bluuebunny/crossref_metadata_2025 huggingface dataset:
Vibrio cholerae
Strains Possess Multiple Strategies for Abiotic and Biotic Surface Colonization
Authors: Mueller Ryan S. , McDougald Diane , Cusumano Danielle , Sodhi Nidhi , Kjelleberg Staffan , Azam Farooq , Bartlett Douglas H.
Published: May 2007

Despite its notoriety as a human pathogen,
Vibrio cholerae
is an aquatic microbe suited to live in freshwater, estuarine, and marine environments where biofilm formation may provide a selective advantage. Here we report characterization of biofilms formed on abiotic and biotic surfaces by two non-O1/O139
V. cholerae
strains, TP and SIO, and by the O1
V. cholerae
strain N16961 in addition to the isolation of 44 transposon mutants of SIO and TP impaired in biofilm formation. During the course of characterizing the mutants, 30 loci which have not previously been associated with
V. cholerae
biofilms were identified. These loci code for proteins which perform a wide variety of functions, including amino acid metabolism, ion transport, and gene regulation. Also, when the plankton colonization abilities of strains N16961, SIO, and TP were examined, each strain showed increased colonization of dead plankton compared with colonization of live plankton (the dinoflagellate
Lingulodinium polyedrum
and the copepod
Tigriopus californicus
). Surprisingly, most of the biofilm mutants were not impaired in plankton colonization. Only mutants impaired in motility or chemotaxis showed reduced colonization. These results indicate the presence of both conserved and variable genes which influence the surface colonization properties of different
V. cholerae
subspecies.
Effects of experience in a dynamic environment on postural control
Authors: Chapman D W , Needham K J , Allison G T , Lay B , Edwards D J
Published: May 2007

Background:

Surfing is a balance-reliant, open skill performed in a dynamic environment rich in visual, somatosensory and vestibular information.

Objective:

To evaluate adaptations to the postural control system by surfing experience.

Methods:

Postural control was assessed in an upright bipedal stance in 60 male volunteers (21 elite surfers, 20 intermediate level surfers, and 19 controls) using various closed-stance positions. Six tasks were performed with two trials including a cognitive task, in the following order: eyes open, head in a neutral position (EO1); eyes closed, head in a neutral position (EC); eyes closed, head back (ECHB); eyes open, head in a neutral position, cognitive task 1 (EOC1); eyes open head in a neutral position, cognitive task 2 (EOC2); eyes open head in a neutral position (EO2). Dependent variables were area of 95th centile ellipse (AoE) and sway path length (SPL).

Results:

All participants showed systematic increases in SPL and AoE in EC and ECHB trials. Expert surfers displayed significantly (p<0.05) increased SPL but not AoE when sharing attention with both concurrent mental tasks compared with controls. Controls showed a slight, non-significant change in postural control (reduced SPL and AoE) when attending to concurrent mental tasks.

Conclusions:

The findings indicate that standard postural sway indices are not able to elucidate whether expertise in surfing facilitates adaptations to the postural control system. However, concurrent mental task findings illustrate that systematic differences in balance abilities between expert surfers and controls may exist.
Exercise pretraining protects against cerebral ischaemia induced by heat stroke in rats
Authors: Chen Yu-Wen , Chen Sheng-Hsien , Chou Willy , Lo Yi-Ming , Hung Ching-Hsia , Lin Mao-Tsun
Published: May 2007

Background:

In the rat brain, heat-stroke-induced damage to cerebral neurons is attenuated through heat-shock-induced overexpression of heat-shock protein 72 (HSP72).

Objective:

To ascertain whether progressive exercise preconditioning induces HSP72 expression in the rat brain and prevents heat-stroke-induced cerebral ischaemia and injury.

Methods:

Male Wistar rats were randomly assigned to either a sedentary group or an exercise group. Those in the exercise group progressively ran on a treadmill 5 days/week, for 30–60 min/day at an intensity of 20–30 m/min for 3 weeks. The effects of heat stroke on mean arterial pressure, cerebral blood flow, brain ischaemia markers (glutamate, lactate/pyruvate ratio and nitric oxide), a cerebral injury marker (glycerol) and brain neuronal damage score in the preconditioned animals were compared with effects in unexercised controls. Heat stroke was induced by exposing urethane-anaesthetised animals to a temperature of 43°C for 55 min, which caused the body temperature to reach 42°C.

Results:

Three weeks of progressive exercise pretreatment induced HSP72 preconditioning in the brain and conferred significant protection against heat-stroke-induced hyperthermia, arterial hypotension, cerebral ischaemia and neuronal damage; it also prolonged survival.

Conclusions:

Exercise for 3 weeks can improve heat tolerance as well as attenuate heat-stroke-induced cerebral ischaemia in rats. The maintenance of mean arterial pressure and cerebral blood flow at appropriate levels in the rat brain may be related to overexpression of HSP72.
Strategies to prevent injury in adolescent sport: a systematic review
Authors: Abernethy Liz , Bleakley Chris
Published: May 2007

