Mechanisms for the transendothelial migration of HIV-1-infected monocytes into brain

HIV-1 penetration of the brain is a pivotal event in the neuropathogenesis of AIDS-associated dementia. The establishment of productive viral replication or up-regulation of adhesion molecule expression on brain microvascular endothelial cells (BMVEC) could permit entry of HIV into the central nervous system. To investigate the contribution of both, we inoculated primary human BMVEC with high titer macrophage-tropic HIV-1 or cocultured them with virus-infected monocytes. In both instances, BMVEC failed to demonstrate productive viral replication. Cell to cell contact between monocytes and microvascular endothelium resulted in E-selectin expression on BMVEC. BMVEC. cocultured with LPS-activated HIV-infected monocytes expressed even higher levels of E-selectin and vascular cell adhesion molecule-1 (VCAM-1). Transwell assays supported a role of soluble factors, from virus-infected monocytes, for the induction of adhesion molecules on BMVEC. To verify the in vivo relevance of these findings, levels of adhesion molecules were compared with those of proinflammatory cytokines and HIV-1 gene products in brain tissue of AIDS patients with or without encephalitis and HIV-seronegative controls. E-Selectin, and to a lesser degree VCAM-1, paralleled the levels of HIV-1 gene products and proinflammatory cytokines in brain tissue of subjects with encephalitis. Most importantly, an association between macrophage infiltration and increased endothelial cell adhesion molecules was observed in encephalitic brains. Monocyte binding to encephalitic brain tissue was blocked with Abs to VCAM-1 and E-selectin. These data, taken together, suggest that HIV entry into brain is, in part, a consequence of the ability of virus-infected and immune-activated monocytes to induce adhesion molecules on brain endothelium.     

The effect of erythromycin on motility of the duodenum, sphincter of Oddi, and gallbladder in the prairie dog

Over the past 9 years, the fertility potential for men with spinal cord injury and other neurological impairments has improved. Approximately 80% of men with spinal cord injury have semen (collected either by vibration or by electroejaculation using rectal probe) of sufficient quality to use in intrauterine insemination or in vitro fertilization. Assuming that other factors are equal, it would seem that length or level of injury are not dominating factors that control the quality of semen from these men.     

Effects of post-deposition annealing on the electrical propertiesand reliability of ultrathin chemical vapor deposited Ta2O5 films

This paper reports the effects of post-deposition rapid thermal annealing on the electrical characteristics of chemical vapor deposited (CVD) Ta₂O₅ (~10 nm) on NH₃-nitrided polycrystalline silicon (poly-Si) storage electrodes for stacked DRAM applications. Three different post-deposition annealing conditions are compared: a) 800°C rapid thermal O₂ annealing (RTO) for 20 sec followed by rapid thermal N₂ annealing (RTA) for 40 sec, b) 800°C RTO for 60 sec and c) 900°C RTO for 60 see. Results show that an increase in RTO temperature and time decreases leakage current at the cost of capacitance. However, over-reoxidation induces thicker oxynitride formation at the Ta₂O₅/poly-Si interface, resulting in the worst time-dependent dielectric breakdown (TDDB) characteristics     

Sibling visitation: how far should the pendulum swing?

This study describes development of early interaction between siblings. Subjects (N = 22) were the older siblings (30 to 52 months) of healthy new babies. Data were collected to describe initial contact, regressive behaviors, and extent and quality of sibling interaction at 3 weeks, 5 months, and 7 months. Patterns of visualization, touch, and communication were observed. There was no evidence of sibling regressive behavior. Behaviors were more positive than negative and older siblings were in proximity for initiation of interaction by the new baby at 5 and 7 months. Findings indicate positive sibling relationships may be the norm rather than the exception.     

Suppression of natural killer cell activity in mouse spleen lymphocytes by several dopamine receptor antagonists

Glomerular diseases are associated with changes in glomerular membrane permeability properties that alter filtration rate of plasma water and barrier function of the capillary wall. To estimate intrinsic permeability properties that regulate transmembrane transport of water and macromolecules, theoretical analysis of renal clearance of tracer molecules can be used. The development of adequate theoretical models is required to achieve sufficient accuracy to simulate complicated biological processes. Current research in this area is aimed at improving and validating the presently available models in order to characterize the nature of permeability changes associated with pathological conditions. This is a key step in understanding the pathophysiological nature of glomerular diseases and in the development of effective treatments.     

