Myocardial contractility is not constant during spontaneous atrial fibrillation in patients

BACKGROUND: The variation in stroke volume and pulse pressure characteristic of atrial fibrillation is usually ascribed to time-dependent ventricular filling, implying a single positive relationship between end-systolic pressure and volume, which defines a single state of myocardial contractility. We tested the hypothesis that contractility also varies. METHODS AND RESULTS: We measured the left ventricular pressure and volume continuously with a conductance catheter with catheter-tip micromanometer introduced retrogradely into the left ventricle. The end-systolic pressure-volume relationship was determined in 6 patients in atrial fibrillation undergoing cardiac catheterization for diagnostic purposes and 4 control patients in sinus rhythm undergoing coronary artery bypass graft surgery. The normal positive relationship between end-systolic pressure and volume was found in the control patients, but no such positive relationship was found in any patient in atrial fibrillation. In the latter, the slopes of the linear regressions were either not significantly different from zero or significantly negative (r values <0.08), both results indicating a change in contractility from beat to beat. Significantly negative relationships were found between end-systolic volume and preceding R-R interval (-0.82相似文献   

Oxygen consumption in relation to work load in students with cerebral palsy

Eighteen adolescents with various forms of cerebral palsy performed tests on a mechanically braked ergometer bicycle. VO2 was measured at different loads and net mechanical efficiency calculated. It was found that efficiency was poor at light loads for most of the students but that there were significant intergroup differences in mechanical efficiency at higher loads. The leveling-off plateau demonstrated by healthy adolescents was only attained by a few of the disabled students. It was concluded that the muscle hypertonia and involuntary movements were responsible for the high level of energy expended in the mechanical work performed.     

Iodine-123-BMIPP myocardial washout and cardiac work during exercise in normal and ischemic hearts

Due to the changes in the frequency of penicillin-resistant strains of S. pneumoniae, it is necessary to perform surveillance studies of bacterial resistance. Isolates from the upper respiratory tract of asymptomatic children have been useful. There is no information about the difference between isolates from children with and without upper respiratory tract infection (URTI). The objective of the authors in this paper is to establish the prevalence of carrier-state, serotype and antimicrobial resistance of S. pneumoniae isolates from children with and without acute upper respiratory tract infection (URTI) in a rural area in Mexico. A cross-sectional comparative study was performed in Tlaxcala, Mexico. Children from one month 5 years of age were included. Nasopharyngeal swabs were obtained. Identification was done by international microbiology standards. Serotyping was done by the capsular Quellung test. The susceptibility testing was performed by the agar dilution method. Four-hundred and fifty patients were included. S. pneumoniae was isolated in 134 children (29.7%). Frequency of carriers was greater in patients with URTI (107/323) than without URTI (27/127) (33.1% vs. 21.1% p = 0.012, OR 1.84, IC 95% 1.1-3.08). The six most frequent serotypes were: 6B (16.4%); 19F (11.9%); 19A (6.7%); 14, 23F, and 35 (5.2% each), with no difference among the groups. Only 3% of the strains had high level resistance to penicillin, and 12.6% had intermediate resistance, and for ampicillin 4%, amoxicillin 4%, amoxicillin-clavulanate 4%, ceftriaxone 3%, cefotaxime 1.5%, erythromycin 6%, miocamycin 3%, chloramphenicol 4%, and vancomycin 0%. Trimethoprim-sulfamethoxazole resistance was very high (42%). In conclusion, colonization is higher in children with URTI. Five of the most frequent serotypes identified in this study were the same as those identified in patients with S. pneumoniae invasive diseases in Mexico City. In Tlaxcala, Mexico, beta-lactams could be the drug of choice for the treatment of S. pneumoniae lower respiratory tract infections. It is necessary to perform clinical assays to evaluate the efficacy of trimethoprim-sulfamethoxazole due to the high resistance in vitro.     

