bluuebunny/crossref_metadata_2025_split huggingface dataset:
β‐Tropomyosin mutations alter tropomyosin isoform composition
Authors: Nilsson J. , Tajsharghi H. 
Published: April 2008

Background and purpose:  Tropomyosin (TM) is an actin‐binding protein, which is localized head to tail along the length of the actin filament. There are three major TM isoforms in human striated muscle. Mutations in β‐tropomyosin (TPM2) have recently been identified as an important cause of neuromuscular disorders. Materials and methods:  The expression of TM isoforms in patients carrying mutations in TPM2 was detected using a combination of SDS‐PAGE, Western blotting, and a new method to measure the relative abundance of the various TM transcripts. Results:  The level of γ‐TM is reduced in patients with mutations in TPM2. β‐Tropomyosin was expressed at high levels in muscle specimens of the patients. Discussion:  Our study indicates that β‐TM gene mutations can alter the expression of other sarcomeric TM isoforms and that the perturbation of TM isoform levels may affect the dimer preference within the thin filaments, which may contribute to muscle weakness as a result of both functional and structural changes in muscle.
A Randomized Double‐Blind Study Comparing Rizatriptan, Dexamethasone, and the Combination of Both in the Acute Treatment of Menstrually Related Migraine
Authors: Bigal Marcelo , Sheftell Fred , Tepper Stewart , Tepper Deborah , Ho Tony W. , Rapoport Alan 
Published: April 2008

Objectives.— To assess the efficacy and tolerability of rizatriptan (RI), dexamethasone (DE), and RI combined with DE (RI+DE) in the acute treatment of menstrually related migraine (MRM).Methods.— This was a randomized, double‐blind, 6‐attack crossover study comparing RI 10 mg, DE 4 mg, and RI+DE (2 attacks each). The primary endpoint was 24‐hour sustained‐relief. The secondary endpoint was 24‐hour sustained pain‐free. We treated the primary and secondary endpoint as dichotomous outcomes and used matched nonparametric statistics to assess proportions. We used logistic regression to determine the effect of treatment order and if response to previous treatment influenced treatment response.Results.— A total of 35 patients treated 190 attacks (mean of 5.4 per participant). For the primary endpoint, RI was significantly superior to DE (62.7% vs 33.3%, P = .001). RI+DE was superior to RI (81.5% vs 62.7%, P < .05) and to DE (81.5% vs 33.3%%, P < .001). For the secondary endpoint RI was also superior to DE (32.2% vs 12.1%, P < .05). RI+DE was superior to RI (50.7% vs 32.2%, P < .05) and DE (P < .01, RR). Similar findings were seen for the other endpoints. More attacks treated with DE+RI (33.8%) were associated with side effects, compared to RI (18.6%) and DE (15.2%).Conclusions.— Rizatriptan is an effective treatment for MRM. RI+DE is significantly more effective than RI alone, although is associated with higher rate of adverse events. The combination should be considered for subjects with high disability, incomplete relief, or recurrence of pain with triptan monotherapy. The use of DE alone in the treatment of MRM is not justified based on our data.
Rizatriptan Efficacy in ICHD‐II Pure Menstrual Migraine and Menstrually Related Migraine
Authors: Nett Robert , Mannix Lisa K. , Mueller Loretta , Rodgers Anthony , Hustad Carolyn M. , Skobieranda Franck , Ramsey Karen E. 
Published: April 2008

