bluuebunny/crossref_metadata_2025 huggingface dataset:
Changing Patient Characteristics and Survival Experience in an Alzheimer’s Center Patient Cohort
Authors: Doody R. , Pavlik V. , Massman Paul , Kenan Mary , Yeh Stephanie , Powell Suzanne , Cooke Norma , Dyer Carmel , Demirovic Jasenka , Waring S. , Chan Wenyaw
Published: August 2005

Background:Large and diverse dementia patient cohorts can further a variety of research programs aimed at improving diagnosis, treatment, and meaningful survival in AD. Method: We recruited 1,502 dementia patients between 1989 and 2002, subclassified using standardized criteria and laboratory procedures, and treated according to established guidelines. Baseline clinical and psychometric measures were repeated annually, in person or by use of a multi-modal telephone follow-up program that included many of the measures obtained at in-person visits. We tracked vital status of all subjects at 6-month intervals and offered autopsies to all participants. We assessed for cohort effects in baseline characteristics by 2-year intervals, examined the characteristics and outcomes for those who remained active compared to those who were eventually lost to follow-up, examined survival times for demographic or diagnostic subgroups, and assessed the accuracy of clinical diagnoses versus neuropathology. Results: The average age at entry, average educational level, and baseline MMSE scores for subjects are increasing over time, and probable AD diagnoses are also increasing. Most (80.6%) subjects have remained active in our Center; those who did not were more likely to have a non-AD diagnosis. Survival averages 5.2 years (CI 4.98–5.37) and is influenced by age and gender, but not by diagnosis of probable versus possible AD. Our diagnostic accuracy is 89.6%, with high sensitivity to the presence of AD (96%). Conclusions: In a large and representative clinical cohort, the demographics of AD are changing over time. Careful analyses of those who continue and those who drop out from follow-up suggest that atypical diagnosis, rather than severity or demographic issues accounts for most of the attrition. Clinicians are likely to encounter increasingly older patients with milder disease, and these trends have implications for the design of clinical trials. Survival from the onset of first symptoms, similar for probable and possible AD cases, may be increasing over time.
Neurophysiological Evaluation of the Optimum Target in Gamma Thalamotomy: Indirect Evidence
Authors: Sato Sumito , Ohye Chihiro , Shibazaki Tohru , Zama Akira , Cai Xiaodong
Published: August 2005

Gamma thalamotomy has been useful for the treatment of Parkinson’s disease and other movement disorders, but it has disadvantages, such as a delayed clinical effect after irradiation and the inaccuracy of targeting because depth recording is not available. Therefore, we sought to determine the optimum target in gamma thalamotomy based on the results of conventional selective thalamotomy with reference to the AC-PC line. To obtain indirect support for the appropriateness of the optimum target, we performed depth recording around the region of the estimated optimum target based on the results of conventional thalamotomy. Four patients with tremor caused by Parkinson’s disease or essential tremor were used as subjects after they gave their fully informed consent. The targets were determined as points 6–8 mm anterior to the posterior commissure, 4–6 mm dorsal to the level of the intercommissural line, and 15–17 mm lateral from the midline. Rhythmic discharge time-locked to tremor and/or kinesthetic neurons were found within the expected target area in all patients. Finally, in all cases, the tremor was abolished without complications after coagulative lesions were made with dual coagulation needles to cover the supposed Vim zone according to the depth recording. We considered that the target point determined in the same way as in gamma thalamotomy is suitable from an anatomophysiological perspective.
Parkinsonian Voice Acoustic Analysis in Real-Time after Stereotactic Thalamotomy
Authors: Nagulic Miryana , Davidovic Jovan , Nagulic Iliya
Published: August 2005

The voice acoustic structure in 7 male patients with Parkinson’s disease was analyzed 1 week before and 1 week after right-sided thalamotomy. The voice signal of the 3-digit number 306 was analyzed in real-time using a digital frequency analyzer. The average value of intensity level during the initial segment of the speech signal became higher after thalamotomy (75.04 vs. 59.24 dB). The voice fundamental frequency increased from 104 to 122 Hz. Before the operation, the energy focus of the speech signal was 73.19 vs. 76.87 dB postoperatively. The voice formants F1 and F2 shifted to the higher energy and frequency regions. The total sound pressure level of the pronounced 3-digit number 306 became two times higher after operation. The overall fluency of pronunciation was improved.
ACE Inhibition Lowers Angiotensin-II-Induced Monocyte Adhesion to HUVEC by Reduction of p65 Translocation and AT1 Expression
Authors: Soehnlein Oliver , Schmeisser Alexander , Cicha Iwona , Reiss Christine , Ulbrich Holger , Lindbom Lennart , Daniel Werner G. , Garlichs Christoph D.
Published: August 2005