Oxygen uptake and cardiac output during progressive and constant load work in patients after acute myocardial infarction

PURPOSE: Simultaneously measured oxygen uptake (VO2) and Doppler echocardiography could verify if an alteration in the VO2 response to progressive and constant load work is due to reduced cardiac output. METHODS: The study group consisted of nine patients after acute myocardial infarction (MI), five age-matched healthy subjects (HE), and five young well-trained subjects (WT). Each subject performed a progressive exercise test and two bouts of constant load work at power outputs equated to 10% below (W1) and 10% above (W2) their ventilatory thresholds. VO2 and cardiac output were measured continuously and simultaneously during the tests. RESULTS: VO2 was significantly reduced for the MI group during the initial stages of the progressive exercise test (P < .02) and remained lower throughout the entire test. During the first 60 seconds of constant load work (W2), VO2 was lower for MI (P < .05). At steady state exercise during W2, cardiac output was significantly less for MI (P < .05). VO2 for the MI group was more reliant on cardiac output during lower power outputs and differences in the arterial and venous O2 content (a-VO2 difference) during greater power outputs. CONCLUSIONS: Cardiac rehabilitation programs must be aware of this delayed VO2 and cardiac output response when setting training workloads or selecting the magnitude of the workload increments during progressive exercise tests.     

Near-infrared estimation of O2 supply and consumption in forearm muscles working at varying intensity

We estimated a blood flow index, O2 supply index, and O2 consumption index from near-infrared (NIR) signals during venous occlusion imposed at rest and immediately after handgrip exercise with loads equal to 5, 10, 15, 20, 25, and 30% of the maximum voluntary contraction. We also estimated forearm blood flow (BFfa) by strain-gauge plethysmography and forearm O2 consumption (VO2fa) by the invasive method. There was a significant correlation between the rate of increase in total hemoglobin during venous occlusion obtained from NIR signals and BFfa in each subject (r = 0.853 approximately 0.981, P < 0.001). There was also a significant correlation (r = 0.854 approximately 0.944, P < 0.001) between the O2 consumption index estimated from NIR signals and VO2fa. The mean values for O2 supply index in five subjects increased with exercise intensity, while the O2 consumption index showed no further increase about 25% of maximum voluntary contraction. We found significant positive correlations between the O2 supply index and BFfa (r = 0.986, P < 0.001) and the O2 consumption index and VO2fa (r = 0.976, P < 0.001) during exercise at 5-30% of maximum voluntary contraction. These results demonstrate that analysis of NIR signals during venous occlusion provides an advantageous method of estimation of O2 supply and consumption in working muscles during exercise of varying intensity.     

Oxygen consumption and biosynthetic function in perfused liver from rats at different stages of development

Changes in mitochondrial function were studied in perfused liver from rats aged 24-365 days. Oxygen consumption together with the rates of gluconeogenesis, urea synthesis and ketogenesis were determined. Basal mitochondrial respiration as well as the ability of the liver to synthesize glucose, urea and ketone bodies declined from 24- to 365-day-old rats. On the other hand, on transition from 24 to 60 days the liver oxidation rate of hexanoate, sorbitol and glycerol is enhanced, but not of ketone bodies or palmitate. Our results show that the transition from weaning to middle age is accompanied by defined changes in hepatic substrate oxidation. From the observed time course of the decrease in basal and substrate-stimulated oxygen consumption, it is concluded that in rat liver cells a decline in respiratory chain function, long-chain fatty acid and ketone body metabolism, gluconeogenesis and ureogenesis occurs at a relatively early life stage.     

Improved contractility and coronary flow in isolated hearts after 1-day hypothermic preservation with isoflurane is not dependent on K(ATP) channel activation

S8 is one of the core ribosomal proteins. It binds to 16 S RNA with high affinity and independently of other ribosomal proteins. It also acts as a translational repressor in Escherichia coli by binding to its own mRNA. The structure of Thermus thermophilus S8 has been determined by the method of multiple isomorphous replacement at 2.9 A resolution and refined to a crystallographic R-factor of 16.2% (Rfree 27.5%). The two domains of the structure have an alpha/beta fold and are connected by a long protruding loop. The two molecules in the asymmetric unit of the crystal interact through an extensive hydrophobic core and form a tightly associated dimer, while symmetry-related molecules form a joint beta-sheet of mixed type. This type of protein-protein interaction could be realized within the ribosomal assembly. A comparison of the structures of T. thermophilus and Bacillus stearothermophilus S8 shows that the interdomain loop is eight residues longer in the former and reveals high structural conservation of an extensive region, located in the C-terminal domain. From mutational studies this region was proposed earlier to be involved in specific interaction with RNA. On the basis of these data and on the comparison of the two structures of S8, it is proposed that the three-dimensional structure of specific RNA binding sites in ribosomal proteins is highly conserved among different species.     

