bluuebunny/crossref_metadata_2025 huggingface dataset:
A PE Protein Expressed by
Mycobacterium avium
Is an Effective T-Cell Immunogen
Authors: Parra Marcela , Cadieux Nathalie , Pickett Thames , Dheenadhayalan Veerabadran , Brennan Michael J.
Published: December 2005

Infection of mice with
Mycobacterium avium
or immunization with a novel PE gene expressed by
M. avium
(MaPE) showed that a dominant T-cell immune response was elicited. Immunization with an MaPE DNA vaccine protected mice against an aerosol challenge with
Mycobacterium tuberculosis
, suggesting that mycobacteria express PE antigens with cross-protective T-cell epitopes.
New World Monkey
Aotus nancymae
as a Model for
Campylobacter jejuni
Infection and Immunity
Authors: Jones Franca R. , Baqar Shahida , Gozalo Alfonso , Nunez Gladys , Espinoza Nereyda , Reyes Sharina M. , Salazar Milagros , Meza Rina , Porter Chad K. , Walz Stephen E.
Published: December 2005

Three groups of six monkeys (
Aotus nancymae
) each were inoculated intragastrically with increasing doses of
Campylobacter jejuni
. Infection resulted in fecal colonization (100% of monkeys), dose-related diarrhea, and robust immune responses. Colonization duration and diarrhea rate were reduced upon secondary challenge.
A. nancymae
may be useful for studying anti-
Campylobacter
vaccine efficacy.
Correlation between Lethal Toxin-Neutralizing Antibody Titers and Protection from Intranasal Challenge with
Bacillus anthracis
Ames Strain Spores in Mice after Transcutaneous Immunization with Recombinant Anthrax Protective Antigen
Authors: Peachman Kristina K. , Rao Mangala , Alving Carl R. , Burge Robert , Leppla Stephen H. , Rao Venigalla B. , Matyas Gary R.
Published: December 2005

Transcutaneous immunization of mice with recombinant protective antigen (rPA) of
Bacillus anthracis
resulted in significantly higher lethal toxin-neutralizing antibody titers than did intramuscular injection of alum-adsorbed rPA. Immunized mice were partially protected against intranasal challenge with 235,000 (10 50% lethal doses) Ames strain
B. anthracis
spores. A highly significant correlation was observed between toxin-neutralizing antibody titer and survival after challenge. Future experiments with rabbits and nonhuman primates should confirm the significance of protection by this vaccine strategy.
Natural Human Antibody Responses to
Plasmodium vivax
Apical Membrane Antigen 1 under Low Transmission and Unstable Malaria Conditions in Sri Lanka
Authors: Wickramarachchi Thilan , Premaratne Prasad H. , Perera K. L. R. Lakshman , Bandara Sumith , Kocken Clemens H. M. , Thomas Alan W. , Handunnetti Shiroma M. , Udagama-Randeniya Preethi V.
Published: December 2005

Plasmodium vivax
apical membrane antigen 1, an important malaria vaccine candidate, was immunogenic during natural malaria infections in Sri Lanka, where low transmission and unstable malaria conditions prevail. Antibody prevalence increased with exposure in areas where malaria was or was not endemic. A marked isotype switch to cytophilic (immunoglobulin G1 [IgG1]/IgG3) antibodies was evident with increasing exposure exclusively in residents from areas of endemicity.
Caspase and Bid Involvement inClostridium difficileToxin A-Induced Apoptosis and Modulation of Toxin A Effects by Glutamine and Alanyl-Glutamine In Vivo and In Vitro
Authors: Carneiro Benedito A. , Fujii Jun , Brito Gerly A. C. , Alcantara Cirle , Oriá Reinaldo B. , Lima Aldo A. M. , Obrig Tom , Guerrant Richard L.
Published: December 2005

Clostridium difficileis the leading cause of nosocomial bacterial diarrhea. Glutamine and its stable and highly soluble derivative alanyl-glutamine, have been beneficial in models of intestinal injury. In this study, we extend our work on the mechanisms ofClostridium difficiletoxin A (TxA)-induced apoptosis in human intestinal epithelial T84 cells and evaluate the effects of glutamine and alanyl-glutamine on TxA-induced apoptosis in vitro and disruption of ileal mucosa in vivo. T84 cells were incubated with TxA (100 ng/ml) in medium with or without glutamine or alanyl-glutamine (3 to 100 mM). Apoptosis was evaluated by DNA fragmentation in vitro and the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling method in vivo. Caspase and Bid involvement were investigated by Western blotting. Ligated rabbit ileal loops were used for the evaluation of intestinal secretion, mucosal disruption, and apoptosis. TxA induced caspases 6, 8, and 9 prior to caspase 3 activation in T84 cells and induced Bid cleavage by a caspase-independent mechanism. Glutamine or alanyl-glutamine significantly reduced TxA-induced apoptosis of T84 cells by 47% and inhibited activation of caspase 8. Both glutamine and alanyl-glutamine reduced TxA-induced ileal mucosal disruption and secretion. Altogether, we further delineated the apoptosis-signaling cascade induced by TxA in T84 cells and demonstrated the protective effects of glutamine and alanyl-glutamine. Glutamine and alanyl-glutamine inhibited the apoptosis of T84 cells by preventing caspase 8 activation and reduced TxA-induced intestinal secretion and disruption.
Dissection of ESAT-6 System 1 of
Mycobacterium tuberculosis
and Impact on Immunogenicity and Virulence
Authors: Brodin Priscille , Majlessi Laleh , Marsollier Laurent , de Jonge Marien I. , Bottai Daria , Demangel Caroline , Hinds Jason , Neyrolles Olivier , Butcher Philip D. , Leclerc Claude , Cole Stewart T. , Brosch Roland
Published: December 2005

