Long-lived plasma cells, residing primarily in the bone marrow, continuously secrete antibody and provide an important component of humoral memory. However, when such cells secrete autoantibodies or become transformed, they can be pathogenic. We have shown recently that the transcriptional repressor B lymphocyte-induced maturation protein 1 (Blimp-1) is required for the formation of plasma cells. To determine what role Blimp-1 might play in maintenance of plasma cells, we generated mice in which the gene encoding Blimp-1 could be deleted in an inducible manner. Deletion of Blimp-1 either in vitro or in vivo leads to loss of previously formed B220(LO)CD138(HI) plasma cells. Using BrdU incorporation, we confirmed that Blimp-1 is required for the maintenance of nondividing, long-lived plasma cells in the bone marrow. Blimp-1 is also required for long-term maintenance of antigen-specific immunoglobulin in serum. Thus Blimp-1 is required not only for the formation but also for the maintenance of long-lived plasma cells. This finding provides the possibility of new drug design strategies for autoimmunity and multiple myeloma focused on blocking Blimp-1 expression or activity.

Prospective data on ethnic differences in hormone receptor-defined subtypes of breast cancer and their risk factor profiles are scarce. The authors examined the joint distributions of estrogen receptor (ER) and progesterone receptor (PR) status across 5 ethnic groups and the associations of established risk factors with ER/PR status in the Multiethnic Cohort Study (Hawaii and Los Angeles, California). During an average of 10.4 years of follow-up of 84,427 women between 1993-1996 and 2004/2005, 2,543 breast cancer cases with data on ER/PR status were identified: 1,672 estrogen receptor-positive (ER+)/progesterone receptor-positive (PR+); 303 ER+/progesterone receptor-negative (PR-); 77 estrogen receptor-negative (ER-)/PR+; and 491 ER-/PR-. ER/PR status varied significantly across racial/ethnic groups even within the same tumor stage (for localized tumors, P < 0.0001; for advanced tumors, P = 0.01). The highest fraction of ER-/PR- tumors was observed in African Americans (31%), followed by Latinas (25%), Whites (18%), Japanese (14%), and Native Hawaiians (14%). Associations differed between ER+/PR+ and ER-/PR- cases for postmenopausal obesity (P = 0.02), age at menarche (P = 0.05), age at first birth (P = 0.04), and postmenopausal hormone use (P < 0.0001). African Americans are more likely to be diagnosed with ER-/PR- tumors independently of stage at diagnosis, and there are disparate risk factor profiles across the ER/PR subtypes of breast cancer.

Reverse immunogenetic approaches attempt to optimize the selection of candidate epitopes, and thus minimize the experimental effort needed to identify new epitopes. When predicting cytotoxic T cell epitopes, the main focus has been on the highly specific MHC class I binding event. Methods have also been developed for predicting the antigen-processing steps preceding MHC class I binding, including proteasomal cleavage and transporter associated with antigen processing (TAP) transport efficiency. Here, we use a dataset obtained from the SYFPEITHI database to show that a method integrating predictions of MHC class I binding affinity, TAP transport efficiency, and C-terminal proteasomal cleavage outperforms any of the individual methods. Using an independent evaluation dataset of HIV epitopes from the Los Alamos database, the validity of the integrated method is confirmed. The performance of the integrated method is found to be significantly higher than that of the two publicly available prediction methods BIMAS and SYFPEITHI. To identify 85% of the epitopes in the HIV dataset, 9% and 10% of all possible nonamers in the HIV proteins must be tested when using the BIMAS and SYFPEITHI methods, respectively, for the selection of candidate epitopes. This number is reduced to 7% when using the integrated method. In practical terms, this means that the experimental effort needed to identify an epitope in a hypothetical protein with 85% probability is reduced by 20-30% when using the integrated method. The method is available at http://www.cbs.dtu.dk/services/NetCTL. Supplementary material is available at http://www.cbs.dtu.dk/suppl/immunology/CTL.php.

