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Biomedical subjects

A Dietrich

Publications and source records attributed to A Dietrich.

At least 19 recordsLinked to original sources
PubMed2007

TRPC6.

TRPC6 is a Ca(2+)-permeable non-selective cation channel expressed in brain, smooth muscle containing tissues and kidney, as well as in immune and blood cells. Channel homomers heterologously expressed have a characteristic doubly rectifying current-voltage relationship and are six times more permeable for Ca2+ than for Na+. In smooth muscle tissues, however, Na+ influx and activation of voltage-gated calcium channels by membrane depolarization rather than Ca2+ elevation by TRPC6 channels is the driving force for contraction. TRPC6 channels are directly activated by the second messenger diacylglycerol (DAG) and regulated by specific tyrosine or serine phosphorylation. Extracellular Ca2+ has inhibitory effects, while Ca2+/calmodulin acting from the intracellular side has potentiator effects on channel activity. Given its specific expression, TRPC6 is likely to play a number of physiological roles. Studies with TRPC6(-/-) mice suggest a role for the channel in the regulation of vascular and pulmonary smooth muscle contraction. TRPC6 was identified as an essential component of the slit diaphragm architecture of kidney podocytes. Other functions in immune and blood cells, as well as in brain and in smooth muscle-containing tissues such as stomach, colon and myometrium, remain elusive.

Animals↗
PubMed2005

Specific plant DNA adducts as molecular biomarkers of genotoxic atmospheric environments.

The general purpose of this study was to determine whether the formation of DNA addition products ('adducts') in plants could be a valuable biomarker of genotoxic air pollution. Plants from several species were exposed to ambient atmosphere at urban and suburban sites representative of different environmental conditions. The levels of NO2 and of the quantitatively major genotoxic air pollutants benzene, toluene, and xylene were monitored in parallel with plant exposure. DNA adducts were measured in bean (Phaseolus vulgaris), rye-grass (Lolium perenne), and tobacco (Nicotiana tabacum) seedlings by means of the [32P]-postlabeling method. Whereas, no correlation was found between the levels of the major genotoxic air pollutants and the total amounts of DNA adducts, individual analyses revealed site-specific and plant species-specific adduct responses, both at the qualitative and quantitative level. Among these, the amount of a specific rye-grass DNA adduct (rgs1) correlated with benzene/toluene/xylene levels above a threshold. For further characterization, rye-grass seedlings were treated in controlled conditions with benzene, toluene, xylene or their derivatives. On the other hand, in vitro DNA adduct formation assays were developed involving benzene, toluene, xylene, or their derivatives, and plant microsomes or purified peroxidase. Although in some cases, these approaches produced specific adduct responses, they failed to generate the rgs1 DNA adduct, which appeared to be characteristic for on-site test-plant exposure. Our studies have thus identified an interesting candidate for further analysis of environmental biomarkers of genotoxicity.

Air Pollutants↗
PubMed2005

Investigation of arthritic joint destruction by a novel fibroblast-based model.

The key pathologic mechanism in rheumatoid arthritis (RA) is the destruction of cartilage by fibroblasts. In a severe combined immunodeficient (SCID) mouse model, this process can be modulated by gene transfer using invasive LS48 fibroblasts. This study aims to investigate the effect of interleukins (IL) -11 and -12 on cartilage destruction when transferred into LS48, and of IL-15 when transfected into non-invasive 3T3 cells; to compare three transduction systems (a lentiviral vector system, a retroviral vector system, and a particle-mediated gene transfer); and to establish an in vitro cartilage destruction system based on LS48 cells. Transduced fibroblasts were injected into SCID mice knee joints, and disease progression assessed microscopically. Distinctive morphologic pattern revealed invasion of fibroblasts into the articular cartilage by transfected, as well as non-transfected, LS48 cells. IL-12 and IL-15 did not alter swelling or cartilage destruction. Animals treated with IL-11-transfected cells showed reduced cartilage damage but no changes in swelling. Efficacy of gene transfer to establish transfected fibroblasts was shown to be >85% for lentiviral transfer, compared to <10% for retroviral transfer and gene gun. Furthermore, cells were co-incubated with porcine cartilage. Transduction of IL-11 led to a reduction of apoptosis in chondrocytes. These findings suggest that cartilage destruction by invasive fibroblasts can be modulated by gene transfer. Lentiviral vector systems offer the most effective approach for gene transduction. In vitro fibroblast/cartilage co-cultures present a convenient system for the assessment of novel therapeutic strategies toward reduction of articular destruction.

