bluuebunny/crossref_metadata_2025 huggingface dataset:
Unexpected similarity of intestinal sugar absorption by SGLT1 and apical GLUT2 in an insect (Aphidius ervi,Hymenoptera) and mammals
Authors: Caccia S. , Casartelli M. , Grimaldi A. , Losa E. , de Eguileor M. , Pennacchio F. , Giordana B.
Published: February 2007

Sugars are critical substrates for insect metabolism, but little is known about the transporters and epithelial routes that ensure their constant supply from dietary resources. We have characterized glucose and fructose uptakes across the apical and basolateral membranes of the isolated larval midgut of the aphid parasitoid Aphidius ervi. The uptake of radiolabeled glucose at the basal side of the epithelium was almost suppressed by 200 μM cytochalasin B, uninhibited by phlorizin, and showed the following decreasing rank of specificity for the tested substrates: glucose > glucosamine > fructose, with no recognition of galactose. These functional properties well agree with the expression of GLUT2-like transporters in this membrane. When the apical surface of the epithelium was also exposed to the labeled medium, a cation-dependent glucose uptake, inhibited by 10 μM phlorizin and by an excess of galactose, was detected suggesting the presence in the apical membrane of a cation-dependent cotransporter. Radiolabeled fructose uptakes were only partially inhibited by cytochalasin B. SGLT1-like and GLUT5-like transporters were detected in the apical membranes of the epithelial cell by immunocytochemical experiments. These results, along with the presence of GLUT2-like transporters both in the apical and basolateral cell membranes of the midgut, as we recently demonstrated, allow us to conclude that the model for sugar transepithelial transport in A. ervi midgut appears to be unexpectedly similar to that recently proposed for sugar intestinal absorption in mammals.
Control and Estimation of Posture During Quiet Stance Depends on Multijoint Coordination
Authors: Hsu Wei-Li , Scholz John P. , Schöner Gregor , Jeka John J. , Kiemel Tim
Published: February 2007

This study tested the hypotheses that all major joints along the longitudinal axis of the body are equally active during quiet standing and that their motions are coordinated to stabilize the spatial positions of the center of mass (CM) and head. Analyses of the effect of joint configuration variance on the stability of the CM and head positions were performed using the uncontrolled manifold (UCM) approach. Subjects stood quietly with arms folded across their chests for three 5-min trials each with and without vision. The UCM analysis revealed that the six joints examined were coordinated such that their combined variance had minimal effect on the CM and head positions. Removing vision led to a structuring of the resulting increased joint variance such that little of the increase affected stability of the CM and head positions. The results reveal a control strategy involving coordinated variations of most major joints to stabilize variables important to postural control during quiet stance.
Causas de variación en el fenotipo de la fibrosis quística
Authors: Cutting Garry R.
Published: February 2007

La causa de la fibrosis quística (FQ) reside en la función anormal del gen regulador de la conductancia transmembránica de la FQ (RTFQ). La FQ es sumamente variable, y mientras algunos pacientes sucumben a la enfermedad durante su primera década, otros viven hasta la cuarta o quinta década. Los pacientes también difieren en la afectación de los sistemas de órganos y en las complicaciones. Una parte de la variación en el fenotipo de la FQ puede atribuirse a la naturaleza del trastorno del gen RTFQ. El fenotipo RTFQ determina fundamentalmente el grado de disfunción exocrina del páncreas y se correlaciona con un grado de anomalía en la concentración de cloruros en el sudor y la malformación del aparato reproductor masculino. No obstante, factores independientes del RTFQ son responsables de la variación en la neumopatía, causa fundamental de morbilidad y mortalidad en la FQ. En el curso de los ultimísimos años se han identificado genes modificadores que influyen sobre la gravedad de la neumopatía en pacientes afectados de FQ. Factores extragenéticos, como el estado socioeconómico y la exposición al tabaquismo pasivo, también afectan el desenlace pulmonar. Estamos asistiendo a un conocimiento más completo de las causas de variación en los pacientes con FQ, lo que facilitará el desarrollo de nuevas medidas pronósticas así como de nuevos tratamientos.
Angiotensin II, Focal Adhesion Kinase, and PRX1 Enhance Smooth Muscle Expression of Lipoma Preferred Partner and its Newly Identified Binding Partner Palladin to Promote Cell Migration
Authors: Jin Li , Kern Michael J. , Otey Carol A. , Wamhoff Brian R. , Somlyo Avril V.
Published: February 2007

Lipoma preferred partner (LPP) is a proline rich LIM domain family protein highly expressed at plasma membrane dense bodies and focal adhesions in smooth muscle cells.

1

Using the C-terminus of LPP as bait in a yeast two hybrid system, palladin, an actin-associated protein was identified. The palladin interacting region of LPP was mapped to the first and second LIM domains. The N-terminus of palladin interacted with LPP both in vitro and in vivo, but not solely through its FPLPPP and FPPPP motifs. Like LPP, palladin, is highly expressed in differentiated smooth muscle, colocalized at focal adhesions, at isolated lamellipodia and at dense bodies in smooth muscle tissue. Both LPP and palladin enhanced cell migration and spreading. LPP and palladin expression was markedly decreased, in contrast to vinculin or paxillin, in migration defective focal adhesion kinase null cells, but was restored by expression of the
paired
-related homeobox gene-1 protein. We have previously shown in focal adhesion kinase null cells, that tetracycline induced expression of focal adhesion kinase upregulated expression of LPP

