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D Labeit

Publications and source records attributed to D Labeit.

8 recordsLinked to original sources
PubMed1998

A survey of the primary structure and the interspecies conservation of I-band titin's elastic elements in vertebrates.

Titin is a >3000-kDa large filamentous protein of vertebrate-striated muscle, and single titin molecules extend from the Z disc to the M line. In its I-band section, titin behaves extensible and is responsible for myofibrillar passive tension during stretch. However, details of the molecular basis of titin's elasticity are not known. We have compared the motif sequences of titin elastic elements from different vertebrate species and from different regions of the molecule. The I-band titin Ig repeats that are expressed in the stiff cardiac muscle and those that are tissue-specifically expressed in more elastic skeletal muscles represent distinct subgroups. Within the tissue-specifically expressed Ig repeats, a super-repeat structure is found. For the PEVK titin sequences, we surveyed interspecies conservation by hybridization experiments. The sequences of the titin gene which code for the C-terminal region of the PEVK domain are conserved in the genomes of a larger variety of vertebrates, whereas the N-terminal PEVK sequences are more divergent. Future comparisons of titin gene sequences from different vertebrates may improve our understanding of how titin contributes to species diversity of myofibrillar elasticity. Within one species, different classes of Ig repeat families may contribute to elastic diversity of the titin spring in different segments.

Amino Acid Sequence↗
PubMed1997

Tissue-specific expression and alpha-actinin binding properties of the Z-disc titin: implications for the nature of vertebrate Z-discs.

Titins are giant filamentous proteins which connect Z-discs and M-lines in the sarcomeres of vertebrate striated muscles. Comparison of the N-terminal region of titin (Z-disc region) from different skeletal and cardiac muscles reveals a 900-residue segment which is expressed in different length variants, dependent on tissue type. When searching for ligands of this differentially expressed domain by a yeast-two hybrid approach, we detected binding to alpha-actinin. The isolated alpha-actinin cDNAs were derived from the C-terminal region of the alpha-actinin isoform (alpha-actinin-2) encoded by the ACTN2 gene. Therefore, the two antiparallel subunits of an alpha-actinin-2 homodimer will attach to actin at their respective C termini, whereas they will bind to the Z-disc titin at their N termini. This may thus explain how alpha-actinins can cross-link antiparallel titin and thin filaments from opposing sarcomeres. The alpha-actinin-2 binding site of the Z-disc titin is located within a sequence of 45-residue repeats, referred to as Z-repeat region. Both the N-terminal and C-terminal Z-repeats have alpha-actinin binding properties and are expressed in all striated muscles. By contrast, the more central Z-repeats are expressed in slow and fast skeletal muscles, as well as embryonic and adult cardiac muscles, in different copy numbers. Such alternative splicing of the Z-disc titin appears to be important for the tissue and fibre type diversity of the Z-disc lattice.

Actinin↗
PubMed1995

[Sequence analysis of PCR amplification products of old formalin fixed conisation tissue sections].

OBJECTIVE: Standard analytical techniques (DNA hybridisation methods) require high-quality DNA. In very small samples and in processed tissue (e.g. analysis of DNA in paraffin-embedded archival tissues) these methods fail due to their restricted sensitivity. METHODS: In this study we used the considerably more sensitive PCR for analysis of HPV-16-e6/-e7 DNA in histologic cone biopsy sections. HPV-16-e6 and -e7 ORF were amplified, subcloned into M13mp18 and sequenced. RESULTS: The sequence is identical to the published e6/e7 sequence. CONCLUSIONS: Due to its high sensitivity the PCR is suitable to give answers to questions in cellular microbiology even in formalin-fixed paraffin-embedded tissues.

Cervix Uteri↗
PubMed1995

[Interferon-alpha controls HPV infection in cervix epithelium].

