Intercellular adhesion molecule-3 is the predominant co-stimulatory ligand for leukocyte function antigen-1 on human blood dendritic cells

Dendritic cells (DC) are potent stimulators of primary T lymphocyte responses to foreign antigen. The initial DC-T lymphocyte interaction involves the binding of the adhesion molecule leukocyte function antigen-1 (LFA-1; CD11a/CD18) on the T lymphocyte to an intercellular adhesion molecule (ICAM) on the DC. Although blood and tonsil DC express ICAM-1 (CD54) and ICAM-2 (CD102) on their surface, anti-ICAM-1 and anti-ICAM-2 monoclonal antibodies (mAb) have little inhibitory activity on the DC-stimulated mixed leukocyte reaction (MLR). We therefore examined the expression of the more recently identified LFA-1 ligand, ICAM-3 (CD50), in comparison to ICAM-1 and ICAM-2 on blood DC and sought a functional role for ICAM-3 in DC-mediated T lymphocyte responses. Resting blood DC expressed significantly more ICAM-3 than ICAM-1 or ICAM-2 as assessed by flow cytometry. Treatment of resting DC with interferon-γ led to increased expression of ICAM-1; however, ICAM-2 and ICAM-3 levels remained relatively constant. Solid-phase recombinant chimeric molecules ICAM-1-, ICAM-2- and ICAM-3-Fc were able to co-stimulate CD4⁺ T lymphocyte proliferation in conjunction with suboptimal solid-phase CD3 mAb 64.1. However, the anti-ICAM-3 mAb CAL 3.10 inhibited a DC-stimulated MLR to a greater extent than anti-ICAM-1 or anti-ICAM-2 reagents and appeared to act by blocking the DC ICAM-3- T lymphocyte LFA-1 interaction. As ICAM-3 is the predominant LFA-1 ligand on resting blood DC, we postulate that DC may utilize ICAM-3 for initial DC-T lymphocyte interactions, and that ICAM-1, which is up-regulated upon DC activation, and/or ICAM-2, may contribute to DC migration or later phases of the T lymphocyte activation process.     

Heart Rate Reactivity and Type A Behavior as Modifiers of Physiological Response to Active and Passive Coping

We examined the long term predictivity of heart rate reactivity (HRR) and its relation to cardiovascular and biochemical activity during rest and during tasks requiring active and passive coping. HRR was determined in 28 young men by measuring peak heart rate change to cold pressor one year after performing tasks eliciting active and passive coping. Heart rate change to cold pressor was significantly correlated with change to active coping (r= .65, p<.01) and to passive coping (r= .53, p<.01). Responses to the tasks were equivalent for Type A and B subjects. On the other hand, high HRRs were significantly more reactive than low HRRs with the effect being most apparent during active coping. HRR appeared to be a trait stable over one year which predicted enhanced cardiac, neuroendocrine, and neuromuscular response.     

Polyene sequence distribution in modified poly(vinyl chloride) after thermal degradation

The products resulting from the reaction of PVC with sodium benzenethiolate were degraded to 0,3% at 180°C in the solid state and at 160°C in solution in trichlorobenzene. The polyene distribution of the polymers after degradation was studied by both UV-visible and resonance Raman spectroscopies, as a function of the degree of substitution. The results show that there are two types of behaviour: that of the PVC sample prior to the substitution reaction together with the samples modified up to a definite degree of substitution which depends on the starting isotactic content, and that of samples with higher degrees of substitution. The former group exhibits not only a steady improvement in thermal stability but also a preferential formation of polyenes of 7 – 9 double bonds whose concentration decreases with increasing degree of substitution. Conversely, for the second group of samples the thermal stability decreases with the degree of substitution and no specific absorption bands are observed. On the basis of earlier work on the selective substitution of the isotactic GTTG and heterotactic TTTG triads during the first stage of the reaction, the present results show that the bands at 393, 416, and 437 nm are related to specific polyenes which result from initiation by the above quoted conformations in PVC, a conclusion for which confirmatory evidence was obtained by resonance Raman spectroscopic examination of the samples. There is, therefore, clear evidence for the occurrence of two distinct degradation mechanisms, one involving initiation by the unstable triad conformations and the other via random initiation at stable and normal structures. To this may be added the initiation by defect structures, which have been extensively documented in the literature.     

