Toxins and genes isolated from scorpions of the genus Tityus

Scorpion venoms contain a variety of low mol. wt peptides toxic to different organisms. These peptides have been intensively studied because they represent excellent models for investigating structure-function relationships and they are also fine probes for studying ionic channel functions. This review deals with the biological and chemical aspects of toxic peptides that affect Na+ or K+ channels and the cloning of the cDNAs and genes encoding the main alpha and beta neurotoxins present in the venom of the three most dangerous species of Brazilian scorpion, Tityus bahiensis, Tityus stigmurus and Tityus serrulatus, and the Venezuelan scorpion Tityus discrepans. At least 16 different peptides specific for Na+ channels and five affecting K+ channels were isolated and characterized from the venom of these scorpions. The isolation of cDNAs and genes encoding four distinct toxins has permitted the elucidation of their nucleotide sequences as well as their genomic organization. Venoms and isolated toxins from scorpions of the genus Tityus were shown to enhance the secretory activity of the pancreas. Antisera obtained against venom of T. serrulatus show cross-reactivity with other species of the Brazilian scorpions.     

Biomechanics of atherosclerotic plaque

Atherosclerosis is the leading cause of death in the U.S. In balloon angioplasty, pressure is applied directly to atherosclerotic plaque to reopen the occluded blood vessel. The mechanical behavior of the plaque often determines the outcome of the angioplasty. Little information on the material properties of atherosclerotic plaque is available, yet the properties govern the plaque's behavior. Our discussion of the experimental testing and numerical analysis of plaque is directed toward summarizing the current knowledge of plaque material properties. Atherosclerotic plaque exhibits a wide range of behaviors consistent with the variability in the underlying composition. Overall, plaques exhibit nonlinear and inelastic mechanical behavior, although geometry and material properties are not well known. The histomorphological composition is critical in determining the plaque's mechanical response. Finite element approximations have been used to study the stresses developed in the diseased vessel; however, material properties are a critical component of a finite element analysis: the predictive capabilities depend on how accurately the material is modeled. When more information on plaque behavior is generated through careful and extensive experimental investigations, better models will be constructed to more accurately predict plaque responses. As the biomechanics community learns about plaque mechanics, we can use the knowledge to enhance the reliability of interventional procedures.     

Glutathione synthesis in the exocrine pancreas

When epithelial cells reach confluency in vitro, a number of energy-requiring activities such as growth and motility are contact-inhibited. We investigated the possible role of the E-cadherin/catenin complex, which acts as an invasion suppressor, in contact inhibition. Three strategies for modulation of the complex were used. Firstly, the cell-cell adhesion and signal transduction functions of E-cadherin were neutralized immunologically in human MCF-7/6 mammary carcinoma cells possessing a complete complex. Secondly, the effect of E-cadherin transfection in E-cadherin negative cell lines was investigated. Thirdly, alpha-catenin deficient variants of the human HCT-8/S11 colon carcinoma cell line were compared with their parent cells. In confluent cultures functional downregulation of the E-cadherin/catenin complex did not alter cell growth nor saturation density. This was shown by cell number counts, protein staining assays, cell cycle analysis, proliferation markers (Ki67 and Proliferating Cell Nuclear Antigen) and apoptosis assays. However, confluent cells with a functionally deficient complex showed positional instability and enhanced succinate dehydrogenase-mediated mitochondrial 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl) tetrazolium bromide (MTT) conversion, as compared to cells with an active complex. Our data indicate that contact inhibition of motility and of mitochondrial enzyme activity, but not of growth is regulated by the E-cadherin/catenin complex in epithelial cells.     

Activation of a distinct arousal state immediately after spontaneous awakening from sleep

In contrast to the many neural studies into the mechanisms of sleep onset and maintenance, few studies have focused specifically on awakening from sleep. However, the abrupt electrographic changes and large brief cardio-respiratory activation at awakening suggest that a distinct, transiently aroused, awake state may exist compared to later wakefulness. To test this hypothesis we utilized the acoustic startle reflex, a standard un-conditioned reflex elicited by a sudden loud noise. This reflex is modulated under specific conditions, one being a diminution of startle when a quieter pre-stimulus is presented immediately before the loud stimulus. This pre-pulse inhibition (PPI) is used as a measure of sensorimotor gating, with smaller PPI indicating less filtering of sensory inputs and increased responsiveness to external stimuli. Eight rats with electrodes for recording sleep-wake state were studied. An accelerometer measured startle responses. The startle reflex was elicited by 115 dB, 40 ms tones. PPI was produced by 74 dB, 20 ms tones preceding the 115 dB tone by 100 ms. Responses within 100 ms were measured. Stimuli were applied either 3-10 s after spontaneous awakenings, or in established wakefulness (> 30 s). Responses to the startle stimuli alone were similar in the different awake states (P = 0.821). However, PPI was smaller at awakening from non-REM sleep compared to established wakefulness (45.4 +/- 7.5% vs. 74.3 +/- 6.1%, P = 0.0002). PPI after awakening from REM sleep (52.8 +/- 17.9%) was not significantly different than established wakefulness (P = 0.297). Reduced PPI of the startle reflex at awakening from non-REM sleep supports the hypothesis that wakefulness immediately after spontaneous sleep episodes is neurophysiologically distinct from later wakefulness and associated with reduced gating of motor responses to sensory inputs. Spontaneous activation of this distinct, transiently aroused, state upon awakening may serve a protective function, preparing an animal to respond immediately to potentially threatening stimuli.     