This systematic review set out to identify randomised controlled trials and controlled intervention studies that evaluated the effectiveness of preventive strategies in adolescent sport and to draw conclusions on the strength of the evidence. A literature search in seven databases (Medline, SportDiscus, EMBASE, CINAHL, PEDro, Cochrane Review and DARE) was carried out using four keywords: adolescent, sport, injury and prevention (expanded to capture any relevant literature). Assessment of 154 papers found 12 studies eligible for inclusion. It can be concluded that injury prevention strategies that focus on preseason conditioning, functional training, education, balance and sport-specific skills, which should be continued throughout the sporting season, are effective. The evidence for the effectiveness of protective equipment in injury prevention is inconclusive and requires further assessment.
Rectus sheath haematoma: a rare presentation of non-contact strenuous exercises
Authors: Sharma Hemant , Shekhawat Narayan Singh , Bhandari Sudhir , Memon Breda , Memon Muhammed Ashraf
Published: May 2007

Rectus sheath haematoma (RSH) is a well-documented but uncommon clinical condition. It is usually a self-limiting condition but can present as a life-threatening emergency. RSH after non-contact vigorous exercise is unknown. Two such cases secondary to yoga and laughter therapy sessions, respectively, are reported. One of them required surgical intervention, whereas the other was successfully treated conservatively.
Sclerosing therapy and eccentric training in flexor carpi radialis tendinopathy in a tennis player: Figure 1
Authors: Knobloch Karsten , Spies Marcus , Busch Kay H , Vogt Peter M
Published: May 2007

Background:

Tendinopathy of the flexor carpi ulnaris tendon is a rare entity. Recent research revealed the role of a neurovascular ingrowth at the point of pain in various tendinopathic locations, such as at the Achilles and patellar tendon, in plantar fasciitis as well as in supraspinatus and tennis elbow tendinopathy. However, beyond the elbow no such neovascularisation has been reported to date.

Methods:

We present a 35-year old tennis player suffering tremendous pain (visual analogue scale (VAS) rating of 9/10) at the flexor carpi ulnaris tendon with adjacent calcification in close proximity to the pisiform bone. The patient was assessed with power Doppler and laser Doppler quantification of neovascularisation at the point of pain.

Results:

Power Doppler and laser Doppler quantification of neovascularisation at the point of pain identified higher capillary blood flow at three points over the painful vs the non-painful tendon (146/240/232rU vs 93/74/70rU at the non-affected side). Sclerosing therapy using polidocanol under power and laser Doppler guidance was initiated, with immediate decrease of capillary blood flow by 25% with resolution of the neovascularisation in power Doppler. Immediately following sclerosing, the patient’s reported pain level on the VAS was reduced from 9/10 to 4/10. Following a short period of rest, eccentric training of the forearm muscle was initiated over 12 weeks with functional complete recovery and complete resolution of wrist pain.

Conclusion:

Sclerosing therapy using polidocanol under power- and laser-Doppler guidance can decrease capillary blood flow by 25% with resolution of the neovascularisation. Subsequent eccentric training of the forearm muscle over 12 weeks can result in complete resolution of wrist pain.
Saccadometry: the possible application of latency distribution measurement for monitoring concussion
Authors: Pearson B C , Armitage K R , Horner C W M , Carpenter R H S
Published: May 2007

Premature return to play after concussion may have debilitating or even fatal consequences. Computerised neuropsychological test batteries are widely used to monitor recovery, but none meet all specified criteria. One possible alternative is to measure saccadic reaction time or latency. Latency reflects the operation of cerebral decision mechanisms, and is strongly influenced by many agents that impair cortical function. A portable, micro-miniature device (saccadometer) was used to record the eye movements of amateur boxers before and after competitive bouts. Individual latency distributions were significantly affected after blows to the head, though the effects seemed to be reversible, with recovery over a few days. This quantitative, objective and easy to use technique should perhaps be deployed more widely to evaluate its potential in monitoring the effects of sports-related head injuries.
Factors associated with menstrual dysfunction and self-reported bone stress injuries in female runners in the ultra- and half-marathons of the Two Oceans
Authors: Micklesfield L K , Hugo J , Johnson C , Noakes T D , Lambert E V
Published: May 2007

Objective:

To investigate factors associated with menstrual dysfunction, self-reported bone stress injuries and energy balance in women runners.

Methods:

613 runners were randomly sampled during the registration period for an endurance event. Demographic information, including self-reported height and weight, training and injury history and menstrual history, was collected by questionnaire.

Results:

Ultra-marathon (ULTRA) participants (n = 276) were significantly older (mean (SD) 39 (8.2) vs 34 (10.5) years; p<0.001), lighter (58.2 (6.6) vs 59.6 (8.3) kg; p<0.05) and reported a higher training volume (p<0.001) than half-marathon (HALF) participants (n = 337). Significantly more ULTRA subjects than HALF subjects reported a previous bone stress injury (21% vs 14%; p<0.05). There was no difference between the groups for menstrual status, but age at menarche was later (p<0.01) in the ULTRA group. Data were combined according to the absence (REG; n = 368/602 (61%)) or presence (IRREG; n = 234/602 (39%)) of a history of menstrual irregularity. Subject morphology was similar between groups, but the IRREG group had a higher self-reported measure on the self-loathing subscale (SLSS; p<0.01). The whole group was then classified according to current menstrual status, with 165 women being classified as currently irregular. (OLIGO/AMEN; 11.6%) and 445 women as currently regular (EUMEN; 88.4%). There were no morphological differences between the groups, however the OLIGO/AMEN group had a later age of menarche (p<0.01) than the EUMEN group. Further, women who reported a previous bone stress injury had higher SLSS scores than those who did not (2.91 (0.98) vs 2.68 (0.84); p<0.05).