Angiotensin-converting enzyme (ACE) inhibitors interfere with several key events of vascular inflammation resulting in impressive reductions in coronary vascular events. However, in human arteries ACE inhibitors block the production of angiotensin II (AngII) incompletely because of the involvement of alternative pathways in local AngII formation. Therefore, our study concentrated on the presumed modulation by ACE inhibition of local AngII-mediated inflammatory actions by a mechanism independent of blockage of AngII formation. We analyzed the effect of the ACE inhibitor ramiprilat on AngII-dependent cell adhesion molecule (CAM) expression and adhesion of monocytic THP-1 cells to endothelial cells. AngII induced upregulation of P-selectin, VCAM-1 and ICAM-1 on endothelial cells via activation of AT1, which was correlated with enhanced THP-1 adhesion in flow chamber assays. Both enhanced adhesion and adhesion molecule expression were significantly reduced by pretreatment with ramiprilat. Ramiprilat reduced AT1 expression on endothelial cells and decreased the AngII-induced p65 translocation into the nucleus. Diminished AT1 expression and adhesion molecule expression in response to ramiprilat treatment were partially reversed after incubation with a bradykinin 2 receptor antagonist, suggesting that elevated bradykinin levels under ACE inhibition may be involved in the beneficial effect of ACE inhibitors. Thus, modulation of the local AngII system by ramiprilat may at least in part contribute to the benefits of ACE inhibition in the treatment of atherosclerotic diseases.
Minimum Audible Angle, Just Noticeable Interaural Differences and Speech Intelligibility with Bilateral Cochlear Implants Using Clinical Speech Processors
Authors: Senn Pascal , Kompis Martin , Vischer Mattheus , Haeusler Rudolf
Published: August 2005

Sound localization and speech intelligibility were assessed in 5 patients implanted bilaterally with Medel C40+ or Medel C40 cochlear implant (CI) systems. The minimum audible angle (MAA) around the head in the horizontal plane was assessed in patients with bilateral CI using white noise bursts of 1000 ms duration presented from a loudspeaker mounted on a rotating boom and compared with the MAA of age-matched normal hearing controls. Spatial discrimination was found to be good in front and in the back of the head with near-normal MAA values (patients: 3–8°, controls: 1–4°). In contrast, poor performance on the sides was found (patients: 30 to over 45°, controls 7–10°). Bilateral CI significantly improved spatial discrimination in front for all patients, when compared with the use of either CI alone. Just noticeable differences (JNDs) in interaural intensity and time were assessed using white noise bursts (1000 ms duration; 50 ms linear ramp). In addition, interaural time JNDs were assessed using click trains (800 ms duration, 40 µs clicks, 50 Hz) and noise bursts in which either only the envelope or only the fine structure was shifted in time. In comparison with normal hearing controls, patients with bilateral CI showed near-normal interaural intensity JNDs but substantially poorer interaural time JNDs depending on the type of stimulus. In contrast to envelope onset/offset cues, interaural fine structure time differences were not perceived by the patients using CI systems employing the continuous interleaved sampling strategy without synchronization between their pulse stimulation times. Speech intelligibility in quiet and CCITT noise from the side (±90°) was assessed using the German HSM sentence test and was significantly better when using bilateral CI in comparison with either unilateral CI, mainly due to a head shadow effect. These favorable results are in agreement with the patients’ subjective experiences assessed with a questionnaire and support the use of bilateral CI.
Evaluation of Vascular Function in Apolipoprotein E Knockout Mice With Angiotensin-Dependent Renovascular Hypertension
Authors: Arruda Roberia M.P. , Peotta Veronica A. , Meyrelles Silvana S. , Vasquez Elisardo C.
Published: August 2005

