The role of decay accelerating factor in the immunopathogenesis of cytomegalovirus infection.

A wide variety of the host immune elements play an influential role in the defence against cytomegalovirus (CMV) infection. However, the role of complement in the clearance of CMV infection is less well studied. Decay accelerating factor (DAF/CD55) is a membrane-bound complement regulatory protein that inhibits the formation and accelerates the decay of C3-convertase. Here we hypothesize that murine CMV (MCMV) utilizes DAF as an immunoevasive strategy through down-regulation of host adaptive responses against the virus. To test our hypothesis, DAF knock-out (DAF KO) C57BL/6 mice and wild-type (WT) littermates were infected with a sublethal dose of MCMV, and their immune responses were compared. WT mice lost 7·8% of their initial weight within the first 4 days after infection and quickly began to recover. This is in contrast to the DAF KO mice, that lost a total of 19·4% of their initial weight and did not start recovery until 6 days post-infection. Flow cytometric analysis of lung digests revealed that infected DAF KO mice had a significantly increased infiltration of inflammatory cells, the majority being CD8(+) T lymphocytes. Serum levels of tumour necrosis factor (TNF)-α and interferon (IFN)-γ were also increased markedly in the DAF KO mice compared to the infected WT mice. More interestingly, increased viral genome copies (DNA) in the splenocytes of DAF KO mice was accompanied with mRNA transcripts in the DAF KO mice, an indication of active viral replication. These data suggest an intriguing effect of reduced DAF expression on host responses following in vivo MCMV infection.

Religious coping and problem-solving by couples faced with prostate cancer.

Religion can be an important resource for people struggling with chronic illness. Problem-solving skills have also been shown to be helpful. This study examined whether turning to religion as a coping resource would be associated with better problem-solving in couples trying to manage challenges associated with prostate cancer. The sample was 101 patients with prostate cancer and their wives. Wives completed the Social Problem-Solving Inventory--Revised at baseline (T1) and 10 weeks later (T2). Patients and their wives also completed a measure that included items on religious coping. These items were used to classify couples into four groups based on whether one or both members engaged in religious coping: (1) husband only, (2) wife only, (3) both husband and wife, and (4) neither husband nor wife. From T1 to T2, wives who used religious coping along with their husbands (group 3) showed a significantly greater reduction in dysfunctional problem-solving (specifically, on impulsive/careless problem-solving) in comparison with wives who used religious coping while their husbands did not (group 2). Findings suggest that when couples share in turning to religion as a source of coping, this may be associated with improved problem-solving, but sole engagement in religious coping by wives may be associated with worse problem-solving.

Parton coalescence and the antiproton/pion anomaly at RHIC.

Coalescence of minijet partons with partons from the quark-gluon plasma formed in relativistic heavy ion collisions is suggested as the mechanism for production of hadrons with intermediate transverse momentum. The resulting enhanced antiproton and pion yields at intermediate transverse momenta give a plausible explanation for the observed large antiproton to pion ratio. With further increasing momentum, the ratio is predicted to decrease and approach the small value given by independent fragmentations of minijet partons after their energy loss in the quark-gluon plasma.

Flavor ordering of elliptic flows at high transverse momentum.

Based on the quark coalescence model for the parton-to-hadron phase transition in relativistic heavy ion collisions, we relate the elliptic flow (upsilon(2)) of high p(T) hadrons to that of high p(T) quarks. For high p(T) hadrons produced from an isospin-symmetric and quark-antiquark-symmetric partonic matter, magnitudes of their elliptic flows follow a flavor ordering as (upsilon(2,pi)=upsilon(2,N))>(upsilon(2,Lambda)=upsilon(2,Sigma))>upsilon(2,K)>upsilon(2,Xi)>(upsilon(2,phi)=upsilon(2,Omega)) if strange quarks have a smaller elliptic flow than light quarks. The elliptic flows of high p(T) hadrons further follow a simple quark counting rule if strange quarks and light quarks have the same high p(T) spectrum and coalescence probability.

Partonic effects on pion interferometry at the relativistic heavy-ion collider.

Using a multiphase transport model that includes both initial partonic and final hadronic interactions, we study the pion interferometry at the Relativistic Heavy-Ion Collider. We find that the two-pion correlation function is sensitive to the magnitude of the parton-scattering cross section, which controls the parton density at which the transition from the partonic to hadronic matter occurs. Also, the emission source of pions is non-Gaussian, leading to source radii that can be more than twice larger than the radius parameters extracted from a Gaussian fit to the correlation function.

