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Biomedical subjects

U Müller

Publications and source records attributed to U Müller.

At least 19 recordsLinked to original sources
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↗
PubMed1992

[Determination of water-soluble vitamins B1, B2, B6 and B12 in milk using HPLC].

Simple methods of determining the water-soluble vitamins B1, B2, B6 and B12 in milk by HPLC are described. Compared to existing procedures, the following improvements can be realized. The oxidation of vitamin B1 to thiochrome is stopped by the addition of sodium sulphite. This step significantly increases repeatability. Thiochrome is then extracted with butan-1-ol, which results in fewer co-extracts and greater selectivity. After the hydrolysis of the 5-phosphates of the vitamin B6 (pyridoxine, pyridoxal and pyridoxamine), these three vitamers are determined by isocratic HPLC as DDS-ion-pairs and with fluorimetric detection. As only microbiological methods have so far been used for the determination of minute quantities of vitamin B12 in milk, a new HPLC procedure is proposed with a detection limit of 0.2 micrograms vitamin B12/L milk.

Animals↗
PubMed1992

Influence of different progestogens on blood pressure of non-anaesthetized male spontaneously hypertensive rats.

The aim of the study was to find out if synthetic progestins with significant antimineralocorticoid activity would have a beneficial effect on blood pressure. Male spontaneously hypertensive rats were treated daily for four weeks with different progestogens by subcutaneous injection. Arterial pressure of the conscious animals was measured at three-day intervals. Progestogens were dosed on the basis of their progestogenic activity, whereby the dosages corresponded to the 10-fold effective dose for inhibition of ovulation in rats. For comparison, spironolactone as well as progesterone itself were included in the study. After four weeks' treatment, plasma volume, extracellular fluid volume (ECFV) and the sodium and potassium concentrations in the plasma were measured. In control animals, there was a slight decrease in blood pressure over the four-week experimental period. Progesterone and spironolactone similarly influenced blood pressure. A new progestin with significant antialdosterone activity, dihydrospirorenone (code No. ZK 30.595), slightly but significantly decreased the ECFV, plasma sodium concentration and slightly but insignificantly decreased blood pressure as compared to vehicle-treated controls. Synthetic progestins lacking this antimineralocorticoid activity did not decrease blood pressure, but rather induced a slight increase in this animal model. The results clearly support the hypothesis that synthetic progestins, like endogenous progesterone, all of them with inherent antialdosterone activity, decrease the ECFV and so might have an impact on extracellular fluid hemostasis as well as blood pressure regulation.

Animals↗
PubMed1992

Immunotherapy with honeybee venom and yellow jacket venom is different regarding efficacy and safety.

Venom immunotherapy (VIT) for Hymenoptera allergy is accepted as safe and effective. However, widely varying success rates and frequencies of side effects are reported. Differences between various Hymenoptera species could account for these diverging results. We therefore analyzed 205 patients with a history of systemic allergic reactions to either honeybee (148 patients) or yellow jacket stings (57 patients) during VIT. All patients had a positive skin test to the respective venom before VIT, were monitored for side effects of VIT, and submitted to a sting challenge while they were receiving VIT. Patients with honeybee-venom allergy had a higher sensitivity in both skin tests (p less than 0.05) and RAST (p less than 0.001) than patients with yellow jacket-venom allergy. They developed systemic side effects to VIT injections significantly more often (41% versus 25%; p less than 0.01) and also reacted more frequently to the sting challenge (23% versus 9%; p less than 0.01) than patients with yellow jacket-venom allergy. We conclude that results obtained from studies on the allergy to one Hymenoptera venom cannot be extrapolated to allergies to other Hymenoptera venoms.

Acute Disease↗
PubMed1992

A human moderately repeated Y-specific DNA sequence is evolutionarily conserved in the Y chromosome of the great apes.