Th1 type cytokine responses are critical in the control of Mycobacterium tuberculosis infection. Recent findings indicate that 5-lipoxygenase-dependent (5-LO-dependent) lipoxins regulate host IL-12 production in vivo. Here, we establish lipoxins as key chemical mediators in resistance to M. tuberculosis infection. High levels of lipoxin A4 (LXA4) were detected in sera from infected WT but not infected 5-LO-deficient mice. Moreover, lungs from M. tuberculosis-infected 5-lo-/- animals showed increased IL-12, IFN-gamma, and NO synthase 2 (NOS2) mRNA levels compared with the same tissues in WT mice. Similarly, splenocyte recall responses were enhanced in mycobacteria-infected 5-lo-/- versus WT mice. Importantly, bacterial burdens in 5-lo-/- lungs were significantly lower than those from WT mice, and this enhancement in the resistance of the 5-lo-/- animals to M. tuberculosis was completely prevented by administration of a stable LXA4 analog. Together our results demonstrate that lipoxins negatively regulate protective Th1 responses against mycobacterial infection in vivo and suggest that the inhibition of lipoxin biosynthesis could serve as a strategy for enhancing host resistance to M. tuberculosis.

We previously reported the identification of a locus on mouse chromosome 6 that confers almost total resistance to atherogenesis, even on a hypercholesterolemic (LDL receptor-null) background. 5-Lipoxygenase (5-LO) is the rate-limiting enzyme in leukotriene synthesis and was among the chromosome 6 locus candidate genes that we examined. The levels of 5-LO mRNA were reduced about 5-fold in a congenic strain, designated CON6, containing the resistant chromosome 6 region derived from the CAST/Ei strain (CAST), as compared with the background C57BL/6J (B6) strain. 5-LO protein levels were similarly reduced in the CON6 mice. Sequencing of the 5-LO cDNA revealed several differences between CON6 and the B6 strain. To test the whether 5-LO is responsible for the resistant phenotype, we bred a 5-LO knockout allele onto an LDL receptor-null (LDLR(-/-)) background. On this background, the mice bred poorly and only heterozygous 5-LO knockout mice were obtained. These mice showed a dramatic decrease (>26-fold; P<0.0005) in aortic lesion development, similar to the CON6 mice. Immunohistochemistry revealed that 5-LO was abundantly expressed in atherosclerotic lesions of apoE(-/-) and LDLR(-/-) deficient mice, appearing to colocalize with a subset of macrophages but not with all macrophage-staining regions. When bone marrow from 5-LO(+/-) mice was transplanted into LDLR(-/-), there was a significant reduction in atherogenesis, suggesting that macrophage 5-LO is responsible, at least in part, for the effect on atherosclerosis. These results indicate that 5-LO contributes importantly to the atherogenic process and they provide strong presumptive evidence that reduced 5-LO expression is partly responsible for the resistance to atherosclerosis in CON6 mice.

Most splenic B cells in mice that lack Aiolos are mature IgD(hi)IgM(lo) follicular lymphocytes, suggesting that maturation signals delivered via the BCR are enhanced in the absence of Aiolos. The enhanced maturation of follicular B cells is accompanied by the absence of MZ B lymphocytes and the downregulation of CD21 expression in follicular B cells, all of which depend on the generation of signals via Btk, which is in epistasis to Aiolos. The inverse relationship between the strength of BCR signaling and MZ B cell development is supported by an examination of MZ B cells in CD21 null mice. These data support the view that antigens (in contrast to "tonic" signals) drive the development of naive B cells.

BACKGROUND

Two strategies for preventing the onset of alcohol abuse, and marijuana and cigarette use were tested in junior high schools in Los Angeles and Orange Counties, California. The first strategy taught skills to refuse substance use offers. The second strategy corrected erroneous normative perceptions about prevalence and acceptability of use among peers and established conservative groups norms regarding use.

METHODS

Four experimental conditions were created by randomly assigning schools to receive (a) neither of the experimental curricula (placebo comparison), (b) resistance skill training alone, (c) normative education alone, or (d) both resistance skill training and normative education. Students were pretested prior to the program and post-tested 1 year following delivery of the program.

RESULTS

There were main effects of normative education for summary measures of alcohol (P = 0.0011), marijuana (P = 0.0096), and cigarette smoking (P = 0.0311). All individual dichotomous measures of alcohol, marijuana, and tobacco use indicated significant reductions in onset attributable to normative education. There were no significant main effects of resistance skill training.

CONCLUSIONS

These results suggest that establishing conservative norms is an effective strategy for preventing substance use.

BACKGROUND

There is concern that the widespread use of antiretroviral drugs to treat human immunodeficiency virus 1 (HIV-1) infection may result in the increased transmission of drug-resistant virus.