The effect of femoral component position on the kinematics of total knee arthroplasty

In a laboratory study using seven fresh-frozen anatomic specimen knees, the effect of total knee arthroplasty on the three-dimensional kinematics of the patella, femur, and tibia were measured. Experiments were performed in the intact knee, after division of the anterior cruciate ligament (ACL), after total knee arthroplasty, and after 10 degrees internal rotation, 10 degrees external rotation, 5-mm medial shift, and 5-mm lateral shift of the femoral component on the femur. The presence of a high lateral ridge on the anterior surface of the femoral component effectively prevented patellar subluxation or dislocation, but displaced and tilted the patella medially. Internal rotation or medial displacement of the femoral component exaggerated this medial patellar displacement and shift. External rotation of the femoral component corrected it, except at flexion angles greater than 100 degrees, where the femur was shifted medially on the tibia and externally rotated 15 degrees. This combination produced a net 10-mm medial displacement of the patella relative to the tibia at 120 degrees knee flexion. Lateral placement of the femoral component compensated for the effect of the high lateral ridge and allowed more normal patellar tracking while allowing tibiofemoral motions similar to those seen after sectioning of the ACL. The kinematics of the patellofemoral and tibiofemoral joints were not reproduced with a total knee prosthesis that sacrifices the ACL. When using a prosthesis with a high lateral ridge, lateral placement of a femoral component prevented patellar dislocation and allowed patellar tracking patterns similar to those seen in the intact knee without further altering tibiofemoral motions.     

Minor head injury in children: current management practices of pediatricians, emergency physicians, and family physicians

OBJECTIVE: To describe variation in the clinical management of minor head trauma in children among primary care and emergency physicians. DESIGN: A survey of pediatricians, family physicians, and emergency physicians drawn from a random sample of members of the American Academy of Pediatrics, the American Academy of Family Physicians, and the appropriate American Medical Association specialty listings, respectively. Physicians were given clinical vignettes describing children presenting with normal physical examination results after minor head trauma. Different clinical scenarios (brief loss of consciousness or seizures) were also presented. Information was gathered on initial and subsequent management steps most commonly used by the physician. RESULTS: Surveys were returned by 765 (51%) of 1500 physicians. Of these, 303 (40%) were pediatricians, 269 (35%) family practitioners, and 193 (25%) emergency physicians. For minor head trauma without complications, observation at home was the most common initial physician management choice (n = 547, 72%). Observation in office or hospital was chosen by 81 physicians (11%). Head computed tomographic (CT) scan was chosen by 7 physicians (1%) and skull x-ray by 24 physicians (3%) as the first management option. Most physicians (n = 445, 80%) who initially chose observation at home would obtain a CT scan if the patient showed clinical deterioration. In the original scenario, if the patient had also sustained a loss of consciousness, 383 physicians (58%) altered management. Of these, 120 (18%) chose CT, 13 (2%) chose skull x-ray, 1 (1%) chose magnetic resonance imaging, 141 (21%) chose inpatient observation, and 125 (19%) chose a combination of CT scanning and observation. With seizures, 595 (90%) altered management, with 176 physicians (27%) choosing CT scan, 5 (1%) skull x-ray, 60 (9%) inpatient observation, and 299 (45%) a combination of radiological evaluation and observation. CONCLUSIONS: Most physicians surveyed chose clinic or home observation for initial management of minor pediatric head trauma. Clinical management was more varied when patients had sustained either loss of consciousness or seizures. Further study of the appropriate management of minor head trauma in children is needed to guide physicians in their care.     

Margatoxin increases dopamine release in rat striatum via voltage-gated K+ channels

The distribution of iodinated margatoxin ([125I]margatoxin) binding sites in rat was investigated by autoradiography. Rat striatum expresses a high density of margatoxin binding sites and, therefore, the effects of margatoxin, charybdotoxin and iberiotoxin have been studied on [3H]dopamine release from rat striatal slices in vitro. Margatoxin (0.1-100 nM) and charybdotoxin (10-1000 nM), but not iberiotoxin increased the spontaneous and the electrically evoked [3H]dopamine release. [3H]dopamine release by margatoxin was inhibited by tetrodotoxin and omega-conotoxin GVIA, but not by atropine, naloxone, N(omega)-nitro-L-arginine and neurokinin or neurotensin receptor antagonists. In the buffer solution used for release experiments, [125I]margatoxin labels a maximum of 0.12 pmol of sites/mg protein in rat striatal membranes with a Kd of 5 pM. [125I]margatoxin binding was inhibited by margatoxin (Ki of 4 pM), charybdotoxin (Ki of 162 pM) but not by iberiotoxin. We conclude that inhibition of margatoxin-sensitive voltage-gated K+ channels increases [3H]dopamine release demonstrating their role in repolarization of nigrostriatal projections. In contrast, iberiotoxin-sensitive, high-conductance Ca2+-activated K+ channels are not involved in release of [3H]dopamine.