The dedicated secretion system ESX-1 of
Mycobacterium tuberculosis
encoded by the extended RD1 region (extRD1) assures export of the ESAT-6 protein and its partner, the 10-kDa culture filtrate protein CFP-10, and is missing from the vaccine strains
M. bovis
BCG and
M. microti
. Here, we systematically investigated the involvement of each individual ESX-1 gene in the secretion of both antigens, specific immunogenicity, and virulence. ESX-1-complemented BCG and
M. microti
strains were more efficiently engulfed by bone-marrow-derived macrophages than controls, and this may account for the enhanced in vivo growth of ESX-1-carrying strains. Inactivation of gene
pe35
(Rv3872) impaired expression of CFP-10 and ESAT-6, suggesting a role in regulation. Genes Rv3868, Rv3869, Rv3870, Rv3871, and Rv3877 encoding an ATP-dependent chaperone and translocon were essential for secretion of ESAT-6 and CFP-10 in contrast to
ppe68
Rv3873 and Rv3876, whose inactivation did not impair secretion of ESAT-6. A strict correlation was found between ESAT-6 export and the generation of ESAT-6 specific T-cell responses in mice. Furthermore, ESAT-6 secretion and specific immunogenicity were almost always correlated with enhanced virulence in the SCID mouse model. Only loss of Rv3865 and part of Rv3866 did not affect ESAT-6 secretion or immunogenicity but led to attenuation. This suggests that Rv3865/66 represent a new virulence factor that is independent from ESAT-6 secretion. The present study has allowed us to identify new aspects of the extRD1 region of
M. tuberculosis
and to explore its role in the pathogenesis of tuberculosis.
Interaction of
Cryptosporidium hominis
and
Cryptosporidium parvum
with Primary Human and Bovine Intestinal Cells
Authors: Hashim Amna , Mulcahy Grace , Bourke Billy , Clyne Marguerite
Published: December 2005

Cryptosporidiosis in humans is caused by the zoonotic pathogen
Cryptosporidium parvum
and the anthroponotic pathogen
Cryptosporidium hominis
. To what extent the recently recognized
C. hominis
species differs from
C. parvum
is unknown. In this study we compared the mechanisms of
C. parvum
and
C. hominis
invasion using a primary cell model of infection. Cultured primary bovine and human epithelial intestinal cells were infected with
C. parvum
or
C. hominis
. The effects of the carbohydrate lectin galactose-
N
-acetylgalactosamine (Gal/GalNAc) and inhibitors of cytoskeletal function and signal transduction mechanisms on entry of the parasites into host cells were tested. HCT-8 cells (human ileocecal adenocarcinoma cells) were used for the purpose of comparison. Pretreatment of parasites with Gal/GalNAc inhibited entry of
C. parvum
into HCT-8 cells and primary bovine cells but had no effect on entry of either
C. parvum
or
C. hominis
into primary human cells or on entry of
C. hominis
into HCT-8 cells. Both
Cryptosporidium
species entered primary cells by a protein kinase C (PKC)- and actin-dependent mechanism. Staurosporine, in particular, attenuated infection, likely through a combination of PKC inhibition and induction of apoptosis. Diversity in the mechanisms used by
Cryptosporidium
species to infect cells of different origins has important implications for understanding the relevance of in vitro studies of
Cryptosporidium
pathogenesis.
PRIME DIVISORS OF LUCAS SEQUENCES AND A CONJECTURE OF SKAŁBA
Authors: LUCA FLORIAN , STĂNICĂ PANTELIMON
Published: December 2005

In this paper, we give some heuristics suggesting that if (un)n≥0is the Lucas sequence given by un= (an- 1)/(a - 1), where a > 1 is an integer, then ω(un) ≥ (1 + o(1)) log n log log n holds for almost all positive integers n.
EXPLICIT EVALUATIONS OF TWO RAMANUJAN–SELBERG CONTINUED FRACTIONS
Authors: ZHANG LIANG-CHENG
Published: December 2005

This paper gives explicit evaluations for two Ramanujan–Selberg continued fractions in terms of class invariants and singular moduli.
THE ILLUSORY SIEVE
Authors: FRIEDLANDER J. B. , IWANIEC H.
Published: December 2005

We study some of the extremely strong statements that can be made about the distribution of primes assuming the (unlikely) existence of exceptional Dirichlet characters. We treat this in general and then apply the results to the particular cases of primes of the form a2 + b6 and of elliptic curves having prime discriminant.
A SURVEY OF FACTORIZATION COUNTING FUNCTIONS
Authors: KNOPFMACHER A. , MAYS M. E.
Published: December 2005

The general field of additive number theory considers questions concerning representations of a given positive integer n as a sum of other integers. In particular, partitions treat the sums as unordered combinatorial objects, and compositions treat the sums as ordered. Sometimes the sums are restricted, so that, for example, the summands are distinct, or relatively prime, or all congruent to ±1 modulo 5. In this paper we review work on analogous problems concerning representations of n as a product of positive integers. We survey techniques for enumerating product representations both in the unrestricted case and in the case when the factors are required to be distinct, and both when the product representations are considered as ordered objects and when they are unordered. We offer some new identities and observations for these and related counting functions and derive some new recursive algorithms to generate lists of factorizations with restrictions of various types.
ON THE p-ADIC GEOMETRY OF TRACES OF SINGULAR MODULI
Authors: EDIXHOVEN BAS
Published: December 2005