2

and now show upregulation of palladin, and
paired
-related homeobox gene-1 protein. The expression of both LPP and palladin, like smooth muscle α-actin, was increased by angiotensin II, regulated by actin dynamics, upregulated by myocardin and expressed in the neointima of injured aorta. Overall, the data suggest that the function of LPP and palladin is context dependent, that they play a critical role in cytoskeletal remodeling, respond to signals induced by vascular injury as well as signals that induce smooth muscle cell hypertrophy, such as angiotension II.
The Right Inferior Frontal Gyrus and Poststroke Aphasia
Authors: Winhuisen Lutz , Thiel Alexander , Schumacher Birgit , Kessler Josef , Rudolf Jobst , Haupt Walter F. , Heiss Wolf D.
Published: February 2007

Background and Purpose—

Recently, a combined repetitive transcranial magnetic stimulation (rTMS) and activation positron emission tomography (PET) study showed essential language function of the right inferior frontal gyrus (IFG) in some right-handed acute poststroke aphasics. We reexamined these patients in the chronic phase to test whether the right IFG remained essential for language performance.

Methods—

We reexamined 9 male right-handed patients, age 41 to 75 years, with aphasia 8 weeks after left hemispheric stroke. rTMS was performed over the maximum activation within the left and right IFG as defined by
15
[O]water PET to interfere with language function. A positive rTMS effect was defined as increased reaction time latency or error rate in the semantic task relative to no stimulation.

Results—

PET activations of the IFG were observed on the left (2 patients) and bilaterally (7). During rTMS interference over the left IFG, all patients had positive TMS effects, indicating that the left IFG remained essential. Stimulation over the right IFG yielded positive rTMS effects in 2 patients with persisting right IFG activation. Two patients with positive rTMS effects over the right side in the initial study did not show these effects at follow-up. Language performance improved in all patients.

Conclusions—

Successful regeneration from poststroke aphasia seems to depend more on the integration of available language-related brain regions than on recruiting new brain regions during the rehabilitation process. Restoration of the left hemisphere network seems to be more effective, although in some cases, right hemisphere areas are integrated successfully.
C-Reactive Protein Predicts Future Cardiovascular Events in Patients With Carotid Stenosis
Authors: Schlager Oliver , Exner Markus , Mlekusch Wolfgang , Sabeti Schila , Amighi Jasmin , Dick Petra , Wagner Oswald , Koppensteiner Renate , Minar Erich , Schillinger Martin
Published: February 2007

Background and Purpose—

Atherosclerosis is a systemic inflammatory disease. We demonstrated previously that high-sensitivity C-reactive protein (hs-CRP) is associated with short-term progression of carotid atherosclerosis. We now investigated whether baseline levels of hs-CRP predict midterm clinical outcome in these patients.

Methods—

We prospectively studied 1065 of 1268 consecutive patients who were initially asymptomatic with respect to carotid artery disease and were investigated with serial carotid ultrasound examinations at baseline and after a 6- to 9-month interval. Patients were followed-up clinically for the occurrence of cardiovascular events, a composite of myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, stroke, and death.

Results—

We recorded progression of carotid stenosis in 93 patients (9%) after 6 to 9 months, and 381 cardiovascular events in 337 patients (27%) during a median of 3 years of clinical follow-up (interquartile range, 2.5 to 3.5 years). The hs-CRP levels were significantly elevated in patients with progressive carotid stenosis (
P
<0.001), and hs-CRP was significantly associated with the occurrence of a first future cardiovascular event (
P
<0.001). Adjusted hazard ratios for a first cardiovascular event for increasing quintiles of hs-CRP were 1.41 (95% confidence interval, 0.92 to 2.17), 1.76 (95% confidence interval, 1.17 to 2.66), 2.22 (95% confidence interval, 1.48 to 3.32), and 2.41 (95% confidence interval, 1.61 to 3.60) as compared with the lowest quintile, respectively. This association was independent of traditional cardiovascular risk factors and the baseline degree of carotid stenosis.

Conclusion—

Inflammation was associated with morphological and clinical progression of atherosclerotic disease. Patients with elevated levels of hs-CRP exhibit an increased risk for adverse cardiovascular outcome attributable to clinical adverse events of progressive atherosclerotic disease.
Effects of the Angiotensin II Type 1 Receptor Antagonist Valsartan on the Expression of Superoxide Dismutase in Hypertensive Patients
Authors: Yang Hung‐Yu , Kao Pai‐Feng , Chen Tso‐Hsiao , Tomlinson Brian , Ko Wen‐Chin , Chan Paul
Published: February 2007

