Biomedical subjects
Publications and source records attributed to J Klein.
The possibilities of invasive diagnostic procedures and their place in examination schedule are evaluated in a group of 36 patients. Authors point out the need of close inter-discipline cooperation. They highly appreciate accuracy and reliability of mediastinoscopy and videothoracoscopy, on the other side they show possible complications and contraindications of these procedures.
Phospholipase D (PLD) activity was investigated in astrocytes prepared from newborn rat cerebral cortex using the transphosphatidylation assay. Basal PLD activity was measurable and was found to be enhanced by ATP, carbachol and noradrenaline. The activation by noradrenaline (EC50, 0.68 microM) was mimicked by methoxamine (EC50, 65 microM), an alpha 1-specific adrenergic agonist, and was inhibited by prazosine, an alpha 1-specific adrenergic antagonist. Clonidin, an alpha 2-adrenergic agonist, slightly lowered PLD activity whereas beta-adrenergic drugs were without effect. Experiments with mitogens indicate that PLD activation in astrocytes may be involved in the control of astrocytic cell proliferation.
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Heart rate variability (HRV) appears to be a strong predictor of death. The reproducibility of HRV measurements in patients with stable coronary artery disease (CAD) who have daily life myocardial ischemia, however, is unknown. Thirty patients with stable CAD (25 men and 5 women; aged 62 +/- 8 years) with daily life ischemia were studied with 2 consecutive 24-hour Holter monitoring recordings. Intra- and interobserver reproducibility of the HRV measures was high, with correlations ranging from 0.990 to 0.999 (p < 0.0001). Strong correlations between time and frequency domain HRV measures were observed (range 0.912 to 0.963; p < 0.0001). Both the frequency and duration of ischemia, measured by ST change, varied significantly by day for each patient (s = 155.5; p < 0.0001; s = 232.5, p < 0.0001, respectively). Correlations for HRV measurements between days remained high (range 0.871 to 0.983; p < 0.0001), despite stratification by magnitude of daily ischemia. Thus, 24-hour HRV measurements are stable in CAD patients with daily life myocardial ischemia over a short period, despite varying magnitudes of daily ischemia. These results support the use of HRV as a clinical tool and an outcome measure in future CAD intervention studies using commercially available equipment.
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The broad-spectrum mercury resistance of Streptomyces lividans 1326 is mediated by six open reading frames (orf). These are arranged in two divergently transcribed operons. The orfs mer A (mercuric reductase) and mer B (organolyase) form one of the two operons. These genes and their regulation were further studied by deletion analysis and transcriptional fusion to the reporter gene xylE in the plasmid pXE4. An increase in XylE activity in response to the presence of mercuric ions was observed. The function of ORF2 (MerT) and ORF3 (MerP) as mercury-specific transport proteins, previously postulated based on the structural features of the predicted proteins, was confirmed. Transcription of the mer genes starts within the intercistronic region and two divergent promoters were identified by S1 nuclease mapping. Expression of the genes was negatively regulated by the product of orf1, now called merR. The repressor function was confirmed by gel retardation assays. MerR, produced in Escherichia coli, bound to two sites (operators) in the fragment containing the promoter region between merA and merR. Addition of mercuric ions and phenylmercuric acetate prevented the binding of MerR.
