Biomedical subjects

H Thomas

Publications and source records attributed to H Thomas.

At least 55 records · Page 3Linked to original sources

PubMed2000

Sequence of the two operons encoding the four core subunits of the cytochrome b(6)f complex from the thermophilic Cyanobacterium synechococcus elongatus.

The genes encoding cytochrome f (petA), cytochrome b(6) (petB), the Rieske FeS-protein (petC), and subunit IV (petD) of the cytochrome b(6)f complex from the thermophilic cyanobacterium Synechococcus elongatus were cloned and sequenced. Similar to other cyanobacteria, the structural genes are arranged in two short, single-copy operons, petC/petA and petB/petD, respectively. In addition, five open reading frames with homology to known orfs from the cyanobacterium Synechocystis PCC 6803 were identified in the immediate vicinity of these two operons.

Cloning, Molecular↗

PubMed2000

Inhibition of extracellular signal-regulated kinase enhances Ischemia/Reoxygenation-induced apoptosis in cultured cardiac myocytes and exaggerates reperfusion injury in isolated perfused heart.

Three major mammalian mitogen-activated protein kinases, extracellular signal-regulated kinase (ERK), p38, and c-Jun NH(2)-terminal protein kinase (JNK), have been identified in the cardiomyocyte, but their respective roles in the heart are not well understood. The present study explored their functions and cross talk in ischemia/reoxygenation (I/R)-induced cardiac apoptosis. Exposing rat neonatal cardiomyocytes to ischemia resulted in a rapid and transient activation of ERK, p38, and JNK. On reoxygenation, further activation of all 3 mitogen-activated protein kinases was noted; peak activities increased (fold) by 5.5, 5.2, and 6.2, respectively. Visual inspection of myocytes exposed to I/R identified 18.6% of the cells as showing morphological features of apoptosis, which was further confirmed by DNA ladder and terminal deoxyribonucleotide transferase-mediated dUTP nick end labeling (TUNEL). Myocytes treated with PD98059, a MAPK/ERK kinase (MEK1/MEK2) inhibitor, displayed a suppression of I/R-induced ERK activation, whereas p38 and JNK activities were increased by 70.3% and 55.0%, respectively. In addition, the number of apoptotic cells was increased to 33.4%. With pretreatment of cells with SB242719, a selective p38 inhibitor, or SB203580, a p38 and JNK2 inhibitor, I/R+PD98059-induced apoptotic cells were reduced by 42.8% and 63.3%, respectively. Hearts isolated from rats treated with PD98059 and subjected to global ischemia (30 minutes)/reoxygenation (1 hour) showed a diminished functional recovery compared with the vehicle group. Coadministration of SB203580 attenuated the detrimental effects of PD98059 and significantly improved cardiac functional recovery. The data taken together suggest that ERK plays a protective role, whereas p38 and JNK mediate apoptosis in cardiomyocytes subjected to I/R, and the dynamic balance of their activities is critical in determining cardiomyocyte fate subsequent to reperfusional injury.

Animals↗

PubMed2000

Rapid access to infrared reference spectra of arbitrary organic compounds: scope and limitations of an approach to the simulation of infrared spectra by neural networks

Substance identification by infrared spectroscopy is performed by comparison of the experimental spectrum with a reference spectrum from a printed compilation or a database. If the analyzed compound can not be found in a database the corresponding reference spectrum has to be simulated. In order to achieve this, several reasonable candidates of structures for the compound at hand have to be conceived and for all these, infrared spectra have to be developed. The simulated spectrum that is most similar to the experimental suggests the correct structure. A rapid spectrum prediction method based on neural networks has been developed that supplies reference spectra for any organic compound. The scope and limitations of this method will be discussed on a test set of 16 compounds representing a broad range of organic chemistry.

Journal Article↗

PubMed2000

Naturally occurring mutations in the human HNF4alpha gene impair the function of the transcription factor to a varying degree.

