Dynamic mechanical compression influences nitric oxide production by articular chondrocytes seeded in agarose

Nitric oxide (NO) has been implicated in the inhibition of cell proliferation in cytokine and lipopolysaccharide (LPS)-stimulated chondrocytes and is known to be influenced by physical forces in several tissues. In this study, a well-characterized model system utilizing bovine chondrocytes embedded in 3% agarose constructs has been used to investigate the effect of dynamic strain at 0.3, 1, or 3 Hz on NO production. LPS induced a significant increase in nitrite levels, which was reversed by both L-NAME and dexamethasone. Dynamic compressive strain produced a significant reduction in nitrite production. The effect was partially blocked by L-NAME but unaffected by dexamethasone. L-NAME also reversed dynamic compression-induced stimulation of [3H]-thymidine incorporation. NO appears to be a constituent of mechanotransduction pathways which influence proliferation of bovine chondrocytes seeded within agarose constructs. The inhibitor experiments also infer that alterations in cNOS activity primarily determine the response.     

Mitogenic and oncogenic properties of the small G protein Rap1b

It has been widely reported that the small GTP-binding protein Rap1 has an anti-Ras and anti-mitogenic activity. Thus, it is generally accepted that a normal physiological role of Rap1 proteins is to antagonize Ras mitogenic signals, presumably by forming nonproductive complexes with proteins that are typically effectors or modulators of Ras. Rap1 is activated by signals that raise intracellular levels of cAMP, a molecule that has long been known to exert both inhibitory and stimulatory effects on cell growth. We have now tested the intriguing hypothesis that Rap1 could have mitogenic effects in systems in which cAMP stimulates cell proliferation. The result of experiments addressing this possibility revealed that Rap1 has full oncogenic potential. Expression of Rap1 in these cells results in a decreased doubling time, an increased saturation density, and an unusual anchorage-dependent morphological transformation. Most significantly, however, Rap1-expressing cells formed tumors when injected into nude mice. Thus, we propose that the view that holds Rap1 as an antimitogenic protein should be restricted and conclude that Rap1 is a conditional oncoprotein.     

k-tree method for high-speed spatial normalization

The general approach to spatial normalization using a deformation field is presented. Current high degree-of-freedom deformation methods are extremely time-consuming (10-40 hr), and a k-tree method is proposed to greatly reduce this time. A general k-tree method for analysis of source and target images and synthesis of deformation fields is described. The k-tree method simplifies scale control and feature extraction and matching, making it highly efficient. A two-dimensional (2-D), or quadtree, application program was developed for preliminary testing. The k-tree method was evaluated with 2-D images to test rotating ability, nonhomologous region matching, inner and outer brain-structure independence, and feasibility with human brain images. The results of these tests indicate that a three-dimensional (3-D), or octree, method is feasible. Preliminary work with an octree application program indicates that a processing time of under 10 min for 256(3) image arrays is attainable on a Sun Ultra30 workstation.     

Transport in vitro fertilization and intracytoplasmic sperm injection: results of a collaborative trial

An arteriovenous vasodilator, flosequinan, has been shown to be effective for the treatment of acute heart failure. However, little is known as to its effect on aortic impedance, which is known to be a proper and precise expression of left ventricular (LV) afterload. To evaluate the acute cardiovascular effect of flosequinan in failing heart, we administered flosequinan intravenously to seven dogs with cardiac failure produced by an infusion of carbon powder (20-50 microm in diameter) into left main trunks of coronary artery. The LV-pump function was severely impaired after intracoronary injection of carbon powder, as evidenced by the findings that cardiac output, circumferential shortening velocity (mean Vcf), and peak +dP/dt of LV pressure were all decreased, associated with a significant increase in LV end-diastolic pressure. Flosequinan (0.9 mg/kg, i.v.) increased cardiac output by 28%, mean Vcf by 44%, and peak +dP/dt by 24%, whereas it decreased total systemic resistance by 32%, time constant of LV pressure decay by 22%, and LV end-diastolic pressure by 18%. Moreover, flosequinan substantially decreased the pulsatile components of LV afterload (i.e., characteristic impedance by 11% and arterial wave reflection coefficient by 45%). Thus flosequinan exerted not only positive inotropic but also positive lusitropic effects, in association with a significant reduction of both pulsatile and steady components of LV afterload, contributing to an improvement of LV-pump function in acute cardiac failure.     

