bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histamine metabolism influences blood vessel branching in zebrafish reg6mutants
Authors: Huang Cheng-chen , Huang Chin-Wei , Cheng Yih-Shyun E , Yu John 
Published: March 2008

Abstract
Background
Vascular branching morphogenesis is responsible for the extension of blood vessels into growing tissues, a process crucial for organogenesis. However, the genetic mechanism for vessel branching is largely unknown. Zebrafish reg6 is a temperature-sensitive mutation exhibiting defects in blood vessel branching which results in the formation of swollen vessel lumina during capillary plexus formation.

Results
We performed a screening for chemical suppressors of reg6 and identified SKF91488, an inhibitor of histamine methyltransferase (HMT), that can rescue the reg6 vessel branching defects in a dose-dependent manner. Inhibition of HMT by SKF91488 presumably blocks histamine degradation, thus causing histamine accumulation. Consistent with this idea, we found that a high level of histamine also showed significant suppression of reg6 vessel phenotypes. Interestingly, when reg6 adults that had already developed swollen vessel lumina in regenerating fins were treated with histamine or SKF91488, either treatment significantly reduced the number of swollen vessels within 12 h, suggesting a rapid and constant influence of histamine on blood vessel branching. Furthermore, the expression of HMT was significantly elevated in reg6 regenerating fins. Conversely, lowering histamine by administering urocanic acid, a histidine decarboxylase inhibitor, enhanced the reg6 phenotypes. Finally, we identified that the transcription factor, egr-1 (early growth response factor 1), was closely associated with the reg6 phenotype and chemical treatments.

Conclusion
Taken together, our results suggest that blood vessel branching is influenced by histamine metabolism, possibly through regulating the expression of the egr-1 transcription factor.
Evolution of the DAZ gene and the AZFc region on primate Y chromosomes
Authors: Yu Yueh-Hsiang , Lin Yi-Wen , Yu Jane-Fang , Schempp Werner , Yen Pauline H 
Published: March 2008

Abstract

Background
The Azoospermia Factor c (AZFc) region of the human Y chromosome is a unique product of segmental duplication. It consists almost entirely of very long amplicons, represented by different colors, and is frequently deleted in subfertile men. Most of the AZFc amplicons have high sequence similarity with autosomal segments, indicating recent duplication and transposition to the Y chromosome. The Deleted in Azoospermia (DAZ) gene within the red-amplicon arose from an ancestral autosomal DAZ-like (DAZL) gene. It varies significantly between different men regarding to its copy number and the numbers of RNA recognition motif and DAZ repeat it encodes. We used Southern analyses to study the evolution of DAZ and AZFc amplicons on the Y chromosomes of primates.

Results
The Old World monkey rhesus macaque has only one DAZ gene. In contrast, the great apes have multiple copies of DAZ, ranging from 2 copies in bonobos and gorillas to at least 6 copies in orangutans, and these DAZ genes have polymorphic structures similar to those of their human counterparts. Sequences homologous to the various AZFc amplicons are present on the Y chromosomes of some but not all primates, indicating that they arrived on the Y chromosome at different times during primate evolution.

Conclusion
The duplication and transposition of AZFc amplicons to the human Y chromosome occurred in three waves, i.e., after the branching of the New World monkey, the gorilla, and the chimpanzee/bonobo lineages, respectively. The red-amplicon, one of the first to arrive on the Y chromosome, amplified by inverted duplication followed by direct duplication after the separation of the Old World monkey and the great ape lineages. Subsequent duplication/deletion in the various lineages gave rise to a spectrum of DAZ gene structure and copy number found in today's great apes.
cDNA-AFLP analysis of plant and pathogen genes expressed in grapevine infected with Plasmopara viticola
Authors: Polesani Marianna , Desario Filomena , Ferrarini Alberto , Zamboni Anita , Pezzotti Mario , Kortekamp Andreas , Polverari Annalisa 
Published: March 2008