Objective.— To examine the efficacy of rizatriptan for the treatment of pure menstrual migraine (PMM).Background.— In 2004, the International Headache Society proposed new research criteria for menstrual migraine (International Classification of Headache Disorders [ICHD‐II]). Two subtypes were defined: PMM, in which attacks occur exclusively with menstruation, and menstrually related migraine (MRM), in which attacks may also occur at other times of the cycle.Methods.— The 2 protocols (MM1 and MM2) were identical randomized, double‐blind studies. Adult patients with ICHD‐II menstrual migraine were assigned to either rizatriptan 10‐mg tablet or placebo (2:1). Patients were to treat a single menstrual migraine attack of moderate or severe pain intensity. This prospectively planned substudy pooled data from patients with a diagnosis of PMM from both studies. The primary substudy endpoint was 2‐hour pain relief. Efficacy data were summarized for patients with a diagnosis of MRM.Results.— Of 707 (MM1: 357, MM2: 350) patients treated in the study, 146 patients (MM1: 81, MM2: 65) had a diagnosis of PMM. The percentage of patients reporting 2‐hour pain relief was significantly greater for rizatriptan than for placebo for both PMM (73% vs 50%, P = .006) and MRM subgroups (71% vs 52%, P < .001). Most other efficacy endpoints favored rizatriptan compared with placebo in patients with either PMM or MRM.Conclusion.— Rizatriptan 10 mg was superior to placebo for the treatment of PMM, as measured by 2‐hour pain relief. Rizatriptan was also effective for the treatment of MRM and for relief of migraine‐associated symptoms for both headache subtypes.
Salivary 8-OHdG: A Useful Biomarker for Predicting Severe ED and Hypogonadism
Authors: Yasuda Mitsuko , Ide Hisamitsu , Furuya Kumiko , Yoshii Takashi , Nishio Kojiro , Saito Keisuke , Isotani Shuji , Kamiyama Yutaka , Muto Satoru , Horie Shigeo 
Published: April 2008

Abstract

Introduction
Erectile and endothelial dysfunction are common pathologies of multiple cardiovascular risk factors and are considered longitudinal predictors of cardiovascular events. Oxidative stress and decreases in testosterone levels play an important role in the pathogenesis of endothelial dysfunction.

Aim
We sought to determine whether the severity of erectile dysfunction (ED) was associated with individual levels of testosterone and oxidative stress, and whether treatment with a phosphodiesterase type 5 inhibitor could reduce oxidative stress and increase testosterone availability.

Methods
We evaluated the association of salivary 8-hydroxy-2′-deoxyguanosine (8-OHdG), salivary testosterone, International Index of Erectile Function-erectile function domain (IIEF-EF) scores, and Medical Outcome Study (MOS) 36-item Short-Form Healthy Survey (SF-36) questionnaires in 128 middle-aged male volunteers. We investigated the changes in testosterone levels, salivary 8-OHdG levels, IIEF-EF scores, and SF-36 scores in 20 ED patients (according to the IIEF-EF) who took 50 mg of sildenafil once a week for 6 months.

Main Outcome Measures
IIEF-EF scores were used to assess ED severity. Antioxidant status was defined by salivary 8-OHdG. Salivary testosterone was used to evaluate serum bioavailable testosterone availability.

Results
Salivary 8-OHdG (OR=9.88, 95% CI: 1.52–64.10), salivary testosterone (Odds ratio [OR]=0.96, 95% CI: 0.93–0.98), and vitality on the SF-36, version 2 (SF-36 v2) (OR=0.92, 95%CI: 0.84–0.98) were significantly associated with the severity of ED in healthy volunteers. Treatment with sildenafil for 6 months significantly increased the total serum testosterone (426.4 ± 174.8 vs. 569.6 ± 146.1 ng/dL, P =0.021) and salivary testosterone levels (56.1 ± 22.3 vs. 110.0 ± 48.4 pg/mL, P &lt;0.001), whereas it decreased salivary 8-OHdG levels (2.30 ± 0.23 vs. 0.90 ± 0.05 ng/mL, P =0.0046).

