bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxygen Regulation of Tumor Perfusion by
S
-Nitrosohemoglobin Reveals a Pressor Activity of Nitric Oxide
Authors: Sonveaux Pierre , Kaz Andrew M. , Snyder Stacey A. , Richardson Rachel A. , Cárdenas-Navia L. Isabel , Braun Rodney D. , Pawloski John R. , Tozer Gillian M. , Bonaventura Joseph , McMahon Timothy J. , Stamler Jonathan S. , Dewhirst Mark W.
Published: May 2005

In erythrocytes,
S
-nitrosohemoglobin (SNO-Hb) arises from
S
-nitrosylation of oxygenated hemoglobin (Hb). It has been shown that SNO-Hb behaves as a nitric oxide (NO) donor at low oxygen tensions. This property, in combination with oxygen transport capacity, suggests that SNO-Hb may have unique potential to reoxygenate hypoxic tissues. The present study was designed to test the idea that the allosteric properties of SNO-Hb could be manipulated to enhance oxygen delivery in a hypoxic tumor. Using Laser Doppler flowmetry, we showed that SNO-Hb infusion to animals breathing 21% O
2
reduced tumor perfusion without affecting blood pressure and heart rate. Raising the pO
2
(100% O
2
) slowed the release of NO bioactivity from SNO-Hb (ie, prolonged the plasma half-life of the SNO in Hb), preserved tumor perfusion, and raised the blood pressure. In contrast, native Hb reduced both tumor perfusion and heart rate independently of the oxygen concentration of the inhaled gas, and did not elicit hypertensive effects. Window chamber (to image tumor arteriolar reactivity in vivo) and hemodynamic measurements indicated that the preservation of tissue perfusion by micromolar concentrations of SNO-Hb is a composite effect created by reduced peripheral vascular resistance and direct inhibition of the baroreceptor reflex, leading to increased blood pressure. Overall, these results indicate that the properties of SNO-Hb are attributable to allosteric control of NO release by oxygen in central as well as peripheral issues.
BMK1/ERK5 Is a Novel Regulator of Angiogenesis by Destabilizing Hypoxia Inducible Factor 1α
Authors: Pi Xinchun , Garin Gwenaele , Xie Liang , Zheng Qinlei , Wei Heng , Abe Jun-ichi , Yan Chen , Berk Bradford C.
Published: May 2005

Big MAP kinase 1 (BMK1 or ERK5) is a key mediator of endothelial cell (EC) function as shown by impaired embryonic angiogenesis and vascular collapse in BMK1 knockout mice. Hypoxia inducible factor 1α (HIF1α), a potent mediator of angiogenesis, is positively regulated by the MAP kinases, ERK1/2. Because BMK1 deficiency is associated with impaired angiogenesis we hypothesized that BMK1 might regulate HIF1α. To test this hypothesis, bovine lung microvascular ECs (BLMECs) were transfected with HIF1α and BMK1 cDNAs, and stimulated by hypoxia. HIF1α activity was measured by a reporter gene assay in which luciferase expression was driven by HIF1α activation. Hypoxia (1% O
2
, 24 hours) stimulated HIF1α activity by 5.1±0.6 fold. In the presence of dominant negative (DN)-BMK1, which inhibited BMK1 activity, hypoxia induced HIF1α activity was enhanced significantly to 6.4±0.4 fold. BMK1 activation by constitutively active (CA)-MEK5 inhibited HIF1α activity by 46±4%, suggesting BMK1 functions as a negative regulator of HIF1α activation. Activation of BMK1 reduced HIF1α protein levels. Ubiquitination inhibitors (30 μmol/L ALLN, 2 μmol/L lactacystin, or 100 nmol/L MG132) reduced the BMK1-mediated effect on HIF1α expression by >80%, suggesting that BMK1 stimulated HIF1α proteolysis. The negative effect of BMK1 on HIF1α was functionally important because transfection with CA-MEK5 significantly decreased EC migration by 68±10%, and inhibited angiogenesis (in vitro Matrigel assay) by 76±7%. In summary, BMK1 is a novel negative regulator of HIF1α and angiogenesis by increasing HIF1α ubiquitination and inhibiting HIF1α activity in endothelial cells.
Early Carotid Atherosclerosis in Subjects With Periodontal Diseases
Authors: Söder Per-Östen , Söder Birgitta , Nowak Jacek , Jogestrand Tomas
Published: May 2005

Background and Purpose—

There is growing experimental evidence implicating chronic inflammation/infection as an atherosclerotic risk factor. In this study, the involvement of periodontal disease in the development of early atherosclerotic vascular lesions has been evaluated.

Methods—

In randomly chosen 82 patients with periodontal disease and 31 periodontally healthy individuals subjected to a clinical oral examination in 1985, atherosclerotic risk factor analysis and carotid ultrasonography was performed during reexamination 16 years later. Common carotid artery intima-media thickness (IMT) and lumen diameter were measured and intima-media area (cIMA) was calculated. The relationship between IMT and cIMA as dependent variables and periodontal disease, age, gender, body mass index, heredity for atherosclerosis, diabetes mellitus, hypertension, plasma cholesterol, smoking, and education as independent variables was evaluated in a multiple logistic regression model.

Results—

The mean values of IMT and cIMA were significantly higher in patients with periodontal disease than in controls, both at the right (
P
<0.01 and
P
<0.001, respectively) and left side (
P
<0.001 for both variables). When the means of the bilateral measurements of these 2 ultrasonographic variables were tested, multiple logistic regression analysis identified periodontal disease as a principal independent predictor of the common carotid artery cIMA (odds ratio [OR], 5.20;
P
=0.003) and IMT (OR, 4.64;
P
=0.004).