The role of oxidative stress in the pathogenesis of vascular diseases such as hypertension has been well recognized. Angiotensin (Ang) II is regarded as a pro‐oxidant because it can stimulate the production of reactive oxygen species. The purpose of this study was to evaluate whether treatment with the Ang II type 1 (AT1) receptor antagonist valsartan has an antioxidant effect in patients with mild to moderate hypertension. A randomized, double‐blind, placebo‐controlled study was conducted in 48 stage I and II hypertensive subjects. Patients were followed every 4 weeks for 12 weeks after randomization to valsartan titrated to 80 to 160 mg once or twice daily or matching placebo. The erythrocyte superoxide dismutase (SOD) activity and expression of SOD–mRNA in polymorphonuclear leukocytes were measured before and after treatment. Valsartan showed concentration‐dependent inhibition of reactive oxygen species generation in polymorphonuclear leukocytes from hypertensive patients. The erythrocyte superoxide dismutase activity before treatment was more than 2 times higher in hypertensive subjects compared to normal controls. Superoxide dismutase activity decreased significantly after 12 weeks of treatment with valsartan but did not change with placebo. The amount of SOD‐mRNA in the polymorphonuclear leukocytes decreased progressively over 3 months in the hypertensive subjects receiving valsartan treatment but did not change in the placebo group. The production of reactive oxygen species is increased in hypertension, and superoxide dismutase activity is increased, presumably as a compensatory mechanism. Treatment with valsartan but not placebo resulted in a progressive down‐regulation of SOD‐mRNA expression and a reduction in superoxide dismutase activity, suggesting antioxidant activity and a reduction of reactive oxygen species generation. These findings imply that AT1 receptor antagonists may provide benefits to hypertensive patients beyond blood pressure reduction.
Pharmacokinetics of Oral Doses of Telmisartan and Nisoldipine, Given Alone and in Combination, in Patients With Essential Hypertension
Authors: Bajcetic Milica , Benndorf Ralf A. , Appel Daniel , Schwedhelm Edzard , Schulze Friedrich , Riekhof Daniel , Maas Renke , Böger Rainer H.
Published: February 2007

This randomized, single‐blind, parallel‐group study was performed to assess pharmacokinetic interactions potentially occurring during concomitant use of telmisartan and nisoldipine. Patients with essential hypertension (n = 37) were treated with once‐daily doses of telmisartan, nisoldipine, or their combination for 6 weeks. The regimen was started at low dose with an increase of dosage after 3 weeks of treatment. AUCss (132%; P < .01) of telmisartan applied in doses of 80 mg was significantly higher after concomitant application with nisoldipine (10 mg), whereas CL/fss (−54%; P < .05) and Vz/fss (−72%; P < .05) were significantly lower. Regarding pharmacokinetic parameters of nisoldipine, significant differences between treatment groups were not detected. In conclusion, the results of this study strongly suggest that concomitant treatment with nisoldipine enhances telmisartan bioavailability in hypertensive individuals. Larger crossover trials will have to establish these observations and investigate whether interaction of both drugs affects telmisartan efficacy and tolerability in clinical use.
Pharmacokinetics and Pharmacodynamics of Once‐Daily Controlled‐Release Oxybutynin and Immediate‐Release Oxybutynin
Authors: Reiz Joseph L. , Salem Paulette , Darke Andrew C.
Published: February 2007

Oxybutynin is used to treat patients with urinary urgency, frequency, and urge incontinence. In this 2‐way, multiple‐dose, crossover study, the pharmacokinetics and pharmacodynamics of once‐daily controlled‐release oxybutynin were compared with immediate‐release oxybutynin. Eighteen healthy male volunteers received one 15‐mg controlled‐release oxybutynin tablet once daily for 5 days or one 5‐mg immediate‐release oxybutynin tablet every 8 hours for 5 days. The washout period between treatments was ≤7 days. The mean steady‐state AUC for oxybutynin following controlled‐release oxybutynin treatment was higher (73.0 ng·h/mL) than following immediate‐release oxybutynin treatment (53.6 ng·h/mL) (P = .0001). The mean Cmax was lower for controlled‐release oxybutynin (5.7 ng/mL) than for immediate‐release oxybutynin (7.5 ng/mL) (P = .0051), with a smaller fluctuation in oxybutynin plasma concentration for controlled‐release oxybutynin (135.6%) than for immediate‐release oxybutynin (319.3%) (P = .0001). Mean stimulated saliva output was greater for controlled‐release oxybutynin, and mean dry mouth severity was less than immediate‐release oxybutynin.
Inhibition of Dll4-mediated signaling induces proliferation of immature vessels and results in poor tissue perfusion
Authors: Scehnet Jeffrey S. , Jiang Weidong , Ram Kumar S. , Krasnoperov Valery , Trindade Alexandre , Benedito Rui , Djokovic Dusan , Borges Cristina , Ley Eric J. , Duarte Antonio , Gill Parkash S.
Published: February 2007

Vascular development is dependent on various growth factors and certain modifiers critical for providing arterial or venous identity, interaction with the surrounding stroma and tissues, hierarchic network formation, and recruitment of pericytes. Notch receptors and ligands (Jagged and Delta-like) play a critical role in this process in addition to VEGF. Dll4 is one of the Notch ligands that regulates arterial specification and maturation events. In the current study, we have shown that loss of function by either targeted allele deletion or use of a soluble form of Dll4 extracellular domain leads to inhibition of Notch signaling, resulting in increased vascular proliferation but defective maturation. Newly forming vessels have thin caliber, a markedly reduced vessel lumen, markedly reduced pericyte recruitment, and deficient vascular perfusion. sDll4 similarly induced defective vascular response in tumor implants leading to reduced tumor growth. Interference with Dll4-Notch signaling may be particularly desirable in tumors that have highly induced Dll4-Notch pathway.
Atiprimod inhibits the growth of mantle cell lymphoma in vitro and in vivo and induces apoptosis via activating the mitochondrial pathways
Authors: Wang Michael , Zhang Liang , Han Xiaohong , Yang Jing , Qian Jianfei , Hong Sungyoul , Samaniego Felipe , Romaguera Jorge , Yi Qing
Published: February 2007