Evolutionary conservation of the human-derived moderately repeated Y-specific DNA sequence Y-190 (DYZ5) was investigated in the chimpanzee, orangutan, and gorilla. Southern blot analysis showed the presence of the sequence in the Y chromosome of all great apes. Pulsed-field gel electrophoresis and in situ hybridization revealed that the repeat is organized in one major block and confined to a small region of the Y chromosome of the three species. DYZ5 was assigned to the proximal short arm of the Y chromosome of the chimpanzee and orangutan and to the long arm of the Y chromosome of the gorilla. In light of its evolutionary conservation, DYZ5 may have an as yet undetermined structural function in the Y chromosome.

Animals↗
PubMed1992

Reduction of side effects from rush-immunotherapy with honey bee venom by pretreatment with terfenadine.

In a double-blind placebo-controlled trial on 52 patients with bee venom allergy we studied the effect of a pretreatment with terfenadine 120 mg twice daily on the occurrence of local and systemic allergic side effects from rush-immunotherapy. Large local reactions were significantly reduced by terfenadine pretreatment (P less than 0.01), while systemic side effects were observed with similar frequencies in both groups. Analysis of individual systemic allergic manifestations showed that cutaneous symptoms like itching (P less than 0.025) and urticaria/angioedema (P less than 0.05) were significantly reduced, while respiratory or cardiovascular symptoms were not influenced. A lower consumption of additional anti-allergic medication was found during terfenadine pretreatment (P less than 0.05). Pretreatment with antihistamines during immunotherapy may thus be helpful in the management of patients with cutaneous side effects.

Adolescent↗
PubMed1992

Allergy to honey: relation to pollen and honey bee allergy.

To identify the allergenic components of honey we studied 22 patients with a history of systemic allergic symptoms following honey ingestion. The group of honey-allergic patients was compared with three control groups: 10 subjects sensitized to artemisia, 10 with honey bee venom allergy and 10 without a history of atopy or bee sting reactions. The allergological tests included skin tests and RAST with three different kinds of Swiss honey (dandelion, forest and rape), pollen of compositae species, celery tuber, extract of bee pharyngeal glands, honey bee venom and bee whole body extract. The results show that 3/4 of honey-allergics are sensitive to dandelion honey and 13 of 22 also to compositae pollen. Nine of the honey allergic patients were sensitized to honey bee venom, 3 also to bee pharyngeal glands and to bee whole body extract. Analysis of diagnostic tests and RAST inhibition studies suggest that besides compositae pollen other allergens, most likely of bee origin are important. In honey allergics primary sensitization may be due either to the honey itself, to airborne compositae pollen or even to cross-reacting bee venom components.

Adolescent↗
PubMed1992

The X-linked dystonia-parkinsonism syndrome (XDP): clinical and molecular genetic analysis.

Dystonia and parkinsonism are two major representatives of movement disorders. The X-linked dystonia-parkinsonism syndrome (XDP) serves as a model system for the study of both dystonia and parkinsonism since both symptom complexes occur together and are inherited as Mendelian traits with very high penetrance. XDP, which is endemic to the Philippine island of Panay, originated by a single mutation ("genetic founder effect"), thus assuring homogeneity of the disorder at the molecular level. The disease locus, DYT3, has been assigned to the proximal long arm (Xq12-21.1) of the human X chromosome. A strategy is described to isolate this gene by positional cloning. The rationale of this strategy, the major methods involved and technical terms are explained.

Base Sequence↗
PubMed1992

Adenovirus E4orf4 protein reduces phosphorylation of c-Fos and E1A proteins while simultaneously reducing the level of AP-1.

Adenovirus E1A protein and cyclic AMP cooperate to induce transcription factor AP-1 and viral gene expression in mouse S49 cells. We report that a protein encoded within the viral E4 gene region acts to counterbalance the induction of AP-1 DNA-binding activity by E1A and cyclic AMP. Studies with mutant adenoviruses demonstrated that in the absence of E4orf4 protein, AP-1 DNA-binding activity is induced to substantially higher levels than in wild-type virus-infected cells. The induction is the result of increased production of JunB and c-Fos proteins. Hyperphosphorylated forms of c-Fos and E1A proteins accumulate in the absence of functional E4orf4 protein. We propose that the E4orf4 protein acts to inhibit the activity of a cellular kinase that phosphorylates both the E1A and c-Fos proteins. Phosphorylation-dependent alterations in the activity of c-Fos, E1A, or some unidentified protein might, then, lead to decreased synthesis of AP-1 components. This E4 function likely plays an important role in natural infections, since a mutant virus unable to express the E4orf4 protein is considerably more cytotoxic than the wild-type virus.