Conclusions—

The present results indicate that periodontal disease is associated with the development of early atherosclerotic carotid lesions.
Vascular Endothelial Growth Factor Antagonist Reduces Brain Edema Formation and Venous Infarction
Authors: Kimura R. , Nakase H. , Tamaki R. , Sakaki T.
Published: May 2005

Background and Purpose—

Cerebral venous ischemia often induces severe brain edema. Vascular endothelial growth factor (VEGF), which induces angiogenesis, is also known as vascular permeability (VP) factor. The present study was undertaken to investigate whether the inhibition of VEGF could reduce brain edema formation and cerebral venous infarction (CVI) in a rat 2-vein occlusion (2-VO) model.

Methods—

We used 2-VO model in which 2 adjacent cortical veins were photochemically occluded. Male Wistar rats (n=25) were divided into 2 groups: one group was treated with a VEGF antagonist (antagonist group, n=10) and the second group was treated with phosphate-buffered solution (PBS) (PBS group, n=15). VEGF antagonist or PBS was injected intraperitoneally immediately after 2-VO. The developing ischemic infarct was evaluated by magnetic resonance imaging (MRI) and histology 24 hours after occlusion.

Results—

VEGF expression was observed in the cytoplasm of neurons exclusively in the area of vasogenic edema that was shown as a high-intensity area in the apparent diffusion coefficient of water map. Ischemic volumes calculated from each MR images, which are related to infarction and/or vasogenic edema, respectively, were significantly smaller in the antagonist group as compared with the PBS group (
P
<0.05)

Conclusions—

Our study is the first to provide evidence that the inhibition of VEGF attenuates VP and reduces CVI in the acute stage. Although VEGF is a significant angiogenesis factor, we concluded that the inhibition of VEGF might be a new therapy for both brain edema formation and CVI.
Protein Z Gene Polymorphisms, Protein Z Concentrations, and Ischemic Stroke
Authors: Staton J. , Sayer M. , Hankey G.J. , Cole V. , Thom J. , Eikelboom J.W.
Published: May 2005

Background and Purpose—

We aimed to determine whether A-13G or G79A polymorphisms of the protein Z gene that have been reported to be an important determinant of blood concentrations of protein Z are associated with risk of ischemic stroke in a broad range of stroke patients and controls.

Methods—

We conducted a case control study of 151 hospital cases of first-ever ischemic stroke and 164 randomly selected community controls. Protein Z genotype was determined for the A-13G promoter polymorphism and the G79A intron F polymorphism, and plasma protein Z concentrations were measured during the first 7 days and at 3 to 6 months after the acute stroke event.

Results—

Geometric mean concentrations of protein Z measured within 7 days of acute stroke were significantly higher in cases compared with controls (1.51 μg/mL versus 1.13 μg/mL;
P
<0·0001). Protein Z concentrations were highest among subjects with the A-13G AA genotype, intermediate among those with the AG genotype, and lowest among those with the GG genotype (1.39 μg/mL versus 1.05 μg/mL versus 0.76 μg/mL;
P
<0.0001); and highest among those with the G79A GG genotype, intermediate among those with the GA genotype, and lowest among those with the AA genotype (1.47 μg/mL versus 1.13 μg/mL versus 0.66 μg/mL;
P
<0.0001). The prevalence of A-13G and G79A genotypes was not significantly different between cases of ischemic stroke and controls. However, compared with the G79A GG genotype (reference), the odds of ischemic stroke was progressively lower for the heterozygote GA (odds ratio [OR], 0.83; 95% CI, 0.52 to 1.33) and the homozygote AA genotype (OR, 0.63; 95% CI, 0.20 to 1.98). A pooled analysis showed that compared with the G79A GG genotype (reference), the odds of ischemic stroke was progressively lower for the heterozygote GA (OR, 0.78; 95% CI, 0.57 to 1.07) and the homozygote AA genotype (OR, 0.31; 95% CI, 0.14 to 0.69).

Conclusion—

The consistency of the association between protein Z genotypes, blood concentrations of protein Z, and ischemic stroke, determined using 2 different methods that have different sources of bias strengthens the evidence that increased blood concentrations of protein Z concentrations are associated causally with an increased risk of ischemic stroke.
Stroke in South West Nigeria
Authors: Ogun S.A. , Ojini F.I. , Ogungbo B. , Kolapo K.O. , Danesi M.A.
Published: May 2005

Background and Purpose—

Stroke is a significant economic, social, and medical problem worldwide. This retrospective follow-up study aimed to review the pattern, types, and case fatality of stroke in Nigeria.

Methods—

Records of all stroke patients admitted into Ogun State University Teaching Hospital (OSUTH), Sagamu, from December 1993 to November 2003 were reviewed. Patients were classified into hemorrhage or infarct using the World Health Organization criteria. Information was obtained as to the time of death in those who died and case fatality at 24 hours, 7 days, 30 days, and 6 months recorded. Autopsy records were also reviewed.

Results—

A total of 708 stroke patients were reviewed and this constituted 2.4% of all emergency admissions. On clinical grounds, 49% of the patients had cerebral infarction (CI) and 45% had intracerebral hemorrhage (ICH), whereas 6% had subarachnoid hemorrhage. Stroke constituted 1.8% of all deaths at the emergency unit and the case fatality was 9% at 24 hours, 28% at 7 days, 40% at 30 days, and 46% at 6 months.

