The interaction of visual and proprioceptive inputs in pointing to actual and remembered targets

Errors in pointing to actual and remembered targets presented in three-dimensional (3D) space in a dark room were studied under various conditions of visual feedback. During their movements, subjects either had no vision of their arms or of the target, vision of the target but not of their arms, vision of a light-emitting diode (LED) on their moving index fingertip but not of the target, or vision of an LED on their moving index fingertip and of the target. Errors depended critically upon feedback condition. 3D errors were largest for movements to remembered targets without visual feedback, diminished with vision of the moving fingertip, and diminished further with vision of the target and vision of the finger and the target. Moreover, the different conditions differentially influenced the radial distance, azimuth, and elevation errors, indicating that subjects control motion along all three axes relatively independently. The pattern of errors suggest that the neural systems that mediate processing of actual versus remembered targets may have different capacities for integrating visual and proprioceptive information in order to program spatially directed arm movements.     

Transfusion and recombinant human erythropoietin requirements differ between dialysis modalities

BACKGROUND: Before the routine use of recombinant human erythropoietin (rHuEpo), patients dialysed by peritoneal dialysis (PD) received fewer blood transfusions than patients on haemodialysis (HD). We compared transfusion practices in these groups now that the use of rHuEpo has become standard, while controlling for variables known to influence anaemia of end-stage renal disease (ESRD). Maintenance rHuEpo doses were also compared. METHODS: Data were examined for 157 HD and 126 PD patients during a 2-year period. Potential confounders included age, gender, albumin, iron deficiency, parathyroid hormone (PTH), underlying renal disease, comorbid illness, renal transplant, dialysis adequacy and duration. An intent-to-treat analysis was used, with sensitivity analyses to account for change in treatment and transplant. RESULTS: Mean haemoglobin (Hb) was not different (10.47 g/dl for HD, 10.71 g/dl for PD; P = 0.45). Mean monthly transfusion rate was higher for HD (0.47 units per month vs 0.19; P < 0.01). More HD patients received at least one transfusion (52.9 vs 40.9%; P < 0.01). The maintenance rHuEpo dose was higher for HD (7370 U/week vs 5790 U/week; P = 0.01). The only factors associated with risk of being transfused were dialysis duration and mode of dialysis (less risk for PD, odds-ratio 0.57; 95% confidence interval 0.35-0.92). CONCLUSIONS: Despite the routine use of rHuEpo, HD patients received more blood and rHuEpo than PD patients to achieve the same Hb. No patient factors were identified to account for this difference. The use of fewer transfusions and less rHuEpo in PD represents an advantage over HD in terms of both cost and safety.     

Distribution and development of short-wavelength cones differ between Macaca monkey and human fovea

Macaca monkey and humans have three cone types containing either long-wavelength (L), medium-wavelength (M), or short-wavelength (S)-specific opsin. The highest cone density is found in the fovea, which mediates high visual acuity. Most studies agree that the adult human fovea has a small S cone-free area, but data are conflicting concerning S-cone numbers in the adult Macaca monkey fovea, and little evidence exists for how either primate fovea develops its characteristic cone pattern. Single- and double-label in situ hybridization and immunocytochemistry have been used to determine the pattern of foveal S cones in both the fetal and adult Macaca and human. Both labels find a clear difference at all ages between monkey and human. Adult humans have a distinct but variable central zone about 100 microm wide that lacks S cones and is surrounded by a ring in which the S-cone density is 8%. This S cone-free zone is detectable at fetal week 15.5 (Fwk15.5), shortly after S opsin is expressed, and is similar to the adult by Fwk20.5. Adult monkey foveas have an overall S-cone foveal density of 10%, with several areas lacking a few S cones that are not coincident with the area of highest cone density. A surrounding zone at 200-microm eccentricity has an S-cone density averaging 25%, but, by 800 microm, this has decreased to 11%. Fetal day 77-135 monkeys all have a distribution and density of foveal S cones similar to adults, although the high-density ring is not obvious in fetal retinas. Estimates of the numbers of S cones missing in the fetal human fovea range from 234 to 328, whereas no more than 40 are missing in the fetal monkey. These results show that, in these two trichromatic primates, S-cone distribution and the developmental mechanisms determining S-cone topography are markedly different from the time that S cones are first detected.     