AbstractBackgroundThe oomycetePlasmopara viticola(Berk. and Curt.) Berl. and de Toni causes downy mildew in grapevine (Vitis viniferaL.). This pathogen is strictly biotrophic, thus completely dependent on living host cells for its survival. The molecular basis of compatibility and disease development in this system is poorly understood. We have carried out a large-scale cDNA-AFLP analysis to identify grapevine andP. viticolagenes associated with the infection process.ResultsWe carried out cDNA-AFLP analysis on artificially infected leaves of the susceptible cultivar Riesling at the oil spot stage, on water-treated leaves and on a sample of pure sporangia as controls. Selective amplifications with 128 primer combinations allowed the visualization of about 7000 transcript-derived fragments (TDFs) in infected leaves, 1196 of which (17%) were differentially expressed. We sequenced 984 fragments, 804 of which were identified as grapevine transcripts after homology searching, while 96 were homologous to sequences inPhytophthoraspp. databases and were attributed toP. viticola. There were 82 orphan TDFs. Many grapevine genes spanning almost all functional categories were downregulated during infection, especially genes involved in photosynthesis. Grapevine genes homologous to known resistance genes also tended to be repressed, as were several resistance gene analogs and carbonic anhydrase (recently implicated in pathogen resistance). In contrast, genes encoding cytoskeletal components, enzymes of the phenylpropanoid and beta-oxidation pathways, and pathogenesis related proteins were primarily upregulated during infection. The majority ofP. viticolatranscripts expressedin plantashowed homology to genes of unknown function or to genomicPhytophthorasequences, but genes related to metabolism, energy production, transport and signal transduction were also identified.ConclusionThis study provides the first global catalogue of grapevine andP. viticolagenes expressed during infection, together with their functional annotations. This will help to elucidate the molecular basis of the infection process and identify genes and chemicals that could help to inhibit the pathogen.
Chlamydophila pneumoniae derived from inclusions late in the infectious cycle induce aponecrosis in human aortic endothelial cells
Authors: Marino Joseph , Stoeckli Isabelle , Walch Michael , Latinovic-Golic Sonja , Sundstroem Hanna , Groscurth Peter , Ziegler Urs , Dumrese Claudia 
Published: March 2008

AbstractBackgroundAtherosclerosis is still the leading cause of death in the western world. Besides known risk factors studies demonstratingChlamydophila pneumoniae(C. pneumoniae) to be implicated in the progression of the disease, little is known aboutC. pneumoniaeinfection dynamics. We investigated whetherC. pneumoniaeinduce cell death of human aortic endothelial cells, a cell type involved in the initiation of atherosclerosis, and whether chlamydial spots derive from inclusions.ResultsLactate dehydrogenase release revealed host cell death to be dependent on the amounts ofChlamydiaused for infection. The morphology of lysed human aortic endothelial cells showed DNA strand breaks simultaneously with cell membrane damage exclusively in cells carryingChlamydiaas spots. Further ultrastructural analysis revealed additional organelle dilation, leading to the definition as aponecrotic cell death of endothelial cells. Exclusive staining of the metabolic active pathogens by chlamydial heat shock protein 60 labelling and ceramide incorporation demonstrated that the bacteria responsible for the induction of aponecrosis had resided in former inclusions. Furthermore, a strong pro-inflammatory molecule, high mobility group box protein 1, was shown to be released from aponecrotic host cells.ConclusionFrom the data it can be concluded that aponecrosis inducingC. pneumoniaestem from inclusions, since metabolically active bacterial spots are strongly associated with aponecrosis late in the infectious cycle in vascular endothelial cells and metabolic activity was exclusively located inside of inclusions in intact cells. Vice versa initial spot-like infection with metabolically inert bacteria does not have an effect on cell death induction. Hence,C. pneumoniaeinfection can contribute to atherosclerosis by initial endothelial damage.
Testosterone influences renal electrolyte excretion in SHR/y and WKY males
Authors: Toot Jonathan , Jenkins Cathy , Dunphy Gail , Boehme Shannon , Hart Mike , Milsted Amy , Turner Monte , Ely Daniel 
Published: March 2008

Abstract

Background
The Y-chromosome (Yc) and testosterone (T) increase blood pressure and may also influence renal electrolyte excretion. Therefore, the goal of this study was to determine if the Yc combined with T manipulation could influence renal Na and K excretion.

Methods
To investigate the role of the Yc and T, consomic borderline hypertensive (SHR/y) and normotensive Wistar-Kyoto (WKY) rat strains were used (15 weeks) in three T treatment groups: castrate, castrate with T implant and gonadally intact males. Urine was collected (24 hrs at 15 weeks of age) for Na and K measurements by flame photometry. RT-PCR was used to demonstrate the presence of renal androgen receptor (AR) transcripts. Plasma T and aldosterone were measured by RIA. In another experiment the androgen receptor was blocked using flutamide in the diet.

Results
Na and K excretion were decreased by T in SHR/y and WKY. AR transcripts were identified in SHR/y and WKY kidneys. Plasma aldosterone was decreased in the presence of T. Blockade of the AR resulted in a significant increase in Na excretion but not in K excretion in both SHR/y and WKY males.