Evidence for brain serotonin-mediated control of carbohydrate consumption in normal weight and obese humans

A plasma insulin and amino acid-mediated mechanism is thought to modulate brain serotonin concentration, thereby regulating carbohydrate consumption on a meal to meal basis. It has been suggested that obesity is associated with a defect in the appetite control system. Furthermore, post-absorptive plasma levels of several amino acids are increased in obese subjects, which is ascribed to obesity-associated insulin resistance and/or hyperinsulinemia. We studied breakfast-induced changes in plasma ratios of tryptophan to other large neutral amino acids and associated differences in macro-nutrient composition of lunch food in normal weight and obese human subjects. The study was randomized, double blind and cross-over with a 2 x 2 factorial design with drug/placebo and type of breakfast as factors. Nineteen healthy, non-obese (body mass index (BMI) 22.5 +/- 1.9 kg/m2, mean +/- s.d.) and 19 obese (BMI 34.7 +/- 6.2 kg/m2) female volunteers were treated with either 60 mg fluoxetine (FXT), a serotonin re-uptake blocker specifically acting in the brain, or placebo for four days with a wash-out period between treatments of four weeks. The subjects received either a carbohydrate (CHO) breakfast (80 g maltodextrin, 300 kcal) or a protein-rich (PROT) breakfast (60% milk protein and 40% CHO, 300 kcal) on two consecutive days (days 4 and 5 of each treatment period). Plasma glucose, insulin and amino acids were measured at several time points after breakfast. Three hours after breakfast, subjects were able to choose from 29 different food items. Total energy content and weight of lunch food and energy percentage of each macronutrient were calculated.(ABSTRACT TRUNCATED AT 250 WORDS)     

p53 activity is essential for normal development in Xenopus

BACKGROUND: The tumor suppressor p53 plays a key role in regulating the cell cycle and apoptosis in differentiated cells. Mutant mice lacking functional p53 develop normally but die from multiple neoplasms shortly after birth. There have been hints that p53 is involved in morphogenesis, but given the relatively normal development of p53 null mice, the significance of these data has been difficult to evaluate. To examine the role of p53 in vertebrate development, we have determined the results of blocking its activity in embryos of the frog Xenopus laevis. RESULTS: Two different methods have been used to block p53 protein activity in developing Xenopus embryos--ectopic expression of dominant-negative forms of human p53 and ectopic expression of the p53 negative regulator, Xenopus dm-2. In both instances, inhibition of p53 activity blocked the ability of Xenopus early blastomeres to undergo differentiation and resulted in the formation of large cellular masses reminiscent of tumors. The ability of mutant p53 to induce such developmental tumors was suppressed by co-injection with wild-type human or wild-type Xenopus p53. Cells expressing mutant p53 activated zygotic gene expression and underwent the mid-blastula transition normally. Such cells continued to divide at approximately normal rates but did not form normal embryonic tissues and never underwent terminal differentiation, remaining as large, yolk-filled cell masses that were often associated with the neural tube or epidermis. CONCLUSIONS: In Xenopus, the maternal stockpile of p53 mRNA and protein seems to be essential for normal development. Inhibiting p53 function results in an early block to differentiation. Although it is possible that mutant human p53 proteins have a dominant gain-of-function or neomorphic activity in Xenopus, and that this is responsible for the development of tumors, most of the evidence indicates that this is not the case. Whatever the basis of the block to differentiation, these results indicate that Xenopus embryos are a sensitive system in which to explore the role of p53 in normal development and in developmental tumors.     