The hepatocyte nuclear factor (HNF)4alpha, a member of the nuclear receptor superfamily, regulates genes that play a critical role in embryogenesis and metabolism. Recent studies have shown that mutations in the human HNF4alpha gene cause a rare form of type 2 diabetes, maturity onset diabetes of the young (MODY1). To investigate the properties of these naturally occurring HNF4alpha mutations we analysed five MODY1 mutations (R154X, R127W, V255M, Q268X and E276Q) and one other mutation (D69A), which we found in HepG2 hepatoma cells. Activation of reporter genes in transfection assays and DNA binding studies showed that the MODY1-associated mutations result in a variable reduction in function, whereas the D69A mutation showed an increased activity on some promoters. None of the MODY mutants acted in a dominant negative manner, thus excluding inactivation of the wild-type factor as a critical event in MODY development. A MODY3-associated mutation in the HNF1alpha gene, a well-known target gene of HNF4alpha, results in a dramatic loss of the HNF4 binding site in the promoter, indicating that mutations in the HNF4alpha gene might cause MODY through impaired HNF1alpha gene function. Based on these data we propose a two-hit model for MODY development.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗

PubMed2000

Lesion of the median raphe nucleus: a combined behavioral and microdialysis study in rats.

The purpose of the present study was to investigate the behavioral consequences and the neurochemical correlates of a 5,7-dihydroxytryptamine (5,7-DHT) lesion of the median raphe nucleus (MRN) in rats. Anxiety-related behavior was assessed in the elevated plus maze test on days 5, 14, and 21 after lesioning. In general, behavior of MRN-lesioned rats was unchanged when compared with sham-lesioned or untreated controls. Neurochemically, microinjection of 5,7-DHT into the MRN resulted in 87.5% depletion of hippocampal 5-HT content. Using the in vivo microdialysis technique, the exposure of 5,7-DHT-lesioned rats to the elevated plus-maze failed to increase extracellular 5-HT release (94%) in the hippocampus, as shown in sham-lesioned (150%) or untreated controls (194%). Moreover, application of fenfluramine (10 mg/kg, i.p.) evoked a 10-fold increase in hippocampal extracellular 5-HT levels in sham-lesioned animals, whereas in 5,7-DHT lesioned rats 5-HT was only slightly increased. The results demonstrate, that a marked reduction of 5-HT release from the MRN is not necessarily accompanied by anxiolytic-like behavior.

5,7-Dihydroxytryptamine↗

PubMed2000

Acute myocardial infarction occurring in versus out of the hospital: patient characteristics and clinical outcome. Maximal Individual TheRapy in Acute Myocardial Infarction (MITRA) Study Group.

OBJECTIVES: We describe the baseline characteristics and clinical course of patients who had an acute myocardial infarction (AMI) during their hospital stay. BACKGROUND: In comparison with patients who had an AMI outside of the hospital (prehospital AMI), the data on patients who had an AMI in the hospital are poorly described. METHODS: Patients with an in-hospital AMI were prospectively registered in the Southwest German Maximal Individual TheRapy in Acute myocardial infarction (MITRA) study and compared with patients with prehospital AMI. RESULTS: Of 5,888 patients with AMI, 403 patients (6.8%) had an in-hospital AMI. These patients were older, more often male and sicker as compared with the patients with a prehospital AMI. They also showed a higher prevalence of concomitant diseases, such as arterial hypertension, diabetes mellitus, renal insufficiency and contraindications for thrombolysis. There was no significant difference regarding the use of reperfusion therapy, either thrombolysis (in-hospital AMI 44.2% vs. prehospital AMI 49.1%; odds ratio [OR] 0.86, 95% confidence interval [CI] 0.70 to 1.05) or primary angioplasty (9.9% vs. 8.2%; OR 1.23, 95% CI 0.88 to 1.73), or a combination of both, between the two groups. The interval from symptom onset to the start of treatment in patients receiving reperfusion therapy was 55 min for patients with an in-hospital AMI versus 180 min for patients with a prehospital AMI (p = 0.001). In-hospital death occurred in 110 (27.3%) of 403 patients with an in-hospital versus 762 (13.9%) of 5,485 patients with a prehospital AMI (OR 2.33, 95% CI 1.85 to 2.94). This was confirmed by logistic regression analysis after adjusting for other confounding variables (OR 1.67, 95% CI 1.23 to 2.24). CONCLUSIONS: In-hospital AMI occurred in 6.8% of patients. Time to intervention was shorter; however, the use of reperfusion therapy for in-hospital AMI was not different from that for prehospital AMI. In particular, primary angioplasty seems to be underused in these patients. This, as well as the selection of patients, may result in the high hospital mortality rate of 27.3%.