Conclusion—

Stroke constitutes a significant cause of mortality and the need for prompt institution of intensive treatment is emphasized. A changing pattern with an increasing frequency of hemorrhagic stroke in our population is suspected. However, because this was a retrospective study based on clinical examination in a highly selected stroke population, neuroimaging confirmation would be needed for any future prospective hospital or population-based studies.
Association of Blood Pressure Indices and Stroke Mortality in Isolated Systolic Hypertension
Authors: Paultre Furcy , Mosca Lori
Published: May 2005

Background and Purpose—

Isolated systolic hypertension (ISH), systolic blood pressure (BP) ≥160 mm Hg and diastolic BP (DBP) <90 mm Hg, is associated with stroke; however, the correlation between specific BP indices and stroke mortality in ISH is not defined.

Methods—

In a pooled analysis of 9 epidemiological studies, we examined whether pulse pressure (PP) was more predictive of stroke mortality than systolic BP (SBP), DBP, or mean BP (MAP) in persons with ISH. Subjects (n=682; 29% male; 77% white; mean age 63.6 years) with ISH, free of cardiovascular disease, and not on antihypertensive drug therapy at baseline were followed a mean of 13.0±7.3 years, and 54 stroke deaths occurred. The relative importance of each BP index was compared by the decrease in the −2 log likelihood (a measure of model agreement with data) because of the addition of 1 or a combination of BP indices to a Cox regression model. Hazards ratios (HRs) for fatal stroke for a 1-SD in BP index were determined.

Results—

PP was the best predictor of stroke mortality based on the decrease in the −2 log likelihood (10.65;
P
=0.001; HR=1.52), followed by SBP (7.19;
P
=0.007; HR=1.40), DBP (2.76;
P
=0.10; HR=0.80), or MAP (0.39;
P
=0.39; HR=1.10). Any combination of BP indices did not exceed a decrease in the −2 log likelihood of 10.72.

Conclusion—

These data suggest that in persons with ISH, PP is a better predictor of fatal stroke than SBP, DBP, or MAP.
Why Human Color Vision Cannot Reliably Detect Cerebrospinal Fluid Xanthochromia
Authors: Petzold Axel , Keir Geoffrey , Sharpe Ted L.
Published: May 2005

Background—

Visual assessment of cerebrospinal fluid (CSF) for xanthochromia (yellow color) is practiced by the majority of laboratories worldwide as a means of diagnosing intracranical bleeds.

Methods—

Colorimetric and spectrophotometric analysis of CSF samples for recognizing the presence of bilirubin either in low concentrations or in the presence of hemolysed blood.

Results—

The experiments provide the physiological and colorimetric basis for abandoning visual assessment of CSF for xanthochromia.

Conclusion—

We strongly recommend relying on spectrophotometry as the analytical method of choice.
Bcl10 can promote survival of antigen-stimulated B lymphocytes
Authors: Tian Maoxin Tim , Gonzalez Gabriel , Scheer Barbara , DeFranco Anthony L.
Published: May 2005

To understand the nature of negative responses through the B-cell antigen receptor (BCR), we have screened an expression cDNA library for the ability to block BCR-induced growth arrest and apoptosis in the immature B-cell line, WEHI-231. We isolated multiple copies of full-length, unmutated Bcl10, a signaling adaptor molecule encoded by a gene found to translocate to the immunoglobulin heavy chain (IgH) locus in some mucosa-associated lymphoid tissue (MALT) lymphomas. A conditionally active form of B-cell lymphoma 10 (Bcl10) protected WEHI-231 cells from BCR-induced apoptosis upon activation. Induction of Bcl10 activity caused rapid activation of nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK), but not activation of extracellular signal-regulated kinase (ERK) or p38 mitogen-activated protein (MAP) kinases. These results support genetic and biochemical experiments that have implicated Bcl10 and its binding partners Carma1 and MALT1 in mediating the ability of the BCR to activate NF-κB. The ability of Bcl10 expression to prevent BCR-induced growth arrest and apoptosis of WEHI-231 cells was dependent on NF-κB activation. Finally, overexpression of Bcl10 in primary B cells activated ex vivo promoted the survival of these cells after removal of activating stimuli. Taken together these results support the hypothesis that enhanced BCL10 expression caused by translocation to the IGH locus can promote formation of MALT lymphomas. (Blood. 2005;106:2105-2112)
Global approach to the diagnosis of leukemia using gene expression profiling
Authors: Haferlach Torsten , Kohlmann Alexander , Schnittger Susanne , Dugas Martin , Hiddemann Wolfgang , Kern Wolfgang , Schoch Claudia
Published: May 2005

Accurate diagnosis and classification of leukemias are the bases for the appropriate management of patients. The diagnostic accuracy and efficiency of present methods may be improved by the use of microarrays for gene expression profiling. We analyzed gene expression profiles in 937 bone marrow and peripheral blood samples from 892 patients with all clinically relevant leukemia subtypes and from 45 nonleukemic controls by U133A and U133B GeneChip arrays. For each subgroup, differentially expressed genes were calculated. Class prediction was performed using support vector machines. Prediction accuracy was estimated by 10-fold cross-validation and was assessed for robustness in a 100-fold resampling approach using randomly chosen test sets consisting of one third of the samples. Applying the top 100 genes of each subgroup, an overall prediction accuracy of 95.1% was achieved that was confirmed by resampling (median, 93.8%; 95% confidence interval, 91.4%-95.8%). In particular, acute myeloid leukemia (AML) with t(15;17), AML with t(8;21), AML with inv(16), chronic lymphatic leukemia (CLL), and pro–B-cell acute lymphoblastic leukemia (pro–B-ALL) with t(11q23) were classified with 100% sensitivity and 100% specificity. Accordingly, cluster analysis completely separated all 13 subgroups analyzed. Gene expression profiling can predict all clinically relevant subentities of leukemia with high accuracy.
The fully human anti-CD30 antibody 5F11 activates NF-κB and sensitizes lymphoma cells to bortezomib-induced apoptosis
Authors: Böll Boris , Hansen Hinrich , Heuck Friederike , Reiners Katrin , Borchmann Peter , Rothe Achim , Engert Andreas , Pogge von Strandmann Elke
Published: May 2005