A subpopulation of small pre-B cells in rabbit bone marrow expresses x light chains and exhibits allelic exclusion of b locus allotypes

The expression of immunoglobulin heavy and light chains by pre-B cells and B lymphocytes was examined by two-color immunofluorescence in heterozygous b⁵b⁹ rabbits. Allelic exclusion of b5 and b9 x light chain allotypes was observed for both surface immunoglobulin-negative pre-B cells and surface immunoglobulin-positive B lymphocytes. In newborn bone marrow, pre-B cells and immature B lymphocytes expressing b9 were as numerous as those expressing b5. In contrast, circulating B cells and bone marrow plasma cells expressing the b5 marker outnumber b9⁺ cells by 2 to 1 in adult b⁵b⁹ animals. Whereas most B lymphocytes expressed x light chain b allotypes, approximately 80% of the μ heavy chain-positive pre-B cells did not. The pre-B cells that expressed detectable light chains were relatively small lymphocytes. A model is presented which includes a “transitional” pre-B cell that expresses both p chains and x chains.     

The measurement of the tacticity of poly(vinyl chloride) by 13C nuclear magnetic resonance spectroscopy

Fourier transform ¹H-decoupled ¹³C NMR spectra were obtained on seven poly(vinyl chloride), (PVC), samples in solution in o-dichlorobenzene. Four of the polymers were of the commercial type and the others were prepared by suspension polymerisation at +90°C, +5°C, and -30°C. Measurements of the spectra were used to assess the precision and accuracy with which information about the tacticity of PVC can be obtained from such spectra. The results show that the well-resolved α-carbon triad and β-carbon tetrad spectra obtained may be reliably analysed to give values of the probability of syndiotactic placement with a precision of about 0,005 for measurements on a single run on a single sample. The simplest and probably the most reliable method of measuring the areas under the peaks which correspond to specific triads ot tetrads is to use the spectrometer integrator, although results of slightly lower precision may be obtained by the use of a curve resolver. Consideration of possible systematic errors due to different T₁ relaxation times, unequal nuclear Overhauser enhancement (NOE) factors, and incomplete dissolution of the polymer has shown that the only one of these which is possibly significant is that due to NOE, which is almost certainly less than 0,008, so that the absolute accuracies of the P_r values should be better than that. A more detailed study of the data shows that the polymers made at 5°C and -30°C are almost certainly non-Bernoullian and that firstoder Markov statistics can adequately describe the observed departures from Bernoullian statistics. These departures may have significant consequences for the physical properties of the polymers.     

Repeated Habituation and Overhabituation of the Orienting Response

This investigation was designed to test (a) whether stimuli presented in the form of repeated blocks of habituation trials, as opposed to.1 single continuous series of stimuli, would produce a progressive decline. in amount of spontaneous recovery and trials to rehabituation of the skin conductance component of the orienting response; and (b) whether 30 or 50 post-habituation trials would produce a return of the orienting response which could be related In sensitization effects. Results showed that repeated habituations strengthened habituation as reflected in progressively decreasing spontaneous recovery across blocks, but not in speed of habituations. Further, neither 30 nor 50 post-habituation trials produced a return of the orienting response, although 30 such trials did result in increased skin conductance level. Discussion centers on whether habituation beyond asymptotic levels (‘below-zero’) within sessions was unambiguously obtained; relationships among stimulus intensity, frequency, and the return of the orienting response; and factors affecting measures of retention of habituation within sessions.     

Comparison of once-daily atazanavir with efavirenz, each in combination with fixed-dose zidovudine and lamivudine, as initial therapy for patients infected with HIV

