Polyenes and vision

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT, E.C.2.4.2.8) from Artemia cysts exhibits maximum activity at 70 degrees C. Its thermal stability has been examined following enzymatic activity as a function of temperature. Cold-induced renaturation experiments of samples heated at increasing temperatures showed that reversibility of thermal inactivation depends on the incubation time and final temperature. Prolonged incubation of the thermoinactivated enzyme at 0 degree C did not afford any further increase of the catalytic activity at 37 degrees C. The complex substrate PRPP:Mg protects HGPRT from thermal inactivation. However, incubations with hypoxanthine rendered a less thermostable enzyme at any temperature tested. The irreversible inactivation of HGPRT proceeds in two exponential steps. The analysis of the apparent rate constants for the fast and the slow phases, lambda 1 and lambda 2 as per the Lumry and Eyring model suggests the existence of more than three states in the thermal denaturation pathway of the free enzyme. In the presence of PRPP:Mg the irreversible process follows a single exponential and proceeds very slowly below 70 degrees C. PRPP:Mg also protects the enzyme from inactivation by NEM and pCMB, suggesting that -SH groups may be in the vicinity of the active site.     

Noninvasive assessment of regional ventilation in the human lung using oxygen-enhanced magnetic resonance imaging

The imaging of regional ventilation in the lungs is essential for the evaluation of a variety of pathological conditions, such as emphysema, pneumonia and pulmonary embolism. We propose a novel approach for ventilation scanning, using magnetic resonance imaging (MRI) and inhaled molecular oxygen as a contrast agent, that directly depicts transfer of oxygen across the alveolus into the pulmonary vasculature. Molecular oxygen is only weakly paramagnetic but produces substantial signal changes in the lungs because of their large surface area. Ventilation defects were shown in a patient with bullous emphysema, and ventilation-perfusion mismatches were shown in two patients with pulmonary embolism.     

High levels of ascorbic acid, not glutathione, in the CNS of anoxia-tolerant reptiles contrasted with levels in anoxia-intolerant species

Ascorbic acid and glutathione (GSH) are antioxidants and free radical scavengers that provide the first line of defense against oxidative damage in the CNS. Using HPLC with electrochemical detection, we determined tissue contents of these antioxidants in brain and spinal cord in species with varying abilities to tolerate anoxia, including anoxia-tolerant pond and box turtles, moderately tolerant garter snakes, anoxia-intolerant clawed frogs (Xenopus laevis), and intolerant Long-Evans hooded rats. These data were compared with ascorbate and GSH levels in selected regions of guinea pig CNS, human cortex, and values from the literature. Ascorbate levels in turtles were typically 100% higher than those in rat. Cortex, olfactory bulb, and dorsal ventricular ridge had the highest content in turtle, 5-6 mumol g-1 of tissue wet weight, which was twice that in rat cortex (2.82 +/- 0.05 mumol g-1) and threefold greater than in guinea pig cortex (1.71 +/- 0.03 mumol g-1). Regionally distinct levels (2-4 mumol g-1) were found in turtle cerebellum, optic lobe, brainstem, and spinal cord, with a decreasing anterior-to-posterior gradient. Ascorbate was lowest in white matter (optic nerve) in each species. Snake cortex and brainstem had significantly higher ascorbate levels than in rat or guinea pig, although other regions had comparable or lower levels. Frog ascorbate was generally in an intermediate range between that in rat and guinea pig. In contrast to ascorbate, GSH levels in anoxia-tolerant turtles, 2-3 mumol g-1 of tissue wet weight, were similar to those in mammalian or amphibian brain, with no consistent pattern associated with anoxia tolerance. GSH levels in pond turtle CNS were significantly higher (by 10-20%) than in rat for several regions but were generally lower than in guinea pig or frog. GSH in box turtle and snake CNS were the same or lower than in rat or guinea pig. The distribution GSH in the CNS also had a decreasing anterior-to-posterior gradient but with less variability than ascorbate: levels were similar in optic nerve, brainstem, and spinal cord. The paradoxically high levels of ascorbate in turtle brain, which has a lower rate of oxidative metabolism than mammalian, suggest that ascorbate is an essential cerebral antioxidant. High levels may have evolved to protect cells from oxidative damage when aerobic metabolism resumes after a hypoxic dive.     

Implanted functional electrical stimulation hand system in adolescents with spinal injuries: an evaluation

