Multivariate Genetic Analysis of Brain Structure in an Extended Twin Design

The hunt for genes influencing behavior may be aided by the study of intermediate phenotypes for several reasons. First, intermediate phenotypes may be influenced by only a few genes, which facilitates their detection. Second, many intermediate phenotypes can be measured on a continuous quantitative scale and thus can be assessed in affected and unaffected individuals. Continuous measures increase the statistical power to detect genetic effects (Neale et al., 1994), and allow studies to be designed to collect data from informative subjects such as extreme concordant or discordant pairs. Intermediate phenotypes for discrete traits, such as psychiatric disorders, can be neurotransmitter levels, brain function, or structure. In this paper we conduct a multivariate analysis of data from 111 twin pairs and 34 additional siblings on cerebellar volume, intracranial space, and body height. The analysis is carried out on the raw data and specifies a model for the mean and the covariance structure. Results suggest that cerebellar volume and intracranial space vary with age and sex. Brain volumes tend to decrease slightly with age, and males generally have a larger brain volume than females. The remaining phenotypic variance of cerebellar volume is largely genetic (88%). These genetic factors partly overlap with the genetic factors that explain variance in intracranial space and body height. The applied method is presented as a general approach for the analysis of intermediate phenotypes in which the effects of correlated variables on the observed scores are modeled through multivariate analysis.     

Trabecular Shear Stresses Predict <Emphasis Type="Italic">In Vivo</Emphasis> Linear Microcrack Density but not Diffuse Damage in Human Vertebral Cancellous Bone

Linear microcracks and diffuse damage (staining over a broad region) are two types of microscopic damage known to occur in vivo in human vertebral trabecular bone. These damage types might be associated with vertebral failure. Using microcomputed tomography and finite element analysis for specimens of cancellous bone, we estimated the stresses in the trabeculae of human vertebral tissue for inferosuperior loading. Microdamage was quantified histologically. The density of in vivo linear microcracks was, but the diffuse damage area was not, related to the estimates of von Mises stress distribution in the tissue. In vivo linear microcrack density increased with increasing coefficient of variation of the trabecular von Mises stress and with increasing average trabecular von Mises stress generated per superoinferior apparent axial stress. Nonlinear increase in linear crack density, similar to the increase of the coefficient of variation of trabecular shear stresses, with decreasing bone stiffness and bone volume fraction suggests that damage may accumulate rather rapidly in diseases associated with low bone density due to the dramatic increase of shear stresses in the tissue. © 2003 Biomedical Engineering Society. PAC2003: 8719Rr, 8719Xx, 8759Ls, 8759Fm, 8710+e     

Cardiovascular ‘reactivity’ to graded splanchnic nerve stimulation in spontaneously hypertensive and normotensive control rats

Cardiovascular ‘reactivity’ to graded splanchnic nerve stimulations was compared in adult spontaneously hypertensive rats (SHR) and normotensive controls (NCR), during abolished adrenal medullary secretion and neurogenic cardiac control and depressed reflex vascular adjustments. Arterial pressure, heart rate and cardiac output were measured, and total peripheral resistance (TPR) and stroke volume (SV) computed before, during and after nerve stimulation. The neurogenic resistance increases in the major gastrointestinal-renal-hepatic circuits expressed themselves as TPR elevations, which were much accentuated in SHR. This reflects an increased w/r₁ of SHR resistance vessels rather than any altered effector sensitivity, since the responses were particularly accentuated at high discharge rates when noradrenaline junction concentrations approach maximal levels. The splanchnic capacitance responses expressed themselves as SV increases, being the most relevant aspect of capacitance control. SV increased less in SHR, mainly reflecting the reduced diastolic compliance of the hypertrophied SHR left ventricle and the consequent rightward shift of its Frank-Starling curve. The results indicate that an elevated resistance may well be maintained by a normal sympathetic discharge in established SHR hypertension. There seems, however, to be an increasing need for accentuated discharge to the capacitance side to maintain proper cardiac filling of the hypertrophied left ventricle.     

不同剂量病毒唑治疗肾综合征出血热306例疗效分析

应用不同剂量病毒唑对３０６例肾综合征同血热患者进行治疗对比观察，发现两治疗组疗效无显著性差异，但两治疗组怀对照组相比，越期率高，肾功能恢复快，血小板数恢复早，病程缩短，并发症减少，病死率也有所下降，但无显著性差异。     

Dependence of the electrogenic pump current of Xenopus oocytes on external potassium

The membrane potential of Xenopus oocytes showed a variable response to an increase of the K⁺ concentration in the bathing solution, [K⁺]_e, from 2.5 mM to 20 mM. In 54% of the cases (n=52) the cells hyperpolarized (by max. 70 mV). In the presence of 10^–5 M ouabain, all cells depolarized suggesting that the hyperpolarization was caused by an electrogenic Na⁺/K⁺ pump. In cells stored overnight in a Na⁺-free solution the transition from 2.5 to 20 mM [K⁺]_e always caused depolarization indicating that the stimulation of the pump requires high internal sodium, [Na⁺]_i. Cells stored overnight in a Na⁺-rich solution had a [Na⁺]_i of 30.7±7 mM, i.e. the Na⁺/K⁺ pump was saturated with sodium (Lafaire and Schwarz 1986). With 9 such cells we determined the K⁺ activation of the Na⁺/K⁺ pump. The activation follows Hill kinetics with I_max=90.5 nA, K_s=2.3 mM, and n=1.68.     