AnkyrinG is required for clustering of voltage-gated Na channels at axon initial segments and for normal action potential firing

Voltage-gated sodium channels (NaCh) are colocalized with isoforms of the membrane-skeletal protein ankyrinG at axon initial segments, nodes of Ranvier, and postsynaptic folds of the mammalian neuromuscular junction. The role of ankyrinG in directing NaCh localization to axon initial segments was evaluated by region-specific knockout of ankyrinG in the mouse cerebellum. Mutant mice exhibited a progressive ataxia beginning around postnatal day P16 and subsequent loss of Purkinje neurons. In mutant mouse cerebella, NaCh were absent from axon initial segments of granule cell neurons, and Purkinje cells showed deficiencies in their ability to initiate action potentials and support rapid, repetitive firing. Neurofascin, a member of the L1CAM family of ankyrin-binding cell adhesion molecules, also exhibited impaired localization to initial segments of Purkinje cell neurons. These results demonstrate that ankyrinG is essential for clustering NaCh and neurofascin at axon initial segments and is required for physiological levels of sodium channel activity.     

Mitochondrial contact sites detected by creatine phosphokinase activity in the hearts of normal and diabetic rats: is mitochondrial contact sites formation a calcium-dependent process?

Reovirus type 2 (Reo-2) infection in DBA/1 sucking mice causes pancreatic islet-cell destruction, which results in a diabetes-like syndrome. To investigate the role of reactive oxygen species (ROS), the protective effect of dimethylthiourea (DMTU) was examined, this substance being an effective scavenger of hydroxyl radicals. The degree of cellular infiltration in and around pancreatic islets was the same in mice receiving either virus only or virus and DMTU. The latter had no effect on (1) the number or type of white blood cells, (2) lymphocyte function-associated antigen 1-alpha-positive splenocytes, or (3) viral multiplication in the pancreas. However, treatment with DMTU inhibited the elevation of blood glucose concentrations and reduced pancreatic islet-cell damage (beta-cell degranulation and necrosis). These results suggest that ROS play a role in the pathogenesis of Reo-2-induced diabetes-like syndrome.     

A low catalase activity in dog erythrocytes is due to a very low content of catalase protein despite having a normal specific activity

Catalase was purified to an apparent homogeneity from dog erythrocytes and its properties were compared with those of human erythrocyte catalase. Purification was unsuccessful without the use of glycerol as the stabilizing agent. Molecular weight of the purified dog catalase was estimated to be about 63,000 Da in monomer and about 230,000 Da in native tetramer form. The ratio of A405/A280, the index of hematin content relative to protein, was 1.15. The isoelectric point was in the range of 5.8 to 6.4. These properties of dog catalase were very similar to those of human catalase. Dog catalase also possessed the same partial amino acid sequence as human catalase. However, the specific activity of dog enzyme was about threefold less than that of human enzyme. The amount of catalase protein in dog erythrocytes determined by immunoblotting analysis was about tenfold less than that of human erythrocytes. This was consistent with the fact that the catalase activity in dog hemolysate was about 1/30 of that in human hemolysate.     

Oxygen regulates human cytotrophoblast differentiation and invasion: implications for endovascular invasion in normal pregnancy and in pre-eclampsia

This review article focuses on the unique process by which the human placenta normally forms and how changes in this process can lead to serious pregnancy complications such as pre-eclampsia. One way to compare normal and pathologic pregnancies is to examine biopsy specimens of the placenta and placental bed for disease-associated morphological changes in cellular architecture. Our recent work has verified the decades-old observation that pre-eclampsia is associated with abnormally shallow placentation. We also discuss how these morphological observations prompted us to use a combination of in vitro modeling and in situ immunolocalization techniques to gain insights into the molecular bases of normal placentation and how these mechanisms go awry in pre-eclampsia.     

BDNF is required for the normal development of taste neurons in vivo

The vallate gustatory epithelium of neonatal trkB null mutant mice (-/-) lacked innervation. This prompted the evaluation of null mutant mice corresponding to the three neurotrophin ligands for tyrosine kinase receptor B (TrkB): brain-derived neurotrophic factor (BDNF), neurotrophin (NT)3, NT4. The vallate gustatory epithelium of nt3-/- mice and of nt4-/- mice appeared normal. Only bdnf-/- mice had a vallate papilla that was stunted, sparsely innervated, and lacked up to 98% of its taste buds. All three defects persisted. For example, the vallate papilla of 12-day-old bdnf-/- mice remained markedly less well innervated than the vallate of 7-day-old or newborn bdnf+/+ mice. The foliate taste papillae of neonatal bdnf-/- mice had similar defects. We conclude that the normal development of taste neurons requires BDNF.     