Conclusions:

There may be two independent mechanisms associated with energy balance, which are related to bone stress injuries, but may not necessarily be related to menstrual dysfunction.
No neurochemical evidence for brain injury caused by heading in soccer
Authors: Zetterberg Henrik , Jonsson Michael , Rasulzada Abdullah , Popa Cornel , Styrud Ewa , Hietala Max Albert , Rosengren Lars , Wallin Anders , Blennow Kaj
Published: May 2007

Background:

The possible injurious effect to the brain of heading in soccer is a matter of discussion.

Objective:

To determine whether standardised headings in soccer are associated with increased levels of biochemical markers for neuronal injury in cerebrospinal fluid (CSF) and serum.

Methods:

23 male amateur soccer players took part in a heading training session involving heading a ball kicked from a distance of 30 m at least 10 m forward. Ten players performed 10 and 13 players performed 20 approved headings. The players underwent lumbar puncture and serum sampling 7–10 days after the headings. The study also included 10 healthy male non-athletic control subjects. CSF was analysed for neurofilament light protein, total tau, glial fibrillary acidic protein, S-100B and albumin concentrations. Serum was analysed for S-100B and albumin.

Results:

None of the biomarker levels were abnormal and there were no significant differences between any of the three groups, except for a slightly increased CSF S-100B concentration in controls compared with headers. Biomarker levels did not correlate with the number of headings performed.

Conclusion:

Repeated low-severity head impacts due to heading in soccer are not associated with any neurochemical signs of injury to the brain.
Influence of exercise on oxidant stress products in elite Indian cyclists
Authors: Lekhi Chhavi , Gupta Pradeep H , Singh Balwant
Published: May 2007

The influence of exercise on free-radical chemistry is not well understood. It is yet to be confirmed whether an adequate biochemical defence system exists in the human body to provide protection from oxy-centred radicals generated by exercise. Fifty trained elite cyclists undertaking exhaustive endurance training were compared with a control group of 50 sedentary workers. Serum malondialdehyde (MDA), uric acid, superoxide dismutase (SOD), catalase, vitamin E, vitamin C and susceptibility to oxidative stress were assessed. Exhaustive exercise resulted in significantly (p<0.05) higher concentrations of serum MDA, vitamin E and vitamin C, significantly (p<0.001) higher SOD activity, but less significantly (p<0.01) higher concentrations of uric acid and significantly (p<0.05) lower catalase activity in elite cyclists than in the controls. Alterations in the activities of erythrocyte scavenger enzymes (SOD) and higher level of non-enzymatic defences in trained subjects may not be sufficient to counteract the increase in reactive oxygen species produced by endurance training.
Head injuries in the female football player: incidence, mechanisms, risk factors and management
Authors: Dvorak Jiri , McCrory Paul , Kirkendall Donald T
Published: May 2007

Although all injuries in sports are a concern for participants, head injuries are particularly troublesome because of the potential for long-term cognitive deficits. To prevent any specific injury, it is important to understand the basic frequency and incidence of injury and then the mechanism of injury. Once these are established, prevention programmes can be tested to see if the rate of injury changes. A primary problem with head injuries is recognising that the injury has occurred. Many athletes are not aware of the seriousness of concussive injury, thus this type of injury is probably under-reported. Once the diagnosis of a concussion is made, the next difficult decision is when to return a player to the game. These two management issues dominate the continuing development of understanding of concussive head injury. This paper explores the known gender differences between head injuries and highlights the areas that need to be considered in future research.
Demystifying basal-like breast carcinomas: Figure 1
Authors: Da Silva L , Clarke C , Lakhani S R
Published: May 2007

“Basal” breast cancers are dominating the breast research literature at present and pathologists are under increasing pressure to evaluate for such a phenotype by their surgical and oncological colleagues. There is also much confusion about how to assess cancers, which immunohistochemical markers to use, what meaning and benefit this provides, and what the surgeons and oncologists will do with the information. Much remains to be done to answer all these questions but here we try to shed light on some of the issues and suggest what is still to come.
Best practice in primary care pathology: review 10
Authors: Smellie W S A , Shaw N , Bowley R , Stewart M F , Kelly A M , Twomey P J , Chadwick P R , Houghton J B , Ng J P , McCulloch A J
Published: May 2007

This tenth best practice review examines four series of common primary care questions in laboratory medicine: (i) antenatal testing in pregnant women; (ii) estimated glomerular filtration rate calculation; (iii) safety testing for methotrexate; and (iv) blood glucose measurement in diabetes. The review is presented in question–answer format, referenced for each question series. The recommendations represent a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus rather than evidence-based. They will be updated periodically to take account of new information.
Diagnostic value of combining immunostaining for CD3 and nuclear morphometry in mycosis fungoides
Authors: Lira M , Schenka A A , Magna L A , Cotta A C , Cintra M L , de Souza E M , Brousset P , Vassallo J
Published: May 2007

Background:

Mycosis fungoides (MF) is the most common skin lymphoid neoplasm. In initial stages, differential diagnosis of MF from other benign dermal lymphoid infiltrates (BDLI) may be impossible on morphological basis alone. In previous studies, only deletion of CD7 in MF proved to be of diagnostic help, but not the ratio between immunoexpression of CD4 and CD8.

Methods:

30 cases of MF and 11 cases of BDLI were analysed, in order to compare morphometric parameters, which could be of diagnostic aid. As CD7 is frequently deleted in MF, immunohistochemical detection of T-cells was made using an antibody to CD3. Images of 100 CD3-positive cells per case in both groups were captured and analysed using a simple computer program for nuclear perimeter, area, diameter and nuclear contour index.