Two cases of lichen planus pigmentosus presenting with a linear pattern

We report two cases of lichen planus pigmentosus (LPP) that developed in a unilateral linear pattern. The patients presented with unilateral linear brown macules on the extremities. Skin biopsy showed orthokeratosis, basal hydropic degeneration with scarce lymphohistiocytic infiltrates, and numerous melanophages in both patients. These patients, to the best of our knowledge, are the first cases of LPP presenting with a linear pattern. LPP should be considered in the differential diagnosis of linear hyperpigmented skin lesions.     

Active response of a one-dimensional cardiac model with gap junctions to extracellular stimulation

To study the response of cardiac tissue to electrical stimulation, a one-dimensional model of cardiac tissue has been developed using linear core-conductor theory and the DiFrancesco-Noble model of Purkinje tissue. The cable lies in a restricted extracellular medium and includes a representation of the junctional resistances known to interconnect cardiac cells. Two electrode geometries are considered: (a) a semi-infinite cable with a monopolar electrode at the end of the cable and (b) a terminated cable with one electrode at each end of the cable. In a series of simulations, stimuli of varying magnitude and polarity are applied at three different times during the plateau of the action potential. The results at the stimulus site show that the action potential duration may either decrease or increase in response to the stimulus, depending on the polarity and application time of the stimulus. The spatial behaviour of the cable in response to the stimulus indicates that sites greater than 200 cells from the stimulating electrode are not affected by the stimulus.     

Finite element solution of steady state temperature distribution in the human torso

A finite element model of the steady state temperature distribution in the human torso is developed. The torso is approximated by a circular cylinder of core surrounded by a layer of muscle and insulating layers of fat and skin. The model is simplified by neglecting longitudinal heat flow. The region occupied by a circular cross-section of the torso is discretized into a mesh of triangles and the boundary of the torso, that is, the skin surface, is consequently approximated by a polygon. The elliptic partial differential equation governing the steady state temperature distribution, together with the associated boundary conditions, are expressed in equivalent variational form. Linear basis functions are used and the resulting integral is minimized over the region bounded by the approximating polygon. Results for two numerical experiments are determined by solving systems of linear equations.     

Effects of para-substituted beta-adrenoceptor blocking agents and methyl-substituted phenoxypropanolamine derivatives on maximum upstroke velocity of action potential in guinea-pig papillary muscles

Summary The effects of atenolol (2–5 mmol/l), sotalol (1–2 mmol/l) and pamatolol (0.1–1 mmol/l), together with N-tertiary butyl phenoxypropanolamines with o-methyl (D-2T: 50–100 mol/l) m-methyl (D-3T: 50–100 mol/l) and p-methyl (D-4T:100–200 mol/l) group as well as with o,p-methyl groups (D-24T) (50–100 mol/l) on action potentials (APs) were investigated in isolated guinea-pig papillary muscles. All the drugs in these concentrations produced a concentration-dependent reduction of the maximum upstroke velocity (V _max). The reduction ofV _max in premature APs induced by stimuli interpolated between the basic driving rate of 0.25, 0.1 or 0.027 Hz decayed exponentially during diastolic intervals. The time constants of these decay processes for atenolol, pamatolol and sotalol ranged between 260–541 ms, those for D-3T and D-4T between 655–1,166 ms, and D-2T and D-24T between 1,565–1,931 ms. A drug which provided larger values caused the reduction ofV _max in a wider range of the frequency. With respect to the aryloxypropanolamine derivatives so far studied (Sada and Ban 1980, 1981 a, b; Sada et al. 1983) fairly good correlations were found as follows: between logn-octanol/water partition coefficient (logP) and ED₂₀ at 0.25 Hz, ED₃₀ at 1 and 4 Hz for 11–14 compounds; between logP and resting block, between molecular weight and A _o ^c i.e. the value extrapolated to the time of APD₉₀ of the conditioning response relative to the predrugV _max value which may represent a fraction of channels blocked per AP for 100 mol/l of 20–22 compounds. With respect to 8 compounds with methyl substituents in the benzene ring or amine part the ortho methyl group makes a major contribution to increase the resting block and to increase log values.