BACKGROUND: The morning peak in myocardial ischemia has been related to diurnal variations in physical and mental activities and to postural changes upon awakening. This study assesses (1) the effects of exogenous activity triggers at different times of the day and (2) the contribution of an endogenous (ie, activity- and posture-independent) circadian vulnerability for ambulatory ischemia. METHODS AND RESULTS: Sixty-three stable coronary artery disease patients underwent ambulatory ECG monitoring and completed a structured diary assessing physical and mental activities. During 2519 hours of observation, a morning increase in ischemia coincided with increases in physical and mental activities, and an evening decrease in ischemia coincided with a decline in activities. During the morning, ischemic versus ischemia-free periods were more likely to occur with high levels of physical activity (P < .001). High physical activity triggered ischemia to a lesser but still significant extent (P < .05) in the afternoon but not in the evening (P = NS). High levels of mental activity triggered ischemia significantly during the morning (P < .04) and evening (P < .04) but not in the afternoon. When a residualized score procedure was used to correct ischemic time for each patient's simultaneously measured activities, for hourly heart rates, or for activity-related heart rate fluctuations, the circadian variation in ischemia was still observed (P < .001), with a peak at 6 AM. A significant increase in ischemia occurred immediately after awakening (P < .05), but activity-adjusted increases in morning ischemia persisted (P < .05) for 2 hours after awakening. CONCLUSIONS: Exogenous factors (physical and mental activities) are most potent as triggers of ischemia during the morning hours, and the postural change after awakening contributes to the morning increase in ischemia. There is also evidence for an endogenous, activity-independent circadian influence on ischemic susceptibility that is independent of exogenous factors and that sustains the increase in ischemia upon awakening.
OBJECTIVES: This study assessed the potency of physical and mental activities and emotions (anger and anxiety) and smoking and other substance use as proximate triggers of ischemia in patients with coronary artery disease during daily life. BACKGROUND: Myocardial ischemia occurs during a wide variety of activities in patients with coronary artery disease, but frequency and relative potency of physical and mental activities, smoking and use of caffeine and alcohol as triggers of ischemia during daily life have not been established. METHODS: Patients (n = 63) with coronary artery disease and evidence of out-of-hospital ischemia kept a validated structured diary of physical and mental activities and psychologic states while undergoing ambulatory electrocardiographic monitoring for 24 to 48 h. RESULTS: Ischemia occurred most frequently during moderately intense physical and mental activities. Patients spent the largest proportion of time engaged in low intensity physical and mental activities (p < 0.05), but the likelihood of ischemia was greatest during intense physical (p < 0.0001) and stressful mental activities (p < 0.03). The percentage of time in ischemia was elevated and approximately equivalent for high intensity physical and high intensity mental activities (5%) compared with 0.2% when patients were engaged in low intensity activities. Strenuous physical activity (e.g., effortful walking, p < 0.05) and the experience of intense anger were potent ischemic triggers, and heart rates at onset of ischemia increased with the intensity of physical and mental activity and with anger. Among smokers, ischemia was more than five times as likely when patients smoked than when they did not (during 24% vs. 5% of diary entries, p < 0.0001). Coffee and alcohol consumption were also related to ischemia (p < 0.05), but this association disappeared after controlling for concurrent cigarette smoking. CONCLUSIONS: Triggers of ischemia in patients with coronary artery disease during daily life include not only strenuous exercise, but also activities involving low levels of exertion, such as anger and smoking. Mental activities appear to be as potent as physical activities in triggering daily life ischemia. Coffee and alcohol consumption are related to ischemia only by virtue of their associations with smoking.
Several sites of nuclear protein interaction within the promoter region of the Antirrhinum majus floral meristem identity gene SQUAMOSA were detected using an electrophoretic mobility shift assay. One of these sites displayed a particularly clear interaction with nuclear protein extracted from inflorescences but not with nuclear protein extracted from young, nonflowering plants. This site could thus represent a binding motif for a transcriptional activator. A South-western screen of an inflorescence cDNA expression library resulted in the isolation of several cDNAs representing two different genes named SBP1 and SBP2 (for SQUAMOSA-pROMOTER BINDING PROTEIN gene 1 and 2). Both genes encode highly similar protein domains which were found to be necessary and sufficient for binding DNA in a sequence-specific manner. This DNA-binding domain showed no similarity to known proteins in the databases. However, it is characteristic for a small family of gene products in A. majus and other plant species. Expression of SBP1 and 2 is developmentally regulated and their transcriptional activation precedes that of SQUAMOSA. The data presented support the idea that members of the newly identified SBP gene family function as transcription factors involved in the control of early flower development.
