An analysis of simultaneous variation in protein structures

The simultaneous substitution of pairs of buried amino acid side chains during divergent evolution has been examined in a set of protein families with known crystal structures. A weak signal is found that shows that amino acid pairs near in space in the folded structure preferentially undergo substitution in a compensatory way. Three different physicochemical types of covariation 'signals' were then examined separately, with consideration given to the evolutionary distance at which different types of compensation occur. Where the compensatory covariation tends towards retaining the combined residue volumes, the signal is significant only at very low evolutionary distances. Where the covariation compensates for changes in the hydrogen bonding, the signal is strongest at intermediate evolutionary distances. Covariations that compensate for charge variations appeared with equal strength at all the evolutionary distances examined. A recipe is suggested for using the weak covariation signal to assemble the predicted secondary structural elements, where the evolutionary distance, covariation type and weighting are considered together with the tertiary structural context (interior or surface) of the residues being examined.      

Pain affect encoded in human anterior cingulate but not somatosensory cortex

Recent evidence demonstrating multiple regions of human cerebral cortex activated by pain has prompted speculation about their individual contributions to this complex experience. To differentiate cortical areas involved in pain affect, hypnotic suggestions were used to alter selectively the unpleasantness of noxious stimuli, without changing the perceived intensity. Positron emission tomography revealed significant changes in pain-evoked activity within anterior cingulate cortex, consistent with the encoding of perceived unpleasantness, whereas primary somatosensory cortex activation was unaltered. These findings provide direct experimental evidence in humans linking frontal-lobe limbic activity with pain affect, as originally suggested by early clinical lesion studies.     

Plasma L-arginine concentration, oxygenation index, and systemic blood pressure in premature infants

OBJECTIVE: To determine the relationships between plasma L-arginine concentrations and the severity of respiratory distress syndrome (RDS) or systemic blood pressure in premature infants. DESIGN: Prospective, observational study. SETTING: Neonatal intensive care, tertiary referral hospital. SUBJECTS: Fifty-three premature infants. INTERVENTIONS: We measured arginine and nutritional intake, plasma arginine concentration, total amino acid concentrations, and blood pressure on days 3, 7, 14, and 21 of life. In 33 infants who received assisted ventilation, oxygenation index could be calculated to reflect the severity of RDS. The relationships between plasma arginine and oxygenation index or blood pressure were analyzed using multiple linear regression. MEASUREMENTS AND MAIN RESULTS: On day 3, plasma arginine concentrations were decreased compared with normal published values. Arginine concentrations increased with the day of life of measurement (p < .001) and with arginine intake (p < .001). After adjusting for arginine intake and day of life, an inverse relationship was found between oxygenation index and plasma arginine concentrations: (p = .025). No similar relationship was found between oxygenation index and the concentration of total amino acids. A weak positive relationship was found between plasma arginine concentration and systemic blood pressure. CONCLUSIONS: Increments in the oxygenation index, reflective of an increased severity of RDS, are associated with a decrease in plasma arginine concentration. This finding may reflect arginine consumption by the nitric oxide synthase pathway in the lungs of premature infants with RDS, or may be explained by increased arginine catabolism. The lack of a similar relationship between total plasma amino acids and oxygenation index supports the first interpretation.     

One hundred years of orthopedics in the Netherlands. IV. Spinal abnormalities]

In recent years there has been spectacular progress in the approach to various disorders of the spinal column. Owing to improved methods of osteosynthesis there is no longer so much need for long periods of postoperative bed rest. Of all the scolioses, idiopathic scoliosis is most common. The vast majority of these cases are not clinically significant. What is seen in the remaining cases if left untreated is a progression in the curvature during growth. Progressive idiopathic scoliosis can be effectively treated using conservative methods. Screening at school is an important part of this process. If the curvature proves progressive and skeletal growth is not complete a brace can be prescribed. Use of this strategy and form of treatment can avoid progression of the curvature and development of serious deformities. This conservative therapy has markedly reduced the need for corrective surgery. Scheuermann's disease is characterized by a fixed dorsal thoracic kyphosis. Progressive Scheuermann's kyphosis can be effectively treated using a brace. The majority of fractures of the vertebral bodies can be treated conservatively. However, serious fractures normally require surgical intervention. In the industrialised Western world, low back pain is a major health problem and the foremost cause of disability and unfitness for work. Low back pain caused by degenerative disease of the spinal column should be treated using a multidisciplinary approach. The development of advanced operative techniques and osteosynthesis methods has made it possible to treat metastases of the spine surgically. The effects of this treatment on the quality of life are encouraging.     

Constrained sintering kinetics of 3YSZ films

3YSZ green layers approximately 10 μm thick were screen-printed onto 3YSZ substrates and their constrained sintering kinetics were measured at 1100-1350 °C using an optical dilatometer. The densification rates of the same powder in the form of pellets and free-standing films were also measured. The constrained densification rate was greatly retarded compared with the free densification rate at a given temperature and density. The retardation increased with increasing density and temperature and could not be properly accounted for by existing theories of constrained sintering. As a result the apparent activation energy is much lower for constrained sintering (135 ± 20 kJ mol⁻¹) than for free sintering (660 ± 30 kJ mol⁻¹). It is proposed that this is because the constrained microstructure exhibits larger and more widely separated pores at the higher temperatures.     

Novel expression and regulation of gastrin gene in human ovarian cancer cell line, SW626

Gastrin-secreting tumors have been identified in ectopic locations including the ovary; the mechanisms regulating gastrin gene expression, its distribution, and signaling pathways in these ectopic tissues are not known. The purpose of our present study was to determine: (1) whether the gastrin gene and peptide could be detected in ovarian cancer cell lines, (2) if functional gastrin releasing peptide receptors (GRP-R) are present, and (3) whether gastrin gene expression is altered by GRP. Five ovarian cancer cell lines (SW626, OVCA 420, OVCA 429, OVCA 432, and OVCA 433) were analyzed. We identified gastrin gene and peptide expression in the SW626 cell line but not in the OVCA lines. SW626 cells express a functional GRP-R that is correctly coupled to the Ca2+ signaling pathway. Treatment of SW626 cells with bombesin, the amphibian equivalent of GRP, inhibited expression of the gastrin gene in a time- and dose-dependent fashion. The SW626 ovarian cancer cell line will provide a useful model to further define regulation and expression of both the gastrin gene and peptide in ectopic (nongastrointestinal) tissues.