5F11, a fully human monoclonal antibody directed against CD30, effectively induces killing of CD30-expressing lymphoma cell lines in vitro and in animal models. A recently conducted phase 1/2 study shows that 5F11 is well tolerated in heavily pretreated patients with relapsed and refractory CD30+ lymphoma and has some clinical activity. In the present study, we demonstrate that 5F11 activates nuclear factor κB (NF-κB) and the anti-apoptotic protein cellular FLICE (Fas-associating protein with death domain-like interleukin-1β-converting enzyme) inhibitory protein (c-flip) in Hodgkin lymphoma (HD)-derived cell lines, which might cause apoptosis resistance, thus limiting the clinical use of 5F11. To overcome this resistance, we combined 5F11 with the proteasome inhibitor bortezomib, which has been shown to suppress NF-κB activity. This combination revealed a synergistic cytotoxic effect in vitro and in a human HD xenograft model provided that 5F11 precedes bortezomib treatment. We conclude that initial 5F11-mediated NF-κB signaling sensitizes the tumor cells to bortezomib-induced cell death. These data suggest a therapeutic value of this combination for HD patients. (Blood. 2005;106:1839-1842)
Providing research results to study participants: support versus practice of researchers presenting at the American Society of Hematology annual meeting
Authors: Rigby Heather , Fernandez Conrad V.
Published: May 2005

Offering to provide research results to study participants is gaining increasing support based, in part, on the principle of respect for persons. The frequency and means of this practice is unknown in national and international research communities. All investigators who presented oral abstracts involving human research at the American Society of Hematology Annual Meeting (December 2003) were surveyed. Responses were received from 197 (42%) of 472 eligible investigators. Nonrespondents did not differ in study type or country of origin. Only 30% (n = 48) of those who completed the survey had a formal plan for the return of research results; 40% of these would return both a summary plus individual level results. Of the respondents, 69% (n = 109) supported or strongly supported the practice; only 3% opposed the practice. The most commonly cited reasons for not returning results were: did not consider it (38%), anticipated contact difficulties (32%), and participant difficulty understanding results (26%). Only 11 (7%) indicated that their institutional review board (IRB) mandates the offer to provide results to all participants; this did not vary significantly by country. Given the high level of support in the international research community, evaluation of well-planned interventions for offering to provide research results to participants should be a priority.
Rapamycin stimulates apoptosis of childhood acute lymphoblastic leukemia cells
Authors: Avellino Raffaella , Romano Simona , Parasole Rosanna , Bisogni Rita , Lamberti Annalisa , Poggi Vincenzo , Venuta Salvatore , Romano Maria Fiammetta
Published: May 2005

The phosphatidyl-inositol 3 kinase (PI3k)/Akt pathway has been implicated in childhood acute lymphoblastic leukemia (ALL). Because rapamycin suppresses the oncogenic processes sustained by PI3k/Akt, we investigated whether rapamycin affects blast survival. We found that rapamycin induces apoptosis of blasts in 56% of the bone marrow samples analyzed. Using the PI3k inhibitor wortmannin, we show that the PI3k/Akt pathway is involved in blast survival. Moreover, rapamycin increased doxorubicin-induced apoptosis even in nonresponder samples. Anthracyclines activate nuclear factor κB (NF-κB), and disruption of this signaling pathway increases the efficacy of apoptogenic stimuli. Rapamycin inhibited doxorubicin-induced NF-κB in ALL samples. Using a short interfering (si) RNA approach, we demonstrate that FKBP51, a large immunophilin inhibited by rapamycin, is essential for drug-induced NF-κB activation in human leukemia. Furthermore, rapamycin did not increase doxorubicin-induced apoptosis when NF-κB was overexpressed. In conclusion, rapamycin targets 2 pathways that are crucial for cell survival and chemoresistance of malignant lymphoblasts—PI3k/Akt through the mammalian target of rapamycin and NF-κB through FKBP51—suggesting that the drug could be beneficial in the treatment of childhood ALL. (Blood. 2005;106:1400-1406)
Human short-term repopulating stem cells are efficiently detected following intrafemoral transplantation into NOD/SCID recipients depleted of CD122+ cells
Authors: McKenzie Joby L. , Gan Olga I. , Doedens Monica , Dick John E.
Published: May 2005

The nonobese diabetic/severe combined immune deficiency (NOD/SCID) xenotransplantation model has emerged as a widely used assay for human hematopoietic stem cells; however, barriers still exist that limit engraftment. We previously identified a short-term SCID-repopulating cell (SRC) following direct intrafemoral injection into NOD/SCID mice, whereas others characterized similar SRCs using NOD/SCID mice depleted of natural killer (NK) cell activity. To determine the model that most efficiently detects short-term SRCs, we compared human engraftment in 6 different xenotransplantation models: NOD/SCID-β2-microglobulin-null mice, anti-CD122 (interleukin-2 receptor β [IL-2Rβ])–treated or unmanipulated NOD/SCID mice, each given transplants by intravenous or intrafemoral injection. Human cell engraftment was highest in intrafemorally injected anti-CD122–treated NOD/SCID mice compared to all other groups at 2 and 6 weeks after transplantation. These modifications to the SRC assay provide improved detection of human stem cells and demonstrate that CD122+ cells provide barriers to stem cell engraftment, a finding with potential clinical relevance.
In vitro identification and in silico utilization of interspecies sequence similarities using GeneChip® technology
Authors: Grigoryev Dmitry N , Ma Shwu-Fan , Simon Brett A , Irizarry Rafael A , Ye Shui Q , Garcia Joe GN
Published: May 2005