3T3 Cells↗
PubMed2004

Endocannabinoids and exercise.

Exercise induces changes in mental status, particularly analgesia, sedation, anxiolysis, and a sense of wellbeing. The mechanisms underlying these changes remain unknown. Recent findings show that exercise increases serum concentrations of endocannabinoids, suggesting a possible explanation for a number of these changes. This article provides an overview of this emerging field.

Analgesia↗
PubMed2003

Exercise activates the endocannabinoid system.

Extensive documentation exists showing that exercise induces analgesia and sedation. Despite decades of research attempting to explicate a neurochemical basis for these phenomena, the mechanism underlying these changes is unknown. Using trained male college students running on a treadmill or cycling on a stationary bike for 50 min at 70-80% of maximum heart rate, we report here the first evidence that exercise of moderate intensity activates the endocannabinoid system, suggesting a new mechanism for exercise-induced analgesia and possibly other physiological and psychological adaptations to exercise.

Adolescent↗
PubMed2002

Indirect lymph node lymphangiography using an iodine-based contrast medium and projection radiography following submucosal injection in a rabbit model.

BACKGROUND: This study investigated the possibility of local lymph node detection and lymphatic mapping following submucosal injection of an iodine-based contrast medium. METHODS AND MATERIALS: We established a contrast medium (oil/water emulsion on iodine basis) with a particle size of mainly 1.7+/-0.1 micro m. Ten rabbits received rectal submucosal injections of the contrast medium and underwent repeated projection radiography. RESULTS: Passage of the contrast medium into lymphatic vessels and storage in lymph nodes was seen in all ten animals. The best contrast was achieved within 24 and 48 h after injection. Lymph nodes were still seen in eight cases with the final radiograph on day 14. There were no clinical side effects observed. Injection sites showed mild signs of inflammation in histological examinations. Pathological signs were not detectable in lymph nodes containing the contrast media. CONCLUSIONS: This method appears useful when investigating local lymph nodes following submucosal injection due to its passage into lymphatic vessels and storage in lymph nodes.

Administration, Rectal↗
PubMed2002

Role of editing in plant mitochondrial transfer RNAs.

Editing in plant mitochondria consists in C to U changes and mainly affects messenger RNAs, thus providing the correct genetic information for the biosynthesis of mitochondrial (mt) proteins. But editing can also affect some of the plant mt tRNAs encoded by the mt genome. In dicots, a C to U editing event corrects a C:A mismatch into a U:A base pair in the acceptor stem of mt tRNA(Phe) (GAA). In larch mitochondria, three C to U editing events restore U:A base pairs in the acceptor stem, D stem and anticodon stem, respectively, of mt tRNA(His) (GUG). For both these mt RNA(Phe) and tRNA(His), editing of the precursors is a prerequisite for their processing into mature tRNAs. In potato mt tRNA(Cys) (GCA), editing converts a C28:U42 mismatch in the anticodon stem into a U28:U42 non-canonical base pair, and reverse transcriptase minisequencing has shown that the mature mt tRNA(Cys) is fully edited. In the bryophyte Marchantia polymorpha this U residue is encoded in the mt genome and evolutionary studies suggest that restoration of a U28 residue is necessary when it is not encoded in the gene. However, in vitro studies have shown that neither processing of the precursor, nor aminoacylation of tRNA(Cys), requires C to U editing at this position. But sequencing of the purified mt tRNA(Cys) has shown that Psi is present at position 28, indicating that C to U editing is a prerequisite for the subsequent isomerization of U into Psi at position 28.