OBJECTIVE: To study the utility and functional benefits of an implanted functional electrical stimulation (FES) system for hand grasp and release in adolescents with tetraplegia secondary to spinal cord injuries. DESIGN: Intervention study with before-after trial measurement with each subject as his or her own control. SETTING: Nonprofit pediatric orthopedic rehabilitation facility specializing in spinal cord injury. PARTICIPANTS: A convenience sample of five adolescents between 16 and 18 years of age with C5 or C6 level tetraplegia at least 1 year after traumatic spinal cord injury. Key muscles for palmar and lateral grasp and release were excitable by electrical stimulation. INTERVENTIONS: A multichannel stimulator/receiver and eight electrodes were surgically implanted to provide stimulated palmar and lateral grasp and release. In conjunction with implantation of the FES hand system, surgical reconstruction in the form of tendon transfers, tendon lengthenings and releases, and joint arthrodeses was performed to augment stimulated hand function. Rehabilitation of the tendon transfers and training in the use of the FES hand system were provided. MAIN OUTCOME MEASURES: Measurements of pinch and grasp force, the Grasp and Release Test (GRT), and an assessment of six activities of daily living (ADL) were administered before implantation of the FES hand system and at regular follow-up intervals. Results of the stimulated response of individual muscles and surgical reconstruction were evaluated using standard and stimulated muscle testing techniques and standard assessment of joint range of motion. All subjects completed followup testing. RESULTS: Lateral and palmar forces were significantly greater than baseline forces (p = .043). Heavy objects on the GRT could only be manipulated with FES, and FES increased the level of independence in 25 of 30 ADL comparisons (5 subjects, 6 activities) as compared to baseline. After training, FES was preferred in 21 of 30 comparisons over the typical means of task completion. Of the 40 electrodes implanted, 37 continue to provide excellent stimulated responses and all of the implanted stimulators have functioned without problems. The surgical reconstruction procedures greatly enhanced FES hand function by either expanding the workspace in which to utilize FES (deltoid to triceps transfer), stabilizing the wrist (brachioradialis to wrist extensor transfer), or stabilizing joints (intrinsic tenodesis transfer, FPL split transfer). CONCLUSION: For five adolescents with tetraplegia, the combination of FES and surgical reconstruction provided active palmar and lateral grasp and release. Laboratory-based assessments demonstrated that the FES system increased pinch force, improved the manipulation of objects, and typically increased independence in six standard ADL as compared to pre-FES hand function. The study also showed that the five adolescents generally preferred FES for most of the ADL tested. Data on the benefits of the implanted FES hand system outside of the laboratory are needed to understand the full potential of FES.     

Management of lymphoproliferative disorders after cardiac transplantation

We conducted a retrospective study of 516 cardiac recipients who underwent transplantation between April 1983 and April 1992, 19 of whom had development of post-transplantation lymphoproliferative disorders (PTLDs). These 19 patients presented with involvement of lung (5), gastrointestinal tract (5), disseminated disease (6), and adenoids and lymph nodes (3). B-cell proliferations ranging from an atypical hyperplasia to malignant lymphoma developed in 18 patients, and mixed cellularity Hodgkin's disease developed in 1 patient. The 19 patients with PTLD displayed a predominance of both women and cardiomyopathy as the indication for transplantation when compared with two separate control populations. No correlation was found between demographic criteria analyzed and (1) early versus late diagnosis of PTLD after transplantation, (2) the site of PTLD involvement, or (3) the histopathologic category of the PTLD lesion. Patients with gastrointestinal tract and lung PTLD involvement enjoyed an improved survival after both transplantation and PTLD diagnosis when compared with patients with PTLD involvement of all other extranodal sites. We report a high incidence of PTLD involving the lung and gastrointestinal tract in our cohort study. These sites of involvement responded better to a reduction in immunosuppression than did the other extranodal sites of involvement.     

An extended HLA-DQ-DR haplotype rather than DRB1 alone contributes to RA predisposition

A family with 1 case of retinitis pigmentosa (III-1) and 2 cases of Oguchi's disease (III-2, 3) was examined in terms of electrophysiology as well as molecular biology. The proband (III-3), a 42-year-old female, and 2 older brothers (III-1, 2, aged 52 and 45 years) and 2 unaffected members in the same family participated in this study. Corrected visual acuities of the individuals with Oguchi's disease (III-2, 3) were 1.2. On funduscopy, blood vessels stood out in relief against a metallic-appearing background and a Mizuo-Nakamura phenomenon was evident. Full-field electroretinograms (ERGs) recorded from the proband were indicative of rod dystrophy, but results of other electrophysiological examinations (multifocal ERG, pattern ERG and visual-evoked cortical potential recordings) were within normal limits. Patient III-1 had corrected visual acuities of RE 20 cm/m.m. and LE 30 cm/n.d., severe chorioretinal atrophy in both fundi, and full-field ERG revealed rod-cone dystrophy. Mutation of the arrestin gene (1147de1A) was detected in all 3 patients. Visual function in each patient coincides with that of retinitis pigmentosa or Oguchi's disease, respectively.     

Primary traits of Eysenck's P-E-N system: three- and five-factor solutions

The Eysenck Personality Profiler (EPP), a set of 21 scales measuring primary traits hypothesized to be definers of Neuroticism, Extraversion, and Psychoticism factors, was administered to 229 adults together with the Eysenck Personality Questionnaire--Revised (H. J. Eysenck & S. B. G. Eysenck, 1991) and the Revised NEO Personality Inventory (NEO-PI-R; P. T. Costa & R. R. McCrae, 1992b). Correlations of EPP scales with NEO-PI-R facet scales provided preliminary evidence supporting the convergent and discriminant validity of the EPP scales. However, varimax and targeted validimax factor analyses suggested that some EPP scales were misclassified and that EPP scales could better be understood in terms of the 5-factor model than the intended 3-factor model.