Skewed sex ratios in familial holoprosencephaly and in people with isolated single maxillary central incisor

Autosomal dominant holoprosencephaly is a rare but well documented entity and it can be the result of mutations in the Sonic Hedgehog gene (SHH). The transmitting parent may be normal or have a single maxillary central incisor. We describe a skewed sex ratio among the transmitting parents with SHH mutations, with more mothers than fathers having the mutation (p=0.002). The mechanism underlying this skewed sex ratio is not clear; the SHH mutations do not involve triplet repeats, imprinting is plausible but untested, and there is no evidence that the risk of holoprosencephaly is greater among males carrying such a mutation (p=0.15). We considered the possibility that males with such a mutation are at greater risk of other malformations outside the central nervous system, which could reduce their reproductive fitness. To avoid ascertainment bias in identifying children with various malformations in kindreds with familial holoprosencephaly, we reviewed the reports of people with single maxillary central incisor and no other congenital malformations. Of the 16 cases identified, 13 were female (p=0.0085). We suggest that boys with mutations associated with autosomal dominant holoprosencephaly may be at greater risk of major malformations outside the central nervous system than girls.     

Sex determination and the maternal dominance hypothesis

The maternal dominance hypothesis has been derived from workwith humans which shows that women who are more dominant thanother women are more likely to conceive sons. In both animalsand humans dominance is a characteristic or personality trait,underpinned by testosterone and responsive to a range of environmentalchanges: physical, social and psychological. Studies of thesex ratio in the social sciences and animal behaviour eithersupport or are compatible with the idea that the sex-determiningrole of X- and Y-chromosome bearing spermatozoa may be precededby factors under maternal control which provide for differentialaccess of spermatozoa. Findings in reproductive physiology andphysiological psychology suggest that folh'cular testosteroneor a related hormone may play a critical role. Reproductivephysiologists have already identified maternal mechanisms whichcould provide the context for such a model.     

Drinking to intracellular dehydration following vagotomy in rats

Abdominally vagotomized rats maintained on a solid diet drank less and had longer latencies to drink than sham vagotomized rats following IP injection of an osmotic load (0.75 M NaCl, 1% BW). However, these two groups did not differ in latency or water intake following injection of isotonic saline. Since both vagotomized and control rats drank more water and had shorter latencies following injection of hypertonic saline than after isotonic saline, vagotomy apparently attenuated but did not abolish osmotic drinking. Maintenance on a liquid diet and a brief fast prior to testing (to ensure an empty stomach) did not alter these results, indicating that the impairment of gastric emptying of solid food that accompanies total abdominal vagotomy cannot account for the attenuation of osmotically induced drinking. Furthermore, this deficit was seen even when intracellular dehydration was produced at different times during the circadian cycle and when water presentation was delayed 0.5 hr postinjection. In addition, vagotomized rats drank less than control rats following 16-hr water deprivation and exhibited a lower water-food ratio on ad lib regimen. However, vagotomized and sham vagotomized rats exhibited the same relative day-night difference in water consumption as well as short latency response to thermal pain, which with other results indicates that vagotomy did not result in a general impairment of behavior. These findings suggest that osmotic perturbations are detected by the viscera and the information conveyed to the brain via afferent vagus nerves.     

Increased central adiposity is associated with pro-inflammatory immunoglobulin G N-glycans

Background

Increased body fat may be associated with an increased risk of developing an underlying pro-inflammatory state, thus leading to greater risk of developing certain chronic conditions. Immunoglobulin G has the ability to exert both anti- and pro-inflammatory effects, and the N-glycosylation of the fragment crystallisable portion is involved in mediating this process. Body mass index, a rudimentary yet gold standard indication for body fat, has been shown to be associated with agalactosylated immunoglobulin G N-glycans.

Amiloride-sensitive Na+ transport across cultured renal (A6) epithelium: evidence for large currents and high NaK selectivity