Background

Genomic approaches in large animal models (canine, ovine etc) are challenging due to insufficient genomic information for these species and the lack of availability of corresponding microarray platforms. To address this problem, we speculated that conserved interspecies genetic sequences can be experimentally detected by cross-species hybridization. The Affymetrix platform probe redundancy offers flexibility in selecting individual probes with high sequence similarities between related species for gene expression analysis.

Results

Gene expression profiles of 40 canine samples were generated using the human HG-U133A GeneChip (U133A). Due to interspecies genetic differences, only 14 ± 2% of canine transcripts were detected by U133A probe sets whereas profiling of 40 human samples detected 49 ± 6% of human transcripts. However, when these probe sets were deconstructed into individual probes and examined performance of each probe, we found that 47% of human probes were able to find their targets in canine tissues and generate a detectable hybridization signal. Therefore, we restricted gene expression analysis to these probes and observed the 60% increase in the number of identified canine transcripts. These results were validated by comparison of transcripts identified by our restricted analysis of cross-species hybridization with transcripts identified by hybridization of total lung canine mRNA to new Affymetrix Canine GeneChip®.

Conclusion

The experimental identification and restriction of gene expression analysis to probes with detectable hybridization signal drastically increases transcript detection of canine-human hybridization suggesting the possibility of broad utilization of cross-hybridizations of related species using GeneChip technology.
A combined approach exploring gene function based on Worm-Human Orthology
Authors: Tamas Ivica , Hodges Emily , Dessi Patrick , Johnsen Robert , Vaz Gomes Ana
Published: May 2005

Background

Many aspects of the nematode Caenorhabditis elegans biology are conserved between invertebrates and vertebrates establishing this particular organism as an excellent genetic model. Because of its small size, large populations and self-fertilization of the hermaphrodite, functional predictions carried out by genetic modifications as well as RNAi screens, can be rapidly tested.

Results

In order to explore the function of a set of C. elegans genes of unknown function, as well as their potential functional roles in the human genome, we performed a phylogenetic analysis to select the most probable worm orthologs. A total of 13 C. elegans genes were subjected to down- regulation via RNAi and characterization of expression profiles using GFP strains. Previously unknown distinct expression patterns were observed for four of the analyzed genes, as well as four visible RNAi phenotypes. In addition, subcellular protein over-expression profiles of the human orthologs for seven out of the thirteen genes using human cells were also analyzed.

Conclusion

By combining a whole-organism approach using C. elegans with complementary experimental work done on human cell lines, this analysis extends currently available information on the selected set of genes.
Investigation of Staphylococcus strains with heterogeneous resistance to glycopeptides in a Turkish university hospital
Authors: Nakipoglu Yasar , Derbentli Sengul , Cagatay Atahan A , Katranci Handan
Published: May 2005

Background

The hetero-glycopeptide intermediate staphylococci is considered to be the precursor of glycopeptide intermediate staphylococci especially vancomycin intermediate Staphylococcus aureus (VISA). For this purpose, we aimed to investigate the heterogeneous resistance to glycopeptide and their frequencies in 135 Staphylococcus strains.

Methods

Heterogeneous resistance of Staphylococcus strains was detected by inoculating the strains onto Brain Heart Infusion agar supplemented with 4 mg/L of vancomycin (BHA-V4). Agar dilution method was used for determining MICs of glycopeptides and population analysis profile was performed for detecting frequency of heterogeneous resistance for the parents of selected strains on BHA-4.

Results

Eight (6%) out of 135 Staphylococcus strains were exhibited heterogeneous resistance to at least one glycopeptide. One (1.2%) out of 81 S. aureus was found intermediate resistance to teicoplanin (MIC 16 mg/L). Other seven strains were Staphylococcus haemolyticus (13%) out of 54 coagulase negative staphylococci (CoNS). Six of the seven strains were detected heterogeneously reducing susceptibility to vancomycin (MICs ranged between 5–8 mg/L) and teicoplanin (MICs ranged between 32–64 mg/L), and one S. haemolyticus was found heterogeneous resistance to teicoplanin (MIC 32 mg/L). Frequencies of heterogeneous resistance were measured being one in 106 – 107 cfu/ml. MICs of vancomycin and teicoplanin for hetero-staphylococci were determined as 2–6 folds and 3–16 folds higher than their parents, respectively. These strains were isolated from six patients (7%) and two (4%) of health care wokers hands. Hetero-VISA strain was not detected.