Cancer education for clergy and lay church leaders.

BACKGROUND: Reaching diverse population subgroups with information about cancer prevention/early detection, pain management, and clinical trials has historically been a significant public health challenge. A partnership between clergy and cancer educators might help reduce this challenge. METHODS: Participating churches were randomized into two programs for delivering cancer education after their church leaders completed a baseline survey about their knowledge, attitudes, and roles related to the cancer ministry. RESULTS: Clergy reported opportunities to use their acquired cancer knowledge, a high receptivity to their information, comfort discussing cancer care and clinical trials, and a strong recommendation that the educational program/partnership continue to be offered.

Korean women: breast cancer knowledge, attitudes and behaviors.

INTRODUCTION: Clustered within the nomenclature of Asian American are numerous subgroups, each with their own ethnic heritage, cultural, and linguistic characteristics. An understanding of the prevailing health knowledge, attitudes, and screening behaviors of these subgroups is essential for creating population-specific health promotion programs. METHODS: Korean American women (123) completed baseline surveys of breast cancer knowledge, attitudes, and screening behaviors as part of an Asian grocery store-based breast cancer education program evaluation. Follow-up telephone surveys, initiated two weeks later, were completed by 93 women. RESULTS: Low adherence to the American Cancer Society's breast cancer screening guidelines and insufficient breast cancer knowledge were reported. Participants' receptiveness to the grocery store-based breast cancer education program underscores the importance of finding ways to reach Korean women with breast cancer early detection information and repeated cues for screening. The data also suggest that the Asian grocery store-based cancer education program being tested may have been effective in motivating a proportion of the women to schedule a breast cancer screening between the baseline and follow-up surveys. CONCLUSION: The program offers a viable strategy to reach Korean women that addresses the language, cultural, transportation, and time barriers they face in accessing breast cancer early detection information.

Kinetic equation with exact charge conservation.

A kinetic master equation for multiplicity distributions is formulated for charged particles which are created or destroyed only in pairs due to the conservation of their Abelian charge. It allows one to study time evolution of the multiplicity distributions in a relativistic many-body system with arbitrary average particle multiplicities. It is shown to reproduce the equilibrium results for both canonical (rare particles) and grand canonical (abundant particles) systems. For canonical systems, the equilibrium multiplicity is much lower and the relaxation time is much shorter than the naive extrapolation from grand canonical results. Implications for chemical equilibration in heavy-ion collisions are also discussed.

Vietnamese American women: breast cancer knowledge, attitudes, and screening adherence.

Breast cancer screening behavior and attitudes was measured among a convenience sample of 275 Vietnamese American women as part of a cancer education program evaluation. Follow-up interviews were completed with 178. Only 36% reported having adequate knowledge on this topic, and 87% indicated an interest in receiving more information. Rates of receiving a mammogram were below recommended levels.

Recruiting older women to research studies: the san diego cooperative mammography project.

BACKGROUND: Despite the growing number of older people in the population, this age group continues to be under represented in clinical trials. As a result, physicians must base treatment decisions for older patients on data from studies involving primarily younger, and presumably healthier, adults. Little experience is available to guide the development of study methodologies that will enhance the recruitment of older patients to clinical studies. METHODS: This pilot study compared two methods of recruiting women 75 years and older to a clinical research study related to their most recent screening mammogram. The effectiveness of a single, "in-person" invitation to participate made during the screening mammogram appointment was compared with the effectiveness of a single invitation to participate sent "by-mail" following a screening mammogram. RESULTS: Both methods succeeded in recruiting a sizable sample (N=2,394). The "in-person" invitation to participate was more labor-intense and less likely to be inclusive of all eligible women, but secured a significantly greater proportion of the women to participate. However, once recruited, women in the "by-mail" method were significantly more likely to comply with the optional elements of the study and to express a willingness to continue with follow-up studies than those recruited by the "in-person" method. CONCLUSIONS: Lack of participation of older women in clinical research may be more a reflection of not being asked, rather than their lack of willingness to participate, thus reinforcing the key role health care providers can play in recruiting older women to clinical studies.

Bringing breast cancer education to deaf women.