The aim of this article is to show that p-adic geometry of modular curves is useful in the study of p-adic properties of traces of singular moduli. In order to do so, we partly answer a question by Ono [7, Problem 7.30]. As our goal is just to illustrate how p-adic geometry can be used in this context, we focus on a relatively simple case, in the hope that others will try to obtain the strongest and most general results. For example, for p = 2, a result stronger than Theorem 2 is proved in [2], and a result on some modular curves of genus zero can be found in [8]. It should be easy to apply our method, because of its local nature, to modular curves of arbitrary level, as well as to Shimura curves.
IRRATIONAL FACTORS SATISFYING THE LITTLE FERMAT THEOREM
Authors: LITSYN SIMON , SHEVELEV VLADIMIR
Published: December 2005

We study possible generalizations of the little Fermat theorem when the base of the exponentiation is allowed to be a non-integer. Such bases we call Fermat factors. We attempt classification of Fermat factors, and suggest several constructions.
RATIONAL TORSION ON OPTIMAL CURVES
Authors: DUMMIGAN NEIL
Published: December 2005

Vatsal has proved recently a result which has consequences for the existence of rational points of odd prime order ℓ on optimal elliptic curves over ℚ. When the conductor N is squarefree, ℓ ∤ N and the local root number wp= -1 for at least one prime p | N, we offer a somewhat different proof, starting from an explicit cuspidal divisor on X0(N). We also prove some results linking the vanishing of L(E,1) with the divisibility by ℓ of the modular parametrization degree, fitting well with the Bloch–Kato conjecture for L( Sym2E,2), and with an earlier construction of elements in Shafarevich–Tate groups. Finally (following Faltings and Jordan) we prove an analogue of the result on ℓ-torsion for cuspidal Hecke eigenforms of level one (and higher weight), thereby strengthening some existing evidence for another case of the Bloch–Kato conjecture.
A SHORT PROOF OF MILNE'S FORMULAS FOR SUMS OF INTEGER SQUARES
Authors: LONG LING , YANG YIFAN
Published: December 2005

We give a short proof of Milne's formulas for sums of 4n2 and 4n2 + 4n integer squares using the theory of modular forms. Other identities of Milne are also discussed.
Liver X receptor agonist TO-901317 upregulates SCD1 expression in renal proximal straight tubule
Authors: Zhang Yahua , Zhang Xiaoyan , Chen Lihong , Wu Jing , Su Dongming , Lu Wendell J. , Hwang Mei-Tsuey , Yang Guangrui , Li Shuo , Wei Minfen , Davis Linda , Breyer Matthew D. , Guan Youfei
Published: December 2005

Liver X receptors (LXRs), including LXRα and LXRβ, are intracellular sterol sensors that regulate expression of genes controlling fatty acid and cholesterol absorption, excretion, catabolism, and cellular efflux. Because the kidney plays an important role in lipid metabolism and dyslipidemia accelerates renal damage, we investigated the effect of TO-901317, an LXR agonist, on the gene expression profile in mouse kidney. Treatment of C57 Bl/6 mice with TO-901317 (3 mg·kg−1·day−1) for 3 days resulted in 51 transcripts that were significantly regulated in the kidney. Among them, the stearoyl-CoA desaturase-1 (SCD1) was upregulated most dramatically. Northern blot analysis revealed that SCD1 mRNA levels were markedly higher than that in control kidneys. Enhanced SCD1 expression by TO-901317 also resulted in increased fatty acid desaturation in the kidney. In control mice, constitutive renal SCD1 expression was low; however, TO-901317 treatment markedly increased SCD1 expression in the outer stripe of the outer medulla as assessed by both in situ hybridization and immunostain. Double-labeling studies further indicated that SCD1 mRNA was selectively expressed in proximal straight tubules negative for aquaporin-2 and Tamm-Horsfall protein. In vitro studies in cultured murine proximal tubule cells further demonstrated that LXR activation enhanced SCD1 transcription via increased sterol regulatory element binding protein-1. Taken together, these data suggest LXR activation of SCD1 expression may play an important role in regulating lipid metabolism and cell function in renal proximal straight tubules.
Keratinocyte-derived chemokine is an early biomarker of ischemic acute kidney injury
Authors: Molls Roshni R. , Savransky Vladimir , Liu Manchang , Bevans Shannon , Mehta Tulsi , Tuder Rubin M. , King Landon S. , Rabb Hamid
Published: December 2005

Renal ischemia-reperfusion injury (IRI) is the leading cause of acute kidney injury [AKI; acute renal failure (ARF)] in native kidneys and delayed graft function in deceased donor kidney transplants. Serum creatinine rises late after renal IRI, which results in delayed diagnosis. There is an important need to identify novel biomarkers for early diagnosis and prognosis in renal IRI. Given the inflammatory pathophysiology of renal IRI, we used a protein array to measure 18 cytokines and chemokines in a mouse model of renal IRI at 3, 24, and 72 h postischemia. A rise in renal keratinocyte-derived chemokine (KC) was the earliest and most consistent compared with other molecules, with 3-h postischemia values being 9- and 13-fold greater than sham and normal animals, respectively. Histological changes were evident within 1 h of IRI but serum creatinine only increased 24 h after IRI. With the use of an ELISA, KC levels in serum and urine were highest 3 h postischemia, well before a significant rise in serum creatinine. The human analog of KC, Gro-α, was markedly elevated in urine from humans who received deceased donor kidney transplants that required dialysis, compared with deceased donor kidney recipients with good graft function and live donor recipients with minimal ischemia. Measurement of KC and its human analog, Gro-α, could serve as a useful new biomarker for ischemic ARF.
Views of the Renin–Angiotensin System
Authors: Bernstein Kenneth E.
Published: December 2005