Atiprimod is a novel cationic amphiphilic compound and has been shown to exert antimyeloma effects both in vitro and in mouse experiments. This study was undertaken to evaluate the therapeutic efficacy of atiprimod on mantle cell lymphoma (MCL) and elucidate the mechanism by which it induces cell apoptosis. Atiprimod inhibited the growth and induced apoptosis of MCL cell lines and freshly isolated primary tumor cells in vitro. More importantly, atiprimod significantly inhibited tumor growth in vivo and prolonged the survival of tumor-bearing mice. However, atiprimod also exhibited lower cytotoxicity toward normal lymphocytes. Atiprimod activated c-Jun N-terminal protein kinases (JNK) and up-regulated the level of Bax, Bad, and phosphorylated Bcl-2, resulting in release of apoptosis-inducing factor (AIF) and cytochrome c from mitochondria and activation and cleavage of caspase-9, caspase-3, and PARP. However, AIF, but not activation of caspases or PARP, was responsible for apoptosis in MCL cells because an AIF inhibitor, but not pan-caspase or paspase-9 inhibitors, completely abrogated atiprimod-induced apoptosis. Taken together, our results demonstrate that atiprimod displays a strong anti-MCL activity. Cell apoptosis was induced mainly via activation of the AIF pathway. These results support the use of atiprimod as a potential agent in MCL chemotherapy.
The effect of a single nucleotide polymorphism on human α2-antiplasmin activity
Authors: Christiansen Victoria J. , Jackson Kenneth W. , Lee Kyung N. , McKee Patrick A.
Published: February 2007

The primary inhibitor of plasmin, α2-antiplasmin (α2AP), is secreted by the liver into plasma with Met as the amino-terminus. During circulation, Met-α2AP is cleaved by antiplasmin-cleaving enzyme (APCE), yielding Asn-α2AP, which is crosslinked into fibrin approximately 13 times faster than Met-α2AP. The Met-α2AP gene codes for either Arg or Trp as the sixth amino acid, with both polymorphic forms found in human plasma samples. We determined the Arg6Trp genotype frequency in a healthy population and its effects on Met-α2AP cleavage and fibrinolysis. Genotype frequencies were RR 62.5%, RW 34.0%, and WW 3.5%. The polymorphism related to the percentage of Met-α2AP in plasma was WW (56.4%), RW (40.6%), and RR (23.6%). WW plasma tended to have shorter lysis times than RR and RW plasmas. APCE cleaved purified Met-α2AP(Arg6) approximately 8-fold faster than Met-α2AP(Trp6), which is reflected in Asn-α2AP/Met-α2AP ratios with time in RR, RW, and WW plasmas. Removal of APCE from plasma abrogated cleavage of Met-α2AP. We conclude that the Arg6Trp polymorphism is functionally significant, as it clearly affects conversion of Met-α2AP to Asn-α2AP, and thereby, the rate of α2AP incorporation into fibrin. Therefore, the Arg6Trp polymorphism may play a significant role in governing the long-term deposition/removal of intravascular fibrin.
Intrinsic differentiation potential of adolescent human tendon tissue: an in-vitro cell differentiation study
Authors: de Mos Marieke , Koevoet Wendy JLM , Jahr Holger , Verstegen Monique MA , Heijboer Marinus P , Kops Nicole , van Leeuwen Johannes PTM , Weinans Harrie , Verhaar Jan AN , van Osch Gerjo JVM
Published: February 2007

Background

Tendinosis lesions show an increase of glycosaminoglycan amount, calcifications, and lipid accumulation. Therefore, altered cellular differentiation might play a role in the etiology of tendinosis. This study investigates whether adolescent human tendon tissue contains a population of cells with intrinsic differentiation potential.

Methods

Cells derived from adolescent non-degenerative hamstring tendons were characterized by immunohistochemistry and FACS-analysis. Cells were cultured for 21 days in osteogenic, adipogenic, and chondrogenic medium and phenotypical evaluation was carried out by immunohistochemical and qPCR analysis. The results were compared with the results of similar experiments on adult bone marrow-derived stromal cells (BMSCs).

Results

Tendon-derived cells stained D7-FIB (fibroblast-marker) positive, but α-SMA (marker for smooth muscle cells and pericytes) negative. Tendon-derived cells were 99% negative for CD34 (endothelial cell marker), and 73% positive for CD105 (mesenchymal progenitor-cell marker). In adipogenic medium, intracellular lipid vacuoles were visible and tendon-derived fibroblasts showed upregulation of adipogenic markers FABP4 (fatty-acid binding protein 4) and PPARG (peroxisome proliferative activated receptor γ). In chondrogenic medium, some cells stained positive for collagen 2 and tendon-derived fibroblasts showed upregulation of collagen 2 and collagen 10. In osteogenic medium Von Kossa staining showed calcium deposition although osteogenic markers remained unaltered. Tendon-derived cells and BMCSs behaved largely comparable, although some distinct differences were present between the two cell populations.

Conclusion

This study suggests that our population of explanted human tendon cells has an intrinsic differentiation potential. These results support the hypothesis that there might be a role for altered tendon-cell differentiation in the pathophysiology of tendinosis.
Use frequency of traditional Chinese medicine in Taiwan
Authors: Chen Fang-Pey , Chen Tzeng-Ji , Kung Yen-Ying , Chen Yu-Chun , Chou Li-Fang , Chen Fan-Jou , Hwang Shinn-Jang
Published: February 2007

Background

Use of Traditional Chinese medicine (TCM), an important category of complementary and alternative medicine (CAM), has increased substantially in Western countries during the past decade. Use of TCM is also widespread in the Chinese population. However, few informative data have been obtained to date by large-scale investigations of TCM use in the Chinese population. This study was aimed at elucidating the demographics and patterns of TCM use in Taiwan.

