Non-invasive assessment of left ventricular relaxation property using color M-mode-derived intraventricular pressure gradients in cats.

INTRODUCTION: Diastolic dysfunction is an early clinical feature of feline hypertrophic cardiomyopathy (HCM). The left ventricular filling in early diastole is facilitated by the diastolic intraventricular pressure gradient (IVPG). The study objectives were to evaluate color Doppler M-mode-derived IVPG calculation in cats as a non-invasive assessment of the left ventricular relaxation property to determine the normal ranges of peak IVPG in cats and investigate the influence of left ventricular function and heart rate (HR). ANIMALS: One hundred and six client-owned apparently healthy cats. METHODS: Prospective cross-sectional study. Quantitative analysis of color Doppler M-mode images was used to estimate total and segmental IVPGs non-invasively. RESULTS: The total IVPG was 0.76 mmHg (95% reference interval (RI): 0.28-1.29 mmHg), the basal IVPG 0.34 mmHg (95% RI: 0.07-0.63 mmHg), and the mid-apical IVPG 0.42 mmHg (95% RI: 0.15-0.71 mmHg). Total and segmental IVPG increased with HR (P < 0.003), while segmental percent IVPG was HR independent. A short isovolumic relaxation time (IVRT) and a high mitral annular velocity in early diastole were associated with an increase in total IVPG (P = 0.008 and P = 0.009, respectively) adjusted for HR. An increase in IVPG was associated with an increase in mitral inflow velocity (P < 0.001). CONCLUSIONS: Feline IVPGs increase with HR and a short IVRT, which was believed to be a normal physiologic adrenergic response associated with an increased sympathetic tone. Future studies of segmental IVPG changes in feline HCM are needed to evaluate the clinical applicability of color Doppler M-mode estimated IVPGs in feline cardiology.

Visceral fat accumulation is associated with cerebral small vessel disease.

BACKGROUND AND PURPOSE: Obesity is associated with the risk of coronary artery disease and stroke. Visceral fat plays a significant role in the atherogenic effects of obesity. Whether visceral fat accumulation, as measured by computed tomography (CT), is an independent risk factor for the presence of cerebral small vessel disease (SVD) was investigated. METHODS: This study comprised 506 Japanese subjects 35-74 years of age (mean 55.3 years) without a history of symptomatic cerebrovascular disease who underwent health screening tests, including brain magnetic resonance imaging, carotid echography and measurements of the visceral fat area (VFA) and subcutaneous fat area (SFA) on abdominal CT. Visceral fat accumulation was defined as VFA ≥ 100 cm(2) . Logistic regression analysis was performed to examine the associations between visceral fat accumulation and cerebral SVD such as white matter lesions (WMLs) and silent lacunar infarction (SLI). RESULTS: The prevalence of WMLs and SLI but not carotid plaque were significantly higher in subjects with VFA ≥ 100 cm(2) than those with VFA < 100 cm(2) . A VFA ≥ 100 cm(2) was associated with WMLs and SLI independent of age, cardiovascular risk factors and other measurements of obesity, such as waist circumference and body mass index. A large waist circumference was independently associated with SLI. SFA, the combination of VFA and SFA, and body mass index were not associated with WMLs or SLI. CONCLUSIONS: Visceral fat accumulation was independently associated with the presence of cerebral SVD in subjects without a history of symptomatic cerebrovascular disease.

Stochastic approach to molecular interactions and computational theory of metabolic and genetic regulations.

The underlying molecular mechanisms of metabolic and genetic regulations are computationally identical and can be described by a finite state Markov process. We establish a common computational model for both regulations based on the stationary distribution of the Markov process with the aim of establishing a unified, quantitative model of general biological regulations. Various existing results regarding intracellular regulations are derived including the classical Michaelis-Menten equation and its generalization to more complex allosteric enzymes in a systematic way. The notion of probability flow is introduced to distinguish the equilibrium stationary distribution from the non-equilibrium one; it plays a crucial role in the analysis of stationary state equations. A graphical criterion to guarantee the existence of an equilibrium stationary distribution is derived, which turns out to be identical to the classical Wegscheider condition. Simple graphical methods to compute the equilibrium and non-equilibrium stationary distributions are derived based crucially on the probability flow, which dramatically simplifies the classical methods still used in enzymology.

Simultaneous multi-section perfusion CT and CT angiography for the assessment of acute ischemic stroke.