The renin–angiotensin system plays a role in many physiological systems, as proven by the phenotype of angiotensin-converting enzyme (ACE) knockout mice. We have used homologous recombination to create novel lines of mice with limited and unusual expression patterns of ACE. These mice show that, as long as an animal can regulate renin, they can tolerate both unusual patterns and reduced expression of ACE. We have also created mice in which one of the two ACE catalytic sites is nonfunctional. These new lines of mice give great insight into the function of the renin–angiotensin system in blood pressure control, response to stress, hematopoiesis, and reproduction.
Angiotensin-Converting Enzyme 2 and Angiotensin-(1-7)
Authors: Ferrario Carlos M.
Published: December 2005

This lecture summarizes the chronology and rationale that led to the discovery of angiotensin-(1-7) as a hormone that, in its own right, opposes the vasoconstrictor and proliferative actions of angiotensin II. The work discussed here additionally analyzes the newest findings on angiotensin-converting enzyme 2, the angiotensin-converting enzyme homologue that efficiently hydrolyzes angiotensin II into angiotensin-(1-7). Both components of this system may significantly influence our future perspective of the role of the renin–angiotensin system, not just in terms of its role in the regulation of cardiovascular and renal function but, moreover, as regulators of a vast array of disease processes in which inflammation and immune mechanisms play a role.
Sodium Bicarbonate Cotransporter Polymorphisms Are Associated With Baseline and 10-Year Follow-Up Blood Pressures
Authors: Hunt Steven C. , Xin Yuanpei , Wu Lily L. , Cawthon Richard M. , Coon Hilary , Hasstedt Sandra J. , Hopkins Paul N.
Published: December 2005

The NaHCO
3
cotransporter gene (
SLC4A5
) on chromosome 2 encodes a protein that transports sodium and bicarbonate across the cell membrane and regulates cellular pH. The National Heart, Lung, and Blood Institute Family Blood Pressure Program found linkage of blood pressure–related traits to the chromosomal region containing
SLC4A5
and phenotype associations with single nucleotide polymorphisms (SNPs) in this gene. However, the results were inconsistent over various phenotypes and SNPs. Nevertheless, the evidence was strong enough to propose this gene as a blood pressure–related gene. To extend these findings,
SLC4A5
SNPs were genotyped in an independent set of 96 Utah pedigrees of 1040 adult subjects at baseline, 760 of whom were followed longitudinally for 10 years. After adjusting for age, gender, body mass index, and polygenic correlations within pedigrees, SNP hcv1137534 was significantly associated with both systolic blood pressure and diastolic blood pressure (DBP) at baseline (unadjusted
P
=0.009 and
P
=0.043; respectively) and at 10-year follow-up (
P
=0.008 and
P
=0.007; respectively). In secondary tests of association of baseline-stressed blood pressure, hcv1137534 was borderline or significantly associated with DBP change during an isometric handgrip test (
P
=0.054), DBP change from supine to standing (
P
=0.020), and DBP change after a 50° tilt (
P
=0.034). There was no evidence for compensation of abnormal
SLC4A5
sodium transport by genotype-specific differences in sodium–lithium countertransport, lithium–potassium cotransport, altered plasma sodium, chloride, or CO
2
levels. Therefore, in these Utah pedigrees, the
SLC4A5
gene was significantly associated with blood pressure and persisted after 10 years of follow-up. These results additionally confirm the involvement of
SLC4A5
with blood pressure control, although the mechanism is still unclear.
Pancreatic Polypeptide-Fold Peptide Receptors and Angiotensin II–Induced Renal Vasoconstriction
Authors: Dubinion John H. , Mi Zaichuan , Zhu Chongxue , Gao Liping , Jackson Edwin K.
Published: December 2005

The Gipathway augments renal vasoconstriction induced by angiotensin II in spontaneously hypertensive but not normotensive Wistar-Kyoto rats. Because the Gi-coupled pancreatic polypeptide (PP)-fold peptide receptors Y1and Y2are expressed in kidneys and are activated by endogenous PP-fold peptides, we tested the hypothesis that these receptors regulate angiotensin II-induced renal vasoconstriction in kidneys from hypertensive but not normotensive rats. A selective Y1-receptor agonist [(Leu31,Pro34)-neuropeptide Y; 6 to 10 nmol/L] greatly potentiated angiotensin II–induced changes in perfusion pressure in isolated, perfused kidneys from hypertensive but not normotensive rats. A selective Y2-receptor agonist (peptide YY3-36; 6 nM) only slightly potentiated angiotensin II–induced renal vasoconstriction and only in kidneys from hypertensive rats. Neither the Y1-receptor nor the Y2-receptor agonist increased basal perfusion pressure. BIBP3226 (1 μmol/L, highly selective Y1-receptor antagonist) and BIIE0246 (1 μmol/L, highly selective Y2-receptor antagonist) completely abolished potentiation by (Leu31,Pro34)-neuropeptide Y and peptide YY3-36, respectively. Y1-receptor and Y2-receptor mRNA and protein levels were expressed in renal microvessels and whole kidneys, but the abundance was similar in kidneys from hypertensive and normotensive rats. Both Y1-receptor–induced and Y2-receptor–induced potentiation of angiotensin II–mediated renal vasoconstriction was completely abolished by pretreatment with pertussis toxin (30 μg/kg IV, blocks Giproteins). These data indicate that, in kidneys from genetically hypertensive but not normotensive rats, Y1-receptor activation markedly enhances angiotensin II–mediated renal vasoconstriction by a mechanism involving Gi. Although Y2receptors can also potentiate angiotensin II–mediated renal vasoconstriction via Gi, the effect is modest compared with Y1receptors. These findings may have important implications for the etiology of genetic hypertension.
A Novel Mechanism Contributing to Development of Dahl Salt–Sensitive Hypertension
Authors: Wang Youping , Wang Donna H.
Published: December 2005