Methods

We employed the complete datasets of TCM outpatient reimbursement claims from 1996 to 2001, including the use of Chinese herbal remedies, acupuncture and traumatology manipulative therapy, to analyse use frequencies, the characteristics of TCM users, and the disease categories that were treated by TCM in Taiwan.

Results

At the end of 2001, 6,142,829 (28.4%) among the 21,653,555 valid beneficiaries of the National Health Insurance in Taiwan had used TCM during the year. However, 13,536,266 subjects (62.5%) had used TCM at least once during the whole 6-year period from 1996 to 2001, with a total of 156,224,266 visits (mean 11.5 visits per user). The mean number of TCM users per annum was 5,733,602, with a mean increment of 1,671,476 (29.2%) of new users yearly. Among TCM users, female was higher than male (female:male = 1.13:1), and the age distribution displayed a peak at around the 30s, followed by the 20s and 40s. Chinese herbal remedies (85.9%) were the most common TCM modality used by this population, followed by acupuncture (11.0%) and traumatology manipulative therapies (3.1%). Private TCM clinics provided most of the TCM care (82.6%), followed by private TCM hospitals (12.0%). The top ten major disease categories for TCM visits were diseases of the respiratory system, musculoskeletal system and connective tissue; symptoms, signs and ill-defined conditions; injury and poisoning; diseases of the digestive system, genitourinary system, skin and subcutaneous tissue, nervous system and sense organs, circulatory and endocrine system; nutritional and metabolic diseases; and immunological disorders.

Conclusion

TCM was popular among the Chinese population in Taiwan during the period studied. More than 60% of all subjects had used TCM during the 6-year interval. TCM was widely used by the Chinese population to treat problems and diseases of major human organ systems recognised by western medicine. This study provides information about the use frequencies of TCM and the disease categories treated by TCM, which should be useful for health policy makers and for those considering the integration of TCM and Western medicine.
Clinical and morphological characteristics of head-facial haemangiomas
Authors: Iannetti Giorgio , Torroni Andrea , Chiummariello Stefano , Cavallotti Carlo
Published: February 2007

Background

Haemangiomas of the head or face are a frequent vascular pathology, consisting in an embryonic dysplasia that involves the cranial-facial vascular network. Haemangiomas show clinical, morphological, developmental and structural changes during their course.

Methods

The clinical characteristics of head-facial haemagiomas were studied in 28 individuals (9 males and 19 females) admitted in our Hospital. Sixteen of these patients(n = 16) underwent surgery for the removal of the haemangiomas. All the removed tissues were transferred in experimental laboratories for the staining of microanatomical details, somatic and visceral nerve fibres, adrenergic and catecholaminergic nerve fibres. Beta-adrenergic receptors were died with a fluorescent method. All results were submitted to the quantitative analysis of images and statistical evaluation of the data.

Results

The morphological results revealed numerous micro-anatomical characteristics of the haemangiomatous vessels. The somatic and visceral nerve fibres were poor and located exclusively in the adventitial layer. There was a marked decrease of adrenergic nerve fibres in the haemangiomatous vessels. The fluorescence of catecholaminergic nerve fibres and the overall area of fluorescent structures were also decreased in haemangiomatous vessels. Beta adrenergic receptors are strongly decreased in haemangiomatous vessels. The morphometrical analysis of images and statistical evaluation of the data confirmed all our experimental results.

Conclusion

The catecholaminergic innervation of the human haemangiomatous vessels comprises nerve fibres containing the main catecholaminergic neurotransmitters that are sympathetic in nature. These neurotransmitters are closely related to beta-adrenergic receptors.

The sympathetic nervous system plays a key role in the control of the vascular bed flow and vascular motility in both normal and haemangiomatous vessels.
Effects of overinflation on procollagen type III expression in experimental acute lung injury
Authors: de Carvalho Maria-Eudóxia Pilotto , Dolhnikoff Marisa , Meireles Sibele Inácio , Reis Luiz FernandoLima , Martins Milton Arruda , Deheinzelin Daniel
Published: February 2007

Introduction

In acute lung injury (ALI), elevation of procollagen type III (PC III) occurs early and has an adverse impact on outcome. We examined whether different high-inflation strategies of mechanical ventilation (MV) in oleic acid (OA) ALI alter regional expression of PC III.

Methods

We designed an experimental, randomized, and controlled protocol in which rats were allocated to two control groups (no injury, recruited [alveolar recruitment maneuver after tracheotomy without MV; n = 4 rats] and control [n = 5 rats]) or four injured groups (one exposed to OA only [n = 10 rats] and three OA-injured and ventilated). The three OA-injured groups were ventilated for 1 hour according to the following strategies: LVHP-S (low volume-high positive end-expiratory pressure [PEEP], supine; n = 10 rats, tidal volume [VT] = 8 ml/kg, PEEP = 12 cm H2O), HVLP-S (high volume-low PEEP, supine; n = 10 rats, VT = 20 ml/kg, PEEP = 5 cm H2O), and HVLP-P (high volume-low PEEP, prone; n = 10 rats). Northern blot analysis for PC III and interleukin-1-beta (IL-1β) and polymorphonuclear infiltration index (PMI) counting were performed in nondependent and dependent regions. Regional differences between groups were assessed by two-way analysis of variance after logarithmic transformation and post hoc tests.