Tension generation and increase in voltage-activated Na+ current by crotamine

It is suggested that working memory comprises a system for the temporary storage and manipulation of information, forming an important link between perception and controlled action. Evidence is presented for a three-component model, comprising an attentional control system, the central executive, and two subsidiary slave systems. One of these the, the visuo-spatial sketch pad holds and manipulates spatial information, while the other, the phonological loop performs a similar function for auditory and speech-based information. Evidence is presented for the view that the phonological loop has evolved as a mechanism to facilitate the acquisition of language.     

Monitoring electroosmotic flow by periodic photobleaching of a dilute, neutral fluorophore

Electroosmotic flow has been monitored in a capillary using a method based on periodic photobleaching of a neutral, fluorescent buffer additive. Rhodamine B was determined to be neutral between pH 6.0 and 10.8 and was added to the running buffer at a concentration of 400 nM. Rhodamine B was photobleached by opening a shutter under computer control for 250 ms every 5.00 s, to expose the dye to a laser beam and create a photobleached zone. The time was measured for the photobleached zone to migrate 6.13 mm to a downstream laser-induced fluorescence detector, to determine the rate of electroosmotic flow in the entire capillary. The flow rate was sampled every 5.00 s, and the precision of the flow measurements was 0.7% or better. Three fluorescent compounds were separated and detected by capillary electrophoresis with laser-induced fluorescence detection, while simultaneously monitoring the electroosmotic flow rate.     

The Arab Muslim client: implications for anesthesia

Oligodendrocytes are preferentially sensitive to the toxic, carcinogenic, and teratogenic effects of methylnitrosourea (MNU). The mechanisms responsible for this enhanced sensitivity have not been fully elucidated. One of the most vulnerable cellular targets for this chemical is mitochondrial DNA (mtDNA). To determine if differences in mtDNA damage and repair capacity exist among the different CNS glial cell types, the effects of MNU exposure on oligodendroglia, astroglia, and microglia cultured separately from neonatal rat brain were compared. Quantitative determinations of mtDNA initial break frequencies and repair efficiencies showed that whereas no cell type-specific differences in initial mtDNA damage were detected, mtDNA repair in oligodendrocytes, oligodendrocyte progenitors, and microglia was significantly reduced compared to that of astrocytes. In astrocytes, and all other cell types previously evaluated in our laboratory, >60% of N-methylpurines were removed from the mtDNA by 24 hr. In contrast, only 35% of lesions were removed from mtDNA of oligodendrocytes, oligodendrocyte progenitors, and microglia during the same time period. Mitochondrial perturbations by a variety of xenobiotics have been linked to apoptosis. In the present study, apoptosis, as determined by DNA laddering and ultrastructural analysis, was clearly induced by MNU treatment of cultured oligodendrocyte progenitors and microglia, but not in astroglia. These data demonstrate a correlation between diminished mtDNA repair capacity and the induction of apoptosis. However, further experimentation is necessary to determine if a causal relationship exists and contributes to the vulnerability of oligodendroglia following exposure to N-nitroso compounds in the environment or in chemotherapeutic regimen.     

Hypertension and the obstetrician-gynecologist

Hypertension is a major risk factor for cardiovascular-related morbidity and death. Antihypertensive therapy markedly reduces the risk caused by elevated blood pressure. Earlier treatment of hypertensive patients should reduce deaths and morbidity even further. The obstetrician-gynecologist has the opportunity and responsibility to identify hypertensive patients early in the course of their disease. He must also confront the problem of elevated blood pressure associated with the use of oral contraceptives. In addition to its impact on the general population, chronic hypertension presents special problems during pregnancy. Pregnant women with elevated blood pressure have an increased fetal mortality rate and develop pre-eclampsia more frequently and earlier than nonhypertensive women. Antihypertensive treatment possibly increases fetal survival; when used appropriately, it definitely does not decrease fetal salvage. The appropriate use of antihypertensive therapy during pregnancy requires an understanding of the mechanism of action of these agents and recognition of side effects, especially those important during pregnancy.     

Accelerated wear testing as an aid to failure diagnosis and materials selection

The needs and advantages of accelerated wear testing are discussed, with particular reference to aerospace applications. Examples are given from recent work on plastics-based dry-bearing liners to illustrate how accelerated wear tests can provide information relevant to materials selection, identification of the main parameters influencing wear and definition of the relationships between wear, material composition and structure. Prediction of the service life of dry-bearing liners, however, presents problems and full-scale component tests are usually required