Disruption of the 11-cis-retinol dehydrogenase gene leads to accumulation of cis-retinols and cis-retinyl esters.

To elucidate the possible role of 11-cis-retinol dehydrogenase in the visual cycle and/or 9-cis-retinoic acid biosynthesis, we generated mice carrying a targeted disruption of the 11-cis-retinol dehydrogenase gene. Homozygous 11-cis-retinol dehydrogenase mutants developed normally, including their retinas. There was no appreciable loss of photoreceptors.

A single camera roentgen stereophotogrammetry method for static displacement analysis.

A new method to quantify motion or deformation of bony structures has been developed, since quantification is often difficult due to overlaying tissue, and the currently used roentgen stereophotogrammetry method requires significant investment. In our method, a single stationary roentgen source is used, as opposed to the usual two, which, in combination with a fixed radiogram cassette holder, forms a camera with constant interior orientation. By rotating the experimental object, it is possible to achieve a sufficient angle between the various viewing directions, enabling photogrammetric calculations.

Becker muscular dystrophy combined with X-linked Charcot-Marie-Tooth neuropathy.

A man was identified with two X-chromosomal neuromuscular disorders, X-linked Charcot-Marie-Tooth disease (CMTX) and Becker muscular dystrophy (BMD). The neuropathy could be tracked in the family and was found to be caused by a mutation in the connexin32 gene on Xq13. 1.

First confirmed case with paternal uniparental disomy of chromosome 16.

The existence of paternal uniparental disomy of chromosome 16 [upd(16)pat] has previously been suspected but has not been proven. We report prenatal detection and follow-up of isodisomic upd(16)pat in a child with minimal defects but otherwise normal development. Our results indicate that isodisomic upd(16)pat is associated with a normal outcome if no recessive mutation is reduced to homozygosity.

Short-term and long-term blood pressure and heart rate variability in the mouse.

Knowledge on murine blood pressure and heart rate control mechanisms is limited. With the use of a tethering system, mean arterial pressure (MAP) and pulse interval (PI) were continuously recorded for periods up to 3 wk in Swiss mice. The day-to-day variation of MAP and PI was stable from 5 days after surgery.

Timed inhibition of the renin-angiotensin system suppresses the rise in blood pressure upon awakening in spontaneously hypertensive rats.

In this study we investigated whether timed administration of drugs that inhibit the renin-angiotensin system can be used to blunt the rise in blood pressure that occurs during the transition from the resting to the active period of the day. For this purpose we compared in spontaneously hypertensive rats (SHR) the antihypertensive efficacy of the angiotensin converting enzyme (ACE) inhibitors captopril (doses: 3, 10, and 30 mg/ kg/6 h) and enalaprilat (0.3 mg/kg/6 h), and the AT1-receptor antagonist losartan (10 mg/kg/6 h) at two different treatment regimens.

Retinoic acid receptors and retinoid X receptors in the mature retina: subtype determination and cellular distribution.

Purpose: In the mature retina retinoic acid (RA) biosynthesis was reported to be regulated by light. RA is of vital importance for proper function of the retina. RA activity is mediated by interaction with nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs).

Transcription of the MAGE-1 gene and the methylation status of its Ets binding promoter elements: a quantitative analysis in melanoma cell lines using a real-time polymerase chain reaction technique.

The human MAGE gene family comprises at least 12 highly homologous genes. This makes it very difficult to assess expression of a single member quantitatively by means of Northern blotting. In order to investigate expression of the MAGE-1 gene quantitatively we therefore used the recently developed real-time polymerase chain reaction (PCR), a novel fluorescence-based quantitative PCR technique.

Phylogenetic relationships and evolution of the KNOTTED class of plant homeodomain proteins.

Knotted-like (KNOX) proteins constitute a group of homeodomain proteins involved in pattern formation in developing tissues of angiosperms and other green plants. We conducted phylogenetic analyses of nucleotide and amino acid sequences of all known KNOX proteins in order to examine their evolution. Our analyses reveal two groups of KNOX proteins, classes I and II.

Molecular diagnosis of type 1c glycogen storage disease.

Glycogen storage disease type 1 (GSD 1) results from deficiency of the microsomal multicomponent glucose-6-phosphatase system. Malfunction of the catalytic subunit characterises GSD 1a. GSD 1b and GSD 1c are characterised by defective microsomal glucose-6-phosphate or pyrophosphate/phosphate transport, respectively.

[Disease picture of myotonic muscular dystrophy in patients with large CTG triplet expansion].

Myotonic dystrophy is an autosomal dominant multisystem disorder involving muscle, brain, heart, eyes, and endocrine organs. The underlying mutation is an expanding trinucleotide CTG repeat in the 3'prime untranslated region of a serine-threonine kinase gene on chromosome 19q. A statistical correlation exists between the CTG copy number and the severity of the disease.

[Quality indicators of patient treatment of schizophrenic patients. Results of a pilot study for external quality assurance using tracer diagnosis].

Purpose: In Germany, measures for assuring the quality of inpatient treatment are regulated by legislation. Treatment quality must be presented in comparison with other hospitals. Tracer diagnosis is an established method for external quality assurance in the sphere of somatic medicine.

Post-transcriptional silencing of chalcone synthase in petunia using a geminivirus-based episomal vector.