Conclusion
T influences electrolyte excretion through an androgen receptor dependent mechanism. There was not a differential Yc involvement in electrolyte excretion between WKY and SHR/y males.
Characterization of VAR2CSA-deficient Plasmodium falciparum-infected erythrocytes selected for adhesion to the BeWo placental cell line
Authors: Yosaatmadja Francisca , Andrews Katherine T , Duffy Michael F , Brown Graham V , Beeson James G , Rogerson Stephen J 
Published: March 2008

Abstract

Background
Malaria in pregnancy is characterized by accumulation of infected erythrocytes (IE) in the placenta. The key ligand identified as mediating this process is a Plasmodium falciparum erythrocyte membrane protein 1 family member, termed VAR2CSA. VAR2CSA appears to be the main ligand responsible for adhesion to chondroitin sulphate A (CSA). Whether other PfEMP1 molecules can also mediate placental adhesion, independent of CSA binding, is unclear.

Methods
The parasite line CS2 carrying a disrupted var2csa gene (CS2KO) was selected for adhesion to the BeWo choriocarcinoma cell line, which has been proposed as a model for placental malaria. The selected and control IE were tested for adhesion to placental sections and flow cytometry was used to measure recognition of IE by three serum sets from malaria-exposed men and women.

Results
Wild-type CS2 adhere to BeWo and placental tissue via CSA. CS2KO IE were successfully selected for adhesion to BeWo, and adhered by a CSA-independent mechanism. They bound to immobilized ICAM-1 and CD36. BeWo-selected CS2KO bound at moderate levels to placental sections, but most binding was to placental villi rather than to the syncytiotrophoblast to which IE adherence occurs in vivo. This binding was inhibited by a blocking antibody to CD36 but not to ICAM-1. As expected, sera from malaria-exposed adults recognized CS2 IE in a gender and parity dependent manner. In one serum set, there was a similar but less pronounced pattern of antibody binding to selected CS2KO IE, but this was not seen in two others. One var gene, It4var19, was particularly abundant in the selected line and was detected as full length transcripts in BeWo-selected IE, but not unselected CS2KO.

Conclusion
This study suggests that IE with characteristics similar to the CS2KO have a limited role in the pathogenesis of placental malaria. VAR2CSA appear to be the major ligand for placental adhesion, and could be the basis for a vaccine against pregnancy malaria.
The impact of the neisserial DNA uptake sequences on genome evolution and stability
Authors: Treangen Todd J , Ambur Ole Herman , Tonjum Tone , Rocha Eduardo PC 
Published: March 2008

Abstract
Background
Efficient natural transformation in Neisseria requires the presence of short DNA uptake sequences (DUSs). Doubts remain whether DUSs propagate by pure selfish molecular drive or are selected for 'safe sex' among conspecifics.

Results
Six neisserial genomes were aligned to identify gene conversion fragments, DUS distribution, spacing, and conservation. We found a strong link between recombination and DUS: DUS spacing matches the size of conversion fragments; genomes with shorter conversion fragments have more DUSs and more conserved DUSs; and conversion fragments are enriched in DUSs. Many recent and singly occurring DUSs exhibit too high divergence with homologous sequences in other genomes to have arisen by point mutation, suggesting their appearance by recombination. DUSs are over-represented in the core genome, under-represented in regions under diversification, and absent in both recently acquired genes and recently lost core genes. This suggests that DUSs are implicated in genome stability rather than in generating adaptive variation. DUS elements are most frequent in the permissive locations of the core genome but are themselves highly conserved, undergoing mutation selection balance and/or molecular drive. Similar preliminary results were found for the functionally analogous uptake signal sequence in Pasteurellaceae.

Conclusion
As do many other pathogens, Neisseria and Pasteurellaceae have hyperdynamic genomes that generate deleterious mutations by intrachromosomal recombination and by transient hypermutation. The results presented here suggest that transformation in Neisseria and Pasteurellaceae allows them to counteract the deleterious effects of genome instability in the core genome. Thus, rather than promoting hypervariation, bacterial sex could be regenerative.
SEB-induced signaling in macrophages leads to biphasic TNF-α
Authors: Khan Aslam Ali , Martin Sunil , Saha Bhaskar 
Published: March 2008