BACKGROUND: Atazanavir, an azapeptide protease inhibitor (PI), has pharmacokinetics that allow once-daily dosing, and it is not associated with significant PI-associated dyslipidemia. METHODS: A randomized, double-blind, double-dummy, active-controlled, 2-arm study comparing the antiviral efficacy and safety of atazanavir 400 mg administered once daily with efavirenz 600 mg administered once daily in combination with open-label fixed-dose zidovudine plus lamivudine twice daily. The 810 treatment-naive patients were stratified by HIV RNA level. The primary efficacy end point was the proportion of treated patients with HIV RNA levels <400 copies/mL through week 48. RESULTS: At week 48, HIV RNA levels were <400 copies/mL in 70% of patients receiving atazanavir and 64% of patients receiving efavirenz (intent-to-treat, difference; 95% confidence interval: 5.2%; -1.2%, 11.7%). Median CD4 cell counts increased at comparable magnitudes and rates in the 2 treatment arms (mean change at week 48: 176 cells/mm with atazanavir, 160 cells/mm with efavirenz). Atazanavir-treated patients relative to comparator-treated patients did not demonstrate significant increases in total cholesterol, fasting low-density lipoprotein cholesterol, or fasting triglycerides over 48 weeks of therapy. Atazanavir-linked bilirubin elevations infrequently resulted in treatment discontinuation (<1%). Atazanavir treatment did not increase fasting glucose or insulin levels. CONCLUSIONS: For initial HIV treatment, a highly active antiretroviral therapy regimen of atazanavir/zidovudine/lamivudine is as efficacious and well tolerated as the combination of efavirenz/zidovudine/lamivudine.     

Acute hormonal responses to heavy resistance exercise in strength athletes versus nonathletes.

The aim of the present study was to investigate acute hormonal and neuromuscular responses and recovery in strength athletes versus nonathletes during heavy resistance exercise performed with the forced and maximum repetitions training protocol. Eight male strength athletes (SA) with several years of continuous resistance training experience and 8 physically active but non-strength athletes (NA) volunteered as subjects. The experimental design comprised two loading sessions: maximum repetitions (MR) and forced repetitions (FR). MR included 12-RM squats for 4 sets with a 2-min recovery between sets. In FR the initial load was higher than in MR so that the subject could lift approximately 8 repetitions by himself and 4 additional repetitions with assistance. Before and after the loading protocols, blood samples were drawn to determine serum testosterone, free testosterone, cortisol and growth hormone concentrations, and blood lactate. Maximal voluntary isometric force and EMG activity of the leg extensors was measured before and after the loading as well as 24 and 48 hrs after the loading. The concentrations of the hormones measured increased significantly (p < .01-.001) after both loadings in both groups. The responses tended to be higher in FR than the MR loading and the increases of testosterone concentrations were significantly (p < .01) greater in both loadings in SA than in NA. Both loading protocols in both groups also led to neuromuscular fatigue observable with significant acute decreases in isometric strength by 32-52% (p < .001) and in maximal iEMG (p < .05-01) associated with large increases in blood lactate. These data suggest that, at least in experienced strength athletes, the forced-repetition protocol is a viable alternative to the more traditional maximum-repetition protocol and may even be a superior approach.     

Extended multilocus sequence typing system for Campylobacter coli, C. lari, C. upsaliensis, and C. helveticus

A multilocus sequence typing (MLST) system has been reported previously for Campylobacter jejuni to both differentiate strains and identify clonal lineages. However, sequence variation at the MLST loci prevents its use for closely related Campylobacter species. We describe herein an expanded MLST method to include three clinically relevant Campylobacter species, C. coli, C. lari, and C. upsaliensis, and a fourth Campylobacter species, C. helveticus. The C. coli and C. helveticus methods use the same seven C. jejuni loci (aspA, atpA, glnA, gltA, glyA, pgm, and tkt); however, adk and pgi were substituted for aspA and gltA in C. lari and for gltA and pgm in C. upsaliensis. Multiple C. coli (n = 57), C. lari (n = 20), C. upsaliensis (n = 78), and C. helveticus (n = 9) isolates, representing both clinical and environmental sources, were typed. All four species were genetically diverse: the majority (> 80%) of the isolates had unique sequence types (STs). Using this method, mixed C. lari, C. upsaliensis, and C. helveticus isolates were identified; upon separation, each isolate was shown to contain two strains of the same species with distinct STs. Additionally, the expanded MLST method was able to detect potential lateral transfer events between C. jejuni and either C. coli or C. lari and between C. upsaliensis and C. helveticus. Thus, the expanded MLST method will prove useful in differentiating strains of five Campylobacter species, identifying mixed Campylobacter cultures, and detecting genetic exchange within the genus.