Results:

All parameters showed statistically significant higher values for MF. Area was the variable with the strongest discriminating power between the two groups of patients. Thus even if morphological evaluation is not accurate to distinguish benign versus malignant dermal lymphoid infiltrates, due to the variability of size and shape of these cells, a more sensitive method promptly shows this difference.

Conclusion:

Results suggest that morphometry of CD3-positive lymphoid cells may add valuable information in the differential diagnosis of MF and benign dermatoses.
Development of real time PCR to detectToxoplasma gondiiandBorrelia burgdorferiinfections in postal samples
Authors: Joss A W L , Evans R , Mavin S , Chatterton J , Ho-Yen D O
Published: May 2007

Background:

Most of the samples sent to reference laboratories are delivered by post. Thus, diagnostic PCR tests on blood samples have to be performed using methods which are optimised and validated for such conditions. There is a low probability that the organismsToxoplasma gondiiandBorrelia burgdorferiwill be present.

Aim:

To confirm that robotic extraction methods followed by real time PCR will detect as little as one organism/test sample in postal specimens.

Methods:

Human blood samples spiked with decreasing numbers of each organism (range 105–1/per extract) were extracted using two commercial kits on a Qiagen BioRobot EZ1 Workstation. Extracts of whole blood and blood fractions were tested by real time PCR. The effect of storage of blood for 1–6 days at room temperature was also investigated.

Results:

Maximum sensitivity (1 organism/test sample) was achieved forT gondiiwith either extraction method; the sensitivity forB burgdorferiwas between 1 and 10 organisms/test. Whole blood was the most suitable sample to extract, as both organisms were as likely to be detectable in the red cell as the white cell fraction. Sensitivity was not reduced by storing spiked samples at room temperature for up to 6 days. Inhibitory effects on PCR were not a significant problem provided that samples were extracted using the blood extraction kit.

Conclusions:

Using appropriate robotic extraction methods, bothT gondiiandB burgdorferican be detected by real time PCR with near maximum possible sensitivity in whole blood samples. Blood samples can be transferred to reference laboratories by post without loss of sensitivity over the likely transit period.
Best of the web in pathology: a practical guide to finding specific pathology resources on the internet
Authors: Boehm J
Published: May 2007

Background:

Although a large number of pathology-specific websites (PSWs) are accessible on the internet, the potential use of PSWs is relatively unknown among pathologists. As a PSW-directory does not exist, it may be difficult to find certain resources that are scattered over the internet.

Aims:

To critically revisit PSWs in order to create a collection of selected websites that may be useful for practising pathologists worldwide.

Methods:

Using special medical databases and link collections, extensive search for PSWs was performed on the world wide web. Each website was evaluated with regard to content and practical use for pathologists.

Results:

PSWs contain electronic training manuals, journals, case collections, photo-archives, link directories, or slide collections of virtual microscopy. PSWs offer lavishly illustrated education material for undergraduates and postgraduates in pathology, but may also be very useful as reference books or as an instrument of continuing medical education for experienced pathologists. The paper shows how to find PSWs, and presents an annotated list of 100 of the best PSWs.

Conclusions:

PSWs as a whole form a heterogeneous patchwork of information. It is suggested that a central catalogue listing all PSWs that are available worldwide be established. This database would enable pathologists to have immediate access to all up-to-date pathology-specific resources on the internet, without the need to perform any laborious web research for themselves. It is hoped that in the future, the repertoire of on-line resources in pathology will be systematically perfected. The internet will then play a central role in the daily practice of pathologists as a medium of information and communication.
A GALLERY OF CHUA ATTRACTORS: PART II
Authors: BILOTTA ELEONORA , PANTANO PIETRO , STRANGES FAUSTO
Published: May 2007

Chua's circuit is a physical system which can be used to investigate chaotic processes. One of its identifying features is the ability to produce a huge variety of strange attractors, each with its own characteristic form, size and model. These characteristics extend to a range of different systems derived from the original circuit.

In the first paper A Gallery of Chua's Attractors. Part I, we presented physical circuits and some generalizations based on Chua's oscillator, together with techniques for building the circuit and a summary description of its chaotic behavior.

In this second part of our work, we present an overview of forms which can only be produced by the physical circuit, using novel techniques of scientific visualization to explore, discover, analyze and validate our large collection of data. Starting with cases already known in the literature, we show that the circuit can produce an infinite set of three-dimensional patterns. A small sample is included in our paper. More specifically, we present 195 strange attractors generated by the circuit. For each attractor we provide three-dimensional images, time series and FFTs. Finally, we provide Lyapunov exponents for a subset of "base attractors".
Effects of D-4F on vasodilation, oxidative stress, angiostatin, myocardial inflammation, and angiogenic potential in tight-skin mice
Authors: Weihrauch Dorothee , Xu Hao , Shi Yang , Wang Jingli , Brien Jennifer , Jones Deron W. , Kaul Sushma , Komorowski Richard A. , Csuka Mary Ellen , Oldham Keith T. , Pritchard Kirkwood A.
Published: May 2007