Adenovirus Early Proteins↗
PubMed1992

Structure, expression, and chromosome location of the gene for the beta subunit of brain-specific Ca2+/calmodulin-dependent protein kinase II identified by transgene integration in an embryonic lethal mouse mutant.

The transgenic mouse strain CAT40 carries in its germ line one copy of a DNA construct consisting of the chloramphenicol acetyltransferase gene and the immunoglobulin heavy-chain enhancer. We show that transgene integration has resulted in a recessive lethal mutation that leads to death of homozygous CAT40 embryos shortly after implantation. The transgene has integrated adjacent to the 3' end of the gene coding for the beta subunit of the brain-specific Ca2+/calmodulin-dependent protein kinase II (Camk-2). The complete cDNA sequence of the Camk-2 gene and most of its exon/intron structure was determined. The deduced amino acid sequence is highly homologous to the previously described rat protein. The chromosomal location of the Camk-2 locus was mapped by interspecific backcross analysis to the proximal region of mouse chromosome 11. This region lacks previously identified recessive embryonic lethal mutations. During embryonic development, Camk-2-specific transcripts are first seen in the head section of 12.5-day-old embryos, and in adult mice the gene is expressed almost exclusively in the brain. Although transcription of the Camk-2 gene in heterozygous CAT40 mice is affected by transgene integration, it is unlikely that this gene is responsible for the mutant phenotype, since it is not expressed in blastocysts and the first transcripts during normal development are detected after the death of homozygous CAT40 embryos. Transgene integration is accompanied by a large deletion of cellular DNA; death is therefore most likely caused by the loss of a gene or genes that are important for early postimplantation development.

Amino Acid Sequence↗
PubMed1992

[Granulomatous vasculitis--an uncommon manifestation of herpes simplex infection of the central nervous system].

A man died at the age of 50 years, following tentative clinical diagnosis of centrotemporal brain tumour. Strongly pronounced, extended, partially necrotized haemorrhagic inflammation of the leptomeninx, considerably thickened and reaching into cerebral tissue above, was recorded from the cerebral basis on post-mortem examination. The spinal leptomeninx was involved in the inflammatory process. Severe exudative and primary productive pseudotuberculous inflammation was the histological finding, although tuberculous origin could not be confirmed by bacteriological culturing. Polymerase chain reaction with subsequent southern-blot hybridization revealed Herpes simplex virus Type I as the cause of inflammation.

Autopsy↗
PubMed1992

Dystonia-parkinsonism syndrome (XDP) locus: flanking markers in Xq12-q21.1.

The study of rare genetic forms of dystonia and parkinsonism permits positional cloning of genes potentially involved in more common, multifactorial forms of these diseases. One movement disorder amenable to molecular genetic analysis is the X-linked dystonia-parkinsonism syndrome (XDP). This disease is endemic to the Philippines where it originated by a genetic founder effect. Linkage analysis was performed with DNA from 14 XDP kindreds by using 12 polymorphic DNA sequences in Xp11-Xq22. Two-point analysis demonstrated maximum lod scores of 5.45, 4.95, 4.28, and 5.99 for DXS106, DXS159, PGK1, and DXS72, respectively, at recombination fractions of zero (DXS106 and DXS159), .01 (PGK1), and .04 (DXS72). Multipoint analysis resulted in a maximum-likelihood score (Zmax) of 8.41 with a (Zmax - 1) support interval of 9 cM between DXS159 and DXS72 (Xq12-q21.1). In 19 XDP kindreds significant linkage disequilibrium was found for loci DXS72 (delta = .47), PGK1 (delta = .36), DXS95 (delta = .30), DXS106 (delta = .28), and DXS159 (delta = .26). These data indicate that the gene mutated in XDP (locus DYT3) is located in Xq12-q21.1.

Chromosome Mapping↗