To determine the role of the transient receptor potential vanilloid type 1 (TRPV1) channels in development of hypertension in Dahl salt–sensitive (DS) rats fed a high-salt diet (HS), male DS and Dahl salt–resistant (DR) rats were maintained on a low-salt diet (LS) or HS for 3 weeks. HS significantly increased systolic blood pressure in DS+HS rats compared with DS+LS, DR+HS, and DR+LS rats. Intravenous bolus injection of capsazepine (3 mg/kg), a selective TRPV1 antagonist, significantly increased mean arterial pressure in conscious DR+HS rats compared with DR+LS, DS±HS, and DS±LS rats. In contrast, capsaicin (10 or 30 μg/kg), a selective TRPV1 agonist, dose-dependently decreased mean arterial pressure in all of the groups with the most profound magnitude in DR+HS rats compared with the other 3 groups. TRPV1 expression in mesenteric resistance arteries and the renal cortex and medulla, calcitonin gene–related peptide levels in dorsal root ganglia, and calcitonin gene–related peptide–positive sensory nerve density in mesenteric resistance arteries were significantly decreased in DS+HS rats compared with DS+LS, DR+HS, and DR+LS rats. Taken together, our data indicate that the TRPV1 receptor is activated and its expression upregulated during HS intake in DR rats, which acts to prevent salt-induced increases in blood pressure. In contrast, TRPV1 expression and function are impaired in DS rats, which renders DS rats sensitive to salt load in terms of blood pressure regulation.
A Role for p38 Mitogen-Activated Protein Kinase and c-Myc in Endothelin-Dependent Rat Aortic Smooth Muscle Cell Proliferation
Authors: Chen Songcang , Qiong Ye , Gardner David G.
Published: December 2005

We have demonstrated recently that endothelin (ET) stimulates rat aortic smooth muscle cell proliferation through an extracellular signal–regulated kinase (ERK)–dependent mechanism. Approximately 70% of ET-dependent [
3
H]-thymidine incorporation in these cells signals through this system. In the present study, we show that the residual mitogenic activity requires an intact p38 mitogen-activated protein kinase (p38 MAPK) system and increased
c-myc
gene expression. ET increased [
3
H]-thymidine incorporation in rat aortic smooth muscle cells ≈5-fold. p38 MAPK inhibition with SB203580 or ERK/ERK kinase inhibition with PD98059 each effected ≈70% inhibition in ET-dependent DNA synthesis, whereas the combination led to nearly complete blockade of the ET effect. ET also increased
c-myc
RNA levels and c-Myc protein levels in these cells. The increment in c-Myc expression was blocked by SB203580 but not by PD98059. Use of antisense oligonucleotides directed against the translation start site of the
c-myc
transcript, but not scrambled oligonucleotide sequence, resulted in ≈60% decrease in ET-dependent [
3
H]-thymidine incorporation. The combination of antisense
c-myc
and PD98059 resulted in near complete inhibition of ET-dependent DNA synthesis. Both ET and c-Myc increased expression and promoter activity of E2F, a transcription factor that has been linked to enhanced cell cycle activity. The ET-dependent increment in E2F promoter activity was suppressed after treatment with SB203580 or antisense
c-myc
but not by PD98059 or a scrambled oligonucleotide sequence. Collectively, these findings demonstrate that ET uses 2 complementary signal transduction cascades (ERK and p38 MAPK) to control proliferative activity of vascular smooth muscle cells.
Disruption of the
Cathepsin K
Gene Reduces Atherosclerosis Progression and Induces Plaque Fibrosis but Accelerates Macrophage Foam Cell Formation
Authors: Lutgens E. , Lutgens S.P.M. , Faber B.C.G. , Heeneman S. , Gijbels M.M.J. , de Winther M.P.J. , Frederik P. , van der Made I. , Daugherty A. , Sijbers A.M. , Fisher A. , Long C.J. , Saftig P. , Black D. , Daemen M.J.A.P. , Cleutjens K.B.J.M.
Published: December 2005

Background—

Cathepsin K (catK), a lysosomal cysteine protease, was identified in a gene-profiling experiment that compared human early plaques, advanced stable plaques, and advanced atherosclerotic plaques containing a thrombus, where it was highly upregulated in advanced stable plaques.

Methods and Results—

To assess the function of catK in atherosclerosis, catK
−/−
/apolipoprotein (apo) E
−/−
mice were generated. At 26 weeks of age, plaque area in the catK
−/−
/apoE
−/−
mice was reduced (41.8%) owing to a decrease in the number of advanced lesions as well as a decrease in individual advanced plaque area. This suggests an important role for catK in atherosclerosis progression. Advanced plaques of catK
−/−
/apoE
−/−
mice showed an increase in collagen content. Medial elastin fibers were less prone to rupture than those of apoE
−/−
mice. Although the relative macrophage content did not differ, individual macrophage size increased. In vitro studies of bone marrow derived–macrophages confirmed this observation. Scavenger receptor–mediated uptake (particularly by CD36) of modified LDL increased in the absence of catK, resulting in an increased macrophage size because of increased cellular storage of cholesterol esters, thereby enlarging the lysosomes.

Conclusions—

A deficiency of catK reduces plaque progression and induces plaque fibrosis but aggravates macrophage foam cell formation in atherosclerosis.
Electrocardiographic Strain Pattern and Prediction of New-Onset Congestive Heart Failure in Hypertensive Patients
Authors: Okin Peter M. , Devereux Richard B. , Nieminen Markku S. , Jern Sverker , Oikarinen Lasse , Viitasalo Matti , Toivonen Lauri , Kjeldsen Sverre E. , Dahlöf Björn
Published: December 2005

Background—

The ECG strain pattern of ST depression and T-wave inversion is strongly associated with left ventricular hypertrophy (LVH) independently of coronary heart disease and with an increased risk of cardiovascular morbidity and mortality in hypertensive patients. However, whether ECG strain is an independent predictor of new-onset congestive heart failure (CHF) in the setting of aggressive antihypertensive therapy in unclear.