OBJECTIVE: To determine if parents prefer single-dose intramuscular (IM) therapy or standard 10-day oral therapy for treatment of acute otitis media (AOM). DESIGN: Parents were asked their preference at the time their child was enrolled in a randomized controlled trial comparing the clinical efficacy of single-dose IM ceftriaxone sodium with 10 days of oral amoxicillin and clavulanate potassium for AOM. Additional information was collected at days 3 to 5 and 14 to 16 after the initiation of the therapy. SETTING: Primarily private practices; 15 sites. PATIENTS: For this study, 648 children aged 3 months to 6 years were randomly assigned to receive IM (n=327) or oral (n=321) therapy. RESULTS: The groups were equivalent in all measured sociodemographic factors. At the time of enrollment, 85% of parents expressed a preference for single-dose IM therapy. At days 3 to 5, no differences were reported in days children were absent from school or day care, parental absence from work, or loss of sleep by children. However, more parents with children in the IM therapy group than in the oral therapy group reported loss of sleep by the parent (35% vs 26%, P=.02, chi(2)). At days 14 to 16, more parents with children in the IM group reported being "very satisfied" with the antibiotic (65%) compared with parents whose children were assigned to the oral therapy group (38%, P<.001). In comparing current therapy to past oral therapy for AOM, 71% of the parents with children in the IM therapy group reported more satisfaction with current therapy, in contrast to 21% of parents with children in the oral therapy group (P<.001). Of the parents, 83% indicated they would prefer single-dose IM therapy for AOM in the future. CONCLUSION: All of the parents prefer single-dose IM therapy for AOM over standard 10-day oral therapy.
The guppy, Poecilia reticulata, a teleostean fish of the order Cyprinodontiformes, has been used extensively in studies of host-parasite interactions, courtship behavior, and mating preference, as well as in ecological and evolutionary genetics. A related species was among the first poikilotherm vertebrates to be used in the study of histocompatibility genes. All these studies could benefit from the identification and characterization of the guppy major histocompatibility complex (Mhc) genes. Here, both class I and class II genes of the guppy are described. The number of expressed loci, as determined by representation of clones in a cDNA library, sequencing, and Southern blot analysis, may be low in both Mhc classes: combined evidence suggests that there may be one expressed class II locus only and one or two expressed class I loci. The variability of aquaristic guppy stocks is very low: only three and two genes have been detected at the class I and class II loci, respectively, in the stocks examined. This genetic paucity is most likely the consequence of breeding practices employed by aquarists and commercial establishments. Limited sampling of wild guppy populations revealed extensive Mhc polymorphism at loci of both classes in nature. Comparison of guppy Mhc sequences with those of other vertebrates has revealed the existence of a set of insertions/deletions which can be used as characters in cladistic analysis to infer phylogenetic relationships among vertebrate taxa and the Mhc genes themselves. These indels are particularly frequent in the regions coding for the loops of alpha 1 and alpha 2 domains of class I proteins.
The major histocompatibility complex (Mhc) consists of class I and class II genes. In the human Mhc (HLA) class II genes, nine DRB loci have been identified. To elucidate the origin of these duplicated loci and allelic divergences at the most polymorphic DRB1 locus, introns 4 and 5 as well as the 3' untranslated region (altogether approximately 1,000 base pairs) of seven HLA-DRB loci, three HLA-DRB1 alleles, and nine nonhuman primate DRB genes were examined. It is shown that there were two major diversification events in HLA-DRB genes, each involving gene duplications and allelic divergences. Approximately 50 million years (my) ago, DRB1*04 and an ancestor of the DRB1*03 cluster (DRB1*03, DRB1*15, and DRB3) diverged from each other and DRB5, DRB7, DRB8, and an ancestor of the DRB2 cluster (DRB2, DRB4, and DRB6) arose by gene duplication. Later, about 25 my ago, DRB1*15 diverged from DRB1*03, and DRB3 was duplicated from DRB1*03. Then, some 20 my ago, the lineage leading to the DRB2 cluster produced two new loci, DRB4 and DRB6. The DRB1*03 and DRB1*04 allelic lineages are extraordinarily old and have persisted longer than some duplicated genes. The orthologous relationships of DRB genes between human and Old World monkeys are apparent, but those between Catarrhini and New World monkeys are equivocal because of a rather rapid expansion and contraction of primate DRB genes by duplication and deletion.