AbstractAPCs express MHC-II molecules. Binding of enterotoxins to MHC-II generates a signal resulting in the production of TNF-α that mediates toxic shock syndrome. However, the signaling events that lead to TNF-α production in macrophages are not well understood. We, for the first time, demonstrate that binding of staphylococcal enterotoxin B to MHC-II results in activation of TNF-α-converting enzyme, epidermal growth factor receptor, p38MAPK, and NF-κB inducing biphasic TNF-α production. Paraformaldehyde-fixed, peptide-specific T cells also activate MHC-II signaling and TNF-α induction in peptide-pulsed macrophages. Our results reveal a novel MHC-II signaling and bidirectional macrophage-T cell interaction regulating macrophage functions. This knowledge may help to develop novel, macrophage-directed, therapeutic strategies.
Effect of Weight Loss and Exercise Therapy on Bone Metabolism and Mass in Obese Older Adults: A One-Year Randomized Controlled Trial
Authors: Villareal Dennis T. , Shah Krupa , Banks Marian R. , Sinacore David R. , Klein Samuel 
Published: March 2008

Abstract
Background: Although weight loss and exercise ameliorates frailty and improves cardiac risk factors in obese older adults, the long-term effect of lifestyle intervention on bone metabolism and mass is unknown.
Objective: The objective was to evaluate the effects of diet-induced weight loss in conjunction with exercise on bone metabolism and mass in obese older adults.
Design and Setting: We conducted a one-year randomized, controlled clinical trial in a university-based research center.
Participants: Twenty-seven frail, obese (body mass index = 39 ± 5 kg/m2), older (age 70 ± 5 yr) adults participated in the study.
Intervention: Participants were randomly assigned to diet and exercise (treatment group; n = 17) or no therapy (control group; n = 10).
Outcome Measures: Body weight decreased in the treatment group but not in the control group (−10 ± 2 vs. +1 ± 1%, P &lt; 0.001). Compared with the control group, the treatment group had greater changes in bone mass, bone markers, and hormones, including 1) bone mineral density (BMD) in total hip (0.1 ± 2.1 vs. −2.4 ± 2.5%), trochanter (0.2 ± 3.3 vs. −3.3 ± 3.1%), and intertrochanter (0.3 ± 2.7 vs. −2.7 ± .3.0%); 2) C-terminal telopeptide (12 ± 35 vs. 101 ± 79%) and osteocalcin (−5 ± 15 vs. 66 ± 61%); and 3) leptin (2 ± 12 vs. −30 ± 25%) and estradiol (0.1 ± 14% vs. −14 ± 21%) (all P &lt; 0.05). Changes in weight (r = 0.55), bone markers (r = −0.54), and leptin (r = 0.61) correlated with changes in hip BMD (all P &lt; 0.05).
Conclusion: Weight loss, even when combined with exercise, decreases hip BMD in obese older adults. It is not known whether the beneficial effects of weight loss and exercise on physical function lower the overall risk of falls and fractures, despite the decline in hip BMD.
The Periphery of the Human Fetal Adrenal Gland Is a Site of Angiogenesis: Zonal Differential Expression and Regulation of Angiogenic Factors
Authors: Ishimoto Hitoshi , Minegishi Kazuhiro , Higuchi Takayuki , Furuya Masataka , Asai Satoshi , Kim Seon Hye , Tanaka Mamoru , Yoshimura Yasunori , Jaffe Robert B. 
Published: March 2008

Abstract
Context: Although the inner fetal zone (FZ) of the midgestation human fetal adrenal (HFA) produces dehydroepiandrosterone sulfate, the function of the outer definitive zone (DZ) remains less clear. We have proposed that the DZ phenotype is that of a pool of progenitor cells, many of which are mitotically active. Recently, we studied HFA expression of a family of vascular endothelial cell-specific angiogenic factors, the angiopoietins (Angs), and demonstrated that Ang2 was localized predominantly in the periphery of the gland. Ang1 stabilizes, whereas Ang2 destabilizes, vessels, increasing responsiveness to angiogenic stimuli such as vascular endothelial growth factor (VEGF)-A and fibroblast growth factor (FGF)-2.
Objective: Our objective was to test the hypothesis that the periphery of the HFA is a site of angiogenesis.
Design: Studies were conducted involving RNA, frozen sections, and primary cell cultures from midgestation HFAs.
Main Outcome Measures: Immunofluorescence, laser capture microdissection, and real-time quantitative RT-PCR were used.
Results: Double immunostaining demonstrated that proliferating endothelial cells were limited to the DZ and DZ/FZ border. Ang2 mRNA was primarily expressed in the DZ, whereas Ang1 mRNA was primarily in the FZ. VEGF-A and FGF-2 mRNA levels were higher in the DZ. FGF-2 (10 ng/ml) induced Ang2 mRNA by 4-fold in both zones of cells (P &lt; 0.01, at 24 h), but not Ang1 or VEGF-A mRNA.
Conclusion: Data suggest that angiogenesis occurs at the periphery of the HFA. The DZ-predominant expression of Ang2 may be explained, in part, by the parallel pattern of FGF-2 expression.
Home Medication Cabinets and Self-Medication: A Source of Potential Health Threats?
Authors: De Bolle Leen , Mehuys Els , Adriaens Els , Remon Jean-Paul , Van Bortel Luc , Christiaens Thierry 
Published: March 2008