Results

A significant interaction for group and region effects was observed for PC III (p = 0.012) with higher expression in the nondependent region for HVLP-S and LVHP-S, intermediate for OA and HVLP-P, and lower for control (group effect, p < 0.00001, partial η2 = 0.767; region effect, p = 0.0007, partial η2 = 0.091). We found high expression of IL-1β (group effect, p < 0.00001, partial η2 = 0.944) in the OA, HVLP-S, and HVLP-P groups without regional differences (p = 0.16). PMI behaved similarly (group effect, p < 0.00001, partial η2 = 0.832).

Conclusion

PC III expression is higher in nondependent regions and in ventilatory strategies that caused overdistension. This response was partially attenuated by prone positioning.
NKT cells direct monocytes into a DC differentiation pathway
Authors: Hegde Subramanya , Chen Xiuxu , Keaton Jason M , Reddington Faye , Besra Gurdyal S , Gumperz Jenny E
Published: February 2007

Monocytes can differentiate into macrophags or dendritic cells (DCs). The processes that promote their differentiation along one pathway rather than the other remain unknown. NKT cells are regulatory T cells that respond functionally to self and foreign antigens presented by CD1d molecules. Hence, in addition to contributing to antimicrobial responses, they may carry out autoreactively activated functions when there is no infectious challenge. However, the immunological consequences of NKT cell autoreactivity remain poorly understood. We show here that human NKT cells direct monocytes to differentiate into immature DCs. The ability to induce monocyte differentiation was CD1d-dependent and appeared specific to NKT cells. Addition of exogenous antigens or costimulation from IL-2 was not required but could enhance the effect. DC differentiation was a result of NKT cell secretion of GM-CSF and IL-13, cytokines that were produced by the NKT cells upon autoreactive activation by monocytes. NKT cells within PBMC samples produced GM-CSF and IL-13 upon exposure to autologous monocytes directly ex vivo, providing evidence that such NKT cell-autoreactive responses can occur in vivo. These results show that when NKT cells are activated by autologous monocytes, they are capable of providing factors that specifically direct monocyte differentiation into immature DCs. Thus, autoreactively activated NKT cells may contribute to the maintenance of the immature DC population, and microbial infection or inflammatory conditions that activate NKT cells further could stimulate them to promote an increased rate of DC differentiation.
Mitogen-Activated Protein Kinases, Inhibitory-κB Kinase, and Insulin Signaling in Human Omental Versus Subcutaneous Adipose Tissue in Obesity
Authors: Bashan Nava , Dorfman Karina , Tarnovscki Tanya , Harman-Boehm Ilana , Liberty Idit F. , Blüher Matthias , Ovadia Shira , Maymon-Zilberstein Tali , Potashnik Ruth , Stumvoll Michael , Avinoach Eliezer , Rudich Assaf
Published: February 2007

MAPKs and inhibitory-κB kinase (IKK) were suggested to link various conditions thought to develop in adipose tissue in obesity (oxidative, endoplasmic reticulum stress, inflammation) with insulin resistance. Yet whether in obesity these kinases are affected in a fat-depot-differential manner is unknown. We assessed the expression and phosphorylation of these kinases in paired omental and abdominal-sc fat biopsies from 48 severely obese women (body mass index > 32 kg/m2). Protein and mRNAs of p38MAPK, ERK, c-Jun kinase-1, and IKKβ were increased 1.5–2.5-fold in omental vs. sc fat. The phosphorylated (activated) forms of these kinases were also increased to similar magnitudes as the total expression. However, phosphorylation of insulin receptor substrate-1 on Ser312 (equivalent of murine Ser307) was not increased in omental, compared with sc, fat. Consistently, fat tissue fragments stimulated with insulin demonstrated that tyrosine phosphorylation and signal transduction to Akt/protein kinase B in omental fat was not inferior to that observable in sc fat. Comparison with lean women (body mass index 23.2 ± 2.9 kg/m2) revealed similar ERK2 and IKKβ expression and phosphorylation in both fat depots. However, as compared with lean controls, obese women exhibited 480 and 270% higher amount of the phosphorylated forms of p38MAPK and c-Jun kinase, respectively, in omental, but not sc, fat, and this expression level correlated with clinical parameters of glycemia and insulin sensitivity. Increased expression of stress-activated kinases and IKK and their phosphorylated forms in omental fat occurs in obesity, potentially contributing to differential roles of omental and sc fat in the pathophysiology of obesity.
Effects of Androgens and Estradiol on Spine Synapse Formation in the Prefrontal Cortex of Normal and Testicular Feminization Mutant Male Rats
Authors: Hajszan Tibor , MacLusky Neil J. , Johansen Jamie A. , Jordan Cynthia L. , Leranth Csaba
Published: February 2007