Interactions between the human immunodeficiency virus and hepatitis C virus

INTRODUCTION: Prevalence of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected subjects is around 9%, varying according to the mode of contamination. Reciprocal interactions between the two viruses have to be evaluated. CURRENT KNOWLEDGE AND KEY POINTS: HCV infection is usually associated with chronic hepatitis and detectable viremia in HIV-infected patients. HIV infection enhances HCV replication, leading to more severe liver lesions and to a more rapid occurrence of cirrhosis. This underlines the need for both early diagnosis and therapy in order to avoid severe evolution of the liver disease. FUTURE PROSPECTS AND PROJECTS: Even though the rate of long-term responses to interferon alpha is low, improvement may be expected from combined therapies, especially with combination including ribavirin. The impact of both antiretroviral triple therapy and accompanying immune restoration on natural history and treatment of HCV infection has to be assessed, as the above mentioned consensual conclusions may be modified in a near future.     

Interactions between subunits of the human epithelial sodium channel

The human epithelial sodium channel (hENaC) mediates Na+ transport across the apical membrane of epithelia, and mutations in hENaC result in hypertensive and salt-wasting diseases. In heterologous expression systems, maximal hENaC function requires co-expression of three homologous proteins, the alpha, beta, and gammahENaC subunits, suggesting that hENaC subunits interact to form a multimeric channel complex. Using a co-immunoprecipitation assay, we found that hENaC subunits associated tightly to form homo- and heteromeric complexes and that the association between subunits occurred early in channel biosynthesis. Deletion analysis of gammahENaC revealed that the N terminus was sufficient but not necessary for co-precipitation of alphahENaC, and that both the N terminus and the second transmembrane segment (M2) were required for gamma subunit function. The biochemical studies were supported by functional studies. Co-expression of gamma subunits lacking M2 with full-length hENaC subunits revealed an inhibitory effect on hENaC channel function that appeared to be mediated by the cytoplasmic N terminus of gamma, and was consistent with the assembly of nonfunctional subunits into the channel complex. We conclude that the N terminus of gammahENaC is involved in channel assembly.     

Interactions between tachykinins and diverse, human nicotinic acetylcholine receptor subtypes

Nicotinic acetylcholine receptors (nAChR) are diverse members of the ligand-gated ion channel superfamily of neurotransmitter receptors and play critical roles in chemical signaling throughout the nervous system. Reports of effects of substance P (SP) on nAChR function prompted us to investigate interactions between several tachykinins and human nAChR subtypes using clonal cell lines as simple experimental models. Acute exposure to SP inhibits carbamylcholine- or nicotine-stimulated function measured using 86Rb+ efflux assays of human ganglionic (alpha 3 beta 4) nAChR expressed in SH-SY5Y neuroblastoma cells (IC50 approximately 2.3 microM) or of human muscle-type (alpha 1 beta 1 gamma delta) nAChR expressed in TE671/RD clonal cells (IC50 approximately 21 microM). SP also acutely blocks function of rat ganglionic nAChR expressed in PC12 pheochromocytoma cells (IC50 approximately 2.1 microM). Neurokinin A and eledoisin inhibit function (extrapolated IC50 values between 60 and 160 microM) of human muscle-type or ganglionic nAChR, but neurokinin B does not, and neither human nAChR is as sensitive as PC12 cell alpha 3 beta 4-nAChR to eledoisin or neurokinin A inhibition. At concentrations that produce blockade of nAChR function, SP fails to affect binding of [3H]acetylcholine to human muscle-type or ganglionic nAChR. SP-mediated blockade of rat or human ganglionic nAChR function is insurmountable by increasing agonist concentrations. Collectively, these results indicate that tachykinins act noncompetitively to inhibit human nAChR function with potencies that vary across tachykinins and nAChR subtypes. They also indicate that tachykinin actions at nAChR could further contribute to complex cross-talk between nicotinic cholinergic and tachykinin signals in regulation of nervous system activity.     