Conclusions
Salivary 8-OHdG is a useful biomarker for predicting severe ED and hypogonadism in middle-aged men. Once-a-week treatment with sildenafil can have beneficial effects on men's health by decreasing oxidative stress and increasing testosterone levels.
Canine serum C‐reactive protein detected by means of a near‐patient test for human C‐reactive protein
Authors: Kjelgaard‐Hansen M. , Stadler M. , Jensen A. L. 
Published: April 2008

Objectives:The aim of the study was to evaluate the reliability of a rapid human C‐reactive protein near‐patient slide reversed passive latex agglutination test (Randox) for the semi‐quantitative determination of canine serum C‐reactive protein.Methods:The concentration of C‐reactive protein was determined in 244 canine serum samples by an established automated immunoturbidimetric method and in various predilutions by a commercially available reversed passive latex agglutination test for human C‐reactive protein. The results were compared to assess if the reversed passive latex agglutination test reflected the results of the established method with special emphasis on the reversed passive latex agglutination test’s ability to identify samples characterised as positive or negative by the established method.Results:The reversed passive latex agglutination test reflected the C‐reactive protein concentration in canine serum samples at all the tested predilutions (undiluted, 1:4, 1:8 and 1:16). When applying a predilution of 1:8, the positive and negative analytical predictive values for discriminating between positive and negative samples (according to the established quantitative method) were high (0·94 [0·82 to 0·99] and 0·97 [0·93 to 0·99], respectively).ClinicalSignificance:In conclusion, this near‐patient test was able to reflect the serum C‐reactive protein concentration in canine samples in a reliable and clinically useful manner and could be applicable for general practice for evaluating C‐reactive protein levels in canine serum.
Photoprotection by Porcine Eumelanin Against Singlet Oxygen Production†
Authors: Wang Alice , Marino Anthony R. , Gasyna Zbigniew , Gasyna Elzbieta , Norris James 
Published: April 2008

AbstractMelanin, a major pigment found in retinal pigment epithelium (RPE) cells, is considered to function in dual roles, one protective and one destructive. By quenching free radical species and reactive oxygen species (ROS) melanin counteracts harmful redox stress. However, melanin is also thought to be capable of creating ROS. In this destructive role, melanin increases redox strain in the cell. This study uses readily available eumelanin extracted from porcine RPE cells as a more authentic model than synthetic melanin to determine specific mechanisms of melanin activity with regard to singlet oxygen in the presence and absence of rose bengal, a singlet‐oxygen photosensitizer. Optical detection of singlet‐oxygen was determined by monitoring the bleaching of p‐nitrosodimethylaniline in the presence of histidine. Production of singlet oxygen in aqueous oxygen‐saturated solutions of rose bengal without eumelanin was readily accomplished. In contrast, detection of singlet oxygen in oxygen‐saturated solutions of eumelanin without rose bengal failed, consistent with results of others. However, a significant decrease in singlet oxygen production by rose bengal was observed in the presence of eumelanin. After correction for light absorption and chemical bleaching of eumelanin, the results show that eumelanin also provides a photoprotective mode arising from chemistry, that is, not just the physical process of light absorption followed by energy dissipation as heat.
Discordant Patterns of Genetic Variation at Two Chloroquine Resistance Loci in Worldwide Populations of the Malaria Parasite
Plasmodium falciparum
Authors: Mehlotra Rajeev K. , Mattera Gabriel , Bockarie Moses J. , Maguire Jason D. , Baird J. Kevin , Sharma Yagya D. , Alifrangis Michael , Dorsey Grant , Rosenthal Philip J. , Fryauff David J. , Kazura James W. , Stoneking Mark , Zimmerman Peter A. 
Published: April 2008