OBJECTIVE

To determine the prevalence of drug resistance-conferring mutations and phenotypic resistance to antiretroviral agents in a cohort of individuals newly infected with HIV-1.

METHODS

Case series with genetic analyses of the HIV-1 plasma-derived pol gene using reverse transcriptase polymerase chain reaction followed by direct sequencing of polymerase chain reaction products. Phenotypic analysis was performed with a recombinant virus assay.

METHODS

Eighty individuals referred, on average, 1.7 months after infection with HIV-1 to the Aaron Diamond AIDS Research Center between July 1995 and April 1999. Subjects were from large urban areas (65 from New York, NY; 11 from Los Angeles, Calif); 60 (75%) were white, and 75 (93.8%) were homosexual men.

METHODS

Prevalence of known resistance-conferring genotypes and reduced susceptibility to individual antiviral agents by phenotype.

RESULTS

Thirteen individuals (16.3%) had genotypes associated with drug resistance to any antiretroviral agent. Virus with known resistance-conferring mutations to any nucleoside reverse transcriptase inhibitors was found in 10 individuals, to any nonnucleoside reverse transcriptase inhibitors in 6 subjects, and to any protease inhibitors in 2 cases. Multidrug-resistant virus was identified in 3 individuals (3.8%). Extensive polymorphism in the protease gene was identified. Interpretation of genotypes and phenotypes was concordant in 57 (85%) of the 67 cases in which both studies were performed.

CONCLUSIONS

The prevalence of HIV-1 variants with known resistance-conferring genotypes to any antiretroviral agent in this cohort of 80 newly infected individuals is 16.3%. These data support expanded use of resistance testing in the setting of primary HIV-1 infection. Clinical trials should be initiated to establish whether therapy guided by resistance testing, compared with the use of empirical triple combination antiretroviral therapy, provides additional virological and immunological benefit when treating primary HIV-1 infection. Further efforts to expand the study of transmission of drug-resistant HIV-1 variants, particularly in cohorts with different epidemiological profiles, are indicated.

OBJECTIVE

To evaluate relapse prevention (relapse prevention) and contingency management (contingency management) for optimizing smoking cessation outcomes using nicotine replacement therapy for methadone-maintained tobacco smokers.

METHODS

Experimental, 2 (relapse prevention)x2 (contingency management) repeated measures design using a platform of nicotine replacement therapy featuring a 2-week baseline period, followed by randomization to 12 weeks of treatment, and 6- and 12-month follow-up visits.

METHODS

Three narcotic treatment centers in Los Angeles.

METHODS

One hundred and seventy-five participants who met all inclusion and no exclusion criteria.

METHODS

Participants received 12 weeks of nicotine replacement therapy and assignment to one of four conditions: patch-only, relapse prevention + patch, contingency management + patch and relapse prevention + contingency management + patch.

METHODS

Thrice weekly samples of breath (analyzed for carbon monoxide) and urine (analyzed for metabolites of opiates and cocaine) and weekly self-reported numbers of cigarettes smoked.

RESULTS

Participants (73.1%) completed 12 weeks of treatment. During treatment, those assigned to receive contingency management showed statistically higher rates of smoking abstinence than those not assigned to receive contingencies (F3,4680=6.3, P=0.0003), with no similar effect observed for relapse prevention. At follow-up evaluations, there were no significant differences between conditions. Participants provided more opiate and cocaine-free urines during weeks when they met criteria for smoking abstinence than during weeks when they did not meet these criteria (F1,2054=14.38, P=0.0002; F1,2419=16.52, P<0.0001).

CONCLUSIONS

Contingency management optimized outcomes using nicotine replacement therapy for reducing cigarette smoking during treatment for opiate dependence, although long-term effects are not generally maintained. Findings document strong associations between reductions in cigarette smoking and reductions in illicit substance use during treatment.

CD8(+) cytotoxic and CD4(+) helper/inducer T cells develop from common thymocyte precursors that express both CD4 and CD8 molecules. Upon T cell receptor signaling, these cells initiate a differentiation program that includes complex changes in CD4 and CD8 expression, allowing identification of transitional intermediates in this developmental pathway. Little is known about regulation of these early transitions or their specific importance to CD4 and CD8 T cell development. Here, we show a severe block at the CD4(lo)CD8(lo) transitional stage of positive selection caused by loss of the nuclear HMG box protein TOX. As a result, CD4 lineage T cells, including regulatory T and CD1d-dependent natural killer T cells, fail to develop. In contrast, functional CD8(+) T cells develop in TOX-deficient mice. Our data suggest that TOX-dependent transition to the CD4(+)CD8(lo) stage is required for continued development of class II major histocompatibility complex-specific T cells, regardless of ultimate lineage fate.

