CD44 and tenascin play critical roles in growth and vascular development of the chick chorioallantoic membrane and are targets of cigarette smoke.

Chorioallantoic membranes (CAMs) were used to determine which extracellular matrix molecules play essential roles in growth and vascular development in vivo and whether expression of critical molecules is affected by cigarette smoke exposure. Treatment of CAMs on day 5 of development with antibodies to CD44 or tenascin, but not to other matrix molecules, inhibited CAM growth and affected various aspects of blood vessel development including normal growth and branching of vessels, migration of vessels, and formation and differentiation of the capillary plexus. DNA synthesis was inhibited by antibodies to both C44 and tenascin which probably accounted for many of the phenotypic changes observed in treated CAMs. CD44 was located on all cells in day 5 CAMs, and tenascin, while present throughout the CAM, was especially abundant around large, non-migratory mesodermal blood vessels and endodermal cells that were positioned away from the direction of blood vessel migration. These data suggest that while tenascin is required for normal blood vessel migration, high levels of tenascin inhibit migration. The different distributions of CD44 and tenascin in CAMs and the observation that antibodies to either CD44 or tenascin produced similar phenotypes indicate that CD44 and tenascin were not functionally redundant. Mainstream smoke solutions, which produce a phenotype similar to that seen with anti-tenascin and anti-CD44, inhibited expression of CD44 mRNA and increased tenascin mRNA expression. 3-Ethylpyridine, a chemical in cigarette smoke that produced changes in CAM development similar to anti-CD44 and anti-tenascin treatment, also increased tenascin mRNA expression, but did not affect CD44. Together these data show that tenascin and CD44 play critical roles in early growth and vascular development of the CAM and support the idea that 3-ethylpyridine in mainstream smoke impairs CAM growth and vascular development by targeting expression of tenascin. 3-Ethylpyridine is generally regarded as safe and is used in many consumer products including food and tobacco.

Normal patterns of angiogenesis and extracellular matrix deposition in chick chorioallantoic membranes are disrupted by mainstream and sidestream cigarette smoke.

The adverse effects of cigarette smoke on mature blood vessels are well established, whereas little is known about the influence of smoke on blood vessel development. To determine if cigarette smoke alters angiogenesis, chick chorioallantoic membranes (CAMs) were exposed for 4 days to culture medium (control) or to mainstream (MS) or sidestream (SS) smoke solution, and then blood vessel patterns were compared in blind tests. In contrast to the normal tree-like branching of control blood vessels, smoke-treated CAMs often had vessels that ran parallel to each other without much branching. A significant increase in the number of fibroblasts was observed in histological sections of treated CAMs, and this increase correlated with alterations in extracellular matrix components. Many more matrix fibrils were observed in treated CAMs than in controls using scanning electron microscopy. Immunohistochemistry showed that type III collagen was distributed in a tight band adjacent to the endoderm in controls but was distributed throughout the mesoderm in both treatment groups. Western blots confirmed that both type I and type III collagen were more abundant in treated CAMs than in controls. Fibronectin, which was localized immunohistochemically in the basal laminae and mesodermal matrix of controls, increased in abundance in CAMs treated with SS smoke solutions. Hyaluronic acid, which was present in a dense band subjacent to the capillary plexus of control CAMs, was greatly reduced in MS-treated CAMs and was absent in SS-treated CAMs. These observations demonstrate that both MS and SS cigarette smoke solutions caused abnormal pattern formation of CAM blood vessels and altered the composition of the extracellular matrix in the CAM mesoderm.

Rapid assessment of radiobiological doses for terrestrial and interplanetary space missions.

This paper presents the doses levels expected in orbits in chart form, covering the range 300-800 km of altitude and 0-90 degrees of inclination behind shieldings similar to the Hermes spacecraft and the EVA spacesuit matter distributions. These charts allow users to rapidly find the radiobiological dose received in the most critical organs of the human body either in normal situations or during a large solar event. Outside the magnetosphere, during interplanetary or lunar missions, when the dose received during crossing of the radiation belts become negligible, the dose is due to galactic cosmic rays (GCR) and solar flares. The correct radiobiological assessment of the components of this radiation field becomes a major problem. On the Moon a permanent ground-based station can be shielded by lunar materials against meteoroids and radiations. The radiobiological hazard, essentially linked to the solar flare risk during the transfer phase and the extra-station activities, may be solved by mission planning. For interplanetary flights the problem comes from both increased risk of solar events and from the continuous exposure to GCR. These energetic particles cannot be easily stopped by shieldings; cost considerations imply that more effective materials must be used. Impact on the vehicle design and the mission planning is important.

