Cytokine stimulation of T lymphocytes regulates their capacity to induce monocyte production of tumor necrosis factor-alpha, but not interleukin-10: possible relevance to pathophysiology of rheumatoid arthritis

Previous studies in the laboratory have shown that the pro-inflammatory cytokine tumor necrosis factor (TNF)-alpha plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA). The mechanisms involved in regulating monocyte/macrophage cytokine production are not yet fully understood, but are thought to involve both soluble factors and cell/cell contact with other cell types. We and others have previously demonstrated that T cells activated through the T cell receptor/CD3 complex induce monocyte TNF-alpha production by contact-mediated signals. In this report, we investigated further whether T cells activated by cytokines in the absence of T cell receptor stimulation also regulate monocyte cytokine production. T cells were activated in an antigen-independent manner using the cytokines interleukin (IL)-15 or IL-2 alone, or in combination with IL-6 and TNF-alpha. Subsequently, T cells were fixed and incubated with monocytes. Fixed, cytokine-stimulated T cells induced monocytes to secrete TNF-alpha in a dose-dependent manner, but did not induce secretion of IL-10, a potent endogenous down-regulator of TNF-alpha and other pro-inflammatory cytokines. Stimulation of monocyte TNF-alpha was markedly inhibited when T cells were physically separated from monocytes within the tissue culture well, confirming that T cell contact is necessary. T cell acquisition of monocyte-activating capacity was shown to be dependent on the period of cytokine stimulation, with T cells activated for 8 days more effective than T cells activated for shorter periods. Addition of interferon-gamma or granulocyte/macrophage colony-stimulating factor to the T cell/monocyte cultures enhanced T cell induction of monocyte TNF-alpha by threefold and ninefold, respectively. The results from this model of cognate interaction suggest that cytokine-stimulated T cells, interacting with macrophages in the rheumatoid synovial membrane, may contribute to the continuous excessive production of TNF-alpha observed in the RA joint, and to the imbalance of pro-inflammatory cytokines over anti-inflammatory cytokines.     

Impact of alpha-skeletal actin but not alpha-cardiac actin on myoblast morphology

A technique was developed to determine the total number of spermatozoa stored in the uterovaginal junction of hens. After insemination of spermatozoa treated with the nuclear fluorescent dye bisbenzimide, oviductal tissue was collected from hens and homogenized. Samples of homogenate were dried, and the number of spermatozoa mm-2 was determined with the use of a fluorescence microscope. When spermatozoa were added to excised uterovaginal junction tissue before homogenization, results indicated a 1:1 linear relationship between actual numbers of spermatozoa added to the tissue and calculated numbers of spermatozoa added to the tissue. This new technique was used to show that insemination of hens with 25, 50 or 100 x 10(6) spermatozoa resulted in a linear increase in the number of spermatozoa stored in the uterovaginal junction. Insemination of hens with 328 x 10(6) spermatozoa produced no increase in uterovaginal junction storage of spermatozoa over insemination with 100 x 10(6) spermatozoa. At the maximum sperm storage tubule filling dose of 100 x 10(6) spermatozoa, only 0.22% of the spermatozoa inseminated were found in the uterovaginal junction 24 h after insemination. Treatment of spermatozoa with bisbenzimide had no detrimental effects on fertility or penetration rates when compared with untreated (control) spermatozoa. However, when spermatozoa were treated with bisbenzimide, hatchability of fertile eggs was reduced. In conclusion, this new fluorescence technique appears to be valuable in determining the total number of spermatozoa stored in the uterovaginal junction of hens.     

A method of reducing grating lobes associated with an ultrasoundlinear phased array intended for transrectal thermotherapy

Some practical aspects of planar linear ultrasound phased arrays for transrectal thermotherapy of prostate diseases are discussed. Several regimens for driving the array are investigated and spatial distributions of ultrasound intensities are measured in water and compared with computer simulations. Practical recommendations for suppressing grating lobes based on the use of subsets of elements and de-activation of several elements in the array are given. Treatment safety could be increased by adopting these measures since the relative intensities and power in grating lobes and other secondary intensity peaks are decreased, as is the overall ultrasound energy introduced into the body without significant reduction in the maximum power at the focus     

A comparison of retinal morphology viewed by optical coherence tomography and by light microscopy