Systemic sclerosis (scleroderma, SSc) is an autoimmune, connective tissue disorder that is characterized by impaired vascular function, increased oxidative stress, inflammation of internal organs, and impaired angiogenesis. Tight skin mice (Tsk−/+) have a defect in fibrillin-1, resulting in replication of many of the myocardial and vascular features seen in humans with SSc. D-4F is an apolipoprotein A-I (apoA-I) mimetic that improves vascular function in diverse diseases such as hypercholesterolemia, influenza, and sickle cell disease. Tsk−/+mice were treated with either phosphate-buffered saline (PBS) or D-4F (1 mg·kg−1·day−1for 6–8 wk). Acetylcholine and flow-induced vasodilation were examined in facialis arteries. Proinflammatory HDL (p-HDL) in murine and human plasma samples was determined by the cell-free assay. Angiostatin levels in murine and human plasma samples were determined by Western blot analysis. Hearts were examined for changes in angiostatin and autoantibodies against oxidized phosphotidylcholine (ox-PC). Angiogenic potential in thin sections of murine hearts was assessed by an in vitro vascular endothelial growth factor (VEGF)-induced endothelial cell (EC) tube formation assay. D-4F improved endothelium-, endothelial nitric oxide synthase-dependent, and flow-mediated vasodilation in Tsk−/+mice. Tsk−/+mice had higher plasma p-HDL and angiostatin levels than C57BL/6 mice, as did SSc patients compared with healthy control subjects. Tsk−/+mice also had higher triglycerides than C57BL/6 mice. D-4F reduced p-HDL, angiostatin, and triglycerides in the plasma of Tsk−/+mice. Tsk−/+hearts contained notably higher levels of angiostatin and autoantibodies against ox-PC than those of control hearts. D-4F ablated angiostatin in Tsk−/+hearts and reduced autoantibodies against ox-PC by >50% when compared with hearts from untreated Tsk−/+mice. Angiogenic potential in Tsk−/+hearts was increased only when the Tsk−/+mice were treated with D-4F (1 mg·kg−1·day−1, 6–8 wk), and cultured sections of hearts from the D-4F-treated Tsk−/+micewere incubated with D-4F (10 μg/ml, 5–7 days). Failure to treat the thin sections of hearts and Tsk−/+mice with D-4F resulted in loss of VEGF-induced EC tube formation. D-4F improves vascular function, decreases myocardial inflammation, and restores angiogenic potential in the hearts of Tsk−/+mice. As SSc patients have increased plasma p-HDL and angiostatin levels similar to the Tsk−/+mice, D-4F may be effective at treating vascular complications in patients with SSc.
Contribution of mitral annular dynamics to LV diastolic filling with alteration in preload and inotropic state
Authors: Carlhäll C. , Kindberg K. , Wigström L. , Daughters G. T. , Miller D. C. , Karlsson M. , Ingels N. B.
Published: May 2007

Mitral annular (MA) excursion during diastole encompasses a volume that is part of total left ventricular (LV) filling volume (LVFV). Altered excursion or area variation of the MA due to changes in preload or inotropic state could affect LV filling. We hypothesized that changes in LV preload and inotropic state would not alter the contribution of MA dynamics to LVFV. Six sheep underwent marker implantation in the LV wall and around the MA. After 7–10 days, biplane fluoroscopy was used to obtain three-dimensional marker dynamics from sedated, closed-chest animals during control conditions, inotropic augmentation with calcium (Ca), preload reduction with nitroprusside (N), and vena caval occlusion (VCO). The contribution of MA dynamics to total LVFV was assessed using volume estimates based on multiple tetrahedra defined by the three-dimensional marker positions. Neither the absolute nor the relative contribution of MA dynamics to LVFV changed with Ca or N, although MA area decreased (Ca, P < 0.01; and N, P < 0.05) and excursion increased (Ca, P < 0.01). During VCO, the absolute contribution of MA dynamics to LVFV decreased ( P < 0.001), based on a reduction in both area ( P < 0.001) and excursion ( P < 0.01), but the relative contribution to LVFV increased from 18 ± 4 to 45 ± 13% ( P < 0.001). Thus MA dynamics contribute substantially to LV diastolic filling. Although MA excursion and mean area change with moderate preload reduction and inotropic augmentation, the contribution of MA dynamics to total LVFV is constant with sizeable magnitude. With marked preload reduction (VCO), the contribution of MA dynamics to LVFV becomes even more important.
Hemodynamic consequences of chronic parasympathetic blockade with a peripheral muscarinic antagonist
Authors: Ayer Antoine , Antic Vladan , Dulloo Abdul G. , Van Vliet Bruce N. , Montani Jean-Pierre
Published: May 2007

Whereas the sympathetic nervous system has a well-established role in blood pressure (BP) regulation, it is not clear whether long-term levels of BP are affected by parasympathetic function or dysfunction. We tested the hypothesis that chronic blockade of the parasympathetic nervous system has sustained effects on BP, heart rate (HR), and BP variability (BPV). Sprague-Dawley rats were instrumented for monitoring of BP 22-h per day by telemetry and housed in metabolic cages. After the rats healed from surgery and a baseline control period, scopolamine methyl bromide (SMB), a peripheral muscarinic antagonist, was infused intravenously for 12 days. This was followed by a 10-day recovery period. SMB induced a rapid increase in mean BP from 98 ± 2 mmHg to a peak value of 108 ± 2 mmHg on day 2 of the SMB infusion and then stabilized at a plateau value of +3 ± 1 mmHg above control ( P < 0.05). After cessation of the infusion, the mean BP fell by 6 ± 1 mmHg. There was an immediate elevation in HR that remained significantly above control on the last day of SMB infusion. SMB also induced a decrease in short-term (within 30-min periods) HR variability and an increase in both short-term and long-term (between 30-min periods) BPV. The data suggest that chronic peripheral muscarinic blockade leads to modest, but sustained, increases in BP, HR, and BPV, which are known risk factors for cardiovascular morbidity.
Vasomotor control in mice overexpressing human endothelial nitric oxide synthase
Authors: van Deel Elza D. , Merkus Daphne , van Haperen Rien , de Waard Monique C. , de Crom Rini , Duncker Dirk J.
Published: May 2007