Interactions between HMR 3647, a new ketolide, and human polymorphonuclear neutrophils

HMR 3647, a new ketolide, is active upon intracellular pathogens. We previously demonstrated that HMR 3004 (RU 64004), another ketolide, is highly concentrated by human polymorphonuclear neutrophils (PMNs). This prompted us to evaluate whether the presence of a 3-keto group instead of an L-cladinose, a neutral sugar characteristic of erythromycin A derivatives, confers peculiar pharmacokinetic properties with regard to cellular accumulation and efflux. After incubation with the radiolabelled drug, HMR 3647 uptake was determined by a velocity gradient centrifugation technique. HMR 3647 was avidly concentrated by PMNs, without saturation, over a 3-h incubation period, with cellular-to-extracellular concentration ratios of 31 +/- 4.2 at 5 min and up to 348 +/- 27.1 at 180 min. About 60% of HMR 3647 was located in the granular compartment; less than 6% was associated with the membranes. HMR 3647 gradually egressed from loaded cells placed in drug-free medium. Uptake was dependent on environmental temperature (activation energy, 128 +/- 9. 4 kJ/mol) but not on extracellular pH. HMR 3647 displayed Michaelis-Menten saturation kinetics with a mean Vmax of 2315 ng/2.5 x 10(6) PMNs/5 min and a mean Km of 117 mg/liter (144 microM). As already observed with erythromycin A-derived macrolides, extracellular Ca2+ was necessary for optimal uptake of HMR 3647. Interestingly, verapamil increased the uptake of HMR 3647 at 5 min, but this was followed by gradual inhibition at later incubation times, a phenomenon probably related to stimulation of drug efflux. The impact of intracellular accumulation of HMR 3647 on PMN functions was also investigated. In contrast to other erythromycin A derivatives, HMR 3647 only weakly triggered granule exocytosis, but it inhibited superoxide anion production in a time- and concentration-dependent manner, with concentrations which inhibited 50% of control response of 55 (67 microM) (5 min) and 30 (36 microM) (30 min) mg/liter for formyl-methionyl-leucyl-phenylalanine stimulation and 117 (143 microM) (5 min) and 44 (54 microM) (30 min) mg/liter for phorbol myristate acetate stimulation.     

Myogenic vestibular-evoked potentials in normal subjects: a comparison between responses obtained from sternomastoid and trapezius muscles

Brief intense clicks cause short latency microcontraction of cervical muscles. Several studies have supported the hypothesis that these microcontractions are of vestibular origin. Averaging these muscular responses enables us to obtain myogenic vestibular evoked potential (MVEP). The receptor of these responses is thought to be the saccule, afferent pathways being the vestibular nerve and efferent pathways the vestibulospinal tract. However, discrepancies are reported with regard to results obtained in healthy subjects: some authors obtained symmetrical response to monaural clicks whereas others obtained responses of greater amplitude on the muscle ispilateral to stimulation. These discrepancies may be due to the presence of different recording sites (inion, sternomastoid or trapezius muscles). The aim of this study was to clarify MVEP results in healthy subjects, using a simple non-traumatic method, and to compare the results obtained on sternomastoid (SM) and trapezius muscles (TRP). Sixteen normal hearing healthy subjects were involved. Latencies and amplitude of both SM and TRP muscle were reproducible in the same subject. Patterns of response were similar to those obtained in previous studies. Following binaural and monaural stimulations, latencies of MVEP were symmetrical on both muscles and amplitudes tended to be greater on muscles contralateral to stimulation, which conflicts with previous results in the literature. Whatever the type of stimulation, latencies of responses obtained on SM were significantly shorter (mean = -3.8 ms), and amplitudes lower (mean = -7.1 microV), than those obtained on TRP. Binaural stimulation resulted in responses of greater amplitude compared to monaural (mean = 0.45 microV). Given the intrasubject reproducibility of the responses, these methods allow MEVP to be recorded in a standardized and reproducible way.     