Recent studies suggest that, in female monkeys and rats, estrogens elicit dendritic spine synapse formation in the prefrontal cortex, an area that, similar to the hippocampus, plays a critical role in cognition. However, whether gonadal hormones induce synaptic remodeling in the male prefrontal cortex remains unknown. Here we report that gonadectomy reduced, whereas administration of 5α-dihydrotestosterone or estradiol-benzoate to castrated male rats increased, the number of medial prefrontal cortical (mPFC) spine synapses, with estradiol-benzoate being less effective than 5α-dihydrotestosterone. To investigate whether the androgen receptor contributes to the mediation of these changes, we compared the response of testicular feminization mutant (Tfm) male rats to that of wild-type animals. The number of mPFC spine synapses in gonadally intact Tfm rats and 5α-dihydrotestosterone-treated castrated Tfm males was considerably reduced compared to intact wild-type animals, whereas the synaptogenic effect of estradiol-benzoate was surprisingly enhanced in Tfm rats. These data are consistent with the hypothesis that remodeling of spine synapses in the prefrontal cortex may contribute to the cognitive effect of gonadal steroids. Our findings in Tfm animals indicate that androgen receptors may mediate a large part of the synaptogenic action of androgens in the mPFC of adult males. However, because this effect of 5α-dihydrotestosterone is not completely lost in Tfm rats, additional mechanisms may also be involved.
Co-assembly of N-type Ca2+ and BK channels underlies functional coupling in rat brain
Authors: Loane David J. , Lima Pedro A. , Marrion Neil V.
Published: February 2007

Activation of large conductance Ca2+-activated potassium (BK) channels hastens action potential repolarisation and generates the fast afterhyperpolarisation in hippocampal pyramidal neurons. A rapid coupling of Ca2+ entry with BK channel activation is necessary for this to occur, which might result from an identified coupling of Ca2+ entry through N-type Ca2+ channels to BK channel activation. This selective coupling was extremely rapid and resistant to intracellular BAPTA, suggesting that the two channel types are close. Using reciprocal co-immunoprecipitation, we found that N-type channels were more abundantly associated with BK channels than L-type channels (CaV1.2) in rat brain. Expression of only the pore-forming α-subunits of the N-type (CaV2.2) and BK (Slo27) channels in a non-neuronal cell-line gave robust macroscopic currents and reproduced the interaction. Co-expression of CaV2.2/CaVβ3 subunits with Slo27 channels revealed rapid functional coupling. By contrast, extremely rare examples of rapid functional coupling were observed with co-expression of CaV1.2/CaVβ3 and Slo27 channels. Action potential repolarisation in hippocampal pyramidal neurons was slowed by the N-type channel blocker ω-conotoxin GVIA, but not by the L-type channel blocker isradipine. These data showed that selective functional coupling between N-type Ca2+ and BK channels provided rapid activation of BK channels in central neurons.
Retrospectives: From Usury To Interest
Authors: Persky Joseph
Published: February 2007

Since the Middle Ages, each epoch has participated in the debate over the conditions in which lending should be prohibited as usury. While disagreements over the definition of usury remain, the debate came to its modern climax on the eve of the industrial revolution, in a well-known interchange between Jeremy Bentham and Adam Smith in the late 1780s. Smith, for all his faith in a system of natural liberty, proved unwilling to let the interest rate float. Bentham argued anything else must reduce total welfare. From a superficial perspective, the entire affair amounts to nothing more than a modest dispute between a failing master (Smith died in 1790) and an over-eager disciple. (Bentham acknowledged in the Defence that all he knew of political economy originated in Smith's works.) Yet the argument struck a fundamental chord. Gilbert K. Chesterton identified Bentham's essay on usury as the very beginning of the “modern world.” I tend to agree.
Ethical conflicts during the social study of clinical practice: the need to reassess the mutually challenging research ethics traditions of social scientists and medical researchers
Authors: Hoeyer Klaus , Dahlager Lisa , Lynöe Niels
Published: February 2007

When anthropologists and other social scientists study health services in medical institutions, tensions sometimes arise as a result of the social scientists and health care professionals having different ideas about the ethics of research. In order to resolve this type of conflict and to facilitate mutual learning, we describe two general categories of research ethics framing: those of anthropology and those of medicine. The latter focuses on protection of the individual through the preservation of autonomy expressed through the requirement of informed consent whereas the former focuses on broader political implications. After providing an example of a conflict, we outline four issues that characterize the occasional clashes between social scientists and medical staff: (1) a discrepancy in the way anthropologists perceive patients and medical staff; (2) ambiguity concerning the role of medical staff in anthropological research; (3) impediments to informed consent in qualitative research projects; and (4) property rights in data. Enhanced dialogue could serve to invigorate the ethical debate in both traditions.
Performance Evaluation of an Automatic Transfer Line with WIP Scrapping During Long Failures
Authors: Liberopoulos George , Kozanidis George , Tsarouhas Panagiotis
Published: February 2007

We develop a model of a failure-prone, bufferless, paced, automatic transfer line in which material flows through a number of workstations in series, receiving continuous processing along each workstation. When a workstation fails, it stops operating, and so do all the other workstations upstream of it. The quality of the material trapped in the stopped workstations deteriorates with time. If this material remains immobilized beyond a certain critical time, its quality becomes unacceptable and it must be scrapped. We develop analytical expressions for important system performance measures for two cases. In the first case, the in-process material has no memory of the quality deterioration that it experienced during previous stoppages, whereas in the second case it has. In both cases, we assume that the workstation uptimes and downtimes follow memoryless distributions. We use the analytical expressions to numerically study the effect of system parameters on system performance. To evaluate the memoryless assumption, we compare the performance of the original model to that of a modified model in which the workstation downtimes do not follow memoryless distributions. The performance of the modified model is obtained via simulation.
Call-Routing Schemes for Call-Center Outsourcing
Authors: Gans Noah , Zhou Yong-Pin
Published: February 2007

Companies may choose to outsource parts, but not all, of their call-center operations. In some cases, they classify customers as high or low value, serving the former with their in-house operations and routing the latter to an outsourcer. Typically, they impose service-level constraints on the time each type of customer waits on hold.