BACKGROUND: The Deaf community has not been adequately served by mainstream public health interventions. METHODS: A breast cancer education program adapted for the needs of the Deaf community was evaluated by 123 deaf and hard-of-hearing women using pre- and post-surveys and focus groups. RESULTS: Among the findings were the difficulty of recruiting Deaf community members to education and research programs; low adherence to breast cancer screening guidelines; insufficient breast-health knowledge; endorsement of the program; and suggestions for strengthening it. CONCLUSION: Deaf women will benefit from breast cancer education programs that specifically address their language, culture, and preferred learning styles.

Chinese women: behaviors and attitudes toward breast cancer education and screening.

A study eliciting Chinese Women's Attitudes and behaviors toward breast cancer screening to identify and overcome barriers to providing access to health promotion information.

In vivo kinematic study of normal wrist motion: an ultrafast computed tomographic study.

OBJECTIVE: To quantify in vivo carpal kinematics of a normal wrist in a dynamic continuous model. DESIGN: The instantaneous changes in the radiocarpal and midcarpal joints during normal wrist motion were analyzed using ultrafast computed tomography (CT). BACKGROUND: Wrist injuries account for a considerable and growing proportion of work-related disorders and disability. However, little is known about normal wrist kinematics. METHODS: Ten uninjured subjects were studied using ultrafast CT to measure the continuous motion of the wrist from full flexion to full extension. Sagittal plane scanning was performed mediolaterally at six different locations as the wrists were moved slowly and repeatedly from full flexion to full extension. The data were printed to X-ray film and transferred to an independent work station with a video camera. The motion of the radiocarpal, midcarpal and wrist joints was determined by an image analyzing system. RESULTS: Wrist motion was expressed as a ratio of capitate-lunate (C-L) (midcarpal) motion and radio-lunate (R-L) (radiocarpal) motion. In the volar flexion of normal wrists, the contribution of the radiocarpal joint and midcarpal joint were approximately equal; while dorsal flexion of the normal wrist occurred mainly at the midcarpal joint. CONCLUSIONS: In normal wrists, the radiocarpal joint and midcarpal joint contribute equally to volar flexion, while the midcarpal joint is more important in dorsal flexion. RELEVANCE: In this study, we demonstrated the suitability of using two-dimensional computed tomographic images in a quantitative study of flexion/extension kinematics of the normal wrist.

Comparative effects of loratadine and terfenadine on cardiac K+ channels.

Nonsedating H1-receptor antagonists appear to have wide and variable effects on the QT interval, mediated through modulation of cardiac K+ channels. By using the whole-cell patch-clamp technique, we examined the effects of terfenadine, loratadine, and descarboethoxyloratadine on a large family of K+ channels in ventricular myocytes and in Xenopus oocytes expressing the HERG delayed rectifier. The channels studied included the inward rectifier (I(Kl)) of rat and guinea pig, the transient outward K+ current (I(to)) of rat, the maintained K+ current (I(ped)) of rat, and the delayed rectifier K+ channels (I(Ks) and I(Kr)) of guinea pig myocytes. Loratadine and descarboethoxyloratadine, at therapeutic concentrations (30 to 100 nM), had no measurable effect on any one of the five types of K+ channels studied. At higher concentrations, 0.3 to 1.0 microM, only terfenadine had a significant suppressive effect on I(Kl) and delayed rectifier K+ channels, I(Kr) and I(Ks). At higher concentrations (1 to 2.5 microM), there were marked differences in the ability of the three drugs to suppress the five K+ channels. Generally, terfenadine was the most and loratadine, the least effective blocker of all K+ channels examined. The most susceptible K+ channels were the delayed rectifier channels (I(Ks) and I(Kr)) in guinea pig and I(ped) in rat myocytes. Comparative effects of loratadine and terfenadine examined on the I(Kr) channel (HERG) expressed in Xenopus oocytes suggest much higher affinity of this channel to terfenadine, such that 1 microM terfenadine completely suppressed the current, whereas loratadine had little or no effect. The preferential suppressive effect of terfenadine on the expressed HERG channel was consistent with data obtained on I(Kr) in isolated guinea pig ventricular myocytes. The strong suppressive effect of terfenadine, noted particularly on the I(Kr) and to a lesser extent on I(to), I(Kl), and I(Ks), may be the cause of the reported incidence of QT prolongation and arrhythmogenesis. The absence of significant effect of loratadine and descarboethoxyloratadine, especially on I(Kr), I(to), I(ped), and I(Kl), even at 100 x highest plasma concentrations achieved, may explain the absence of significant reports of QT prolongation and arrhythmogenesis by the latter drugs.