Cytidine↗
PubMed2001

AVP (4-8) improves concept learning in PFC-damaged but not hippocampal-damaged rats.

A position reversal task was used to test the memory-enhancing effects of the arginine vasopressin analog [pGlu4, Cyt6] AVP (4-8) at a dose of 1.5 microg/kg. Rats received either sham operations (SHM), medial prefrontal cortex lesions (PFC), or hippocampal lesions (HIP). The peptide was administered daily, via s.c. injection, 30 min prior to training to half of the animals in each group. As expected, all animals performed equally well on the initial position habit and the first reversal. Overall, it was found that AVP (4-8)-treated animals performed significantly better across trials than saline (SAL)-treated animals. Further analysis showed that PFC animals that received AVP (4-8) (PFC+AVP) performed significantly better (at the level of controls) across trials than saline-treated PFC (PFC+SAL) animals. Sham animals that received the AVP (4-8) analog (SHM+AVP) only showed significant improvement on the last two reversals when compared to the sham saline-treated animals (SHM+SAL), which was likely due to a ceiling effect as performance reached high levels early in the reversal task. Trial 2 analysis across reversals revealed enhanced cognitive abilities in both sham groups (SHM+SAL, SHM+AVP) and the PFC+AVP group, but not in the PFC+SAL, HIP+AVP or the HIP+SAL groups. Hippocampal lesioned animals performed poorly on the task and injections of AVP (4-8) did not improve their performance. It is thus concluded that AVP (4-8) enhanced the acquisition of concept learning (win-stay/loose-shift) in this paradigm in PFC-damaged animals and ameliorated the perseverance habit that is often seen in PFC animals on this task. It is suggested that AVP (4-8) might have an enhancing effect on general cognitive abilities that is not limited to memory processes.

Animals↗
PubMed2001

Conservative functional treatment of ankle fractures.

Thirty-eight patients (mean age 49 years; range 19-91 years; nine of them over 60 years; 28 women, 10 men) suffering from an isolated Weber B fracture with a dislocation of less than 1 mm underwent functional therapy using a pneumatic ankle brace and were included in a prospective study. The clinical outcome was measured according to the Olerud-Molander ankle score. Functional therapy was finished in 34 cases successfully. Twenty-one patients were scored after 17 months on average (range 8-27 months) with the Olerud-Molander ankle score. A very good result was seen in 18 patients, including 12 with 100 points, a complete remission. The remaining 3 patients showed good results (1 had 90, 2 had 85). However, functional treatment failed in 4 cases due to secondary dislocation. These patients underwent surgery without further complications. The control group, 31 operated patients, did not show as good results. Functional therapy of stable Weber-B ankle fractures appears to be superior to surgery. We were able to avoid surgery in 90% of our patients and got better results than with patients undergoing open reduction and internal fixation.

Adolescent↗
PubMed2001

Activation of Trp3 by inositol 1,4,5-trisphosphate receptors through displacement of inhibitory calmodulin from a common binding domain.

Mammalian homologues of Drosophila Trp form plasma membrane channels that mediate Ca(2+) influx in response to activation of phospholipase C and internal Ca(2+) store depletion. Previous studies showed that human Trp3 is activated by inositol 1,4,5-trisphosphate (IP(3)) receptors (IP(3)Rs) and identified interacting domains, one on Trp and two on IP(3)R. We now find that Trp3 binds Ca(2+)-calmodulin (Ca(2+)/CaM) at a site that overlaps with the IP(3)R binding domain. Using patch-clamp recordings from inside-out patches, we further show that Trp3 has a high intrinsic activity that is suppressed by Ca(2+)/CaM under resting conditions, and that Trp3 is activated by the following: a Trp-binding peptide from IP(3)R that displaces CaM from Trp3, a myosin light chain kinase Ca(2+)/CaM binding peptide that prevents CaM from binding to Trp3, and calmidazolium, an inactivator of Ca(2+)/CaM. We conclude that inhibition of the inhibitory action of CaM is a key step of Trp3 channel activation by IP(3)Rs.

