Aberrant gene expression associated with recurrent pregnancy loss

Recent studies indicate that a number of factors including chromosomal abnormalities, immunological feto-maternal rejection, hormonal irregulation and anatomical factors are involved in provoking recurrent pregnancy loss (RPL). This indicates that normal cellular regulation of these factors is required for maintaining normal pregnancy. In addition, it is expected that biological processes for maintaining normal pregnancy require a series of differential gene expression. As expected, our previous investigations revealed that there are >/=30 genes showing different levels of expression between normal and RPL patients. In addition, other research groups have also identified a number of genes that are expressed aberrantly in pregnancy failure. In this review, recent study on aberrant expression levels of genes, which are grouped as immunity-related, angiogenesis-related, apoptosis-related and other groups of genes, will be discussed.     

Biomechanical assessment with electromyography of post-stroke ankle plantar flexor spasticity

Spasticity has been defined as a motor disorder characterized by a velocity-dependent increase in tonic stretch reflex (muscle tone). Muscle tone consists of mechanical-elastic characteristics, reflex muscle contraction and other elements. The aims of this study were to determine whether to assess spasticity quantitatively, and to characterize biomechanical and electromyographic spasticity assessment parameters. These assessment parameters were described by investigating the correlation between clinical measures and the response to passive sinusoidal movement with consecutive velocity increments. Twenty post-stroke hemiplegic patients and twenty normal healthy volunteers were included in the study. Five consecutive sinusoidal passive movements of the ankle were performed at specific velocities (60, 120, 180, and 240 degrees/ sec). We recorded the peak torque, work, and threshold angle using a computerized isokinetic dynamometer, and simultaneously measured the rectified integrated electromyographic activity. We compared these parameters both between groups and between different velocities. The peak torque, threshold angle, work, and rectified integrated electromyographic activity were significantly higher in the post-stroke spastic group at all angular velocities than in the normal control group. The threshold angle and integrated electromyographic activity increased significantly and linearly as angular velocity increased, but the peak torque and work were not increased in the post-stroke spastic group. Peak torque, work, and threshold angle were significantly correlated to the Modified Ashworth scale, but the integrated electromyographic activity was not. The biomechanical and electromyographic approach may be useful to quantitatively assess spasticity. However, it may also be very important to consider the different characteristics of each biomechanical parameter.     

Facial neglect

Following a stroke, a retired industrial chemist, K.L., complained that faces looked "different" and had become difficult to recognize. Investigation of this problem revealed that it particularly affected the left half of a face as seen by K.L. Defective recognition of this (left) half was found for normal faces, chimaeric faces, and for half-faces presented in isolation, whether upright or inverted. The problem was apparent for both internal and external facial features. Further studies with chimaeric faces demonstrated inattention to left-side features in K.L.'s judgements of facial expression and of resemblance between faces. Moreover, the left-half of a chimaeric face was affected even when it was itself forming part of the face positioned on the right in a display of two horizontally aligned chimaerics. K.L.'s spatial contrast sensitivity function was within normal limits for his age. He did not experience differential difficulty in recognizing the left side of everyday objects or of car-fronts (another stimulus class demanding within-category discrimination between visually similar items that display approximate left-right symmetry). He was also able to sort left or right half-stimuli correctly into the categories "human face", "dog face", or "tree". Although K.L. had a left visual field defect, the problem with faces occurred within otherwise intact parts of his field of vision. We suggest that his disorder can be considered a domain-specific form of unilateral neglect.     

Ferromagnetism and MR imaging: safety of carotid vascular clamps

Metallic extracranial carotid vascular clamps of the Selverstone, Crutchfield, Poppen-Blaylock, Salibi, Kindt, and tantalum varieties have been placed for treatment of large, giant, or inoperable intracranial aneurysms. To ascertain what adverse effect, if any, MR imaging would have on these clamps, magnetic deflection at 1.5 T was measured for various carotid clamps. Marked magnetic deflection (and torque) was displayed by stainless steel Poppen-Blaylock clamps. Relatively mild magnetic deflection was displayed by the stainless steel Selverstone, Salibi, Crutchfield, and Kindt clamps. Three patients with previously placed carotid clamps (two Selverstone, one Salibi) and one patient with a nonferromagnetic tantalum carotid clip had cranial or cervical MR studies at field strengths ranging from 0.35 to 0.60 T. No patient experienced any discomfort or neurologic sequelae as a result of MR imaging. Although the ferromagnetic clamps created severe "black-hole" artifacts and image distortion within the cervical and facial regions, no significant image degradation was apparent during spin-echo imaging of the brain. The tantalum clip created a far smaller MR artifact than did ferromagnetic clamps and allowed effective spin-echo and gradient-echo imaging in the cervical region. Our findings indicate that most patients with carotid vascular clamps (and nonferromagnetic clips) can probably be imaged safely with MR.     

