratase (HGDA/B) from Acidaminococcus fermentans requires an activator protein for activity. This activator (HGDC) has not yet been purified from its natural source due to its low concentration combined with an extreme sensitivity towards oxygen. Gene expression in Escherichia coli identified an open reading frame (780 bp) as the gene encoding HGDC. Dehydratase activity was stimulated at least tenfold by cell-free extracts of E. coli cells transformed with a plasmid carrying hgdC. On the chromosome the hgdC gene is located just before hgdA and hgdB.

Amino Acid Sequence↗
PubMed1993

Newly recognized autosomal dominant disorder with craniosynostosis.

We report a family with a newly recognized form of autosomal dominant craniosynostosis. The disorder has high penetrance and variable expression with respect to sutural involvement and cranial abnormalities, ranging from fronto-orbital recession to clover-leaf skull deformity. Associated problems included headache, poor vision, and seizures; intelligence, however, is normal. Assignment of a well-described syndromic designation, e.g., Crouzon, Pfeiffer, Saethre-Chotzen, or Jackson-Weiss, is precluded based upon the absence of characteristic changes, i.e., midfacial hypoplasia, orbital hypertelorism, blepharoptosis, hand anomalies, or foot anomalies. The large size of this family and high penetrance of the disorder suggests that this may be an excellent candidate for positional cloning of a locus important in craniofacial development.

Craniosynostoses↗
PubMed1993

Assignment of a gene locus involved in craniosynostosis to chromosome 5qter.

Craniosynostosis, the abnormal development of the calvarial sutures, occurs as an autosomal dominant trait in many clinically distinct syndromes. We performed linkage analysis of a provisionally novel type of autosomal dominant craniosynostosis in a large three generational family. Linkage was established between the craniosynostotic locus and D5S211, a locus defined by the short tandem repeat polymorphism (STRP) marker Mfd 154 in distal 5q. The maximum LOD score, Zmax, was 4.8 at a recombination fraction of zero. No significant linkage was found with markers located 30 cM and more proximal to D5S211. The findings assign the craniosynostotic locus in this family to a telomeric region in the long arm of chromosome 5. Linkage analysis with Mfd 154 in other autosomal dominant craniosynostotic syndromes should reveal whether these disorders are caused by mutations of genes at the same or at different loci.

Adult↗
PubMed1993

Fine mapping of the human SCIDX1 locus at Xq12-13.1.

Previous linkage analysis of families with X-linked severe combined immunodeficiency (SCIDX1) mapped this locus to a large region encompassing about 10 to 20 cM at Xq12-21. We have analyzed in SCIDX1 families the segregation of 7 highly polymorphic microsatellites repeats localized to this region, including a new polymorphic microsatellite at the DXS135 locus described in this study, to refine the mapping of this disease locus. The observations of genetic recombinants within the previously defined SCIDX1-region allow us to establish new flanking markers at the DXS135 and DXS227 loci, which significantly reduce the region harboring the SCIDX1 locus to a distance estimated between 3 to 5 cM. The existence of multiple, highly polymorphic markers in the refined SCIDX1 region will greatly improve the accuracy of carrier detection and prenatal diagnosis for SCIDX1.

Alleles↗
PubMed1993

Gonadal function after MACOP-B or VACOP-B with or without dose intensification and ABMT in young patients with aggressive non-Hodgkin's lymphoma.

BACKGROUND: The late effects of chemotherapy of aggressive non-Hodgkin's lymphoma on gonadal function are largely unknown. PATIENTS AND METHODS: In a retrospective study the gonadal function after chemotherapy with MACOP-B or VACOP-B with or without dose intensification and ABMT in first remission was examined in patients with aggressive non-Hodgkin's lymphoma by patient history and determination of hormonal function. Thirty adult patients of age 40 or less at diagnosis who were alive and free of relapse for at least 1 year after completion of chemotherapy were included in the study. RESULTS: With a median time of 28 months (range 11 to 62 months) after completion of therapy, gonadal dysfunction was found in 1 of 7 female and none of 15 male patients, or a total of 5% of patients treated with chemotherapy alone. Of patients receiving dose intensification and ABMT in first remission, gonadal dysfunction was present in 2/6 (33%) treated with cyclophosphamide, BCNU and etoposide in 3/4 treated with cyclophosphamide and TBI. CONCLUSIONS: Our data suggest that therapy of aggressive non-Hodgkin's lymphomas with MACOP-B or VACOP-B has little impact on future fertility and that fertility may be preserved in the majority of patients receiving dose-intensification with CBV in first remission.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

PCR amplification of SRY-related gene sequences reveals evolutionary conservation of the SRY-box motif.