Amino Acid Sequence↗
PubMed2001

Overlapping destinations for two dual targeted glycyl-tRNA synthetases in Arabidopsis thaliana and Phaseolus vulgaris.

In plant mitochondria, some of the tRNAs are encoded by the mitochondrial genome and resemble their prokaryotic counterparts, whereas the remaining tRNAs are encoded by the nuclear genome and imported from the cytosol. Generally, mitochondrial isoacceptor tRNAs all have the same genetic origin. One known exception to this rule is the group of tRNA(Gly) isoacceptors in dicotyledonous plants. A mitochondrion-encoded tRNA(Gly) and at least one nucleus-encoded tRNA(Gly) coexist in the mitochondria of these plants, and both are required to allow translation of all four GGN glycine codons. We have taken advantage of this atypical situation to address the problem of tRNA/aminoacyl-tRNA synthetase coevolution in plants. In this work, we show that two different nucleus-encoded glycyl-tRNA synthetases (GlyRSs) are imported into Arabidopsis thaliana and Phaseolus vulgaris mitochondria. The first one, GlyRS-1, is similar to human or yeast glycyl-tRNA synthetase, whereas the second, GlyRS-2, is similar to Escherichia coli glycyl-tRNA synthetase. Both enzymes are dual targeted, GlyRS-1 to mitochondria and to the cytosol and GlyRS-2 to mitochondria and chloroplasts. Unexpectedly, GlyRS-1 seems to be active in the cytosol but inactive in mitochondrial fractions, whereas GlyRS-2 is likely to glycylate both the organelle-encoded tRNA(Gly) and the imported tRNA(Gly) present in mitochondria.

Amino Acid Sequence↗
PubMed2001

Memory and DNA.

A model is presented for the storage of long-term memory. In our model consolidation takes place by specific DNA sequences. These DNA sequences are obtained by the recombination of DNA in a similar way to that during meiosis and the production of immunological antibodies. DNA has the potential of the production of large numbers of specific DNA sequences. These sequences can be attached to images of neural networks. The following considerations lead to the theory: (1)Most of the DNA is not used: approximately 3% of our DNA is used. (2)There are no cell divisions in the brain after adulthood is reached. Structural DNA arrangements will not be altered nor disrupted as a consequence of cell division and mitosis. (3)Chromosomal pairing is demonstrated in the brain, which could indicate the exchange of DNA. In addition, in our first survey experiments we found a positive reaction of components of the synaptonemal complex (SC) in the nuclei of brain cells. The SC is highly meiosis specific and plays a major role in genetic recombination.

Adult↗
PubMed2001

Crohn's disease: bowel resection to protect the proctium in severe perianal disease?

Patients with anal Crohn's disease generally have a bad prognosis. Up to 50% end up with an anus praeter or proctectomy. Many of these young people develop psychological and social problems causing them to become invalids. Local surgery and conservative therapy in such aggressive cases of Crohn's disease presenting with recurring perianal fistulae and abscesses are often unsuccessful; the destruction of the proctium continues. The purpose of our study was to look at the outcome of our patients with regard to these aspects. We included all 56 patients suffering from Crohn's disease treated at our clinic from 1984 until 1991 in a retrospective study and focused on the 13 patients with anal manifestation. The mean follow-up was 15.8 years (3-28 years). Often there was no improvement of perianal disease without resection of the involved bowel, especially in cases where both the colon and the rectum were affected. Anal destruction went on. Seven of the 13 patients suffering from anal complications finally received an anus praeter. An previous bowel-resection or the construction of a temporary anus praeter seem to be necessary to protect the proctium irrespective of abdominal symptoms in patients with recurrent severe perianal Crohn's disease.

Adolescent↗
PubMed2001

Accuracy of visual determination of neutral position of the immobilized pediatric cervical spine.