Resting metabolic rate in young Polynesian and Caucasian women

OBJECTIVE: To investigate whether resting metabolic rate (RMR) differs between Caucasian and Polynesian women. DESIGN: Cross-sectional comparison. SUBJECTS: Eighty-two (42 Caucasian, 40 Polynesian) healthy women aged between 18 and 27 y. MEASUREMENTS: RMR (indirect calorimetry) and body composition (fat-free mass and fat mass derived from oxygen-18 dilution measurement of total body water). RESULTS: RMR was similar in the Caucasian (6956 +/- 1291 (s.d.) kJ/d) and Polynesian (7125 +/- 1290 kJ/d) groups while fat-free mass was significantly lower in the Caucasian group (45.3 +/- 6.8 vs 51.0 +/- 6.4 kg, P < 0.002). After adjustment for fat-free mass and fat mass, RMR was lower in the Polynesian than the Caucasian groups (6783 +/- 904 vs 7281 +/- 901 kJ/d, P = 0.023). CONCLUSION: The significantly lower relative RMR observed in Polynesian compared to Caucasian women may predispose Polynesian women to eventual onset of obesity.     

Severe defects in immunity and hematopoiesis caused by SHP-1 protein-tyrosine-phosphatase deficiency

Spontaneous mouse mutations that cause severe immunodeficiency or autoimmunity are invaluable tools with which to investigate the mammalian immune system. Mutations at the 'motheaten' locus result in severe immunological dysfunction due to disruption of the structural gene encoding Src-homology 2-domain phosphatase-1 (SHP-1). This natural model for a specific protein-tyrosine-phosphatase deficiency is being widely utilized to determine the role of SHP-1 in the negative regulation of multiple signaling pathways in a number of hematopoietic lineages.     

Patterns of hospitalization in elderly patients with asthma and chronic obstructive pulmonary disease

The purpose of this study was to describe the impact of asthma and chronic obstructive pulmonary disease (COPD) in the elderly on health care utilization. The Health Care Financing Administration (HCFA) file for the year 1984 through 1991 involving beneficiaries < or = 65 yr were searched for the diagnoses of asthma and COPD by ICD-9 codes. The study groups were created by determining the first admission for an exacerbation of either disease during each year from 1984 through 1991. Patients were identified by their social security number. The 1984 cohort consisted of 56,692 patients with asthma exacerbation and 162,899 with COPD exacerbation. The 1991 cohort consisted of 67,758 patients with asthma exacerbation and 131,974 patients with COPD exacerbation. In addition, the 1984 cohort was tracked by social security number for evidence of rehospitalization for either asthma or COPD through 1991. Length of hospitalization increased as patients grew older. The discharge rate to an independent living facility diminished as age increased. The use of convalescent and nursing homes or home health care after discharge more than doubled from 1984 through 1991. The utilization of health care resources by elderly patients with asthma and COPD is immense, both during hospitalization and after discharge.     

Effects of a low-dose amino acid supplement on adaptations to cycling training in untrained individuals

The purpose of this study was to determine if amino acid supplementation influences blood and muscle lactate response to exercise and the time course of the metabolic adaptations to training. Two groups of untrained males (n = 7 each) were given (double-blind) a daily supplement (2.9 g.day-1) containing a mixture of leucine, isoleucine, valine, glutamine, and carnitine (EXP) or 3 g.day-1 of lactose (CON). Following 7 days of supplementation there was no significant change in VO2peak, time to exhaustion (TTX) at 120% VO2peak, or muscle and blood lactate in either EXP or CON. Subjects then initiated 6 weeks of combined aerobic and anaerobic training on a Monark cycle ergometer. It was found that amino acid supplementation had no effect on either blood or muscle lactate accumulation during exercise, while supplementation resulted in a faster adaptation in buffer capacity. Performance during intense exercise was not improved with amino acid supplementation.     

Evidence for a selectively favourable reduction in the mutation rate of the X chromosome

The equilibrium per-genome mutation rate in sexual species is thought to result from a trade-off between the benefits of reducing the deleterious mutation rate and the costs of increasing fidelity. We propose that selection will often favour a lower mutation rate on the X chromosome than on autosomes, owing to the exposure of deleterious recessive mutations on hemizygous chromosomes. We tested this hypothesis by examining 33 X-linked genes that have been sequenced in both mouse and rat, and compared their rate of evolution against 238 autosomal genes. The X-linked genes were found to have a significantly lower rate of synonymous substitution than the autosomal genes. Neither the supposed higher mutation rate in males nor stronger purifying selection against slightly deleterious mutations on the X chromosome can account for the low value. The most parsimonious explanation is that rodents have a lower mutation rate on the X chromosome than on autosomes. It is therefore likely that previous indirect estimates of the excess male mutation rate are inaccurate. Indeed, after correction we find no evidence for a male-biased mutation rate in rodents. Furthermore, the rate of synonymous substitution in Y-linked genes is not significantly different from that in autosomal ones. The extent to which enhanced male mutation rates are problematic for the mutational deterministic model of the evolution of sex must, in turn, be questioned.