Methods and Results—

The relationship of ECG strain at study baseline to the development of CHF was examined in 8696 patients with no history of CHF who were enrolled in the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study. All patients had ECG LVH by Cornell product and/or Sokolow-Lyon voltage criteria on a screening ECG, were treated in a blinded manner with atenolol- or losartan-based regimens, and were followed up for a mean of 4.7±1.1 years. Strain was defined as a downsloping convex ST segment with inverted asymmetrical T-wave opposite the QRS axis in lead V
5
or V
6
. ECG strain was present in 923 patients (10.6%), and new-onset CHF occurred in 265 patients (3.0%), 26 of whom had a CHF-related death. Compared with patients who did not develop CHF, hypertensive patients who developed CHF were older; were more likely to be black, current smokers, and diabetic; were more like to have a history of myocardial infarction, ischemic heart disease, stroke, or peripheral vascular disease; and had greater baseline severity of LVH by Cornell product and Sokolow-Lyon voltage, higher baseline body mass indexes, higher serum glucose levels and albuminuria, similar baseline systolic and diastolic pressures, and reductions in diastolic pressure with treatment but greater reductions in systolic pressure. In univariate Cox analyses, ECG strain was a significant predictor of new-onset CHF (hazard ratio [HR], 3.27; 95% CI, 2.49 to 4.29) and CHF mortality (HR, 4.74; 95% CI, 2.11 to 10.64). In Cox multivariable analyses adjusting for baseline differences between patients with and without new-onset CHF, in-treatment differences in systolic and diastolic pressures, Sokolow-Lyon voltage, and Cornell product, and the impact of treatment with losartan versus atenolol on outcomes, ECG strain remained a significant predictor of incident CHF (HR, 1.80; 95% CI, 1.30 to 2.48) and CHF-related death (HR, 2.78; 95% CI, 1.02 to 7.63).

Conclusions—

ECG strain identifies hypertensive patients at increased risk of developing CHF and dying as a result of CHF, even in the setting of aggressive blood pressure lowering.
Distribution of Coronary Artery Calcium by Race, Gender, and Age
Authors: McClelland Robyn L. , Chung Hyoju , Detrano Robert , Post Wendy , Kronmal Richard A.
Published: December 2005

Background—

Coronary artery calcium (CAC) has been demonstrated to be associated with the risk of coronary heart disease. The Multi-Ethnic Study of Atherosclerosis (MESA) provides a unique opportunity to examine the distribution of CAC on the basis of age, gender, and race/ethnicity in a cohort free of clinical cardiovascular disease and treated diabetes.

Methods and Results—

MESA is a prospective cohort study designed to investigate subclinical cardiovascular disease in a multiethnic cohort free of clinical cardiovascular disease. The percentiles of the CAC distribution were estimated with nonparametric techniques. Treated diabetics were excluded from analysis. There were 6110 included in the analysis, with 53% female and an average age of 62 years. Men had greater calcium levels than women, and calcium amount and prevalence were steadily higher with increasing age. There were significant differences in calcium by race, and these associations differed across age and gender. For women, whites had the highest percentiles and Hispanics generally had the lowest; in the oldest age group, however, Chinese women had the lowest values. Overall, Chinese and black women were intermediate, with their order dependent on age. For men, whites consistently had the highest percentiles, and Hispanics had the second highest. Blacks were lowest at the younger ages, and Chinese were lowest at the older ages. At the MESA public website (http://www.mesa-nhlbi.org), an interactive form allows one to enter an age, gender, race/ethnicity, and CAC score to obtain a corresponding estimated percentile.

Conclusions—

The information provided here can be used to examine whether a patient has a high CAC score relative to others with the same age, gender, and race/ethnicity who do not have clinical cardiovascular disease or treated diabetes.
Do “high commitment” human resource practices affect employee commitment?
Authors: Whitener Ellen M.
Published: December 2005

Relying on a cross-level paradigm and on social exchange theory (i.e., perceived organizational support) I explore the relationships among human resource practices, trust-in-management, and organizational commitment. Individual-level analyses from a sample of 1689 employees from 180 credit unions indicate that trust-in-management partially mediates the relationship between perceived organizational support and organizational commitment. Cross-level analyses using hierarchical linear modeling indicate that human resource practices affect the relationship between perceived organizational support and organizational commitment or trust-in-management.
Dominating Interpersonal Behavior and Perceived Victimization in Groups: Evidence for a Curvilinear Relationship
Authors: Aquino Karl , Byron Kristin
Published: December 2005

A victim precipitation model was used to predict that members of workgroups who were perceived by others as exhibiting either high or low levels of dominating behavior would report being more frequent targets of personally injurious behaviors than those who were perceived as moderately dominating. However, we expected this effect to be moderated by the target’s gender. Data obtained from 131 MBA students who were randomly assigned to workgroups supported both the curvilinear relationship and the moderating effect of gender.
Determinants of Risk Taking in a Dynamic Uncertain Context
Authors: Slattery Jeffrey P. , Ganster Daniel C.
Published: December 2005