SRY (sex-determining region of the Y chromosome) has recently been identified as a key regulatory gene in mammalian sex determination. The open reading frame of this gene contains an 80-amino-acid motif, the SRY-box, which shares a high degree of homology with a DNA-binding domain found in the high-mobility-group (HMG) proteins HMG1 and HMG2. The SRY box motif is highly conserved in several sequence-specific DNA-binding proteins that are known to act as transcription factors. Here we describe the use of degenerate PCR primers to identify SRY-related sequences containing the SRY-box motif from the genomic DNA of a variety of species. The results of this study suggest that in a diverse array of species SRY-related genes may serve as transcription factors that regulate a variety of developmental pathways, including sex determination.

Alligators and Crocodiles↗
PubMed1993

Second polar body incorporation into a blastomere results in 46,XX/69,XXX mixoploidy.

A case of 46,XX/69,XXX mixoploidy is described. The patient had a normal 46,XX diploid karyotype in lymphocytes but a triploid 69,XXX cell line in most of her fibroblasts. In order to learn more about the underlying mechanism resulting in mixoploidy, we studied short tandem repeat polymorphisms (STRPs) in lymphocyte DNA of the patient's parents and in both lymphocyte and fibroblast DNA of the proband. The findings showed maternal origin of the supernumerary chromosome complement and are best explained by second polar body incorporation into a blastomere.

Abnormalities, Multiple↗
PubMed1993

Human papillomavirus, type 16, DNA in multicentric anogenital neoplasia associated with idiopathic panmyelopathy. A case report.

A 27-year-old woman suffering from panmyelopathy for six years presented with a cervical low grade squamous intraepithelial lesion (SIL), vulvar high grade SIL and perianal squamous cell carcinoma with an inguinal metastasis. Southern blot hybridization with 32P-labeled human papillomavirus (HPV) DNA revealed HPV 16 DNA in varying copy numbers in material from the four locations. HPV 16 genomes persisting after surgery on the perianal tumor area were no longer detectable after betatron radiotherapy.

Abdominal Neoplasms↗
PubMed1992

Cloning and expression analysis of two ZFY-related zinc finger genes from Alligator mississippiensis, a species with temperature-dependent sex determination.

In order to investigate the molecular mechanism of temperature-dependent sex determination, a human zinc finger gene (ZFY), known to be highly conserved amongst other species, was used to isolate homologues from the genome of the American alligator, Alligator mississippiensis. ZFY was originally a candidate for the primary testis-determining gene in man, but is now thought to function further down the sex-determining cascade. Two alligator genes are described, Zfc and Znc6. Both code for zinc finger proteins and exhibit amino acid (aa) homologies to ZFY of 91% and 73%, respectively. Znc6 shows aa homology of 88% to the protein encoded by the zinc finger exon of the human ZFY-related gene, ZNF6, recently found on the X chromosome. Analysis of Zfc and Znc6 expression during embryonic development identified two major transcripts of 5.9 kb and 2.7 kb coding for Zfc, whilst only one transcript of 4.8 kb was detected for Znc6. Both genes are transcribed at all stages tested, from day 3 (post egg laying) throughout gestation. The expression level of all transcripts appears to decline towards the time of hatching (65-72 days). No sex-specific differences in the expression were observed. The extensive sequence conservation of the genes between reptiles and humans suggests major functional constraints. The expression patterns indicate that these genes do not play a primary role in temperature-dependent sex determination.

Alligators and Crocodiles↗
PubMed1992

Delineation of the dystonia-parkinsonism syndrome locus in Xq13.