Interactions between pacemakers and security systems

BACKGROUND: Hot flashes are often a troublesome symptom in breast carcinoma survivors and men with prostate carcinoma who have undergone androgen deprivation therapy. A previous clinical study demonstrated that, on a short term basis, low dose megestrol acetate markedly reduced hot flashes and was well tolerated. Little information has been available regarding the long term use of low dose megestrol acetate for hot flashes. METHODS: Patients previously enrolled on a randomized placebo-controlled trial that evaluated the short term use of megestrol acetate for hot flashes were contacted and interviewed by telephone. RESULTS: A total of 132 persons were contacted. Nine percent of the patients discontinued megestrol acetate after resolution of their hot flashes. Forty-five percent of the patients contacted were continuing to utilize megestrol acetate approximately 3 years beyond the conclusion of the 1992 study. Three-quarters of these patients were utilizing < or =20 mg of megestrol acetate per day. Potential toxicities attributed to megestrol acetate included episodes of chills, appetite stimulation/weight gain, vaginal bleeding, and carpal tunnel syndrome symptoms. CONCLUSIONS: A substantial proportion of patients continue to use megestrol acetate for periods of up to 3 years or longer with continued control of hot flashes. This treatment appears to be relatively well tolerated.     

Short-latency EMG potentials elicited by head taps in sternocleidomastoid muscles: a study on normal human subjects and patients with central or vestibular lesions

Ten subjects with diabetes mellitus and unilateral chronic foot ulcer were investigated. Local tissue concentrations of glucose and lactate were measured using the microdialysis method at a distance of 0.5-1 cm from the edge of the ulcer and in normal skin in the contralateral foot. Subcutaneous blood flow in the area investigated was measured using the 133Xewashout technique. The interstitial glucose concentration in the ulcer was found to be lower than in intact skin (8.0 +/- 1.0 mmol l-1 vs. 8.5 +/- 1.1 mmol l-1) (P < 0.02), and the interstitial lactate concentration was higher in the ulcer than in intact skin (3.2 +/- 0.2 mmol l-1 vs. 2.1 +/- 0.3 mmol l-1) (P < 0.01). The subcutaneous blood flow was on average 40% higher in the ulcer than in the intact skin. The calculated local glucose uptake and lactate outputs were twofold higher in the ulcer than in the intact skin. However, the molar ratio between lactate output and glucose uptake was approximately two, both in the ulcer and in the intact skin, indicating that the glucose metabolism was qualitatively the same in the two regions.     

Transmitter-induced calcium responses differ in astrocytes acutely isolated from rat brain and in culture

Glial fibrillary acid protein (GFAP)-positive astrocytes isolated from the cerebral cortices of 3-10-day-old rats frequently showed increased intracellular Ca2+ concentration responses to L-glutamate and glutamate analogues. However, few of the acutely isolated cells responded to ATP, and no such cells responded to serotonin [5-hydroxytryptamine (5-HT)]. The same cell that failed to respond to ATP or 5-HT often responded to glutamate. Culturing acutely isolated cells in media containing horse serum decreased Ca2+ responses to glutamate but increased the responses to ATP and induced responses to 5-HT. In primary cultures prepared from the cerebral cortices of 1-day-old rats and cultured in horse serum, fewer of the cells responded to glutamate, but almost all cells responded to ATP and 5-HT. The lack of or limited response to, 5-HT or ATP in the acutely isolated cells seems unlikely to be due to selective damage to the respective receptors because acutely isolated GFAP-negative cells showed responses to ATP, several different proteases and mechanical dissociation yielded cells that also responded to glutamate but not to ATP, and exposure of primary cultures to papain did not abolish Ca2+ responses to several transmitters. The responses of the acutely isolated cells to glutamate but limited or lack of responses to ATP and 5-HT also correspond to what has been seen so far for astrocytes in situ. Thus, the present studies provide direct evidence that some of the receptors seen in primary astrocyte cultures may reflect a response to culture conditions and that, in the context of the relevant information so far available, acutely isolated astrocytes seem to reflect better the in vivo state.     

Interactions between bacterial toxins and intestinal cells

Bacterial toxins which act on intestinal cells display a great diversity of size, structure and mode of action. Some toxins interact with the cell by transducing a signal across the membrane leading to stimulation of intracellular second messenger (E. coli heat stable enterotoxin), others form pores (C. perfringens enterotoxin, ...) permitting the leakage of cellular components and cell lysis. The most sophisticated toxins comprise at least two functional domains or components, one being a binding domain permitting the internalization into the cell of an enzymatic domain which modifies an intracellular target. The enzymatic modification (ADP-ribosylation, UDP-glucosylation, glycohydrolysis, proteolysis, ...) of a specific target (heterotrimeric G-protein, small G-protein, monomeric actin, ribosomal RNA, ...) alters the cell physiology (increase of ions and water secretion, cytoskeleton rearrangement, protein synthesis inhibition, apoptosis, ...) and tissue organization (modification of barrier permeability, necrosis, ...). The study of bacterial toxins leads to the understanding of the interactions between pathogenic bacteria and their hosts and constitutes also a new approach in cell biology, by facilitating the exploration of certain regulatory pathways such as that controlling actin polymerization.     