It is known that the endothelial function is compromised in atherosclerosis and arterial hypertension and that angiotensin is an important factor contributing to both pathophysiologies. The aim of this study was to evaluate the vascular function in a hypercholesterolemia/atherosclerosis model, in the angiotensin II–dependent 2-kidney 1-clip (2K1C) hypertension model and when both conditions coexist. Eight-week-old apolipoprotein E knockout (apoE; n=20) and C57BL/6 (C57; n=20) mice underwent a 2K1C or sham operation and were studied 28 days later. Mean arterial pressure was higher in apoE—2K1C and C57–2K1C (126±3 and 128±3 mm Hg) when compared with the apoE–Sham and C57–Sham (103±2 and 104±2 mm Hg, respectively;
P
<0.05). The vascular reactivity to norepinephrine (NE; 10
−9
to 2×10
−3
mol/L), acetylcholine (ACh), and sodium nitroprusside (SNP; 10
−10
to 10
−3
mol/L) was evaluated in the mesenteric arteriolar bed through concentration–effect curves. NE caused vascular hyper-reactivity in apoE–Sham, apoE–2K1C, and C57–2K1C (maximal response 146±5, 144±5, and 159±4 mm Hg, respectively) compared with C57–Sham (122±7 mm Hg;
P
<0.05). The ACh-induced relaxation was smaller (
P
<0.05) in apoE–2K1C and C57–2K1C (maximal response 53±3% and 46±3%) than in apoE–Sham and C57–Sham mice (78±5% and 73±4%). SNP-induced vascular relaxation showed similar concentration–effect curves in all groups. We conclude that in C57–2K1C mice, the increased reactivity to NE and the decreased endothelium-dependent relaxation contribute to the maintenance of hypertension. The apoE mouse, at early stages of atherosclerosis, shows hyper-reactivity to NE but does not have endothelium dysfunction yet. However, the concurrence of both pathophysiologies does not result in additive effects on the vascular function.
PKCα Activates eNOS and Increases Arterial Blood Flow In Vivo
Authors: Partovian Chohreh , Zhuang Zhenwu , Moodie Karen , Lin Michelle , Ouchi Noriyuki , Sessa William C. , Walsh Kenneth , Simons Michael
Published: August 2005

Endothelial nitric oxide synthase (eNOS) plays an important role in control of vascular tone and angiogenesis among other functions. Its regulation is complex and has not been fully established. Several studies have emphasized the importance of phosphorylation in the regulation of eNOS activity. Although it is commonly accepted that protein kinase C (PKC) signaling inhibits eNOS activity by phosphorylating Thr
497
and dephosphorylating Ser
1179
, the distinct role of different PKC isoforms has not been studied so far. The PKC family comprises roughly 12 different isozymes that activate distinct downstream pathways. The present study was designed to investigate the role of PKCα isoform in regulation of eNOS activity. Overexpression of PKCα in primary endothelial cells was associated with increased eNOS-Ser
1179
phosphorylation and increased NO production. Inhibition of PKCα activity either by siRNA transfection or by overexpression of a dominant negative mutant resulted in a marked decrease in FGF2-induced Ser
1179
phosphorylation and NO production. In vivo, PKCα transduction in rat femoral arteries resulted in a significant increase in the resting blood flow that was suppressed by treatment with
l
-NAME, an eNOS inhibitor. In conclusion, these data demonstrate for the first time that PKCα stimulates NO production in endothelial cells and plays a role in regulation of blood flow in vivo.
Major Risk Factors for Intracerebral Hemorrhage in the Young Are Modifiable
Authors: Feldmann Edward , Broderick Joseph P. , Kernan Walter N. , Viscoli Catherine M. , Brass Lawrence M. , Brott Thomas , Morgenstern Lewis B. , Wilterdink Janet Lee , Horwitz Ralph I.
Published: August 2005

Background and Purpose—

To identify risk factors for intracerebral hemorrhage (ICH), we examined data from the Hemorrhagic Stroke Project (HSP), a case-control study of hemorrhagic stroke among men and women aged 18 to 49 years.

Methods—

Case subjects for the HSP were recruited from 44 hospitals in the United States. Eligibility criteria included an ICH within 30 days preceding enrollment, no history of stroke or known brain lesion. For this report, we focused on patients with primary ICH, defined as not associated with an aneurysm, arteriovenous malformation or other structural lesion. Two control subjects were sought for each case subject. A multivariate regression analysis was performed to determine risk factors for primary ICH.