We studied the existence, localization and attentional modulation of gamma-band oscillatory activity (30-130 Hz) in the human intracranial region. Two areas known to play a key role in visual object processing: the lateral occipital (LO) cortex and the fusiform gyrus. These areas consistently displayed large gamma oscillations during visual stimulus encoding, while other extrastriate areas remained systematically silent, across 14 patients and 291 recording sites scattered throughout extrastriate visual cortex. The lateral extent of the responsive regions was small, in the range of 5 mm. Induced gamma oscillations and evoked potentials were not systematically co-localized. LO and the fusiform gyrus displayed markedly different patterns of attentional modulation. In the fusiform gyrus, attention enhanced stimulus-driven gamma oscillations. In LO, attention increased the baseline level of gamma oscillations during the expectation period preceding the stimulus. Subsequent gamma oscillations produced by attended stimuli were smaller than those produced by unattended, irrelevant stimuli. Attentional modulations of gamma oscillations in LO and the fusiform gyrus were thus very different, both in their time-course (preparatory period and/or stimulus processing) and direction of modulation (increase or decrease). Our results thus suggest that the functional role of gamma oscillations depends on the area in which they occur.

Spanish-language measures of the Big Five personality dimensions are needed for research on Hispanic minority populations. Three studies were conducted to evaluate a Spanish version of the Big Five Inventory (BFI) (O. P. John et al., 1991) and explore the generalizability of the Big Five factor structure in Latin cultural groups. In Study 1, a cross-cultural design was used to compare the Spanish and English BFI in college students from Spain and the United States, to assess factor congruence across languages, and to test convergence with indigenous Spanish Big Five markers. In Study 2, a bilingual design was used to compare the Spanish and English BFI in a college-educated sample of bilingual Hispanics and to test convergent and discriminant validity across the two languages as well as with the NEO Five Factor Inventory in both English and Spanish. Study 3 replicated the BFI findings from Study 2 in a working-class Hispanic bilingual sample. Results show that (a) the Spanish BFI may serve as an efficient, reliable, and factorially valid measure of the Big Five for research on Spanish-speaking individuals and (b) there is little evidence for substantial cultural differences in personality structure at the broad level of abstraction represented by the Big Five dimensions.

Excavations of a complex of caves in the Sierra de Atapuerca in northern Spain have unearthed hominin fossils that range in age from the early Pleistocene to the Holocene. One of these sites, the 'Sima de los Huesos' ('pit of bones'), has yielded the world's largest assemblage of Middle Pleistocene hominin fossils, consisting of at least 28 individuals dated to over 300,000 years ago. The skeletal remains share a number of morphological features with fossils classified as Homo heidelbergensis and also display distinct Neanderthal-derived traits. Here we determine an almost complete mitochondrial genome sequence of a hominin from Sima de los Huesos and show that it is closely related to the lineage leading to mitochondrial genomes of Denisovans, an eastern Eurasian sister group to Neanderthals. Our results pave the way for DNA research on hominins from the Middle Pleistocene.

This study examined the prevalence of child sexual abuse in a multi-stage stratified probability sample of Afro-American and white-American women, 18 to 36 years of age, in Los Angeles County. The sample ranged in demographic characteristics by age, marital status, education and the presence of children. Of the total sample of 248 women, 154 (62%) reported at least one incident of sexual abuse prior to age 18, with 57% of Afro-American women and 67% of white-American women having been abused. Sexual abuse before the age of 18 appears to be of equal concern for both ethnic groups, although similarities and differences in the circumstances under which abuse incidents occurred were subtle and deserve attention. The need for identifying contemporary factors that contribute to the prevalence of abuse over the past 40 years is stressed.