A vector that produces DNA replicons (multicopy plant episomes) was constructed using elements of the geminivirus tobacco yellow dwarf virus (TYDV). All plant cells contain an integrated chromosomal T-DNA copy of the TYDV elements that provides a template for the production of episomes in the cell nucleus. Transgenic Petunia hybrida plants containing a CaMV 35S promoter-driven chalcone synthase A (ChsA) gene cloned into the episomal vector produced flowers with a white-spotted phenotype at high frequency.

Overexpression of a homeobox gene, LeT6, reveals indeterminate features in the tomato compound leaf.

The cultivated tomato (Lycopersicon esculentum) has a unipinnate compound leaf. In the developing leaf primordium, major leaflet initiation is basipetal, and lobe formation and early vascular differentiation are acropetal. We show that engineered alterations in the expression of a tomato homeobox gene, LeT6, can cause dramatic changes in leaf morphology.

Sporadic imprinting defects in Prader-Willi syndrome and Angelman syndrome: implications for imprint-switch models, genetic counseling, and prenatal diagnosis.

The Prader-Willi syndrome (PWS) and the Angelman syndrome (AS) are caused by the loss of function of imprinted genes in proximal 15q. In approximately 2%-4% of patients, this loss of function is due to an imprinting defect. In some cases, the imprinting defect is the result of a parental imprint-switch failure caused by a microdeletion of the imprinting center (IC).

An alternative route for multistep tumorigenesis in a novel case of hereditary renal cell cancer and a t(2;3)(q35;q21) chromosome translocation.

Through allele-segregation and loss-of-heterozygosity analyses, we demonstrated loss of the translocation-derivative chromosome 3 in five independent renal cell tumors of the clear-cell type, obtained from three members of a family in which a constitutional t(2;3)(q35;q21) was encountered. In addition, analysis of the von Hippel-Lindau gene, VHL, revealed distinct insertion, deletion, and substitution mutations in four of the five tumors tested. On the basis of these results, we conclude that, in this familial case, an alternative route for renal cell carcinoma development is implied.

Isolation and characterization of two knotted-like homeobox genes from tomato.

Homeobox genes are known to play a role in developmental regulation. The knotted-like homeobox (knox) genes fall into two classes. The class I knox genes like knl, stml, and knatl are involved in maintaining meristem identity in cells.

Did homeodomain proteins duplicate before the origin of angiosperms, fungi, and metazoa?

Homeodomain proteins are transcription factors that play a critical role in early development in eukaryotes. These proteins previously have been classified into numerous subgroups whose phylogenetic relationships are unclear. Our phylogenetic analysis of representative eukaryotic sequences suggests that there are two major groups of homeodomain proteins, each containing sequences from angiosperms, metazoa, and fungi.

Cloning and structural analysis of the murine GCN5L1 gene.

We recently cloned the murine 11-cis retinol dehydrogenase gene. A second gene, the murine GCN5L1 gene, was found to be situated upstream of the murine 11-cis retinol dehydrogenase gene. We have isolated and sequenced the complete coding sequence of the murine GCN5L1 gene.

Sublocalization of the breakpoints of a t(5;16) in myelodysplasia.

As a first step in characterizing a t(5;16)(q31;p11.2) in a patient with the diagnosis refractory anemia with ring sideroblasts, a cell fusion was carried out between bone marrow cells from the patient and the Chinese hamster cell line A3. Using PCR and FISH analysis on hybrid lines containing the human derivative 16 chromosome, the breakpoints could be mapped between the markers TCF-7 and IL-9 on chromosome 5 and OL-7 and s30A4 on chromosome 16, both regions spanning approximately 1 Mb.

Blood pressure and heart rate variability in early pregnancy in rats.

Changes in the autonomic control of the circulation may contribute to the maternal hemodynamic adaptation to early pregnancy. To evaluate this, we studied mean arterial pressure (MAP) and heart rate (HR) in chronically instrumented, conscious rats in early (days 4, 6, 8, and 10) and late (day 18) pregnancy (n = 8) and in nonpregnant rats (n = 9). MAP and HR were recorded on a beat-to-beat basis and analyzed by spectral analysis.

Nuclear localization of SYT, SSX and the synovial sarcoma-associated SYT-SSX fusion proteins.

Synovial sarcoma is characterized by a prevalent chromosomal translocation, t(X;18)(p11;q11). As a result of this translocation the SYT gene on chromosome 18 fuses to either the SSX1 or the SSX2 gene on the X chromosome. In this study, we generated polyclonal antibodies against the SYT and SSX2 proteins.

Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the widespread development of distinctive tumors termed hamartomas. TSC-determining loci have been mapped to chromosomes 9q34 (TSC1) and 16p13 (TSC2). The TSC1 gene was identified from a 900-kilobase region containing at least 30 genes.

A gene fusion at a homeobox locus: alterations in leaf shape and implications for morphological evolution.

Compound leaves are seen in many angiosperm genera and are thought to be either fundamentally different from simple leaves or elaborations of simple leaves. The knotted1-like homeobox (knox) genes are known to regulate plant development. When overexpressed in homologous or heterologous species, this family of genes can cause changes in leaf morphology, including excessive leaf compounding in tomato.