A stress relaxation method for following carbonitride precipitation in austenite at hot working temperatures

Stress relaxation measurements were carried out on a plain carbon and four solution-treated Ti steels over the temperature range 850 to 1050 °C. The results show that the stress relaxation of plain carbon austenite after a 5 pct prestrain (i.e., in the absence of precipitation) can be described by the relation σ = σ₀ -α ln(l + βt). By contrast, in the solution-treated Ti steels, relaxation is arrested at the start of precipitation and is resumed when precipitation is completed. As a result, this mechanical method is particularly suitable for following carbonitride precipitation in microalloyed austenite at hot working temperatures. A new model regarding the effect of precipitation on dislocation motion is proposed, on the basis of which, the phenomenology of the stress relaxation technique is clarified. Precipitation-time-temperature (PTT) diagrams were determined for the Ti bearing steels containing 0.05, 0.11, 0.18, and 0.25 pct Ti. The PTT curves obtained are C-shaped for all the steels. The upper parts of these curves are shifted to significantly longer times as the Ti and C concentrations are reduced. By contrast, the positions of the lower arms of the curves are relatively independent of the compositions of the steels tested.     

MCAT is not required for in vitro polyketide synthesis in a minimal actinorhodin polyketide synthase from Streptomyces coelicolor

BACKGROUND: It has been proposed that Streptomyces malonyl CoA: holo acyl carrier protein transacylases (MCATs) provide a link between fatty acid and polyketide biosynthesis. Two recent studies have provided evidence that the presence of MCAT is essential for polyketide synthesis to proceed in reconstituted minimal polyketide synthases (PKSs). In contrast to this, we previously showed that the holo acyl carrier proteins (ACPs) from type II PKSs are capable of catalytic self-malonylation in the presence of malonyl CoA, which suggests that MCAT might not be necessary for polyketide biosynthesis. RESULTS: We reconstituted a homologous actinorhodin (act) type II minimal PKS in vitro. When act holo-ACP is present in limiting concentrations, MCAT is required by the synthase complex in order for polyketide biosynthesis to proceed. When holo-ACP is present in excess, however, efficient polyketide synthesis proceeds without MCAT. The rate of polyketide production increases with holo-ACP concentration, but at low ACP concentration or equimolar AC:KS:CLF (KS, ketosynthase; CLF, chain length determining factor) concentrations this rate is significantly lower than expected, indicating that free holo-ACP is sequestered by the KS/CLF complex. CONCLUSIONS: The rate of polyketide biosynthesis is dictated by the ratio of holo-ACP to KS and CLF, as well as by the total protein concentration. There is no absolute requirement for MCAT in polyketide biosynthesis in vitro, although the role of MCAT during polyketide synthesis in vivo remains an open question. MCAT might be responsible for the rate enhancement of malonyl transfer at very low free holo-ACP concentrations or it could be required to catalyse the transfer of malonyl groups from malonyl CoA to sequestered holo-ACP.     

Hippocampal volumes in cognitively normal persons at genetic risk for Alzheimer's disease

Brain imaging techniques have the potential to characterize neurobiological changes that precede the onset of cognitive impairment in persons at risk for Alzheimer's disease. As previously described, positron emission tomography (PET) was used to compare 11 cognitively normal persons 50 to 62 years of age who were homozygous for the epsilon4 allele of apolipoprotein E and 22 persons without the epsilon4 allele with a reported family history of Alzheimer's dementia who were matched for sex, age, and level of education. The epsilon4 homozygotes had significantly reduced glucose metabolism in the same brain regions as patients with Alzheimer's dementia; the largest reduction was in the posterior cingulate cortex. As described here, magnetic resonance imaging (MRI) was used to compare hippocampal volumes in the same subject groups. The epsilon4 homozygotes showed nonsignificant trends for smaller left and right hippocampal volumes; overall, smaller hippocampal volumes were associated with reduced performance on a long-term memory test. Whereas PET measurements of cerebral glucose metabolism begin to decrease before the onset of memory decline, MRI measurements of hippocampal volume begin to decrease in conjunction with memory decline in cognitively normal persons at risk for Alzheimer's disease.