Aged↗

PubMed2000

Chlorophyll breakdown in Chlorella protothecoides: characterization of degreening and cloning of degreening-related genes.

Chlorella protothecoides cultures grown in a nitrogen-free bleaching medium (BM-N) in the dark rapidly degraded chlorophyll (Chl) to red catabolites. This degreening process was investigated under different growth conditions. Supply of nitrogen to the culture medium (BM+N) inhibited bleaching and the synthesis of catabolites as did the addition to BM-N of cycloheximide or a chelator, 2,2'-bipyridyl. In contrast, chloramphenicol or the protease inhibitor E64 had no effect. During bleaching, Chl breakdown was accompanied by the degradation of cellular proteins such as light-harvesting complex II, cytochrome f and protochlorophyllide oxido-reductase. During growth in BM-N, protease activity increased and proteins immunologically detectable with an antibody against a senescence-enhanced cysteine protease accumulated. cDNAs from BM-N and BM+N cells were used for differential and subtractive screening to isolate cDNAs representing genes with degreening-enhanced expression (dee) in C. protothecoides. Several different dees were identified with different patterns of expression during Chlorella growth but which were all expressed at higher levels during bleaching. Among these, dee4 was most abundant and its expression was exclusive in BM-N cultures. Analysis of the dee sequences showed that they encode different proteins including a novel amino acid carrier (dee4), ferritin, ATP-dependent citrate lyase, a Ca2+-binding protein, MO25, ubiquinone-cytochrome c-reductase and several new proteins.

Algal Proteins↗

PubMed2000

Inferring children's categorizations from sequential touching behaviors: an analytical model.

A child is assumed to belong to 1 of 2 classes: categorizer or noncategorizer. To determine which, 4 toy animals and 4 toy vehicles were randomly arrayed for touching for 2 min. The task was to infer whether the child was a categorizer or a noncategorizer for vehicles and similarly for animals. A model is proposed that assumes a child's sequence of touches follows one probability distribution if the child is a categorizer and another distribution if the child is a noncategorizer. The proportion of children in each category and the probability of a child being a categorizer for, say, vehicles are among the quantities that can be estimated. Data from 18-month-old children are illustrative. The model appears efficient and robust.

Child Development↗

PubMed2000

Controversial attachments: the indirect treatment of fostered and adopted children via Parent Co-Therapy.

Fostered and adopted children often show a large array of psychosocial problems and are conceptualized as having attachment disorders. It can be necessary to engage such children in direct mental health treatment, in addition to interventions set up to deal with their problems through agencies such as Education and Social Services. In order to protect children from a multitude of treating professionals, thereby potentially further weakening the emerging parental attachments, a model is proposed of indirect treatment of children, with the adoptive parents as co-therapists. This elevates the status of parents and is controversial in child mental health work as it challenges traditional hierarchies. We refer to this model, based on a single case study, as Parent Co-Therapy (PCT). It is proposed that this may be a suitable treatment model for fostered and adopted children, particularly in the early years of placement. The model has the potential to strengthen the children's attachments to the parents and vice versa, with a concomitant reduction in symptomatology.

Adoption↗

PubMed2000

De novo evolution of satellite DNA on the rye B chromosome.

The most distinctive region of the rye B chromosome is a subtelomeric domain that contains an exceptional concentration of B-chromosome-specific sequences. At metaphase this domain appears to be the physical counterpart of the subtelomeric heterochromatic regions present on standard rye chromosomes, but its conformation at interphase is less condensed. In this report we show that the two sequence families that have been previously found to make up the bulk of the domain have been assembled from fragments of a variety of sequence elements, giving rise to their ostensibly foreign origin. A single mechanism, probably based on synthesis-dependent strand annealing (SDSA), is responsible for their assembly. We provide evidence for sequential evolution of one family on the B chromosome itself. The extent of these rearrangements and the complexity of the higher-order organization of the B-chromosome-specific families indicate that instability is a property of the domain itself, rather than of any single sequence. Indirect evidence suggests that particular fragments may have been selected to confer different properties on the domain and that rearrangements are frequently selected for their effect on DNA structure. The current organization appears to represent a transient stage in the evolution of a conventional heterochromatic region from complex sequences.