ABSTRACT

Mutations in the chloroquine resistance (CQR) transporter gene of
Plasmodium falciparum
(Pf
crt
; chromosome 7) play a key role in CQR, while mutations in the multidrug resistance gene (Pf
mdr1
; chromosome 5) play a significant role in the parasite's resistance to a variety of antimalarials and also modulate CQR. To compare patterns of genetic variation at Pf
crt
and Pf
mdr1
loci, we investigated 460 blood samples from
P. falciparum
-infected patients from four Asian, three African, and three South American countries, analyzing microsatellite (MS) loci flanking Pf
crt
(five loci [∼40 kb]) and Pf
mdr1
(either two loci [∼5 kb] or four loci [∼10 kb]). CQR Pf
mdr1
allele-associated MS haplotypes showed considerably higher genetic diversity and higher levels of subdivision than CQR Pf
crt
allele-associated MS haplotypes in both Asian and African parasite populations. However, both Pf
crt
and Pf
mdr1
MS haplotypes showed similar levels of low diversity in South American parasite populations. Median-joining network analyses showed that the Pf
crt
MS haplotypes correlated well with geography and CQR Pf
crt
alleles, whereas there was no distinct Pf
mdr1
MS haplotype that correlated with geography and/or CQR Pf
mdr1
alleles. Furthermore, multiple independent origins of CQR Pf
mdr1
alleles in Asia and Africa were inferred. These results suggest that variation at Pf
crt
and Pf
mdr1
loci in both Asian and African parasite populations is generated and/or maintained via substantially different mechanisms. Since Pf
mdr1
mutations may be associated with resistance to artemisinin combination therapies that are replacing CQ, particularly in Africa, it is important to determine if, and how, the genetic characteristics of this locus change over time.
In Vitro Susceptibility of Isolates of
Francisella tularensis
Types A and B from North America
Authors: Urich Sandra K. , Petersen Jeannine M. 
Published: April 2008

ABSTRACT

Due to concern that
Francisella tularensis
, the causative agent of tularemia, may be used as a bioterrorist weapon, the Clinical and Laboratory Standards Institute recently provided a susceptibility testing method with breakpoints. Here, 169 isolates (92 type A and 77 type B) from North America were tested against seven antimicrobial agents (streptomycin, gentamicin, tetracycline, doxycycline, ciprofloxacin, levofloxacin, and chloramphenicol) used for the treatment of tularemia. The MICs for all of the isolates fell within the susceptible range. In addition, all isolates had MICs for erythromycin of 0.5 to 4 μg/ml, in contrast to an MIC of >256 μg/ml for the common laboratory strain LVS (live vaccine strain).
Role for Myosin II in Regulating Positioning ofSalmonella-Containing Vacuoles and Intracellular Replication
Authors: Wasylnka Julie A. , Bakowski Malina A. , Szeto Jason , Ohlson Maikke B. , Trimble William S. , Miller Samuel I. , Brumell John H. 
Published: April 2008

ABSTRACTSalmonella entericaserovar Typhimurium grows within host cells in a permissive compartment termed theSalmonella-containing vacuole (SCV). These bacteria use two distinct type III secretion systems (T3SS) to deliver virulence proteins (effectors) into cells. Effectors secreted by theSalmonellapathogenicity island 1 (SPI-1)-encoded T3SS mediate invasion and early SCV maturation steps, while those secreted by the SPI-2 T3SS affect the SCV at later stages postinfection. Some SPI-2 effectors modulate microtubule motor activity on the SCV. Here, we show that the actin-based motor myosin II also affects SCV dynamics during infection. Following invasion, myosin II is required for SCV positioning near the nucleus of host cells. Later, myosin II counteracts the activities of the SPI-2 effectors PipB2 and SseJ to maintain SCV positioning and stability, respectively. Myosin II activity was required for maximal bacterial growth in macrophages. Rho kinase activity was required for SCV positioning. The effector SopB, a known activator of Rho GTPases, was found to be required for SCV positioning, and transfection of cells with SopB was sufficient to induce myosin II phosphorylation. These studies reveal a novel role for myosin II in controlling SCV dynamics during infection and suggest that SopB activates myosin II.
The Surface-Exposed Carboxyl Region of
Mycoplasma pneumoniae
Elongation Factor Tu Interacts with Fibronectin
Authors: Balasubramanian Sowmya , Kannan T. R. , Baseman Joel B. 
Published: April 2008