Autosomal dominant familial spastic paraplegia: description of a large New England family and a study of management.

A large New England family with autosomal dominant familial spastic paraplegia (ADFSP) is described. In a pedigree of 173 family members, 71 affected individuals were identified. 16 cases examined by the authors are described with regard to the natural history of ADFSP in this family, and a staging system for following progress and planning interventions is proposed. Three illustrative cases are presented. In this family, ADFSP was found to have a homogeneous clinical course, with nearly complete penetrance. Onset, with involvement limited to the lower extremities, occurred by three years of age, after which no significant progression was noted. Early, aggressive habilitative care may result in more functional ambulation for the youngest family members.

Postoperative electromyographic function of tendon transfers in patients with cerebral palsy.

Electromyographic studies were performed on 13 patients with cerebral palsy before and after flexor carpi ulnaris transfers. No changes in activity of the extensor digit communis were noted in the transferred muscles. This further validates the rationale of pre-operative planning based on such studies.

Autosomal dominant familial spastic paraplegia: report of a large New England family.

A large New England family with autosomal dominant familial spastic paraplegia is described. In a pedigree of 173 individuals, 71 affected individuals are identified. Seventeen cases examined by the authors are described with regard to the natural history of FSP in this family. A staging system for following progress and planning interventions is proposed. Three illustrative cases are presented. In this family, FSP is found to have a homogeneous clinical course with nearly complete penetrance. Onset occurs at or before 3 years of age with involvement limited to the lower extremities. After the initial onset, no significant progression was noted. Early aggressive habilitative care may result in more functional ambulation.

Radiation protection of astronauts in LEO.

Radiological protection for space flights is often perceived as a technico-scientific problem. All this is the result of the effects of radiation encountered in space and manned flight conditions. The main characteristics of this radiation come from its complex composition and its large energy spectrum which must be taken into account as well as flux variations by both solar activity and the vehicle position on orbit. Inside a vehicle, structures constitute irregularly distributed shields and lead to a specific dose at each location. To be able to protect the crew, it is first necessary to understand the threat and therefore to identify the radiation environment: extraterrestrial and orbital. As the environment varies with both the orbit position and time, the dose received in each critical organ during missions must be determined and compared with acceptable limits. To counter the threat, which may exceed acceptable limits, a strategy is required, including the complementary aspects of prevention, detection, protection and possibly treatment.

Dynamic gait electromyography study in Duchenne muscular dystrophy (DMD) patients.

Preoperative and postoperative dynamic gait electromyography (EMG) weas performed on 15 patients 8 to 13 year of age with Duchenne's muscular dystrophy who underwent Achilles tendon lengthening and posterior tibial tendon transfer anteriorly through the interosseous ligament for correction of equinus and equinovarus foot deformities. The muscles tested preoperatively (anterior tibial, soleus, gastrocnemius, posterior tibial, peroneal longus, and peroneal brevis) showed phase changes. It is believed that patients with weakened leg muscles fire multiple muscle groups out of phase in an attempt to overcome the action of the stronger muscles, thus stabilizing the limb for ambulation. Postoperative EMGs, performed with the patients walking in long leg braces after the deformity had been corrected, showed little activity in the muscles tested. As the patients became dependent on the brace, the need for the muscles to be active out of phase was eliminated. The transferred posterior tibial muscle appeared to be active both clinically and electromyographically.

Dynamic electromyography and decision-making for surgery in the upper extremity of patients with cerebral palsy.

Seventeen children with cerebral palsy were selected for improvement in upper extremity function. Each had normal or nearly normal intelligence; each hand had good or mildly impaired sensibility; each arm had relatively good placement. Electromyograms with wire electrodes were utilized to study the patterns of activity of the planned tendon transfers. Only muscles with isolated activity in grasp were utilized to transfer in hands with weak grasp. Only muscles with isolated activity in release were utilized to transfer in hands with poor release.