A characteristic feature of the major histocompatibility complex (Mhc) polymorphism in mammals is the existence of allelic lineages shared by related species. This trans-species polymorphism has thus far been documented only in primates, rodents, and artiodactyls. In this communication we provide evidence that it also exists in cyprinid (bony) fishes at the class II A and B loci coding for the alpha and beta polypeptide chains of the class II alpha:beta heterodimers. The study has focused on three species of the family Cyprinidae, subfamily Rasborinae: the zebrafish (Danio rerio), the giant danio (D. malabaricus), and the pearl danio (D. albolineatus). The polymerase chain reaction was used to amplify and then sequence intron 1 and exon 2 of the class II B loci and exon 2 of the class II A loci in these species. Phylogenetic analysis of the sequences revealed the existence of allelic lineages whose divergence predates the divergence of the three species at both the A and B loci. The lineages at the B locus in particular are separated by large genetic distances. The polymorphism is concentrated in the peptide-binding region sites and is apparently maintained by balancing selection. Sharing of this unique Mhc feature by both bony fishes and mammals suggests that the main function of the Mhc (presentation of peptides to T lymphocytes) has not changed during the last 400 million years of its evolution.
We have generated a high-resolution genetic map, 0.071 cM per backcross animal, of the 13 cM T-H2 region of the mouse Chromosome (Chr) 17. The map contains two phenotypic loci, T and Hst1, 12 RFLP markers, and 24 microsatellite loci. The Hst1 gene was mapped to a chromosomal interval contained within a single 580-kb YAC clone. The FFEH11 YAC is 0.44 cM long and carries, besides the Hst1 gene, five polymorphic DNA markers and recombination breakpoints of six backcross animals. Two candidate genes for Hst1 were identified based on their location and testicular expression. These are Tbp and D17Ph4e. The submilliMorgan map of the T-H2 region revealed significant clustering of (CA)n loci. The clustering, if shown to be a common feature in the mouse genome, may cause gaps in the physical map of the mouse genome.
High-dose nicotinamide (1000 mg/kg) leads to a minor increase of plasma choline but to a major increase of the choline concentrations in the intra- and extracellular spaces of the brain. In the hippocampus, the nicotinamide-induced increase in choline was associated with an increase in the release of acetylcholine under stimulated conditions. In young rats, nicotinamide in doses between 10 and 1000 mg/kg did not influence spatial learning, as tested in the Morris water maze. In old rats, low doses of nicotinamide were ineffective whereas the high dose of 1000 mg/kg even impaired spatial learning. The combined administration of choline and nicotinamide had a synergistic effect on brain choline levels but had similar effects as nicotinamide given alone in the behavioral experiments. Additional tests for spontaneous behaviour and locomotion revealed procholinergic and sedative effects of the compound. We conclude that the ineffectiveness of the putative cognition enhancer nicotinamide in the learning task may be due to the observed sedative effect. Therefore, the development of nonsedative nicotinamide derivatives is recommended.
An important molecule in the activation of the complement system in vertebrates is factor B, a serine protease with a molecular mass of 95,000. Factor B and the complement component C2 are thought to have arisen by gene duplication. In mammals and in Xenopus the factor B gene is linked to the major histocompatibility complex (MHC), whereas in domestic fowl it segregates independently of the MHC. Here we describe the isolation of a cDNA clone coding for factor B in the zebrafish, Brachydanio rerio. The deduced protein sequence exhibits a characteristic mosaic structure consisting of the short consensus repeat (SCR), the von Willebrand factor, and the serine protease domains. The estimated time of factor B and C2 divergence (approximately 350 million years ago), combined with the fact that C2 has thus far been found only in mammals, suggest that the factor B-C2 gene duplication occurred after the divergence of mammal-like reptiles from other reptiles and hence also birds. After the duplication, the C2 component evolved significantly faster than factor B.