Conclusion

Heterogeneous resistance to glycopeptide in CoNS strains was observed to be significantly more emergent than those of S. aureus strains (vancomycin P 0.001, teicoplanin, P 0.007). The increase MICs of glycopeptide resistance for subpopulations of staphylococci comparing with their parents could be an important clue for recognizing the early steps in the appearance of VISA strains. We suggested to screen clinical S. aureus and CoNS strains, systematically, for the presence of heterogeneously resistance to glycopeptide.
Molecular breakpoint cloning and gene expression studies of a novel translocation t(4;15)(q27;q11.2) associated with Prader-Willi syndrome
Authors: Schüle Birgitt , Albalwi Mohammed , Northrop Emma , Francis David I , Rowell Margaret , Slater Howard R , Gardner RJ McKinlay , Francke Uta
Published: May 2005

Background

Prader-Willi syndrome (MIM #176270; PWS) is caused by lack of the paternally-derived copies, or their expression, of multiple genes in a 4 Mb region on chromosome 15q11.2. Known mechanisms include large deletions, maternal uniparental disomy or mutations involving the imprinting center.De novobalanced reciprocal translocations in 5 reported individuals had breakpoints clustering inSNRPNintron 2 or exon 20/intron 20. To further dissect the PWS phenotype and define the minimal critical region for PWS features, we have studied a 22 year old male with a milder PWS phenotype and ade novotranslocation t(4;15)(q27;q11.2).

Methods

We used metaphase FISH to narrow the breakpoint region and molecular analyses to map the breakpoints on both chromosomes at the nucleotide level. The expression of genes on chromosome 15 on both sides of the breakpoint was determined by RT-PCR analyses.

Results

Pertinent clinical features include neonatal hypotonia with feeding difficulties, hypogonadism, short stature, late-onset obesity, learning difficulties, abnormal social behavior and marked tolerance to pain, as well as sticky saliva and narcolepsy. Relative macrocephaly and facial features are not typical for PWS. The translocation breakpoints were identified withinSNRPNintron 17 and intron 10 of a spliced non-coding transcript in band 4q27. LINE and SINE sequences at the exchange points may have contributed to the translocation event. By RT-PCR of lymphoblasts and fibroblasts, we find that upstream SNURF/SNRPN exons and snoRNAs HBII-437 and HBII-13 are expressed, but the downstream snoRNAs PWCR1/HBII-85 and HBII-438A/B snoRNAs are not.

Conclusion

As part of the PWCR1/HBII-85 snoRNA cluster is highly conserved between human and mice, while no copy of HBII-438 has been found in mouse, we conclude that PWCR1/HBII-85 snoRNAs is likely to play a major role in the PWS- phenotype.
Phrenic nerve afferents elicited cord dorsum potential in the cat cervical spinal cord
Authors: Chou Yang-Ling , Davenport Paul W
Published: May 2005

Background

The diaphragm has sensory innervation from mechanoreceptors with myelinated axons entering the spinal cord via the phrenic nerve that project to the thalamus and somatosensory cortex. It was hypothesized that phrenic nerve afferent (PnA) projection to the central nervous system is via the spinal dorsal column pathway.

Results

A single N1 peak of the CDP was found in the C4 and C7 spinal segments. Three peaks (N1, N2, and N3) were found in the C5 and C6 segments. No CDP was recorded at C8 dorsal spinal cord surface in cats.

Conclusion

These results demonstrate PnA activation of neurons in the cervical spinal cord. Three populations of myelinated PnA (Group I, Group II, and Group III) enter the cat's cervical spinal segments that supply the phrenic nerve
A controlled trial of automated classification of negation from clinical notes
Authors: Elkin Peter L , Brown Steven H , Bauer Brent A , Husser Casey S , Carruth William , Bergstrom Larry R , Wahner-Roedler Dietlind L
Published: May 2005

Background

Identification of negation in electronic health records is essential if we are to understand the computable meaning of the records: Our objective is to compare the accuracy of an automated mechanism for assignment of Negation to clinical concepts within a compositional expression with Human Assigned Negation. Also to perform a failure analysis to identify the causes of poorly identified negation (i.e. Missed Conceptual Representation, Inaccurate Conceptual Representation, Missed Negation, Inaccurate identification of Negation).

Methods

41 Clinical Documents (Medical Evaluations; sometimes outside of Mayo these are referred to as History and Physical Examinations) were parsed using the Mayo Vocabulary Server Parsing Engine. SNOMED-CT™ was used to provide concept coverage for the clinical concepts in the record. These records resulted in identification of Concepts and textual clues to Negation. These records were reviewed by an independent medical terminologist, and the results were tallied in a spreadsheet. Where questions on the review arose Internal Medicine Faculty were employed to make a final determination.

Results

SNOMED-CT was used to provide concept coverage of the 14,792 Concepts in 41 Health Records from John's Hopkins University. Of these, 1,823 Concepts were identified as negative by Human review. The sensitivity (Recall) of the assignment of negation was 97.2% (p < 0.001, Pearson Chi-Square test; when compared to a coin flip). The specificity of assignment of negation was 98.8%. The positive likelihood ratio of the negation was 81. The positive predictive value (Precision) was 91.2%

Conclusion

Automated assignment of negation to concepts identified in health records based on review of the text is feasible and practical. Lexical assignment of negation is a good test of true Negativity as judged by the high sensitivity, specificity and positive likelihood ratio of the test. SNOMED-CT had overall coverage of 88.7% of the concepts being negated.
Recent developments in the funding and organisation of the New Zealand health system
Authors: Ashton Toni
Published: May 2005

During the 1990s, the New Zealand health sector went through a decade of turbulence with a series of major structural changes being introduced in a relatively short period of time. The new millennium brought further change, with the establishment of 21 district health boards and the restoration of a less commercially-oriented system. The sector now appears to be more stable. However many incremental changes are in train and there has been considerable turbulence below the surface as key players jostle for position. This paper reports on some of the recent changes that have occurred in the restructuring of the New Zealand health system. Three issues are discussed: the devolution of funds and decision-making to district health boards, developments in primary health care, and the position of the private health insurance industry.
Lysophospholipids Enhance Matrix Metalloproteinase-2 Expression in Human Endothelial Cells
Authors: Wu Wen Ting , Chen Chiung-Nien , Lin Chi Iou , Chen Jiun Hong , Lee Hsinyu
Published: May 2005

Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are both low-molecular-weight lysophospholipids, which promote cell proliferation, migration, and invasion via interaction with a family of specific G protein-coupled receptors. Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes, which are involved in degradation of the extracellular matrix and play critical roles in endothelial cell migration and matrix remodeling during angiogenesis. Among these MMPs, MMP-2 is known to trigger cell migration. In our present study, we examined the effects of LPA and S1P on MMP-2 expression in human endothelial cells. We showed that LPA and S1P enhanced MMP-2 expression in mRNA, protein levels, and also enzymatic activity of cells of the EAhy926 human endothelial cell line. The enhancement effects occurred in concentration- and time-dependent manners. Results from real-time PCR, Western blots, and substrate gels indicated that these enhancement effects were mediated through MAPK kinase/ERK-, nuclear factor-κB-, and calcium influx-dependent pathways. Furthermore, we show that endothelial cell invasion of the gel was enhanced by lysophospholipids, and the induction could be prevented by an MMP inhibitor, GM6001. These observations suggest that LPA and S1P may play important roles in endothelial cell invasion by regulating the expression of MMP-2.
Effect of Follicle-Stimulating Hormone and Estrogen on the Expression of Betaglycan Messenger Ribonucleic Acid Levels in Cultured Rat Granulosa Cells
Authors: Omori Yuki , Nakamura Kazuto , Yamashita Soichi , Matsuda Hiroko , Mizutani Tetsuya , Miyamoto Kaoru , Minegishi Takashi
Published: May 2005

Betaglycan (TGFβ type III receptor) was recently identified as a coreceptor to enhance the binding of inhibin A to activin type II receptor. This inhibin/betaglycan/activin type II receptor complex prevents activins from binding to their own receptors. The present study was undertaken to identify the expression and the regulation of the betaglycan gene in cultured rat granulosa cells. Northern blot analysis indicated betaglycan mRNA transcript of approximately 6.4 kbp. The treatment of the cells with FSH increased the betaglycan mRNA level, and a concurrent treatment with estradiol brought a significant increase in betaglycan mRNA. The protein kinase A activator, 8-bromoadenosine-cAMP, also increased the expression of its mRNA. Furthermore, betaglycan mRNA was induced additively by estradiol, which was blocked by estrogen receptor antagonists [ICI 182780, (R, R)-cis-diethyltetrahydro-2,8-chrysenediol]. In the luciferase assay, FSH altered the promoter activity of betaglycan. Moreover, when FSH plus estradiol was added to the granulosa cells, a significant increase in the half-life of betaglycan mRNA transcript was seen. In summary, FSH and estradiol increased betaglycan mRNA expression, most possibly through the protein kinase A pathway and the estrogen receptor-β. The increase of betaglycan mRNA was due to an increase in transcription and altered mRNA stability. In ovarian regulatory function, the expression of betaglycan may involve the functional antagonism of inhibin A in activin signal transduction.
Testosterone and Estradiol Regulate Free Insulin-Like Growth Factor I (IGF-I), IGF Binding Protein 1 (IGFBP-1), and Dimeric IGF-I/IGFBP-1 Concentrations
Authors: Veldhuis Johannes D. , Frystyk Jan , Iranmanesh Ali , Ørskov Hans
Published: May 2005

The present study tests the clinical postulate that elevated testosterone (Te) and estradiol (E2) concentrations modulate the effects of constant iv infusion of saline vs. recombinant human IGF-I on free IGF-I, IGF binding protein (IGFBP)-1, and dimeric IGF-I/IGFBP-1 concentrations in healthy aging adults. To this end, comparisons were made after administration of placebo (Pl) vs. Te in eight older men (aged 61 ± 4 yr) and after Pl vs. E2 in eight postmenopausal women (62 ± 3 yr). In the saline session, E2 lowered and Te increased total IGF-I; E2 specifically elevated IGFBP-1 by 1.5-fold and suppressed free IGF-I by 34%; and E2 increased binary IGF-I/IGFBP-1 by 5-fold more than Te. During IGF-I infusion, the following were found: 1) total and free IGF-I rose 1.4- to 2.0-fold (Pl) and 2.1–2.5-fold (Te) more rapidly in men than women; 2) binary IGF-I/IGFBP-1 increased 3.4-fold more rapidly in men (Te) than women (E2); and 3) end-infusion free IGF-I was 1.6-fold higher in men than women. In summary, E2, compared with Te supplementation, lowers concentrations of total and ultrafiltratably free IGF-I and elevates those of IGFBP-1 and binary IGF-I/IGFBP-1, thus putatively limiting IGF-I bioavailability. If free IGF-I mediates certain biological actions, then exogenous Te and E2 may modulate the tissue effects of total IGF-I concentrations unequally.
Effects of size and behavior on aerial performance of two species of flying snakes (Chrysopelea)
Authors: Socha John J. , LaBarbera Michael
Published: May 2005