This paper considers four schemes for routing low-value calls between the client company and the outsourcer. These schemes vary in the complexity of their routing algorithms, as well as the sophistication of the telephone and information technology infrastructure they require of the two operations. For three of these schemes, this paper provides a direct characterization of system performance. For the fourth, most complex, scheme the paper provides performance bounds for the important special case in which the service requirements of high- and low-value callers are the same. These results allow the systematic comparison of the performance of the various routing schemes. The results suggest that, for clients with large outsourcing requirements, the simpler schemes that require little client-outsourcer coordination can perform very well.
Dynamic Competitive Newsvendors with Service-Sensitive Demands
Authors: Liu Liming , Shang Weixin , Wu Shaohua
Published: February 2007

When two firms compete for service-sensitive demands based on their product availability, their actions will affect the future market share reallocation. This problem was first studied by Hall and Porteus (2000) using a dynamic game model. We extend their work by incorporating a general demand model, which enables us to obtain properties that reveal the dynamics of the game and the behavior of the players. In particular, we provide conditions under which the market share of a firm has a positive value and give it an upper bound. We further extend the game competition model to an infinite-horizon setting. We prove that there exists a stationary equilibrium policy and that the dynamic equilibrium policy always converges to a stationary equilibrium policy. We demonstrate that demand patterns will dictate how firms compete rationally and show the likely outcomes of the competition.
Monoclonal Antibody-Based Time-Resolved Fluorescence Immunoassays for Daidzein, Genistein, and Equol in Blood and Urine: Application to the Isoheart Intervention Study
Authors: Talbot Duncan CS , Ogborne Richard M , Dadd Tony , Adlercreutz Herman , Barnard Geoff , Bugel Susanne , Kohen Fortune , Marlin Sandra , Piron Jerry , Cassidy Aedin , Powell Jonathan
Published: February 2007

Background: Time-resolved fluorescence immunoassays (TR-FIAs) for phytoestrogens in biological samples are an alternative to mass spectrometric methods. These immunoassays were used to test urine and plasma samples from individuals in a dietary intervention trial aimed at determining the efficacy of dietary isoflavones in reducing the risk of coronary heart disease in postmenopausal women.

Methods: We established murine monoclonal TR-FIA methods for daidzein, genistein, and equol. These assays could be performed manually or adapted to an automated analyzer for high throughput and increased accuracy. Analysis of urine was conducted on nonextracted samples. Blood analysis was performed on nonextracted samples for daidzein, whereas genistein and equol required diethyl-ether extraction.

Results: Comparison of monoclonal TR-FIA, commercial polyclonal antibody–based TR-FIA, and gas chromatography–mass spectrometry showed correlations (r, 0.911–0.994) across the concentration range observed in the Isoheart study (50 mg/day isoflavones). The concentrations of urinary daidzein and genistein observed during intervention demonstrated good compliance, and a corresponding increase in serum daidzein and genistein confirmed bioavailability of the isoflavone-rich foods; 33 of the 117 volunteers (28.2%) were classified as equol producers on the basis of their urinary equol concentration (>936 nmol/L), and significant differences in the numbers of equol producers were observed between Berlin and the 3 other European cohorts studied.

Conclusions: The validated monoclonal TR-FIA methods are applicable for use in large-scale human phytoestrogen intervention studies and can be used to monitor compliance, demonstrate bioavailability, and assess equol producer status.
Quantification of Human β-Defensin-2 and -3 in Body Fluids: Application for Studies of Innate Immunity
Authors: Ghosh Santosh K , Gerken Thomas A , Schneider Keith M , Feng Zhimin , McCormick Thomas S , Weinberg Aaron
Published: February 2007

Background: Human β-defensins (hBDs) are epithelial cell-derived antimicrobial and immunoregulatory cationic peptides. Our objective was to establish an analytical tool to quantify inducible hBD-2 and -3 in body fluids.

Methods: We developed sandwich ELISAs using commercially available capture and detection antibodies and determined optimal assay conditions (with 250 mmol/L CaCl2) to overcome masking by endogenous components of body fluids. We used recombinant hBD as calibrators and for recovery testing.

Results: hBD-2 and -3 detection limits were ∼75 ng/L and ∼3 μg/L, respectively. Mean (SD range) values in saliva samples from healthy donors (n = 60) were 9.5 (1.2–21) μg/L for hBD-2 and 326 (50–931) μg/L for hBD-3. We did not detect hBD-3 in suction blister fluid (BF; n = 10) or bronchoalveolar lavage (BAL; n = 5) from healthy participants. We detected low hBD-2 peptide concentrations in BF and BAL, 0.16 (0.03–0.32) and 0.04 (0–0.049) μg/g total protein, respectively. We observed no correlation of hBD-2 in BF and saliva or BAL and saliva from the same person. In vaginal swabs from healthy women (n = 2), mean hBD-2 and -3 concentrations were 3.42 and 103 μg/g total protein, respectively. Cervicovaginal lavage from the same women contained mean concentrations of 1.46 and 55.5 μg/g total protein.

Conclusion: These ELISA assays can measure inducible hBD peptide concentrations in body fluids by overcoming masking effects of anionic molecules. This approach may therefore be applicable for quantifying these peptides in health and disease.
Retrospective study of monoclonal gammopathies detected in the clinical laboratory of a Spanish healthcare district: 14-year series
Authors: Bergón Enrique , Miravalles Elena
Published: February 2007

Clin Chem Lab Med 2007;45:190–6.