Tumour profile ofN-[2-(dimethylamino)ethyl]acridine-4-carboxamide after intraperitoneal administration in the mouse

N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (AC) is an experimental antitumour agent that is being considered for phase I trials. After i.p. administration of 150 mg/kg [³H]-AC to tumour-bearing mice, AC was absorbed rapidly into the plasma and tissues such as the heart, liver, kidney and brain but more slowly into the s.c. tumour. The maximal AC concentration (86±36 mol/kg) in the tumour occurred at 35–60 min and was 3-fold the maximal plasma concentration, which occurred at 15 min. Although higher maximal concentrations were observed in other tissues, these concentrations fell rapidly in parallel with plasma concentrations. In contrast, AC concentrations in the tumour remained elevated, thet1/2 value (16.3 h) and mean residence time (MRT, 9.5 h) being prolonged in comparison with those in the plasma and other tissues (t1/2 range, 1.0–2.9 h; MRT, 1.2–1.4 h). AC concentrations were not detectable by our high-performance liquid chromatographic (HPLC) method (limit of detection, 0.02 mol/l) in the plasma or other tissues at 24 or 48 h after administration but were measurable in the tumour (1.6±0.8 and 0.6±0.3 mol/kg, respectively). Radioactivity concentrations in the plasma, tissues and tumour were very variable but were greater than the corresponding levels of unchanged parent AC. By 24 h, radioactivity concentrations in the plasma, tissues and tumour had fallen to similar levels with prolonged elimination profiles. Thus, the exposure of the s.c. implanted tumour to a threshold AC concentration for a prolonged time (>24 h) may partly explain the greater efficacy of AC against this tumour, whereas the shorter period of exposure of blood and other tissues may explain its low haematological toxicity.     

Stages of adolescent tobacco-use acquisition

The present study extended the results of previous research in applying the "stages of acquisition" model to the onset of smokeless tobacco as well as cigarette use. Three expert judges classified an initial pool of items as to whether they represented "precontemplation," "contemplation," "action," or "maintenance" stages of smokeless tobacco acquisition. Fifty items with adequate inter-rater reliability were combined with 21 previously developed items pertaining to cigarette smoking acquisition in an overall tobacco acquisition questionnaire, which in turn was administered to 358 junior and senior high public school students. Three distinct components labeled precontemplation, action, and maintenance were delineated through principal component analyses. Coefficient alphas and discriminant analyses according to self-reported use demonstrated adequate reliability and validity for the new smokeless tobacco- and previously developed smoking-acquisition scale.     

The Liposome as a Model Membrane in Correlations of Partitioning with α-Adrenoceptor Agonist Activities

The apparent partition coefficients of a group of imidazoline -adrenoceptor agonists in liposome/buffer systems (K_m) and in the n-octanol/buffer system (P) have been compared in quantitative structure–activity relationships (QSAR) employing biological activities and receptor binding affinities. A parabolic relationship between log K _m and log P was found, and log K _m was greater than log P for all liposome compositions. In liposomes, log K _m decreased in the order, negatively charged > neutral > positively charged. Overall, hyper- and hypotensive activities of these drugs correlated better with log K _m than with log P; however, poor correlations were obtained between partition coefficients and in vitro binding affinities. Linear correlations of log K _m with hypotensive activities were obtained with negatively charged liposomes, whereas correlations with hypertensive activities were obtained using positively charged liposomes. Multiple regressions of biological activities with binding affinities showed positive correlations with hypotensive but not hypertensive activities with or without the inclusion of log K _m or log P. Thus, the liposome represents a more selective model membrane system than a bulk oil phase for predicting the biological activities of imidazoline -adrenoceptor agonists.     

Temporal Bone Histopathology in Connexin 26–Related Hearing Loss

Objective: Mutations in GJB2, a gene that encodes a gap junction protein, Connexin 26 (Cx26), are responsible for approximately one third of sporadic severe‐to‐profound or profound congenital deafness and half of severe‐to‐profound or profound autosomal recessive nonsyndromic hearing loss (ARNSHL). Mouse mutants homozygous for knockouts of this gene are nonviable, precluding histopathologic studies of the associated inner ear pathology in this animal model. Therefore, we studied archival temporal bone sections to identify temporal bone donors with Cx26‐related deafness. Study Design: Temporal bone donors with a history of congenital severe‐to‐profound or profound deafness were identified in the registry of the Temporal Bone Library at the University of Iowa. Histological findings were interpreted in a blinded fashion. DNA extracted from two celloidin‐embedded mid‐modiolar sections from each temporal bone was screened for the 35delG Cx26 mutation. The entire coding region of Cx26 was screened for other deafness‐causing mutations if the 35delG mutation was detected. Results: Of five temporal bone donors with congenital severe‐to‐profound deafness, one donor was found to have Cx26‐related deafness. This individual was a Cx26 compound heterozygote, carrying the 35delG mutation and a noncomplementary Cx26 missense mutation on the opposing allele. Microscopic evaluation of this temporal bone showed no neural degeneration, a good population of spiral ganglion cells, near‐total degeneration of hair cells in the organ of Corti, a detached and rolled‐up tectorial membrane, agenesis of the stria vascularis, and a large cyst in the scala media in the region of the stria vascularis. Conclusion: This study is the first to report the temporal bone histopathology associated with Cx26‐related deafness. Preservation of neurons in the spiral ganglion suggests that long‐term successful habilitation with cochlear implants may be possible in persons with severe‐to‐profound or profound Cx26‐related deafness.