Suppression of mammalian K+ channel family by ebastine.

Nonsedating H1 receptor (H1-R) antagonists exert variable effects on QT interval, most likely mediated through modulation of cardiac K+ channels. We examined the effects of a novel H1-R antagonist, ebastine, on a family of K+ currents in isolated rat and guinea pig ventricular cardiomyocytes as well as on HERG-induced rapidly delayed rectifier K+ current (I(Kr)) in Xenopus laevis oocytes. The effect of ebastine was compared with that of two other H1-R antagonists, terfenadine and loratadine, with and without reported cardiotoxicity, respectively. In guinea pig ventricular myocytes, ebastine at concentrations approximating those found in plasma under certain conditions suppressed in a voltage-independent manner the I(Kr) (Kd = 0.14 microM, maximum block 74%) more effectively than the slowly delayed rectifier K+ current (I(Ks)) (Kd = 0.8 microM, maximum block 60%). Ebastine also suppressed I(Kr) in HERG-expressing X. laevis oocytes with the Kd value of 0.3 microM and a maximal block of 46% at 3 microM. The block of the rapidly activating delayed rectifier channel in rat myocytes (Iped) (Kd = 1.7 microM, maximum block 58%) had a small voltage dependence. Ebastine only minimally suppressed rat transient K+ current (Ito) (Kd = 1.1 microM, maximum block 10%). The drug was also not a very potent blocker of the inwardly rectifier K+ current (I(K1)) of rat and guinea pig (15 +/- 3% block at 3 microM). At concentrations of <100 nM, ebastine produced negligible effect on all K+ currents. We conclude that ebastine blocks various cardiac K+ channels with different potencies. The group of delayed rectifier K+ currents appeared to be most susceptible to ebastine with the order of sensitivity of I(Kr) > I(Ks) > Iped. Ebastine-induced inhibition of all K+ current types was always weaker than that observed with similar concentrations of terfenadine.

Mechanism of decrease in heart rate by peripheral dopaminergic D2-receptors.

We performed this study in order to verify the heart rate decrease caused by the D2-receptor on cardiac sympathetic nerve endings and its relation to the concentration of norepinephrine in synaptic clefts. Sprague-Dawley rats were pithed and the heart rate was increased either by electrical stimulation of the cardiac accelerator nerve or by intravenous infusion of norepinephrine, tyramine, or isoproterenol. Increased heart rate by electrical stimulation of cardiac accelerator nerve was dose-dependently lowered by lisuride and its effect was blocked by pretreatment with sulpiride but not with yohimbine and SCH 23390. Also, the heart rate was decreased in a dose-dependent manner by clonidine and this effect was blocked by pretreatment with yohimbine, but not with sulpiride. For increased heart rate by infusion of norepinephrine, tyramine, or isoproterenol, the heart rate lowering effect of lisuride was more marked in the norepinephrine-and tyramine-infusion groups, in which the intrasynaptic concentration of norepinephrine was elevated, compared to the isoproterenol-infusion group, in which intrasynaptic concentration of norepinephrine was not elevated. In conclusion, there is a D2-receptor on the cardiac sympathetic nerve endings which decreases the heart rate and is different from the presynaptic alpha 2-receptor. Also, the heart rate lowering effect via stimulation of the D2-receptor by lisuride was more marked with increased concentration of norepinephrine in the synaptic cleft.

Transposition, amplification, and divergence in the origin of the DNF15 loci, a polymorphic repetitive sequence family on chromosomes 1 and 3.

The loci DNF15S1 and DNF15S2 are members of a small repetitive sequence family at discrete chromosomal locations, namely, 1p36 and 3p21, respectively. Studies of the structure, arrangement, and interrelations of the family suggest that the single copy on chromosome 3 is the original member and that this gave rise to the several members on chromosome 1 by transposition, partial duplication, and amplification. Several restriction fragment length polymorphisms have been discovered at the DNF15S1 locus and these have been assigned to the different subfamilies of the repeat at this locus. The existence of these RFLPs, and the nonallelic restriction site variation also found in this sequence family, suggests that transposition and amplification occurred as discrete events. We sequenced across the ancient junction between chromosomes 1 and 3 and noted features which might explain the mechanics of the transposition and amplification events.