ABSTRACT

Mycoplasma pneumoniae
is a bacterial pathogen of the human respiratory tract that causes a wide range of airway diseases as well as extrapulmonary symptoms. It possesses a distinct, differentiated terminal structure, termed the attachment organelle, that mediates adherence to the host respiratory epithelium. Previously, we reported that surface-associated
M. pneumoniae
elongation factor Tu (EF-Tu, also called MPN665) serves as a fibronectin (Fn)-binding protein, facilitating interactions between mycoplasmas and extracellular matrix. In the present study, we determined that binding of
M. pneumoniae
EF-Tu to Fn is primarily mediated by the EF-Tu carboxyl region. A 179-amino-acid region spanning the carboxyl terminus (designated EC; amino acids 192 to 394) binds Fn in a dose-dependent manner. Further analysis of carboxyl constructs (ED3 and ED4) and their deletion truncations (ED3.1, ED3.2, and ED4.1) revealed that the carboxyl region possessed two distinct sites with different Fn-binding efficiencies. Immunogold electron microscopy using antibodies raised against recombinant ED3 and ED4 demonstrated the surface accessibility of the EF-Tu carboxyl region. Competitive binding assays using intact radiolabeled mycoplasmas and purified recombinant ED3 and ED4 proteins, along with antibody blocking assays, reinforced the role of the surface-exposed EF-Tu carboxyl region in Fn binding. Alkali and high-salt treatment of mycoplasma membranes and Triton X-114-partitioned mycoplasma fractions confirmed the stable association of EF-Tu within the mycoplasma membrane. These observations highlight the unique, multifaceted, and unpredictable role of the classically defined cytoplasmic protein EF-Tu relative to cellular function, compartmentalization, and topography.
The Signal Recognition Particle Pathway Is Required for Virulence in
Streptococcus pyogenes
Authors: Rosch Jason W. , Vega Luis Alberto , Beyer John M. , Lin Ada , Caparon Michael G. 
Published: April 2008

ABSTRACT

The signal recognition particle (SRP) pathway is a universally conserved pathway for targeting polypeptides for secretion via the cotranslational pathway. In particular, the SRP pathway is thought to be the main mechanism for targeting polypeptides in gram-positive bacteria, including a number of important human pathogens. Though widely considered to be an essential cellular component, recent advances have indicated this pathway may be dispensable in gram-positive bacteria of the genus
Streptococcus
under in vitro conditions. However, its importance for the pathogenesis of streptococcal disease is unknown. In this study, we investigated the importance of the SRP pathway for virulence factor secretion in the human pathogen
Streptococcus pyogenes
. While the SRP pathway was not found to be essential for viability in vitro, SRP mutants demonstrated a medium-specific growth defect that could be rescued by the addition of glucose. We also observed that a distinct subset of virulence factors were dependent upon the SRP pathway for secretion, whereas others were completely independent of this pathway. Significantly, deletion of the SRP pathway resulted in mutants that were highly attenuated in both a zebrafish model of necrotic myositis and a murine subcutaneous ulcer model, highlighting the importance of this pathway in vivo. These studies emphasize the importance of the SRP pathway for the in vivo survival and pathogenesis of
S. pyogenes
.
Nasal Vaccination with the 40-Kilodalton Outer Membrane Protein ofPorphyromonas gingivalisand a Nontoxic Chimeric Enterotoxin Adjuvant Induces Long-Term Protective Immunity with Reduced Levels of Immunoglobulin E Antibodies
Authors: Momoi Fumiki , Hashizume Tomomi , Kurita-Ochiai Tomoko , Yuki Yoshikazu , Kiyono Hiroshi , Yamamoto Masafumi 
Published: April 2008