We tested the effects of positive and negative framing on risky decision making in a simulated managerial judgement task. Until now the extensive research on framing effects has been characterized by static contexts, explicit probabilities, and hypothetical gambles. In contrast we simulated a more realistic decision making environment in which individuals chose more or less risky goals in a complex dynamic task that featured uncertain outcomes and meaningful consequences. Decision makers chose a series of performance goals under conditions of either potential losses or gains and also received feedback about their goal attainment. Our results failed to replicateProspect Theory predictions about initial gain vs.loss framing typically found in static decision making contexts. In addition, we tested competing hypotheses derived from Prospect Theory and Quasi-Hedonic Editing (QHE) Theory about the effects of performance outcome feedback on subsequent decisions. Consistent with QHE Theory, decision makers who had failed to reach their goals set lower, less risky goals in subsequent decisions. Our findings illustrate the need for further risk taking research in environments that more closely resemble managerial decision making.
Where Should the Femoral Tunnel of a Posterior Cruciate Ligament Reconstruction be Placed to Best Restore Anteroposterior Laxity and Ligament Forces?
Authors: Markolf Keith L. , Feeley Brian T. , Jackson Steven R. , McAllister David R.
Published: December 2005

Background

Objective results of posterior cruciate ligament reconstruction are often less than satisfactory, with many patients exhibiting excessive posterior laxity.

Hypothesis

Changes in the position of the femoral tunnel within the posterior cruciate ligament's femoral footprint will significantly affect anteroposterior laxities and graft forces.

Study Design

Controlled laboratory study.

Methods

The posterior cruciate ligament's femoral origin was mechanically isolated in 13 fresh-frozen knee specimens, and the bone cap containing the ligament's insertion was attached to a load cell that recorded resultant force during tibial loading tests. Anteroposterior laxity (at ± 200 N applied force) was also measured. Cast acrylic replicas of the bone cap were fabricated, with tunnels placed in anterolateral, central, and posteromedial regions of the footprint. A graft reconstruction was tested in each tunnel.

Results

Mean laxities with the anterolateral tunnel were + 0.9 mm to + 1.7 mm greater than normal between 0 ° and 45 ° of flexion. Mean laxities with the posteromedial tunnel were –2.4 mm to –3.7 mm less than normal between 10 ° and 45 ° of flexion. Mean laxities with the central tunnel were not significantly different from intact knee values, except at 0 ° (0.9 mm greater). Mean graft forces with the anterolateral tunnel were normal for most modes of loading, whereas there were significant increases in graft forces with the posteromedial and central tunnels.

Conclusion

The anterolateral tunnel reproduced normal posterior cruciate ligament force profiles but produced a knee that was more lax than normal between 0 ° and 45 ° of flexion. The central tunnel best matched intact knee laxities, but graft forces were higher than posterior cruciate ligament forces between 0 ° and 45 ° of flexion. The posteromedial tunnel overconstrained anteroposterior laxity approximately 2 to 4 mm between 0 ° and 45 ° of flexion and generated higher graft forces in the same flexion range.

Clinical Relevance

This study suggests that a posteromedial tunnel should not be used for single-bundle posterior cruciate ligament reconstruction.
Anterior Cruciate Ligament Revision Reconstruction
Authors: Noyes Frank R. , Barber-Westin Sue D.
Published: December 2005

Background

The quadriceps tendon is a viable graft source for revision anterior cruciate ligament reconstruction.

Purpose

To determine the functional results and graft failure rates in knees in which the patellar tendon had been previously harvested or was unavailable, expanded tunnels precluded the use of a semitendinosus-gracilis graft, or patients requested autogenous tissues instead of allografts for revision reconstruction.

Study Design

Case series; Level of evidence, 4.

Methods

The authors observed 21 patients for a mean of 49 months postoperatively after revision anterior cruciate ligament reconstruction with a quadriceps tendon graft. The results were determined by KT-2000 arthrometer testing, the Cincinnati Knee Rating System, and the International Knee Documentation Committee Rating System. Fifteen knees required a concurrent procedure, including reconstruction of posterolateral structures in 5 knees, meniscal repairs in 5 knees, and high tibial osteotomy in 2 knees.

Results

Significant improvements occurred in symptoms (P< .0001), daily activities (P< .05), sports activities (P< .01), and the overall rating scores (P< .0001). Eighteen patients rated their knee condition as improved. Total mean anterior-posterior displacements decreased from 8.4 ± 3.1 mm preoperatively to 2.0 ± 2.3 mm at follow-up (P< .001). On the International Knee Documentation Committee knee ligament rating, 17 knees were graded as normal or nearly normal, 3 were graded as abnormal, and 1 was graded as severely abnormal.

Conclusion

The revision operation provided reasonable results in this group of complex knees. However, the functional and overall results were inferior to those reported for primary anterior cruciate ligament reconstruction. Many knees (90%) had compounding problems of articular cartilage damage, meniscectomy, varus malalignment, or additional ligamentous injury that most likely affected the results.
Arthroscopic Treatment of Posterolateral Elbow Impingement from Lateral Synovial Plicae in Throwing Athletes and Golfers
Authors: Kim David H. , Gambardella Ralph A. , Elattrache Neal S. , Yocum Lewis A. , Jobe Frank W.
Published: December 2005

Background

Although elbow pain is common in throwing athletes and golfers, posterolateral impingement from a hypertrophic synovial plica is a rare but possibly underdiagnosed condition.

Purpose

To evaluate the clinical results of arthroscopic treatment of symptomatic lateral elbow plicae in this athletic population.

Study Design

Case series; Level of evidence, 4.

Methods

Twelve patients, 9 male and 3 female, whose mean age was 21.6 years (range, 17-33 years), were reviewed. There were 7 baseball pitchers, 2 softball players, and 3 golfers. All patients had diagnosed isolated lateral elbow plica; none had lateral epicondylitis, instability, osteochondritis dissecans, arthritis, loose bodies, or nerve conditions. The mean time from onset of symptoms to treatment was 9.25 months (range, 3-24.5 months). At a mean follow-up of 33.8 months (range, 24-65.5 months), patients were evaluated with a questionnaire and examination, based on the American Shoulder and Elbow Surgeons standardized elbow assessment and previously reported elbow outcome score.