Electrical techniques were used to determine the NaK selectivity of the amiloride-sensitive pathway and to characterize cellular and paracellular properties of A6 epithelium. Under control conditions, the mean transepithelial voltage (V _T) was –57±5 mV, the short-circuit current (I _sc) averaged 23±2 A/cm² and the transepithelial resistance (R _T) was 2.8±0.3 kcm² (n=13). V _T and I _sc were larger than reported in previous studies and were increased by aldosterone. The conductance of the amiloride-sensitive pathway (G _amil) was assessed before and after replacement of Na⁺ in the mucosal bath by K⁺, using two independent measurements: (1) the slope conductance (G _T), determined from current-voltage (I-V) relationships for control and amiloride-treated tissues and (2) the maximum amiloride-sensitive conductance (G _max) calculated from the amiloride dose-response relationship. The ratio of G _amil in mucosal Na⁺ solutions to G _amil for mucosal K⁺ solutions was 22±6 for G _T measurements and 15±2 for G _max data. Serosal ion replacements in tissues treated with mucosal nystatin indicated a potassium conductance in the basolateral membrane. Equivalent circuit analyses of nystatin and amiloride data were used to resolve the cellular (E _c) and paracellular (R _j) resistances (5 kcm² and 8–9 kcm², respectively). Analysis I-V relationships for tissues depolarized with serosal K⁺ solutions revealed that the amiloride-sensitive pathway could be described as a Na⁺ conductance with a permeability coefficient (P _Na)=1.5±0.2× 10^–6 cm/s and the intracellular Na⁺ concentration (Na_i)=5±1 mM (n=5), similar to values from other tight epithelia. We conclude that A6 epithelia are capable of expressing large amiloride-sensitive currents which are highly Na⁺ selective.     

Gender differences at birth and differences in fetal growth

The discrepancy between the number of boys and girls born hasbeen interpreted as a natural selection response to differentialsurvival prospects. There also exists a discrepancy in birthweight, length, head circumference at birth of boys and girls;on the other hand, placental weights were not so strongly biasedby the sex of the fetus. Metabolic differences between the sexesare clearly recognized in adults. It is therefore argued thatthe anthropometric differences at birth, examples of which arepresented in this paper, can only be achieved if the productsof conception are also expressing a sexual bias in metabolismand physiology. It would then be this bias which would determinethe efficiency of the implantation and growth processes andlead to rates of survival to birth. The speculation arisingfrom this and the experimental manipulation of the sex ratiois that the physiological component most likely to be involvedwould be the lipid compartment with its strong sex difference.     

Nonhomogeneous Deformation in the Anterior Leaflet of the Mitral Valve

In the mitral valve, regional variations in structure and material properties combine to affect the biomechanics of the entire valve. Previous biaxial testing has shown that mitral valve leaflet tissue is highly extensible, and exhibits nonlinear, anisotropic material properties. In this study, experimental measurements of mitral valve leaflet deformation under quasi-static pressure loading were performed on isolated porcine hearts. Biplane video images of markers placed on the anterior leaflet surface were used to reconstruct the 3D position of the markers at several pressure levels over the physiological range. A least-squares finite-element method was used to fit parametric models to the markers and to calculate the deformation over the surface. The results showed that the leaflet deformations were anisotropic, exhibiting a large nonhomogeneous radial stretch and a small circumferential stretch. This information can be used to better understand how the valve deforms under physiological loading, and to help design treatments for valve problems, such as mitral regurgitation.     

CORRELATION OF SKIN POTENTIAL AND SKIN RESISTANCE MEASURES

Simultaneous measurements of skin potential (SP) and skin resistance (SR) obtained from 20 male and 20 female adult subjects during 2 sessions held 2 to 9 days apart were used in studying (1) the correlation of change measurements and prestimulus level in the two measures, and (2) the amount of correlation between SP and SR using both simple difference and residual change scores in which the regression of poststimulus values on initial level (prestimulus) has been controlled. Correlations within Ss and correlations among Ss showed large individual variability, correlation differences between males and females, and high correlation between SP and SR change scores. Although the law of initial value (LIV) seemed to have little applicability to the measurement of electrodermal responses, the results underscored the need to control for contamination of change measures by initial level regardless of direction.     

Remission of persistent childhood asthma: Early predictors of adult outcomes

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不同时间犬缺血心肌对^99Tc^m-MIBI摄取比值的观察

目的：观察犬冠状动脉左旋支狭窄后心肌细胞对^99碍^m-甲氧基异丁基异腈（^99Tc^m-MIBI）摄取与时间变化之间的关系。方法：建立犬冠状动脉左旋支狭窄模型（12只），分别注射^99Tc^m-MIBI，剂量为185MBq（5mCi）。注射1h和4h后，各处死6只犬，取出心脏，于左室侧壁（缺血区）和前壁（正常区）分别取心肌组织约100rag，用1计数器测定其放射性计数，换算成每克组织放射性计数值，求出侧壁与前壁放射性比值。结果：注射后1h犬左心室缺血区与正常区组织放射性计数比值为0．726±O．054，4h为0．673±0．080，两者之间比较差鼻无昂薯件（t=1．3452．P〉0．05）．结论．砸长时问不能摇高按血心肌对辨^99Tc^m-MIBI梧取比．