BACKGROUND: Data regarding the contents of home medication cabinets (HMCs), the management of leftover medications, and the inclination of patients toward self-initiated treatment using nonprescription drugs are scarce. OBJECTIVE: To evaluate the nature and safety of medication storage and intended self-medication in a general population. METHODS: A cross-sectional study was conducted in 72 Belgian community pharmacies. Pharmacy customers (N = 288, aged 18–80 y) were visited in their homes by pharmacy students. The HMCs were inventoried and the participants were interviewed. RESULTS: A mean of 31 ± 17 (range 6–136) drug packages were identified per household; in one-third of the cases, the packages were not stored safely. Prescription drugs accounted for 34% of the total. The most frequently encountered categories of registered medicines were nonopioid analgesics (7.2%), nonsteroidal antiinflammatory drugs (NSAIDs) (6.9%), nasal decongestants (3.5%) and antinausea agents (3.2%). Despite their high prevalence, NSAIDs and non-opioid analgesics did not predominate among the most frequently used drugs, whereas food supplements were used daily in 23.3% of households. Twenty-one percent of the drugs were expired, 9% were not stored in the original container, and the package insert was missing for 18%. Self-initiated treatment was considered for 56% of all drugs (over-the-counter drugs, 74%; prescription drugs, 21%). Indication, dosage, or treatment duration was misjudged by only 5.2% of the participants, but consulting the package insert was allowed. The tendency toward self-treatment decreased with age and with increasing number of medications taken daily (p = 0.002). CONCLUSIONS: We found large amounts of drugs per household, with a high prevalence of analgesics and NSAIDs. Self-medication, although generally acceptable in terms of indication and dosage, was commonly practiced, also with prescription drugs. Taking into account that younger people showed a significantly higher intention of self-medication, a sustained awareness of the risks of self-medication is warranted for the future.
Clinical Outcomes of a Home‐Based Medication Reconciliation Program After Discharge from a Skilled Nursing Facility
Authors: Delate Thomas , Chester Elizabeth A. , Stubbings Troy W. , Barnes Carol A. 
Published: March 2008

Study Objective. To assess the impact of a pilot pharmacist‐managed medication reconciliation program on mortality and use of health care services in patients discharged to home from a skilled nursing facility (SNF).Design. Quasi‐experimental, controlled trial.Setting. Health maintenance organization (HMO).Patients. Five hundred twenty‐one HMO members.Intervention. Patients were assigned to the medication reconciliation program (113 patients) or to the usual care control group (408 patients) after discharge to home from an SNF. Assignment to the medication reconciliation group or to the control group was based on provider submission of a discharge summary within 0–48 hours of discharge or more than 48 hours after discharge, respectively.Measurements and Main Results. Integrated electronic medical and pharmacy data and multivariate analyses were used to assess the medication reconciliation program with regard to its impact on postdischarge mortality, rehospitalization, and ambulatory clinic and emergency department visits. Compared with usual care during the 60 days after discharge from the SNF, patients who received the medication reconciliation intervention had an adjusted 78% reduction in the risk of death (adjusted hazard ratio 0.22, 95% confidence interval [CI] 0.06‐0.88) and a trend toward an increased rate of ambulatory care visits (adjusted incidence risk ratio 1.17, 95% CI 0.99‐1.37). No significant differences were noted in adjusted risks of an emergency department visit and rehospitalization (p>0.05) between the medication reconciliation and usual care groups.Conclusion. Our data support the hypothesis that a formal medication reconciliation process, with its increased coordination of information between health care providers and patients, can decrease mortality after discharge from an SNF. Our findings support the role of medication reconciliation as an integral step in the transitional care process and interests of health care accrediting agencies, such as the Joint Commission, that have included medication reconciliation as an important initiative.