Aerial locomotion in snakes (genus Chrysopelea) is kinematically distinct from any other type of gliding or powered flight, with prominent,high amplitude body undulations visually dominating the behavior. Because it is not known how flying snakes produce aerodynamic forces in flight, the factors that determine snake flight performance are not clear. In this study,the effects of size and behavior on aerial performance were examined both within a species (C. paradisi) and between two species (C. paradisi and C. ornata), using stepwise multiple regressions to identify relevant variables. Smaller C. paradisi traveled farther than larger snakes at lower sinking speeds, with trajectories that shallowed more quickly and reached lower minimum glide angles. Although wing loading increased faster than expected for isometric size increase, wing loading per se was not responsible for performance differences between large and small snakes. Snakes with higher interactions between relative undulation amplitude and body size transitioned out of the initial acceleration phase at higher airspeeds and sinking speeds, and attained higher maximum airspeeds and horizontal speeds; snakes that used higher average relative amplitudes transitioned out of the initial acceleration phase at higher horizontal speeds. Undulation frequency was not significantly related to any performance variable within C. paradisi and was not significantly different between the two species, suggesting that this variable (in contrast to relative undulation amplitude) may have a minor influence on the aerodynamic mechanism of force production in snake flight. C. paradisi and C. ornata differed significantly in most performance comparisons. C. ornata were more massive than C. paradisi at any given body length and in general exhibited poorer gliding performance than C. paradisi. This study contributes towards understanding how an unconventional body form and kinematics can produce a novel mode of aerial locomotion in a vertebrate glider.
Physiological control of diving behaviour in the Weddell sealLeptonychotes weddelli: a model based on cardiorespiratory control theory
Authors: Stephenson Richard
Published: May 2005

Despite being obligate air breathers, many species of marine mammal are capable of spending most of their lives submerged in water. How they do this has been a subject of intense interest to physiologists for over a century,yet we still do not have a detailed understanding of the physiological mechanisms underlying this behaviour. What are the proximate mechanisms that trigger the 'decisions' to submerge and return to the surface? The present study proposes a model intended to address this question, based on fundamental concepts of cardiorespiratory control. Two basic hypotheses are examined by computer simulation, using a mathematical model of the mammalian cardiorespiratory control system with parameter values for an adult Weddell seal: (1) that the control of diving can be considered to be a respiratory control problem, and (2) that dives are initiated and maintained by disfacilitation of respiratory drive, not inhibition. Computer simulations confirmed the plausibility of these hypotheses. Simulated diving behaviour and physiological responses (ventilation, cardiac output, blood and tissue gas tensions) were consistent with published data from freely diving Weddell seals. Dives up to the estimated aerobic dive limit (ADL, 18-25 min) could be simulated without the need for active inhibition of breathing in this model. This theoretical analysis suggests that the most important physiological adjustments occur during the surface interval phase of the dive cycle and include hyperventilation accompanied by high cardiac output, appropriate regulation of cerebral blood flow and central chemoreceptor threshold shifts. During dives, cardiac output, distribution of peripheral blood flow, splenic contraction and peripheral chemoreflex drives were found to modulate physiological and behavioural responses, but were not essential for simulated dives to occur. The main conclusion from this study is that the central chemoreceptor may be an important mechanism involved in the regulation of diving behaviour, implying that CO2, not O2, is the key regulatory variable in this model. This model includes and extends the ADL concept and suggests an explicit mechanism by which the respiratory control system may play a central role in the regulation of diving behaviour. It is likely that respiratory mechanisms are an important component of a hierarchical behavioural control system and further studies are required to test the qualitative and quantitative validity of the model.
Colouration in crab spiders: substrate choice and prey attraction
Authors: Heiling Astrid M. , Chittka Lars , Cheng Ken , Herberstein Marie E.
Published: May 2005

Australian crab spiders Thomisus spectabilis ambush pollinating insects, such as honeybees (Apis mellifera) on flowers, and can change their body colour between yellow and white. It is traditionally assumed that the spiders change their colour to match the flower colour, thus rendering them cryptic to insect prey. Here, we test this assumption combining state-of-the-art knowledge of bee vision and behavioural experiments.

In the field, yellow spiders are only found on yellow daisies(Chrysanthemum frutescens), whereas white spiders are found on yellow and white daisies. These field patterns were confirmed in the laboratory. When given the choice between white and yellow daisies, yellow spiders preferred yellow daisies, whereas white spiders showed only a slight but non-significant preference for white flowers. Thus, T. spectabilis select background colours according to their own body colour. When viewed from a distance, bees use an achromatic signal produced by their green receptors for target detection. Through this visual channel, white spiders on white flowers, and yellow spiders on yellow flowers are virtually undetectable. From a closer distance of a few centimetres, when bees evaluate colour contrast, the combination of spider colour against different flower backgrounds affected the response of honeybees, but not in ways predicted by a classical crypsis/conspicuousness interpretation. Yellow spiders on yellow flowers are not perfectly matched when interpreted through the colour vision of a honeybee. Nevertheless, honeybees showed indifference to the presence of a spider, equally landing on vacant or spider-occupied flowers. Likewise, white spiders are poorly hidden on white flowers, as white spiders reflect ultraviolet light strongly, while white flowers do not. Surprisingly, bees are attracted to this contrast, and significantly more honeybees preferred white flowers occupied by white spiders. White spiders on yellow flowers produce the highest colour contrast and bees again preferred spider-occupied flowers. Yellow spiders on white flowers were the only pairing where bees rejected spider-occupied flowers, especially in cases where the contrast between the two was relatively strong. Thus, T. spectabilis select flower colours adaptively in a way that deceives honeybees, or at least does not deter them.
A Political Economy Model of Congressional Careers
Authors: Diermeier Daniel , Keane Michael , Merlo Antonio
Published: May 2005

Our main goal is to quantify the returns to a career in the United States Congress. We specify a dynamic model of career decisions of a member of Congress andestimate this model using a newly collected dataset. Given estimates of the structural model, we assess reelection probabilities, estimate the effect of congressional experience on private and public sector wages, and quantify the value of a congressional seat. Moreover, we assess how an increase in the congressional wage or the imposition of term limits would affect the career decisions of politicians and the returns from a career in Congress.