SELECTIVE HABITUATION OF GALVANIC SKIN RESPONSE COMPONENT OF THE ORIENTATION REACTION TO AN AUDITORY STIMULUS

The prediction from Sokolov's (1960) theory that, following OR habituation, size of OR return is proportional to the amount of difference between the new stimulus and the habituating stimulus was tested using an auditory stimulus varying in frequency and intensity. Five Ss were allocated to each of 16 conditions, three conditions involving changes in frequency, three involving changes in intensity, nine involving changes in both frequency and intensity, with one control condition involving a repetition of the habituating stimulus. Following habituation of the GSR component of the OR to a criterion of response failure for three successive trials, magnitude of GSR under the 16 conditions was measured. Contrary to Sokolov's theory, only increase in intensity had a significantly different effect on OR return. More importantly, it was found that Ss habituating rapidly to the initial stimulus were less likely to show OR return to stimulus change. It was concluded that individual differences in habituation rate may be more important than stimulus difference effects in selective habituation.     

Actions of recombinant human gamma-interferon and tumor necrosis factor alpha on the proliferation and osteoblastic characteristics of human trabecular bone cells in vitro

Using cultured human osteoblast-like cells, we studied the effects of tumor necrosis factor (TNF) and recombinant human gamma-interferon (gamma-IFN) on osteoblast growth and function, and demonstrated that TNF stimulated bone cell proliferation and prostaglandin production while inhibiting 1,25-(OH)2D3-stimulated alkaline phosphatase activity and osteocalcin release. In contrast, gamma-IFN inhibited proliferation and stimulated alkaline phosphatase activity of the cells, while inhibiting 1,25-(OH)2D3-stimulated osteocalcin production and having variable effects on the release of prostaglandins, depending on the presence of other factors. Our results suggest that TNF and gamma-IFN can act directly on bone-forming cells to affect both their proliferation and their differentiated function, and that changes in the ability of cells to produce these factors in disease states may contribute to alterations in the integrity of connective tissue matrices.     

Insight into the molecular basis of pathogen abundance: group A Streptococcus inhibitor of complement inhibits bacterial adherence and internalization into human cells

Streptococcal inhibitor of complement (Sic) is a secreted protein made predominantly by serotype M1 Group A Streptococcus (GAS), which contributes to persistence in the mammalian upper respiratory tract and epidemics of human disease. Unexpectedly, an isogenic sic-negative mutant adhered to human epithelial cells significantly better than the wild-type parental strain. Purified Sic inhibited the adherence of a sic negative serotype M1 mutant and of non-Sic-producing GAS strains to human epithelial cells. Sic was rapidly internalized by human epithelial cells, inducing cell flattening and loss of microvilli. Ezrin and moesin, human proteins that functionally link the cytoskeleton to the plasma membrane, were identified as Sic-binding proteins by affinity chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis. Sic colocalized with ezrin inside epithelial cells and bound to the F-actin-binding site region located in the carboxyl terminus of ezrin and moesin. Synthetic peptides corresponding to two regions of Sic had GAS adherence-inhibitory activity equivalent to mature Sic and inhibited binding of Sic to ezrin. In addition, the sic mutant was phagocytosed and killed by human polymorphonuclear leukocytes significantly better than the wild-type strain, and Sic colocalized with ezrin in discrete regions of polymorphonuclear leukocytes. The data suggest that binding of Sic to ezrin alters cellular processes critical for efficient GAS contact, internalization, and killing. Sic enhances bacterial survival by enabling the pathogen to avoid the intracellular environment. This process contributes to the abundance of M1 GAS in human infections and their ability to cause epidemics.     