Nitric oxide (NO) plays a key role in regulating vascular tone. Mice overexpressing endothelial NO synthase [eNOS-transgenic (Tg)] have a 20% lower systemic vascular resistance (SVR) than wild-type (WT) mice. However, because eNOS enzyme activity is 10 times higher in tissue homogenates from eNOS-Tg mice, this in vivo effect is relatively small. We hypothesized that the effect of eNOS overexpression is attenuated by alterations in NO signaling and/or altered contribution of other vasoregulatory pathways. In isoflurane-anesthetized open-chest mice, eNOS inhibition produced a significantly greater increase in SVR in eNOS-Tg mice compared with WT mice, consistent with increased NO synthesis. Vasodilation to sodium nitroprusside (SNP) was reduced, whereas the vasodilator responses to phosphodiesterase-5 blockade and 8-bromo-cGMP (8-Br-cGMP) were maintained in eNOS-Tg compared with WT mice, indicating blunted responsiveness of guanylyl cyclase to NO, which was supported by reduced guanylyl cyclase activity. There was no evidence of eNOS uncoupling, because scavenging of reactive oxygen species (ROS) produced even less vasodilation in eNOS-Tg mice, whereas after eNOS inhibition the vasodilator response to ROS scavenging was similar in WT and eNOS-Tg mice. Interestingly, inhibition of other modulators of vascular tone [including cyclooxygenase, cytochrome P-450 2C9, endothelin, adenosine, and Ca-activated K+channels] did not significantly affect SVR in either eNOS-Tg or WT mice, whereas the marked vasoconstrictor responses to ATP-sensitive K+and voltage-dependent K+channel blockade were similar in WT and eNOS-Tg mice. In conclusion, the vasodilator effects of eNOS overexpression are attenuated by a blunted NO responsiveness, likely at the level of guanylyl cyclase, without evidence of eNOS uncoupling or adaptations in other vasoregulatory pathways.
Tumor necrosis factor-α reduces argininosuccinate synthase expression and nitric oxide production in aortic endothelial cells
Authors: Goodwin Bonnie L. , Pendleton Laura C. , Levy Monique M. , Solomonson Larry P. , Eichler Duane C.
Published: May 2007

Endothelial dysfunction associated with elevated serum levels of TNF-α observed in diabetes, obesity, and congenital heart disease results, in part, from the impaired production of endothelial nitric oxide (NO). Cellular NO production depends absolutely on the availability of arginine, substrate of endothelial nitric oxide synthase (eNOS). In this report, evidence is provided demonstrating that treatment with TNF-α (10 ng/ml) suppresses not only eNOS expression but also the availability of arginine via the coordinate suppression of argininosuccinate synthase (AS) expression in aortic endothelial cells. Western blot and real-time RT-PCR demonstrated a significant and dose-dependent reduction of AS protein and mRNA when treated with TNF-α with a corresponding decrease in NO production. Reporter gene analysis demonstrated that TNF-α suppresses the AS proximal promoter, and EMSA analysis showed reduced binding to three essential Sp1 elements. Inhibitor studies suggested that the repression of AS expression by TNF-α may be mediated, in part, via the NF-κB signaling pathway. These findings demonstrate that TNF-α coordinately downregulates eNOS and AS expression, resulting in a severely impaired citrulline-NO cycle. The downregulation of AS by TNF-α is an added insult to endothelial function because of its important role in NO production and in endothelial viability.
Regulation of surfactant secretion in alveolar type II cells
Authors: Andreeva Alexandra V. , Kutuzov Mikhail A. , Voyno-Yasenetskaya Tatyana A.
Published: May 2007

Molecular mechanisms of surfactant delivery to the air/liquid interface in the lung, which is crucial to lower the surface tension, have been studied for more than two decades. Lung surfactant is synthesized in the alveolar type II cells. Its delivery to the cell surface is preceded by surfactant component synthesis, packaging into specialized organelles termed lamellar bodies, delivery to the apical plasma membrane and fusion. Secreted surfactant undergoes reuptake, intracellular processing, and finally resecretion of recycled material. This review focuses on the mechanisms of delivery of surfactant components to and their secretion from lamellar bodies. Lamellar bodies–independent secretion is also considered. Signal transduction pathways involved in regulation of these processes are discussed as well as disorders associated with their malfunction.
Identification of multiple MAPK-mediated transcription factors regulated by tobacco smoke in airway epithelial cells
Authors: Zhao Jinming , Harper Richart , Barchowsky Aaron , Di Y. P. Peter
Published: May 2007