ABSTRACTIn this study, we demonstrated that the 40-kDa outer membrane protein ofPorphyromonas gingivalis(40-kDa OMP) nasally administered with a nontoxic chimeric adjuvant that combines the A subunit of mutant cholera toxin E112K with the pentameric B subunit of heat-labile enterotoxin from enterotoxigenicEscherichia coli(mCTA/LTB) elicited a long-term protective immune response. Immunization with the 40-kDa OMP and mCTA/LTB induced high levels of 40-kDa-OMP-specific immunoglobulin G (IgG) and IgA antibodies (Abs) in sera and elicited a significant IgA anti-40-kDa OMP Ab response in saliva. These Ab responses were maintained for at least 1 year after the immunization. Although using adjuvant mCTA/LTB gave Ab responses in the saliva comparable to those obtained using native cholera toxin (nCT) as the adjuvant, the levels of total IgE and 40-kDa-OMP-specific IgE Abs as well as interleukin-4 levels induced by the immunization with mCTA/LTB were lower than those induced by the immunization with nCT. Importantly, IgG Abs generated by nasal immunization with the 40-kDa OMP plus mCTA/LTB inhibited the coaggregation and hemagglutinin activities ofP. gingivalis. Furthermore, the mice given nasal 40-kDa OMP plus mCTA/LTB showed a significant reduction of alveolar bone loss caused by oral infection withP. gingivaliseven 1 year after the immunization compared to the loss in unimmunized mice. Because mCTA/LTB is nontoxic, nasally administered 40-kDa OMP together with mCTA/LTB should be an effective and safe mucosal vaccine againstP. gingivalisinfection in humans and may be an important tool for the prevention of chronic periodontitis.
Helicobacter hepaticus
Infection Promotes Colon Tumorigenesis in the BALB/c-
Rag2
−/−
Apc

Min
/+

Mouse
Authors: Nagamine Claude M. , Sohn Jane J. , Rickman Barry H. , Rogers Arlin B. , Fox James G. , Schauer David B. 
Published: April 2008

ABSTRACT

Adenomatous polyposis coli (
APC
) mutations are linked to human and mouse colorectal cancers. The
Apc
multiple intestinal neoplasia (Min) mouse mutation causes adenomas to develop throughout the small and large intestines. The BALB-Min (C.B6-
Apc

Min
/+

) congenic strain was generated by backcrossing into BALB/c the
Apc

Min

allele from C57BL/6J-
Apc

Min
/+

mice. BALB-Min mice have a low tumor multiplicity (27.4 small intestine tumors/mouse) and a relatively long life span (>1 year) that makes them amenable to long-term studies. To investigate the interplay of the adaptive immune system and intestinal tumorigenesis, the immunodeficient compound mutant strain BALB-RagMin (C.Cg-
Rag2
−/−
Apc

Min
/+

) was generated. BALB-RagMin mice had a significant increase in tumors in the small, but not large, intestine relative to their BALB-Min counterparts (43.0 versus 24.0 tumors/mouse, respectively). The results suggest that the adaptive immune system plays a role in either the elimination or the equilibrium phase of cancer immunoediting in the small intestine in this model. We investigated the effect of the enterohepatic bacterial pathogen
Helicobacter hepaticus
on liver and intestine tumorigenesis in BALB-RagMin mice.
H. hepaticus
-infected BALB-RagMin mice developed moderate hepatitis, moderate typhlitis, and mild colitis. There were no differences in small intestine and cecal tumor multiplicity, regionality, or size relative to that in uninfected mice. However,
H. hepaticus
-infected BALB-RagMin mice had a significant increase in colon tumor incidence relative to uninfected BALB-RagMin mice (23.5% versus 1.7%, respectively). The data suggest that
H. hepaticus
, which is present in many research colonies, promotes colon tumorigenesis in the BALB-RagMin mouse and that it has the potential to confound colon tumorigenesis studies.
The Quest for the1p36Tumor Suppressor
Authors: Bagchi Anindya , Mills Alea A. 
Published: April 2008

AbstractGenomic analyses of late-stage human cancers have uncovered deletions encompassing 1p36, thereby providing an extensive body of literature supporting the idea that a potent tumor suppressor resides in this interval. Although several genes have been proposed as 1p36 candidate tumor suppressors, convincing evidence that their encoded products protect from cancer has been scanty. A recent functional study identified chromodomain helicase DNA-binding protein 5 (CHD5) as a novel tumor suppressor mapping to 1p36. Here, we discuss evidence supporting the tumor-suppressive role of CHD5. Together, these findings suggest that strategies designed to enhance CHD5 activity could provide novel approaches for treating a broad range of human malignancies. [Cancer Res 2008;68(8):2551–6]