Results

Posterolateral elbow pain was present in all patients. Fifty-eight percent (7 of 12 patients) complained of clicking or catching, whereas only 25% (3 of 12) experienced swelling or effusion. At elbow arthroscopy, a thickened synovial lateral plica was debrided in all cases. Ninety-two percent (11 of 12 patients) reported an excellent outcome with a mean elbow score of 92.5 points (maximum, 100 points). Return to competitive play averaged 4.8 months (range, 3-9.5 months). One patient with a fair outcome developed medial elbow instability that later required reconstructive surgery.

Conclusion

Posterolateral elbow impingement from hypertrophic synovial plicae can cause significant pain and disability in throwing athletes and golfers. With careful diagnosis and exclusion of other elbow problems, treatment with arthroscopic debridement and focused rehabilitation is highly successful and allows these athletes to return to their previous level of play.
Magnetic Resonance Imaging of Articular Cartilage
Authors: Potter Hollis G. , Foo Li F.
Published: December 2005

The assessment of articular cartilage using magnetic resonance imaging has seen considerable advances in recent years. Cartilage morphologic characteristics can now be evaluated with a high degree of accuracy and reproducibility using dedicated pulse sequences, which are becoming standard at many institutions. These techniques detect clinically unsuspected traumatic cartilage lesions, allowing the physician to study their natural history with longitudinal evaluation and also to assess disease status in degenerative osteoarthritis. Magnetic resonance imaging also provides a more objective assessment of cartilage repair to augment the information obtained from more subjective clinical outcome instruments. Newly developed methods that provide detail at an ultrastructural level offer an important addition to cartilage evaluation, particularly in the detection of early alterations in the extracellular matrix. These methods have created an undeniably important role for magnetic resonance imaging in the reproducible, noninvasive, and objective evaluation and monitoring of cartilage. An overview of the advances, current techniques, and impact of magnetic resonance imaging in the setting of trauma, degenerative arthritides, and surgical treatment for cartilage injury is presented.
Intimate Partner Violence and HIV/STD Risk Among Lesbian, Gay, Bisexual, and Transgender Individuals
Authors: Heintz Adam Jackson , Melendez Rita M.
Published: December 2005

To date, there has been little research examining HIV/STD risk among lesbian, gay, bisexual, and transgender (LGBT) individuals who are in abusive relationships. This article uses data collected from a community-based organization that provides counseling for LGBT victims of intimate partner violence (IPV). A total of 58 clients completed the survey, which inquired as to sexual violence and difficulties negotiating safer sex with their abusive partners. A large percentage of participants reported being forced by their partners to have sex (41%). Many stated that they felt unsafe to ask their abusive partners to use safer sex protection or that they feared their partners’ response to safer sex (28%). In addition, many participants experienced sexual (19%), physical (21%), and/or verbal abuse (32%) as a direct consequence of asking their partner to use safer sex protection. Training counselors on issues of sexuality and safer sex will benefit victims of IPV.
The Roles of Victim and Perpetrator Alcohol Use in Intimate Partner Violence Outcomes
Authors: Thompson Martie P. , Kingree J. B.
Published: December 2005

Alcohol use increases the risk of intimate partner violence (IPV), yet little research has examined its role in victimization outcomes (e.g., physical injury, police reporting). This study examined the roles of perpetrator and victim incident-specific alcohol use in IPV outcomes. The sample included 501 men and 1,756 women who had experienced an IPV physical assault. Logistic regression analyses showed that after controlling for relevant covariates, women whose partners had been drinking were significantly more likely to be injured than were women whose partners had not been drinking. A woman’s own alcohol use was unrelated to victimization outcomes. Men were significantly more likely to report the incident if their partners had been drinking but were marginally less likely to report if they had been drinking. Findings suggest that perpetrators’ incident-specific alcohol use is important in understanding which victims are most likely to be injured and report the incident to the police.
Feelings of Revenge, Retaliation Motive, and Posttraumatic Stress Reactions in Crime Victims
Authors: Orth Ulrich , Montada Leo , Maercker Andreas
Published: December 2005

Individuals with posttraumatic stress disorder (PTSD) are often said to experience strong feelings of revenge. However, there is a need for confirmatory empirical studies. Therefore, in a study of 174 victims of violent crimes, the relation between feelings of revenge and posttraumatic stress reactions was investigated. Feelings of revenge were correlated with intrusion and hyperarousal but not with avoidance. Feelings of revenge explained incremental variance of intrusion and hyperarousal when the variance explained by victimological variables was controlled. The retaliation motive implied in feelings of revenge did not account for the relation between feelings of revenge and posttraumatic stress reactions. However, the relation was moderated by the time since victimization. Therefore, feelings of revenge must presumably be regarded as a maladaptive coping reaction to experienced injustice, but not in the first period after victimization.
Childhood Physical Punishment and Problem Solving in Marriage
Authors: Cast Alicia D. , Schweingruber David , Berns Nancy
Published: December 2005

Drawing from social learning theories and symbolic interactionist understandings of social life, the authors suggest that physical punishment teaches aggressive and controlling strategies for solving the problems of living together and hinders the development of important problem-solving skills, specifically the ability to role take with others. These strategies and skills become part of an individual’s toolkit for problem resolution within his or her marriage. The analysis is based on 188 married couples in Washington State who participated in a longitudinal study of the first 2 years of marriage. The analysis reveals the following: Individuals who were physically punished during childhood are more likely to engage in physical and verbal aggression with their spouses, individuals who were physically punished during childhood are more controlling with their spouses, and individuals who were physically punished during childhood are less able to take their spouse’s perspective.