OBJECTIVE: To compare the cross-sectional images of primate retinal morphology obtained by optical coherence tomography (OCT) with light microscopy to determine the retinal components represented in OCT images. METHODS: Laser pulses were delivered to the retina to create small marker lesions in a Macaca mulatta. These lesions were used to align in vivo OCT scans and ex vivum histologic cross sections for image comparison. RESULTS: The OCT images demonstrated reproducible patterns of retinal morphology that corresponded to the location of retinal layers seen on light microscopic overlays. Layers of relative high reflectivity corresponded to horizontally aligned retinal components such as the nerve fiber layer and plexiform layers, as well as to the retinal pigment epithelium and choroid. In contrast, the nuclear layers and the photoreceptor inner and outer segments demonstrated relative low reflectivity by OCT. CONCLUSIONS: Retinal morphology and macular OCT imaging correlate well, with alignment of areas of high and low reflectivity to specific retinal and choroidal elements. Resolution of retinal structures by OCT depends on the contrast in relative reflectivity of adjacent structures. Use of this tool will enable expanded study of retinal morphology, both normal and pathologic, as it evolves in vivo.     

Relations among children's social goals, implicit personality theories, and responses to social failure.

Two studies examined children's thought patterns in relation to their responses to social challenge. In Study 1, 4th and 5th graders tried out for a pen pal club under either a performance goal (stressing the evaluative nature of the tryout) or a learning goal (emphasizing the potential learning opportunities). In their behavior and attributions following rejection, children who were focused on a performance goal reacted with more helplessness, whereas children given a learning goal displayed a more mastery-oriented response. Study 2 found that in response to hypothetical socially challenging situations, 4th, 5th, and 6th graders who believed personality was nonmalleable (entity theorists) vs. malleable (incremental theorists) were more likely to endorse performance goals. Together, these studies indicate that children's goals in social situations are associated with their responses to social failure and are predicted by their implicit theories about their personality. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impact of chromosome 14q loss on survival in primary head and neck squamous cell carcinoma

OBJECTIVE: To investigate somesthetic functions of the perisylvian cortex. METHODS: Somatosensory evoked magnetic fields (SEFs) and somatosensory evoked potentials (SEPs) of the perisylvian cortex were recorded directly from subdural electrodes in a patient with a left frontal brain tumour. RESULTS: The most prominent SEP components after electrical stimulation of the right and left hands and the right foot were double peaked negativity recorded just above the sylvian fissure (latency 80 to 150 ms), respectively (N1a and N1b). Generator sources for the magnetoencephalographic counterparts of those peaks (N1a(m) and N1b(m)) were both localised at the upper bank of the sylvian fissure, and those of N1a(m) were more anteromedially located than those of N1b(m). CONCLUSIONS: These findings suggest the existence of at least two separate somatosensory areas within the human perisylvian cortex.     

Mammalian AMP-activated protein kinase is homologous to yeast and plant protein kinases involved in the regulation of carbon metabolism

In mammals, an AMP-activated protein kinase (AMPK) phosphorylates both acetyl-CoA carboxylase and 3-hydroxy-3-methylglutaryl-CoA reductase in vitro and has been proposed to play a major role in the regulation of lipid metabolism in vivo. We report here the primary sequence of rat AMPK and show that antibodies raised against synthetic peptides based on the deduced sequence of AMPK immunoprecipitate AMPK activity from rat liver extracts. AMPK has a remarkable degree of sequence identity to the proteins encoded by the yeast SNF1 gene and the plant RKIN1 gene. SNF1 protein kinase activity is essential for release of genes from glucose repression in Saccharomyces cerevisiae. Expression of cRKIN1 in yeast snf1 mutants restores SNF1 function. These results indicate that AMPK, SNF1, and RKIN1 form part of a family of protein kinases that have been highly conserved throughout evolution. Our results suggest that AMPK may be involved in the regulation of a wide range of metabolic pathways.     

Spine injuries in combat troops--Panama, 1989

Operation Just Cause was until recently the largest American combat operation since Vietnam, and remains the largest nighttime parachute operation since World War II. All 252 casualties were airlifted to San Antonio, Texas, for medical treatment. Greater than 80% sustained orthopedic injuries. Sixteen patients were admitted for injuries to the back or neck. Three of the four patients with significant fractures or fracture-dislocations were paraplegic. Two of the three patients with gunshot wounds to the back required extensive reconstruction for wound management. In addition to the 252 casualties, there were 23 fatalities, among whom 7 suffered major injuries to the spine. Spine injuries represented the most significant source of long-term morbidity among those soldiers wounded in combat in Panama, and were common among the fatalities. Noteworthy in these cases was the high percentage of severe neurologic injuries in patients with significant fractures (75%), particularly fractures associated with gunshot wounds. Also of interest were the cases of major soft tissue injury associated with high-velocity gunshot wounds (66%) and the extensive soft tissue surgery needed to treat these injuries.