Results—

A total of 1714 patients with hemorrhagic stroke were identified for participation in the HSP. Of these, 217 cases met the criteria for primary ICH. Cases with primary ICH were matched to 419 controls. Independent risk factors for ICH included hypertension (adjusted odds ratio [OR], 5.71; 95% CI, 3.61 to 9.05), diabetes (adjusted OR, 2.40; 95% CI, 1.15 to 5.01), menopause (adjusted OR, 2.50; 95% CI, 1.06 to 5.88), current cigarette smoking (adjusted OR, 1.58; 95% CI, 1.02 to 2.44), alcoholic drinks≥2/day (adjusted OR, 2.23; 95% CI, 1.16 to 4.32), caffeinated drinks≥5/day (adjusted OR, 1.73; 95% CI, 1.08 to 2.79), and caffeine in drugs (adjusted OR, 3.55; 95% CI, 1.24 to 10.20).

Conclusions—

Among young men and women, the major risk factors for primary ICH can be modified, suggesting that this type of stroke may be preventable. Our findings for caffeine and menopause warrant further study.
Is Prehypertension a Risk Factor for Cardiovascular Diseases?
Authors: Qureshi Adnan I. , Suri M. Fareed K. , Kirmani Jawad F. , Divani Afshin A. , Mohammad Yousef
Published: August 2005

Background and Purpose—

The Joint National Committee on High Blood Pressure identified a new category of blood pressure in adults termed prehypertension. Our objective was to determine the long-term risk of cardiovascular diseases associated with this new category in a well-defined cohort of adults.

Methods—

We evaluated the association of prehypertension (120 to 139/80 to 89 mm Hg) and hypertension (>140/90 mm Hg) with the incidence of atherothrombotic brain infarction (ABI), all strokes, myocardial infarction (MI), and coronary artery disease (CAD) using pooled repeated measures and Cox proportional hazards analyses during follow-up after adjusting for age, gender, obesity, diabetes mellitus, hypercholesterolemia, cigarette smoking, and study period in a cohort of 5181 persons who participated in the Framingham Study.

Results—

Among the 11 116 person observations with a mean follow-up period of 9.9±1.0 years, prehypertension was not associated with an increased risk for ABI (relative risk [RR], 2.2; 95% CI, 0.5 to 9.3). Among the 11 802 person observations with a mean follow-up period of 9.7±1.5 years, prehypertension was associated with an increased risk for MI (RR, 3.5; 95% CI, 1.6 to 7.5). Prehypertension was also associated with an increased risk of CADs among the 11 570 person observations (RR, 1.7; 95% CI, 1.2 to 2.4).

Conclusions—

Prehypertension appears to be associated with an increased risk of MI and CAD but not stroke. Further studies are required to confirm the anticipated benefits of identifying and intervening in persons with prehypertension.
Use of Time by Stroke Patients
Authors: De Wit Liesbet , Putman Koen , Dejaeger Eddy , Baert Ilse , Berman Peter , Bogaerts Kris , Brinkmann Nadine , Connell Louise , Feys Hilde , Jenni Walter , Kaske Christiane , Lesaffre Emmanuel , Leys Mark , Lincoln Nadina , Louckx Fred , Schuback Birgit , Schupp Wilfried , Smith Bozena , De Weerdt Willy
Published: August 2005

Background and Purpose—

Differences exist between European countries in the proportion of patients who die or become dependent after stroke. The aim of the present study was to identify differences in the use of time by stroke patients in 4 rehabilitation centers in 4 European countries.

Methods—

In each of the 4 centers, 60 randomly selected stroke patients were observed at 10-minute intervals using behavioral mapping. Observations took place on 30 weekdays selected at random, on equal numbers of morning, afternoon, and evening sessions. A logistic generalized estimating equation model with correction for differences in case mix and multiple testing was used for the analysis.

Results—

Overall time available from different professions was the highest in the United Kingdom, but patients in the United Kingdom spent on average only 1 hour per day in therapy. This was significantly less than patients in Belgium and Germany, who spent ∼2 hours, and patients in Switzerland who spent ∼3 hours per day in therapy. In all centers, patients spent less than half their time in interactions and >72% of the time in nontherapeutic activities.

Conclusions—

Important differences in the use of time were established, which appeared dependent on management decisions rather than the number of staff available. Patients in the Swiss and German centers spent more time in therapy, possibly because of the structured organization of rehabilitation. Further studies will verify whether this has an effect on outcome.
Community-Based Stroke Incidence in a Scottish Population
Authors: Syme Paul D. , Byrne Anthony W. , Chen Ruoling , Devenny Robert , Forbes John F.
Published: August 2005

Background and Purpose—

The purpose of this study was to determine the incidence and case fatality of stroke in a geographically defined region of Scotland, a nation with a high cardiovascular risk.