Activation and regulation of transcription factors (TFs) are the major mechanisms regulating changes in gene expression upon environmental exposure. Tobacco smoke (TS) is a complex mixture of chemicals, each of which could act through different signal cascades, leading to the regulation of distinct TFs and alterations in subsequent gene expression. We proposed that TS exposure affects inflammatory gene expression at the transcriptional level by modulating the DNA binding activities of TFs. To investigate transcriptional regulation upon TS exposure, a protein/DNA array was applied to screen TFs that are affected by TS exposure. This array-based screening allowed us to simultaneously detect 244 different TFs. Our results indicated that multiple TFs were rapidly activated upon TS exposure. DNA-binding activity of differentially expressed TFs was confirmed by EMSA. Our results showed that at least 20 TFs displayed more than twofold expressional changes after smoke treatment. Ten smoke-induced TFs, including NF-κB, VDR, ISRE, and RSRFC4, were involved in MAPK signaling pathways. The NF-κB family, which is involved in inflammation-induced gene activation, was selected for further study to characterize TS exposure-induced transcriptional activation. Western blot analysis and immunofluorescence microscopy indicated that TS exposure induced phosphorylation of IκB and translocation of NF-κB p65/p50 heterodimers into the nucleus. This activity was abrogated by the MAPK inhibitors PD98059 and U0126. Our results confirmed that activation of MAPK signaling pathways by TS exposure increased transcriptional activity of NF-κB. These data provide a potential mechanism for TS-induced inflammatory gene expression.
Nitric oxide attenuates epithelial-mesenchymal transition in alveolar epithelial cells
Authors: Vyas-Read Shilpa , Shaul Philip W. , Yuhanna Ivan S. , Willis Brigham C.
Published: May 2007

Patients with interstitial lung diseases, such as idiopathic pulmonary fibrosis (IPF) and bronchopulmonary dysplasia (BPD), suffer from lung fibrosis secondary to myofibroblast-mediated excessive ECM deposition and destruction of lung architecture. Transforming growth factor (TGF)-β1 induces epithelial-mesenchymal transition (EMT) of alveolar epithelial cells (AEC) to myofibroblasts both in vitro and in vivo. Inhaled nitric oxide (NO) attenuates ECM accumulation, enhances lung growth, and decreases alveolar myofibroblast number in experimental models. We therefore hypothesized that NO attenuates TGF-β1-induced EMT in cultured AEC. Studies of the capacity for endogenous NO production in AEC revealed that endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) are expressed and active in AEC. Total NOS activity was 1.3 pmol·mg protein−1·min−1with 67% derived from eNOS. TGF-β1 (50 pM) suppressed eNOS expression by more than 60% and activity by 83% but did not affect iNOS expression or activity. Inhibition of endogenous NOS with l-NAME led to spontaneous EMT, manifested by increased α-smooth muscle actin (α-SMA) expression and a fibroblast-like morphology. Provision of exogenous NO to TGF-β1-treated AEC decreased stress fiber-associated α-SMA expression and decreased collagen I expression by 80%. NO-treated AEC also retained an epithelial morphology and expressed increased lamellar protein, E-cadherin, and pro-surfactant protein B compared with those treated with TGF-β alone. These findings indicate that NO serves a critical role in preserving an epithelial phenotype and in attenuating EMT in AEC. NO-mediated regulation of AEC fate may have important implications in the pathophysiology and treatment of diseases such as IPF and BPD.
Memantine in Moderate to Severe Alzheimer’s Disease: a Meta-Analysis of Randomised Clinical Trials
Authors: Winblad Bengt , Jones Roy W. , Wirth Yvonne , Stöffler Albrecht , Möbius Hans Jörg
Published: May 2007

The efficacy of memantine in Alzheimer’s disease (AD) has been investigated in multiple randomised, placebo-controlled phase III trials. Recently, the indication label for memantine in Europe was extended to cover patients with moderate to severe AD, i.e. Mini-Mental State Exam total scores below 20. The efficacy data for memantine in this patient subgroup has been summarised by a meta-analysis of 1,826 patients in six trials. Efficacy was assessed using measures of global status (Clinician’s Interview-Based Impression of Change Plus Caregiver Input), cognition (Alzheimer’s Disease Assessment Scale – Cognitive Subscale, or Severe Impairment Battery), function (Alzheimer’s Disease Cooperative Study Activities of Daily Living 19- or 23-item scale), and behaviour (Neuropsychiatric Inventory). Results (without replacement of missing values) showed statistically significant effects for memantine (vs. placebo) in each domain. Memantine was well tolerated, and the overall incidence rates of adverse events were comparable to placebo. This meta-analysis supports memantine’s clinically relevant efficacy in patients with moderate to severe AD.
Trousseau's syndrome: multiple definitions and multiple mechanisms
Authors: Varki Ajit
Published: May 2007

In 1865, Armand Trousseau noted that unexpected or migratory thrombophlebitis could be a forewarning of an occult visceral malignancy. An analysis by Sack and colleagues in 1977 extended the term Trousseau's syndrome to include chronic disseminated intravascular coagulopathy associated with microangiopathy, verrucous endocarditis, and arterial emboli in patients with cancer, often occurring with mucin-positive carcinomas. In recent times the term has been ascribed to various clinical situations, ranging all the way from these classic descriptions to any kind of coagulopathy occurring in the setting of any kind of malignancy. These multiple definitions of Trousseau's syndrome are partly the consequence of multiple pathophysiologic mechanisms that apparently contribute to the hypercoagulability associated with cancer. Even the classic syndrome probably represents a spectrum of disorders, ranging from exaggerated fluid-phased thrombosis dependent on prothrombotic agents such as tissue factor to a platelet- and endotheliumum-based selectin-dependent microangiopathy associated with mucin-producing carcinomas, along with thrombin and fibrin production. Also considered here are recent hypotheses about genetic pathways within tumor cells that might trigger these thrombotic phenomena, and the reasons why therapy with heparins of various kinds remain the preferred treatment, probably because of their salutary actions on several of the proposed pathologic mechanisms.
Stable differentiation and clonality of murine long-term hematopoiesis after extended reduced-intensity selection for MGMT P140K transgene expression
Authors: Ball Claudia R. , Pilz Ingo H. , Schmidt Manfred , Fessler Sylvia , Williams David A. , von Kalle Christof , Glimm Hanno
Published: May 2007