Biology of Termites: A Modern Synthesis (Bignell DE, Roisin Y, Lo N, (Editors), Springer, Dordrecht, 576pp, ISBN 978-90-481-3976-7, e-ISBN 978-90-481-3977-4, DOI 10.1007/978-90-481-3977-4) was published in 2011. With the agreement of the publishers, we give a taxonomic index of the book comprising 494 termite entries, 103 entries of other multicellular animal species mentioned as associates or predators of termites, with 9 fungal, 60 protist, and 64 prokaryote identities, which are listed as termite symbionts (sensu stricto). In addition, we add descriptive authorities for living (and some fossil) termite genera and species. Higher taxonomic groupings for termites are indicated by 25 code numbers. Microorganisms (prokaryotes, protists, and fungi) are listed separately, using broad modern taxonomic affiliations from the contemporary literature of bacteriology, protozoology, and mycology.

BACKGROUND

Cross-sectional studies suggest an association between exposure to ambient air pollution and atherosclerosis. We investigated the association between outdoor air quality and progression of subclinical atherosclerosis (common carotid artery intima-media thickness, CIMT).

RESULTS

We examined data from five double-blind randomized trials that assessed effects of various treatments on the change in CIMT. The trials were conducted in the Los Angeles area. Spatial models and land-use data were used to estimate the home outdoor mean concentration of particulate matter up to 2.5 micrometer in diameter (PM2.5), and to classify residence by proximity to traffic-related pollution (within 100 m of highways). PM2.5 and traffic proximity were positively associated with CIMT progression. Adjusted coefficients were larger than crude associations, not sensitive to modelling specifications, and statistically significant for highway proximity while of borderline significance for PM2.5 (P = 0.08). Annual CIMT progression among those living within 100 m of a highway was accelerated (5.5 micrometers/yr [95%CI: 0.13-10.79; p = 0.04]) or more than twice the population mean progression. For PM2.5, coefficients were positive as well, reaching statistical significance in the socially disadvantaged; in subjects reporting lipid lowering treatment at baseline; among participants receiving on-trial treatments; and among the pool of four out of the five trials.

CONCLUSIONS

Consistent with cross-sectional findings and animal studies, this is the first study to report an association between exposure to air pollution and the progression of atherosclerosis--indicated with CIMT change--in humans. Ostensibly, our results suggest that air pollution may contribute to the acceleration of cardiovascular disease development--the main causes of morbidity and mortality in many countries. However, the heterogeneity of the volunteering populations across the five trials, the limited sample size within trials and other relevant subgroups, and the fact that some key findings reached statistical significance in subgroups rather than the sample precludes generalizations to the general population.

Noninflammatory clearance of apoptotic cells (ACs) is crucial to maintain self-tolerance. Here, we have reported a role for the enzyme 12/15-lipoxygenase (12/15-LO) as a central factor governing the sorting of ACs into differentially activated monocyte subpopulations. During inflammation, uptake of ACs was confined to a population of 12/15-LO-expressing, alternatively activated resident macrophages (resMΦ), which blocked uptake of ACs into freshly recruited inflammatory Ly6C(hi) monocytes in a 12/15-LO-dependent manner. ResMΦ exposed 12/15-LO-derived oxidation products of phosphatidylethanolamine (oxPE) on their plasma membranes and thereby generated a sink for distinct soluble receptors for ACs such as milk fat globule-EGF factor 8, which were essential for the uptake of ACs into inflammatory monocytes. Loss of 12/15-LO activity, in turn, resulted in an aberrant phagocytosis of ACs by inflammatory monocytes, subsequent antigen presentation of AC-derived antigens, and a lupus-like autoimmune disease. Our data reveal an unexpected key role for enzymatic lipid oxidation during the maintenance of self-tolerance.

In humans and many other primates, the visual system plays the major role in object recognition. But objects can also be recognized through haptic exploration, which uses our sense of touch. Nonetheless, it has been argued that the haptic system makes use of 'visual' processing to construct a representation of the object. To investigate possible interactions between the visual and haptic systems, we used functional magnetic resonance imaging to measure the effects of cross-modal haptic-to-visual priming on brain activation. Subjects studied three-dimensional novel clay objects either visually or haptically before entering the scanner. During scanning, subjects viewed visually primed, haptically primed, and non-primed objects. They also haptically explored non-primed objects. Visual and haptic exploration of non-primed objects produced significant activation in several brain regions, and produced overlapping activation in the middle occipital area (MO). Viewing visually and haptically primed objects produced more activation than viewing non-primed objects in both area MO and the lateral occipital area (LO). In summary, haptic exploration of novel three-dimensional objects produced activation, not only in somatosensory cortex, but also in areas of the occipital cortex associated with visual processing. Furthermore, previous haptic experience with these objects enhanced activation in visual areas when these same objects were subsequently viewed. Taken together, these results suggest that the object-representation systems of the ventral visual pathway are exploited for haptic object perception.