Interactions between lonidamine and beta- or hydroxypropyl-beta-cyclodextrin

Equilibrium dialysis and Scatchard plots were used to establish that human and rabbit paraoxonases both have two calcium binding sites. Independent-site and stepwise constant analyses were used to calculate a higher affinity site (Kd1) of 3.6 +/- 0.9 x 10(-7) M for human A paraoxonase, and 1.4 +/- 0.5 x 10(-8) M for rabbit paraoxonase, and a lower affinity site (Kd2) of 6.6 +/- 1.2 x 10(-6) M for human A paraoxonase, and 5.3 +/- 0.94 x 10(-6) M for rabbit paraoxonase. In both species, the higher affinity sites were found to be essential to maintain hydrolytic activity; complete removal of calcium led to irreversible inactivation. The lower affinity sites were required for catalytic activity, and their binding of calcium was reversible. Experimentally estimated values of Kd2 based on the concentration of calcium required to obtain half the maximum enzymatic activity were 3 microM for human A and B paraoxonases, and also in the order of 3 microM for rabbit paraoxonase, using three different substrates. Calcium was the only metal found that protects against denaturation and also confers hydrolytic activity with these two mammalian paraoxonases.     

Interactions between the jaw-opening reflex and mastication

Electrical stimulation of the anterior hard palate or upper lip was used to evoke the jaw-opening reflex in rabbits lightly anesthetized with urethane. The amplitude of each excitatory response recorded in the digastric electromyogram during mastication was compared with the mean amplitude of 10 prior control responses. When weak stimuli were used, the mean amplitude of the reflex dropped markedly during mastication and was smallest when the digastric muscle was inactive (closing and occlusal phases of the masticatory cycle). As the stimulus strength was increased, the size of the response during closing rose progressively until it exceeded values obtained during the control period or the jaw-opening phase. In addition, strong stimuli altered the total cycle length and the duration and amplitude of muscle activity in a phase-dependent manner. Stimuli given during closing were particularly effective in causing inhibition of jaw-closing muscle activity and in reducing the velocity and amplitude of closure. It is concluded that the cyclical gain changes of the reflex response to noxious stimuli are controlled to a large extent by premotoneuronal mechanisms and that the overall effect on the masticatory cycle structure is phase dependent.     

Interactions between nurses and patients on ventilators

Image cytometric analysis of DNA ploidy status of 40 fresh primary breast carcinomas was performed in a comparative study on cytologic preparations stained directly by the Feulgen method and smears from the same tumors Feulgen-stained after Papanicolaou staining. There was a 0.82 overall concordance in diploid and aneuploid tumor classification and a good correlation (r = 0.736, P < 0.001) between the DNA indices determined by the two methods. Discordances are probably due to tumor heterogeneity. This study demonstrates that image cytometric DNA analysis on previously routine-stained cytologic preparations is feasible and reliable for pretreatment DNA analysis and suggests potential applications in retrospective studies with cytologic material from archives.     

Interactions between PVC Geomembranes and Compacted Clays

The interactions between plastic soils and polyvinyl chloride (PVC) geomembranes were studied using a direct shear device under as-compacted conditions. The PVC geomembranes had smooth or textured surfaces, and the soils were of plasticity index (PI) ranging from 35 to 100%. The peak and residual failure envelopes were expressed using Coulomb failure criteria. The adhesion and angle of friction increased for PIs up to 70% and subsequently recorded a decrease. The adhesion is larger for the peak strength compared to the residual strength, but it was the reverse for the angle of friction. The efficiency in terms of adhesion appeared more relevant than that of the angle of friction in expressing the interactions between geomembrane and cohesive soils. The smooth and textured geomembranes showed little difference in results at the residual state.