Development of an apparatus to evaluate Adolescent Idiopathic Scoliosis by dynamic surface topography.

For cases of Adolescent Idiopathic Scoliosis (AIS), commonly the first indicator is a change in the surface shape of the back over time. A proportion of patients so diagnosed require surgical intervention to prevent further progression and to improve cosmesis. The results of a preliminary literature survey have revealed that significant work has already been published on the static acquisition and analysis of back surface shape. There is new interest in establishing correlations between breathing, posture, the underlying spinal deformity and changes in the surface topography of the back during clinical sessions together with an increased focus on the impact of the cosmetic defect on the patient and in the measurement of pre and post-operative dynamic capability.The continuing development of an apparatus based on established optical motion capture technologies, that generates a sequence of tri-dimensional images and provides measurements derived from changes in the position of anatomical reference landmarks and of the surface topography of the back will be presented. If, using the same landmarks, the trunk range of motion could be captured concurrently, it is hoped that the resulting data would form the basis of a useful clinical study.

Specific and effective interaction of a guanine nucleotide analogue with small G proteins.

G proteins are molecular switches that use a cycle of GTP binding and hydrolysis to regulate a wide variety of cellular biochemical processes. Because the functional state of these proteins is allosterically determined by bound guanine nucleotides, a nucleotide analogue with protein specificity might have pharmacological or biochemical value. The binding of [alpha-32P]GTP to four small G proteins immobilized on nitrocellulose was competed by a series of analogues with modifications at multiple sites. One analogue, N2-(p-n-butylphenyl)guanosine 5'-(beta,gamma-difluoromethylene)triphosphate, had a approximately 40-fold higher affinity for one small G protein than for two of the others. Systematic analysis of each modification in the synthetic nucleotide revealed that specificity was conferred by the carbon substitution in the beta,gamma-phosphoanhydride bond. These observations were then extended to purified proteins of known sequence in solution by filtration binding studies with H-ras and rab5. Ras was 9-fold more discriminant between guanosine-5'-(beta,gamma-difluoromethylene)triphosphate and guanosine-5'-O-(3-thiotriphosphate) than was rab5, and the Q79L GTPase-defective mutant of rab5 was 6-fold more discriminant than wild-type rab5. Guanosine-5'-(beta,gamma-difluoromethylene)triphosphate protected a 20-kDa fragment of rab5 from tryptic proteolysis with greater efficacy than guanosine-5'-O-(3-thiotriphosphate) or guanosine-5'-(beta,gamma-imido)triphosphate despite its lower affinity, and GMP stabilized a conformation indistinguishable from apo-rab5. These results identify a synthetic guanine nucleotide analogue with differential affinity for closely related G proteins, determine the atomic substitution in the analogue that confers specificity, demonstrate discrimination by the analogue between wild-type and a point-mutant G protein, and establish efficacy of the analogue in inducing conformational change of a target protein disproportionate to the affinity of the interaction.

Life-threatening pulmonary hemorrhage with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia.

The occurrence of significant pulmonary hemorrhage associated with pulmonary arteriovenous malformations (PAVMs) and hereditary hemorrhagic telangiectasia (HHT) and the incidence of PAVMs in family members of patients with PAVMs and HHT are poorly defined. We reviewed our experience in 143 patients with PAVMs and HHT. Eleven (8 percent) of the 143 patients with HHT and PAVMs had a history of either massive hemoptysis or of hemothorax which required hospitalization. One patient died directly related to the pulmonary hemorrhage. There were four men and seven women. Three of the seven women experienced pulmonary hemorrhage during pregnancy. Seven of the 11 families participated in screening for PAVMs. Thirty-six (80 percent) of the 45 screened family members were found to have HHT. Thirteen (36 percent) of the 36 family members with HHT were proven to have PAVMs by pulmonary angiography. Pulmonary hemorrhage due to spontaneous rupture of the PAVM is a potentially life-threatening complication that should be treated aggressively with transcatheter embolotherapy. It occurs more frequently than previously recognized in patients with PAVMs and HHT. In addition, because of the increased incidence of PAVMs in family members of patients with HHT and PAVM, screening of family members with HHT is recommended especially in women of childbearing age.

Identification of ras and ras-related low-molecular-mass GTP-binding proteins associated with rat lung lamellar bodies.

Recent evidence from genetic experiments in yeast and from studies using guanosine triphosphate (GTP) analogues in mammalian cells suggests a key role for low-molecular-mass GTP-binding proteins (LMM-GBPs) (Mr 19 to 28 kD) in processes of intracellular vesicular sorting and secretion. Assembly and exocytosis of the lamellar body (LB), the secretory organelle of the pulmonary alveolar type 2 pneumocyte, may be regulated by LMM-GBPs. We used [alpha-32P]GTP binding to Western blotted proteins, ultraviolet crosslinking of [alpha-32P]GTP to membrane proteins, immunoblotting with specific antisera, and botulinum exoenzyme C3-catalyzed ADP ribosylation to detect LMM-GBPs in LB. With the first two techniques, we have identified six LMM-GBPs of approximately 27, 25.5, 24.5, 23, 22, and 21 kD that are enriched in a highly purified LB fraction compared with type 2 pneumocyte homogenate, crude membranes, and cytosol. Further characterization of the LB LMM-GBPs by immunoblotting revealed that ras p21 is greatly enriched in the LB fraction compared with other type 2 pneumocyte fractions. In addition, botulinum exoenzyme C3 catalyzed the ADP ribosylation of 20- to 21-kD proteins that were similarly enriched in the LB fraction. In contrast, a monospecific antibody to ADP-ribosylation factor reacted with a 19-kD protein only in the type 2 pneumocyte homogenate and cytosol fractions. Monospecific antibodies to yeast Sec4 protein and to rab 3A did not react with any type 2 pneumocyte proteins. The LMM-GBPs specifically associated with LB may participate in intracellular events required for surfactant packaging and secretion.

Noncardiac manifestations of rheumatoid arthritis in the thorax.

The noncardiac manifestations of rheumatoid arthritis (RA) in the thorax are complex and varied. The bony thorax, pleura, lung parenchyma, tracheobronchial tree, larynx, an upper airway can all be sites of disease. Drug therapy for RA can result in thoracic disease that is difficult to distinguish from the manifestations of RA itself. This article reviews the available literature pertinent to noncardiac thoracic manifestations of RA and focuses on clinical and radiographic presentations in order to provide an organized approach to patient care.

The inhibition of dictyosome vesicle formation in higher plant cells by cytochalasin D.

We have examined the effect of cytochalasin D on secretory processes in plant root tips and pollen tubes. While confirming that inhibition of vesicle transport is the immediate effect of the drug, we now present quantitative evidence to show that vesicle formation by elements of the Golgi apparatus in plants, the dictyosomes, is progressively inhibited. Total inhibition of vesicle formation occurs within exposure times ranging from one-half to two hours. It is concluded that vesicle formation is a cytochalasin-sensitive process.