OBJECTIVE

The objective of this study was to compare insulin resistance relative to body fat and the associated compensatory responses in 57 healthy children living in Los Angeles, California (14 Caucasians, 15 African-Americans, and 28 Hispanics).

METHODS

Insulin sensitivity and acute insulin response were determined by intravenous glucose tolerance test. Insulin secretion, hepatic insulin extraction, and insulin clearance were estimated by C-peptide and insulin modeling.

RESULTS

Insulin sensitivity was significantly lower in Hispanics and African-Americans compared with Caucasian children, and acute insulin response was significantly higher in African-American children. No ethnic differences were noted in the first-phase secretion, but second-phase insulin secretion was significantly higher in Hispanic children than in African-American children (200 +/- 53 vs. 289 +/- 41 nmol/min; P = 0.03). The greater acute insulin response in African-Americans, despite lower secretion, was explained by a lower hepatic insulin extraction in African-Americans compared with Hispanics (36.6 +/- 2.9 vs. 47.3 +/- 2.2%; P = 0.0006).

CONCLUSIONS

In conclusion, Hispanic and African-American children are more insulin resistant than Caucasian children, but the associated compensatory responses are different across ethnic groups.

BACKGROUND

Lung cancer in individuals who have never smoked tobacco products is an increasing medical and public-health issue. We aimed to unravel the genetic basis of lung cancer in never smokers.

METHODS

We did a four-stage investigation. First, a genome-wide association study of single nucleotide polymorphisms (SNPs) was done with 754 never smokers (377 matched case-control pairs at Mayo Clinic, Rochester, MN, USA). Second, the top candidate SNPs from the first study were validated in two independent studies among 735 (MD Anderson Cancer Center, Houston, TX, USA) and 253 (Harvard University, Boston, MA, USA) never smokers. Third, further replication of the top SNP was done in 530 never smokers (UCLA, Los Angeles, CA, USA). Fourth, expression quantitative trait loci (eQTL) and gene-expression differences were analysed to further elucidate the causal relation between the validated SNPs and the risk of lung cancer in never smokers.

RESULTS

44 top candidate SNPs were identified that might alter the risk of lung cancer in never smokers. rs2352028 at chromosome 13q31.3 was subsequently replicated with an additive genetic model in the four independent studies, with a combined odds ratio of 1.46 (95% CI 1.26-1.70, p=5.94x10(-6)). A cis eQTL analysis showed there was a strong correlation between genotypes of the replicated SNPs and the transcription level of the gene GPC5 in normal lung tissues (p=1.96x10(-4)), with the high-risk allele linked with lower expression. Additionally, the transcription level of GPC5 in normal lung tissue was twice that detected in matched lung adenocarcinoma tissue (p=6.75x10(-11)).

CONCLUSIONS

Genetic variants at 13q31.3 alter the expression of GPC5, and are associated with susceptibility to lung cancer in never smokers. Downregulation of GPC5 might contribute to the development of lung cancer in never smokers.

BACKGROUND

US National Institutes of Health; Mayo Foundation.

OBJECTIVE

Peak power declines more precipitously than strength with advancing age and is a reliable measure of impairment and a strong predictor of functional performance. We tested the hypothesis that a high-velocity resistance-training program (HI) would increase muscle power more than a traditional low-velocity resistance-training program (LO).

METHODS

Randomized controlled trial.

METHODS

University-based human physiology laboratory.

METHODS

Thirty women with self-reported dis-ability (aged 73 + 1, body mass index 30.1 + 1.1 kg/mn).

METHODS

We conducted a randomized trial comparing changes in skeletal muscle power and strength after 16 weeks of HI or LO. Training was performed three times per week, and subjects completed three sets (8-10 repetitions) of leg press (LP) and knee extension (KE) exercises at 70% of the one-repetition maximum (IRM).

METHODS

One-repetition maximum (1 RM) and peak power for KE and LP.