Efficient in vivo selection increases survival of gene-corrected hematopoietic stem cells (HSCs) and protects hematopoiesis, even if initial gene transfer efficiency is low. Moreover, selection of a limited number of transduced HSCs lowers the number of cell clones at risk of gene activation by insertional mutagenesis. However, a limited clonal repertoire greatly increases the proliferation stress of each individual clone. Therefore, understanding the impact of in vivo selection on proliferation and lineage differentiation of stem-cell clones is essential for its clinical use. We established minimal cell and drug dosage requirements for selection of P140K mutant O6-methylguanine-DNA-methyltransferase (MGMT P140K)–expressing HSCs and monitored their differentiation potential and clonality under long-term selective stress. Up to 17 administrations of O6-benzylguanine (O6-BG) and 1,3-bis(2-chloroethyl)-1-nitroso-urea (BCNU) did not impair long-term differentiation and proliferation of MGMT P140K–expressing stem-cell clones in mice that underwent serial transplantation and did not lead to clonal exhaustion. Interestingly, not all gene-modified hematopoietic repopulating cell clones were efficiently selectable. Our studies demonstrate that the normal function of murine hematopoietic stem and progenitor cells is not compromised by reduced-intensity long-term in vivo selection, thus underscoring the potential value of MGMT P140K selection for clinical gene therapy.
Dosage-dependent requirement of BMP type II receptor for maintenance of vascular integrity
Authors: Liu Dong , Wang Jian , Kinzel Bernd , Müeller Matthias , Mao Xiaohong , Valdez Reginald , Liu Yongxing , Li En
Published: May 2007

Germ-line mutations in bone morphogenic protein type II receptor (Bmpr2) confer susceptibility to pulmonary arterial hypertension (PAH), which is characterized by obstructive vascular lesions in small arteries. The molecular and cellular mechanisms that account for the etiology of this disorder remain elusive, as does the role of Bmpr2 in postnatal tissue homeostasis. Here we show that in adult mice, stably silencing Bmpr2 expression by RNA interference does not increase pulmonary arterial resistance but results in severe mucosal hemorrhage, incomplete mural cell coverage on vessel walls, and gastrointestinal hyperplasia. We present evidence that BMP receptor signaling regulates vascular remodeling during angiogenesis by maintaining the expression of endothelial guidance molecules that promote vessel patterning and maturation and by counteracting growth factor–induced AKT activation. Attenuation of this function may cause vascular dysmorphogenesis and predisposition to angioproliferative diseases. Our findings provide a mechanistic link between PAH and other diseases associated with the BMP/TGF-β pathways, such as hereditary hemorrhagic telangiectasia and juvenile polyposis syndrome.
Expansion and evolution of insect GMC oxidoreductases
Authors: Iida Kaori , Cox-Foster Diana L , Yang Xiaolong , Ko Wen-Ya , Cavener Douglas R
Published: May 2007

Background

The GMC oxidoreductases comprise a large family of diverse FAD enzymes that share a homologous backbone. The relationship and origin of the GMC oxidoreductase genes, however, was unknown. Recent sequencing of entire genomes has allowed for the evolutionary analysis of the GMC oxidoreductase family.

Results

Although genes that encode enzyme families are rarely linked in higher eukaryotes, we discovered that the majority of the GMC oxidoreductase genes in the fruit fly (D. melanogaster), mosquito (A. gambiae), honeybee (A. mellifera), and flour beetle (T. castaneum) are located in a highly conserved cluster contained within a large intron of theflotillin-2(Flo-2) gene. In contrast, the genomes of vertebrates and the nematodeC. eleganscontain few GMC genes and lack a GMC cluster, suggesting that the GMC cluster and the function of its resident genes are unique to insects or arthropods. We found that the development patterns of expression of the GMC cluster genes are highly complex. Among the GMC oxidoreductases located outside of the GMC gene cluster, the identities of two related enzymes, glucose dehydrogenase (GLD) and glucose oxidase (GOX), are known, and they play major roles in development and immunity. We have discovered that several additional GLD and GOX homologues exist in insects but are remotely similar to fungal GOX.

Conclusion

We speculate that the GMC oxidoreductase cluster has been conserved to coordinately regulate these genes for a common developmental or physiological function related to ecdysteroid metabolism. Furthermore, we propose that the GMC gene cluster may be the birthplace of the insect GMC oxidoreductase genes. Through tandem duplication and divergence within the cluster, new GMC genes evolved. Some of the GMC genes have been retained in the cluster for hundreds of millions of years while others might have transposed to other regions of the genome. Consistent with this hypothesis, our analysis indicates that insect GOX and GLD arose from a different ancestral GMC gene than that of fungal GOX.