The X chromosome-linked dystonia-parkinsonism syndrome (XDP) is a severe movement disorder, characterized by both dystonia and parkinsonism. XDP is a genetically homogeneous disorder. Known ancestry of all patients has been traced back to Panay, Philippines, where the disease probably originated from a single mutation (founder effect). The gene locus, DYT3, has been previously assigned to the proximal long arm of the X chromosome (Xq12-q21.1). Using four dinucleotide tandem repeat (DNTR) sequences from Xq13-derived yeast artificial chromosomes (YACs), we further delineate DYT3 within Xq13. Observation of a recombination event between DYT3 and DNTR locus 4548-7, derived from a YAC encompassing locus DXS56, establishes 4548-7 as a distal flanking marker. Assignment of DYT3 to a region in Xq13, flanked by loci 4548-7 and DXS159, is further supported by highly significant allelic association between DYT3 and a total of four DNTR loci--PY2-31, PY5-10, 4548-1, and 4548-7--located in a region defined by PGK1 and DXS56. /phi/ and /delta/ values were 0.82/0.35, 0.78/0.42, 0.65/0.34, and 0.88/0.58 for PY2-31, PY5-10, 4548-1, and 4548-7 at P less than 10(-2), P less than 10(-4), P less than 10(-3), and P less than 10(-6).

Base Sequence↗
PubMed1992

Functional analysis of defined mutations in the immunoglobulin heavy-chain enhancer in transgenic mice.

We have analyzed the effect of defined mutations in the mouse immunoglobulin heavy-chain enhancer after introduction into the germline of transgenic mice. We have tested a mutation of the enhancer octamer motif, a double mutation of the octamer motif and the microB-site, and a triple mutation in the microE2, microE3 and microE4-sites. All constructs are expressed in the spleen of transgenic mice. Furthermore, expression is exclusively detectable in lymphoid organs and not in several nonlymphoid tissues. Whereas mutations in the microE-sites have a more pronounced effect on transgene activity in thymocytes as compared to bone marrow and spleen cells, the octamer/microB double mutation shows significantly reduced expression levels only in B-cells. Finally, our results demonstrate that the intronic heavy-chain enhancer element does not contribute to the increase steady state levels of heavy-chain mRNA after stimulation of spleen cells with LPS.

Animals↗
PubMed1992

Molecular analysis of aberrations of Xp and Yq.

Three cases of Y chromosomal aberrations were studied using a panel of Y-specific DNA sequences from both Yp and euchromatic Yq. One case was a phenotypic male fetus with a Y-derived marker chromosome. The short arm of this chromosome was intact, but most of its long arm was missing. The second case had a 46,XYq- karyotype with portions of euchromatic Yq, including the spermatogenesis region, missing. The third case was a phenotypic female with a 46,XXp+ karyotype. The extra material on the Xp+ chromosome was derived from the heterochromatic, and part of the euchromatic, portion of Yq. Application of X-specific DNA sequences demonstrated that the distal portion of the short arm of the translocation X chromosome was deleted (Xpter-p22.3). The three examples demonstrate the importance of diagnostic DNA analysis in cases of marker chromosomes, and X and Y chromosomal aberrations. In addition, the findings in the patients facilitate further deletion mapping of euchromatic Yq.

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

Isolation of DNTR polymorphisms from yeast artificial chromosomes encompassing X chromosomal loci PGK1 and DXS56.

Five dinucleotide tandem repeat (DNTR) sequences were isolated from yeast artificial chromosomes containing the PGK1 and DXS56 loci in Xq13. Sequence information of these DNTR loci is given. Four of the five DNTR sequences were polymorphic. Polymorphism information content values were 0.44, 0.49, 0.47, and 0.76 for loci PY5-10, PY2-31, 4548-1, and 4548-7, respectively. Corresponding heterozygosities were 0.55, 0.55, 0.56, and 0.78. These DNTRs are useful for the fine mapping of disease loci in Xq13 and provide sequence tagged sites for this region of the X chromosome.

Base Sequence↗