RESULTS

LP and KE relative training force and total work were similar between groups (P>> .05). However, HI generated significantly higher power during training sessions than LO for LP (3.7-fold greater, P < .001) and KE (2.1-fold greater, P < .001). Although LP and KE 1RM muscle strength increased similarly in both groups asa result of the training (P < .001), LP peak power increased significantly more in HI than in LO (267 W vs 139 W, P < .001). Furthermore, HI resulted in a significantly greater improvement in LP power at 40%, 50%, 60%,70%, 80%, and 90% of the 1 RM than did LO (P <.05).

CONCLUSIONS

HI improved 1RM strength similarly and was more effective in improving peak power than was traditional LO in older women. Improvements in lower extremity peak power may exert a greater influence on age-associated reductions in physical functioning than other exercise interventions.

Campylobacter jejuni, a Gram-negative spiral bacterium, is the most common bacterial cause of acute human gastroenteritis and is increasingly recognized for its association with the serious post-infection neurological complications of the Miller-Fisher and Guillain-Barré syndromes. C. jejuni lipopolysaccharide (LPS) is thought to be involved in the pathogenesis of both uncomplicated infection and more serious sequelae, yet the LPS remains poorly characterized. Current studies on C. jejuni suggest that all strains produce lipooligosaccharide (LOS), with about one-third of strains also producing high-molecular-weight LPS (referred to as O-antigen). In this report, we demonstrate the presence of the high-molecular-weight LPS in all C. jejuni strains tested. Furthermore, we show that this LPS is biochemically and genetically unrelated to LOS and is similar to group II and group III capsular polysaccharides. All tested kpsM, kpsS and kpsC mutants of C. jejuni lost the ability to produce O-antigen. Moreover, this correlated with serotype changes. We demonstrate for the first time that the previously described O-antigen of C. jejuni is a capsular polysaccharide and a common component of the thermostable antigen used for serotyping of C. jejuni.

The outer cores of the lipooligosaccharides (LOS) of many strains of Campylobacter jejuni mimic human gangliosides in structure. A population of cells of C. jejuni strain 81-176 produced a mixture of LOS cores which consisted primarily of structures mimicking GM(2) and GM(3) gangliosides, with minor amounts of structures mimicking GD(1b) and GD(2). Genetic analyses of genes involved in the biosynthesis of the outer core of C. jejuni 81-176 revealed the presence of a homopolymeric tract of G residues within a gene encoding CgtA, an N-acetylgalactosaminyltransferase. Variation in the number of G residues within cgtA affected the length of the open reading frame, and these changes in cgtA corresponded to a change in LOS structure from GM(2) to GM(3) ganglioside mimicry. Site-specific mutation of cgtA in 81-176 resulted in a major LOS core structure that lacked GalNAc and resembled GM(3) ganglioside. Compared to wild-type 81-176, the cgtA mutant showed a significant increase in invasion of INT407 cells. In comparison, a site-specific mutation of the neuC1 gene resulted in the loss of sialic acid in the LOS core and reduced resistance to normal human serum but had no affect on invasion of INT407 cells.

The mechanisms that mediate the tightly controlled production and clearance of glucose during muscular work are unclear, and it has been suggested that an unidentified "work factor" exists that influences the contraction-induced increase in endogenous glucose production (EGP). The cytokine interleukin (IL)-6 is released from skeletal muscle during contraction. Here we show that IL-6 contributes to the contraction-induced increase in EGP. Six men performed 2 h of bicycle exercise on three separate occasions, at a relatively high intensity (HI) or at a low intensity with (LO + IL-6) or without (LO) an infusion of recombinant human IL-6 that matched the circulating concentration of IL-6 seen in HI exercise. The stable isotope 6,6 (2)H(2) glucose was infused to calculate EGP (rate of glucose appearance [R(a)]), whole-body glucose disposal (rate of glucose disappearance [R(d)]), and metabolic clearance rate (MCR) of glucose. Glucose R(a), R(d), and MCR were higher (P < 0.05) at HI than at LO. Throughout exercise at LO + IL-6, glucose R(a) and R(d) were higher (P < 0.05) than LO, even though the exercise intensity was identical. In addition, MCR was higher (P < 0.05) at LO + IL-6 than at LO at 90 min. Insulin, glucagon, epinephrine, norepinephrine, cortisol, and growth hormone were identical when comparing LO + IL-6 with LO. These data suggest that IL-6 influences glucose homeostasis during exercise. Our results provide potential new insights into factors that mediate glucose production and disposal and implicates IL-6 in the so-called "work factor."