BACKGROUND: The definition of neutral position for the immobilized pediatric cervical spine is not well standardized. In this study, we attempted to determine whether 1) physicians and/or paramedics could accurately assess visually if the cervical spine was in a neutral position, 2) the visual assessments of the observers were in agreement, and 3) a radiographic Cobb angle would correlate with the visual determination. METHODS: Children presenting to a pediatric emergency department (ED) in full spinal immobilization were randomly selected (convenience sample) for this prospective study. The emergency physician and transporting paramedic independently determined positioning of the cervical spine. A radiologist, blinded to clinical information, determined Cobb angles from radiographs of the immobilized cervical spines. RESULTS: Of the 59 children studied, the evaluation of cervical spine position by the physician and paramedic correlated in 88% of the cases. For the 22 children with non-neutral Cobb angles (definition of neutral: between 5 degrees flexion and 5 degrees extension), observers agreed in 100% of the cases. However, in 21 of these cases (95%) the position was observed as neutral. CONCLUSIONS: Although visual determinations of neutral position of the cervical spine by two observers may correlate, radiographic studies demonstrate that neutral position was not achieved in 37% of the cases.

Accidental Falls↗
PubMed2001

The open reading frame 1-encoded ('36K') protein of Carnation Italian ringspot virus localizes to mitochondria.

The localization of the 36 kDa ('36K') protein encoded by open reading frame 1 of Carnation Italian ringspot virus was studied in infected cells and in cells transiently expressing the 36K protein fused to green fluorescent protein (GFP). Subcellular fractionation demonstrated that the 36K protein accumulated in fractions containing mostly mitochondria. Fluorescence microscopy of transiently transformed cells showed that the 36K-GFP fusion protein accumulated in structures which could be stained with the mitochondrial-specific dye MitoTracker. However, these structures were larger than normal mitochondria and were irregular in shape and distribution in the cytoplasm. Electron microscopy showed severe alterations of mitochondria, which were often clumped. The stroma was more electron-opaque, the cristae were irregularly shaped, the intermembrane space was enlarged and the outer membrane was covered with an electron-dense amorphous material whose nature could not be determined. The organelle-targeted 36K protein seems to promote the overgrowth of the mitochondrial outer membrane.

Cells, Cultured↗
PubMed2001

Tailor-made dyes for fluorescence correlation spectroscopy (FCS).

Two new fluorescent labels are presented that are optimized for excitation with He/Ne laser and red diode lasers. Application in FCS and labeling of proteins and oligomers are demonstrated. A strong rise of quantum yield and emission life time upon binding to biomolecules are characteristic features of the dyes.

Benzopyrans↗
PubMed2001

Editing of plant mitochondrial transfer RNAs.

Editing in plant mitochondria consists in C to U changes and mainly affects messenger RNAs, thus providing the correct genetic information for the biosynthesis of mitochondrial (mt) proteins. But editing can also affect some of the plant mt tRNAs encoded by the mt genome. In dicots, a C to U editing event corrects a C:A mismatch into a U:A base-pair in the acceptor stem of mt tRNAPhe (GAA). In larch mitochondria, three C to U editing events restore U:A base-pairs in the acceptor stem, D stem and anticodon stem, respectively, of mt tRNAHis (GUG). For both these mt tRNAs editing of the precursors is a prerequisite for their processing into mature tRNAs. In potato mt tRNACys (GCA), editing converts a C28:U42 mismatch in the anticodon stem into a U28:U42 non-canonical base-pair, and reverse transcriptase minisequencing has shown that the mature mt tRNACys is fully edited. In the bryophyte Marchantia polymorpha this U residue is encoded in the mt genome and evolutionary studies suggest that restoration of the U28 residue is necessary when it is not encoded in the gene. However, in vitro studies have shown that neither processing of the precursor nor aminoacylation of tRNACys requires C to U editing at this position. But sequencing of the purified mt tRNACys has shown that psi is present at position 28, indicating that C to U editing is a prerequisite for the subsequent isomerization of U into psi at position 28.

Mitochondria↗