Amino Acid Sequence↗

PubMed2000

Retrotransposon evolution in diverse plant genomes.

Retrotransposon or retrotransposon-like sequences have been reported to be conserved components of cereal centromeres. Here we show that the published sequences are derived from a single conventional Ty3-gypsy family or a nonautonomous derivative. Both autonomous and nonautonomous elements are likely to have colonized Poaceae centromeres at the time of a common ancestor but have been maintained since by active retrotransposition. The retrotransposon family is also present at a lower copy number in the Arabidopsis genome, where it shows less pronounced localization. The history of the family in the two types of genome provides an interesting contrast between "boom and bust" and persistent evolutionary patterns.

Amino Acid Sequence↗

PubMed2000

Transgenic overexpression of human Bcl-2 in islet beta cells inhibits apoptosis but does not prevent autoimmune destruction.

Insulin-dependent diabetes mellitus results when > 90% of the insulin-producing beta cells in the pancreatic islets are killed as a result of autoimmune attack by T cells. During the progression to diabetes, islet beta cells die as a result of different insults from the immune system. Agents such as perforin and granzymes, CD95 ligand and tumor necrosis factor-alpha, or cytokines and free-radicals have all been shown to cause beta cell apoptosis. The anti-apoptotic protein, Bcl-2, might protect against some of these stimuli. We have therefore generated transgenic mice expressing human Bcl-2 in their islet beta cells. Although Bcl-2 was able to prevent apoptosis induced by cytotoxic agents against beta cells in vitro, Bcl-2 alone could not prevent or ameliorate cytotoxic or autoimmune beta cell damage in vivo.

Age of Onset↗

PubMed2000

Annuality, perenniality and cell death.

This essay considers annuality and perenniality as quantitative traits and discusses the application of established and new genetic tools to the analysis of plant life histories. Annual/perennial status is a function of meristem determinacy in combination with the processes of cell death and disposal employed by plants to generate well-adapted anatomies and morphologies. Creeping perennials, like clover or bracken, seem to move around in the environment. They do this by extending into unoccupied space while the oldest tissues behind the growing and mature regions senesce, die and decompose. Trees do essentially the same thing, except that they develop vertically and the old dead tissue does not disappear but instead persists as wood. A root system is a kind of upended vertical perennial. The balance between exploratory growth and the wave of tissue death that succeeds it is a major determinant of perenniality. So although perenniality and annuality may appear to be dramatically different traits, extremes of behaviour can arise by a relatively minor change in the relationship between growth and death. This conclusion is supported by evidence from genome dosage studies, from the practical experiences of breeding perennial-type traits into annual backgrounds and from molecular cladistics. Applications of methods for the genetic analysis of quantitative characters are described, including the exploitation of introgression mapping in Lolium-Festuca and quantitative trait locus mapping in cereals and other species.

Apoptosis↗

PubMed2000

Five ways to stay green.

The relationship between carbon income and expenditure over the life of a leaf is described and related to the productivity benefits of altering the timing of senescence initiation. In genetic variants with delayed leaf senescence ('stay-greens') deconstruction of the photosynthetic apparatus during leaf senescence is partially or completely prevented. Although the staygreen phenotype is superficially similar in all species and genotypes, the genetic and physiological routes to the trait are diverse. In one type of stay-green, chlorophyll catabolism is disabled. Legumes and monocots with pigment breakdown lesions are discussed. Sorghum is presented as an example of another kind of stay-green in which perennial tendencies have been bred into a monocarpic annual crop species. Transgenic approaches are briefly discussed (enhanced endogenous cytokinins, reduced ethylene production or perception). An alternative route towards making a stay-green phenotype is through quantitative trait mapping and marker-assisted selection. Loci for greenness in pearl millet have been identified, some of which are associated with drought responses or flowering time. Finally the question of the limits on stay-green as a productivity-enhancing character is addressed.

Carbon↗

PubMed2000