Actions of recombinant human γ-interferon and tumor necrosis factor α on the proliferation and osteoblastic characteristics of human trabecular bone cells in vitro

Using cultured human osteoblast-like cells, we studied the effects of tumor necrosis factor (TNF) and recombinant human γ-interferon (γ-IFN) on osteoblast growth and function, and demonstrated that TNF stimulated bone cell proliferation and prostaglandin production while inhibiting 1,25-(OH)₂D₃—stimulated alkaline phosphatase activity and osteocalcin release. In contrast, γ-IFN inhibited proliferation and stimulated alkaline phosphatase activity of the cells, while inhibiting 1,25-(OH)₂D₃—stimulated osteocalcin production and having variable effects on the release of prostaglandins, depending on the presence of other factors. Our results suggest that TNF and γ-IFN can act directly on bone-forming cells to affect both their proliferation and their differentiated function, and that changes in the ability of cells to produce these factors in disease states may contribute to alterations in the integrity of connective tissue matrices.     

Characteristics of saccadic intrusions

Primary fixation is never perfectly stable, but is frequently interrupted by slow drifts, microsaccades and saccadic intrusions (SI). SI are involuntary, conjugate movements which take the form of an initial fast movement away from the desired eye position and followed after a short duration, by either a return secondary saccade or a drift. The purpose of this study was to examine the prevalence and metrics of SI in a population of 50 healthy subjects. Using both one and two dimensional recordings we find that all 50 members of the subject group exhibited SI. The SI were bilateral, conjugate and horizontal. No purely vertical SI were detected when examined in three subjects. SI amplitude mean and range was 0.6° ± 0.5°, 0.1°-4.1°; SI frequency mean and range was 18.0 ± 14.3 per min, 1.0-54.8 per min; SI duration mean and range was 225 ± 150, 20-870 ms. The mean SI amplitude and frequency when SI < 0.5° were removed was 0.97° ± 0.56° and 7.0 ± 11.4 per min respectively. Age was positively correlated with SI amplitude (p < 0.01), but there was no correlation between age and SI frequency. Three of four types of SI monophasic square wave intrusions (MSWI), biphasic square wave intrusions (BSWI) and double saccadic pulses (DSP) were found to be exclusively saccadic, whilst the fourth type, the single saccadic pulses (SSP), were confirmed to exhibit a slow secondary component. MSWI were the most frequently observed SI occurring in 47 out of 50 (94%) of the subjects with a mean amplitude, frequency and duration of 0.7° ± 0.5°, 11.5 ± 11.6 per min, and 255 ± 147 ms respectively. Mean amplitudes and frequencies for BSWI (n = 20), SSP (n = 11) and DSP (n = 34) were found to be 0.50° ± 0.2°, 1.2 ± 2.5 per min; 0.40° ± 0.20°, 0.4 ± 1.0 per min and 0.3° ± 0.4°, 5.0 ± 8.7 per min respectively. No differences in MSWI characteristics were found between binocular and monocular viewing. Possible explanations for SI occurrence include experimental viewing conditions, subject fatigue and covert shifts in attention.     

Identification and initial characterization of 5000 expressed sequenced tags (ESTs) each from adult human normal and osteoarthritic cartilage cDNA libraries

OBJECTIVE: To prepare, sequence and analyse adult human cartilage cDNA libraries to study the gene expression pattern between normal and osteoarthritic cartilage. METHODS: Poly A(+)RNA from adult human normal and osteoarthritic articular cartilage was isolated and used to prepare cDNA libraries. Approximately 5000 ESTs from each library were sequenced and analysed using bioinformatic tools. The expression of select genes was confirmed by Northern blot and in situ hybridization analysis. RESULTS: Multiple gene families including several classical cartilage matrix protein encoding genes were identified. Approximately 28-40% of the genes sequenced from these libraries were novel, while half of the genes encoded known proteins and 4-6% of the genes encoded novel homologs of known proteins. Several known genes, whose expression has not been reported previously in cartilage, were also identified. We have confirmed the cartilage expression of three known (CTGF, CTGF-L and clusterin) and two novel homologs of known genes (PCPE-2 and Gal-Nac transferase) by Northern blot and in situ hybridization analysis. CONCLUSION: This is the first report of the preparation and sequencing of cDNA libraries from adult human normal and osteoarthritic articular cartilage. Further analysis of genes identified from these libraries may provide molecular targets for diagnosis and/or treatment of osteoarthritis (OA).