BACKGROUND: Introduction of helical computed tomography (CT) scanning has enabled rapid imaging of the vascular status by means of CT angiography and perfusion CT. By virtue of recent multi-detector technology, helical CT has the ability to perform both CT angiography and multi-section perfusion CT simultaneously. This study investigated the clinical feasibility of simultaneous assessment of perfusion CT and CT angiography in patients with acute ischemic stroke. METHOD: Perfusion CT and CT angiography were performed simultaneously in a series of consecutive 31 acute ischemic stroke patients. The time required for the entire processing was about 15 minutes. Contrast agent was used in a total dose of 100 ml (35 ml for perfusion CT and 65 ml for CT angiography). FINDINGS: Simultaneous perfusion CT scans and CT angiographies were of diagnostic quality for 29 patients (94%). In large territorial infarct patients, perfusion CT could predict all perfusion deficits of the final lesions (10 out of 10 lesions) and CT angiography could detect 9 of 10 occlusions of major cerebral arteries (90%). In patients with small lacunar or subcortical infarcts, perfusion CT could predict 9 out of 19 lesions (47.4%), and false-negative were encountered in small lesions (three patients) or in inadequate coverage of data acquisition (seven patients). Acute stage thrombolytic intervention could be carried out based on the findings, and the success of thrombolytic therapy could be demonstrated by follow-up study. CONCLUSIONS: Simultaneous perfusion CT and CT angiography is the very useful tool for the rapid and adequate diagnosis of almost all of the large territorial infarcts and some of non-territorial lacunar infarcts. It is an easy-to-perform and safe imaging technique to assess acute ischemic stroke.

Assessment of abdominal muscle contractility, strength, and fatigue.

We evaluated abdominal muscle contractility and fatigue by measuring twitch gastric pressure (Pgat) after percutaneous supramaximal electrical stimulation of the abdominal wall before and after sit-ups to task failure. Mouth pressures during maximal voluntary expulsive maneuvers (PEmax) at TLC and FRC with superimposed twitches, and maximum voluntary ventilation (MVV) were also assessed. Mean fresh Pgat was 36.1 +/- 3.0 cm H2O with a coefficient of variation that ranged between 3.0 to 4.8%. Pgat decreased by 25% (p < 0.001) and 37% (p < 0.001) at 1 and 30 min after sit-ups. During maximal voluntary contraction twitch occlusion never occurred. PEmax at TLC and FRC decreased by 15% (p < 0.001) and 11% (p < 0.017) at 1 min, and 8% (p < 0.036) and 9% (p < 0.030) at 30 min after sit-ups, respectively. Despite the abdominal muscle fatigue, MVV values at 1 and 30 min after sit-ups were not significantly different from the value obtained before the sit-ups. We conclude that (1) Pgat is a useful objective indicator of abdominal muscle contractility and fatigue; (2) during maximal voluntary expulsive maneuvers the abdominal muscles are never fully activated; (3) sit-ups lead to substantial low-frequency fatigue but little high-frequency fatigue of the abdominal muscles, which has little effect on maximal breathing capacity.

Model for the complex between protein G and an antibody Fc fragment in solution.

BACKGROUND: Streptococcal protein G and staphylococcal protein A are bacterial antibody-binding proteins, widely used as immunological tools, whose antibody-binding domains are structurally quite different. The binding of protein G to Fc fragments is competitive with respect to protein A, suggesting that the binding sites for protein A and protein G on Fc overlap, notwithstanding the fact that they lack sequence or structural similarity. RESULTS: To resolve this issue, the residues involved in the interaction between an IgG-binding domain of protein G (domain II) and the Fc fragment of mouse IgG2a have been identified by use of 13C and 15N NMR. Binding of protein G domain II selectively perturbed resonances from residues between the CH2 and CH3 domains of Fc, whereas in domain II the residues affected are primarily those on the alpha-helix and the third strand of the beta-sheet. This information was used, together with the structures of the two uncomplexed proteins, to construct a model of the complex, using Monte Carlo minimization techniques. In this model, the alpha-helix of protein G lies in the same position as helix 1 of protein A in the crystal structure of the protein A:Fc complex, but its orientation differs from the latter by 180 degrees. CONCLUSIONS: The interactions of the bacterial antibody-binding proteins with their 'target' immunoglobulins involve a very versatile set of protein-protein interactions. First, the IgG-binding domains of protein A and protein G have quite different three-dimensional structures, but bind to sites on the Fc fragment that overlap extensively. Secondly, protein G employs two quite different regions of its surface to bind to the Fab and Fc regions of IgG.