UNLABELLED: Decreased immune response is necessary for a prolonged HPV-infection and allows HPV to be virulent as an oncogene. This study shows that HPV-infection in cervical epithelium is determined by the immune system and IFN-alpha can be shown to be a prognostic parameter for the HPV-infection. The cytokines (IFN-alpha, IFN-gamma, and TNF-alpha) from stimulated peripheral blood mononuclear cells (PBMC) were measured using monoclonal IFN-antibodies and ELISA test. To detect HPV-16, PCR (e6 and e7 areas) was used, followed by southern-blot of the PCR-products. In all of our patients (n = 139) no cytological change was observed in the cervical epithelium over a period of 3 years. Comparison was made between 3 groups: 1: controls (n = 89, HPV-pos. n = 6) 2: registered prostitutes without drug abuse (n = 30, HPV-pos. n = 6) and 3: HIV-infected, previous drug users (CDC II, n = 20, HPV-pos. n = 2). RESULTS: The stimulated IFN-alpha values are highest in the control collective (169 +/- 35 U/ml) and are significantly lower in the prostitutes (98 +/- 26 U/ml, p < 0.05) and in the HIV-infected group (49 +/- 15 U/ml, p < 0.01). The difference between the latter groups being significant as well (p < 0.05). Dividing the controls into HPV-16 positive and HPV-16 negative subgroups, the IFN-alpha values are significantly higher in HPV-16 negative group (193 +/- 48 U/ml) compared to HPV-16 positive group (38 +/- 3 U/ml, p < 0.05). Also in the collective of prostitutes and HIV infected patients there is a similar significant difference between the HPV-16 positive and HPV-16 negative patients (Prostitutes: HPV-16 negative = 94 +/- 21 U/ml, HPV-16 positive = 36 +/- 7 U/ml, p < 0.05; HIV-infected: HPV-16 negative = 35 +/- 13 U/ml, HPV-16 positive = 13 +/- 3 U/ml).

AIDS-Related Opportunistic Infections↗
PubMed1992

Increased detection of HPV 16 virus in invasive, but not in early cervical cancers.

Human papilloma virus type 16 (HPV 16) DNA is found in about 50% of cervical squamous cell carcinomas (SCCs), and this association has raised the possibility of a causal role for HPV 16 in cervical carcinogenesis. We have tested this hypothesis by assaying a series of biopsies (n = 119) ranging from normal mucosa to infiltrating SCC with the PCR-technique for the presence of HPV 16 DNA. While HPV 16 DNA was detected in 50% of our cases with invasive SCC, the incidence of HPV 16-positive samples was about 10% in all other biopsies ranging from normal mucosa to cases of carcinoma in situ. HPV 16 therefore appears to be involved in late tumor promotion but not in early tumor development.

Base Sequence↗
PubMedDate not supplied

[A knowledge-based system for the interpretation of pelvimetric findings].

Digital Image Intensifier Radiography (DIR) as well as Nuclear Magnetic Resonance Tomography (NMR) using an especially developed imaging routine for pelvimetry are suitable tools for the assessment of the anatomical conditions when mechanical problems are supposed to occur during birth (cephalopelvic disproportion, breech presentation). A concept for an optimised evaluation procedure of these imaging techniques has been developed, including: a more elaborate measuring protocol, easily and precisely executable due to appropriate software packages being implemented in the diagnostic units, calculation of obstetrically relevant parameters not deriving immediately from the imaging procedures. This is possible by means of multiple regression analysis of a data base from 467 evaluated female pelvis computed tomograms, calculation of intrapelvic soft tissue place requirements by means of correlative analysis of female computed tomograms and weight-/height-index, empirical determination of cut off values in borderline pelvi-fetometric constellations evaluating 190 births by means of logistic regression of the according pelvic-fetometric data. The calculations necessary to obtain all these parameters are implemented in a software package which also contains an algorithm for the general characterisation of an individual pelvis. Thus, a rather sophisticated knowledge base for pelvic assessment becomes easily accessible.

Adult↗