Methods—

All strokes occurring in residents of the Scottish Borders (population 106 352) were identified during a 24-month period from 1998 to 2000 using multiple overlapping methods of case-ascertainment. Standard criteria were used to define stroke and case fatality. Stroke subtypes were determined by computer tomography (CT) scan, MRI, or autopsy.

Results—

790 strokes were identified; 596 were first-ever-in-a-lifetime strokes (FES). 91.1% of FES underwent CT scan and/or autopsy. The crude annual incidence rate per 100 000 per year was: 280 (95% CI, 258 to 304) overall, 197 (95% CI 179–217) cerebral infarction, 24 (95% CI 17–31) intracerebral haemorrhage, 11 (95% CI 7–16) subarachnoid haemorrhage and 49 (95% CI 40–59) undetermined stroke. 28 day FES case fatality was 15.9% (95% CI, 13.2 to 19.1) increasing to 26.3% (95% CI, 23.0 to 30.0) at 1 year. Comparing 18 previous worldwide incidence studies with the SBSS showed a similar relative risk of stroke incidence and case fatality for FES and FES subtypes.

Conclusions—

The SBSS crude incidence rate is one of the highest in the world but age-adjusted rates, case fatality and relative risk for all stroke and stroke subtypes were not significantly different from the majority of previous studies. Unlike cardiovascular disease, the Scottish risk of stroke would appear to be similar to other populations worldwide.
Role of the Bloodstream Impacting Force and the Local Pressure Elevation in the Rupture of Cerebral Aneurysms
Authors: Shojima Masaaki , Oshima Marie , Takagi Kiyoshi , Torii Ryo , Nagata Kazuya , Shirouzu Ichiro , Morita Akio , Kirino Takaaki
Published: August 2005

Background and Purpose—

Inertial force of the bloodstream results in the local elevation of intravascular pressure secondary to flow impact. Previous studies suggest that this “impacting force” and the local pressure elevation at the aneurysm may have a large contribution to the development of cerebral aneurysms. The goal of the present study is to evaluate how the bloodstream impacting force and the local pressure elevation at the aneurysm influences the rupture of cerebral aneurysms.

Methods—

A total of 29 aneurysms were created in 26 patient-specific vessel models, and computer simulations were used to calculate pressure distributions around the vessel branching points and the aneurysms.

Results—

Direct impact of the parent artery bloodstream resulted in local elevation in pressure at branch points, and bends in arteries (231.2±198.1 Pa; 100 Pa=0.75 mm Hg). The bloodstream entered into the aneurysm with a decreased velocity after it impacted on the branching points or bends. Thus, the flow impact at the aneurysm occurred usually weakly. At the top or the rupture point of the aneurysm, the flow velocity was always delayed. The local pressure elevation at the aneurysm was 119.3±91.2 Pa.

Conclusions—

The pressure elevation at the area of flow impact and at the aneurysm constituted only 1% to 2% of the peak intravascular pressure. The results suggest that the bloodstream impacting force and the local pressure elevation at the aneurysm may have less contribution to the rupture of cerebral aneurysms than was expected previously.
Tidal Resonance in Juan de Fuca Strait and the Strait of Georgia
Authors: Sutherland Graig , Garrett Chris , Foreman Mike
Published: August 2005

The resonant period and quality factor Q are determined for the semienclosed sea comprising Juan de Fuca Strait, Puget Sound, and the Strait of Georgia. The observed tidal elevation gain and phase change, from the Pacific Ocean to this inland sea, are fitted to the predictions of simple analytic models, which give a resonant period of 17–21 h and a Q of about 2. The low Q value, indicative of a highly dissipative system, is consistent with the need for numerical models for the area to employ large bottom friction coefficients. These include the effects of form drag.
Reevaluating the Roles of Eddies in Multiple Barotropic Wind-Driven Gyres
Authors: Fox-Kemper Baylor
Published: August 2005

Multiple-gyre ocean models have a weaker mean subtropical circulation than single-gyre calculations with the same viscosity and subtropical forcing. Traditionally, this reduction in circulation is attributed to an intergyre eddy vorticity flux that cancels some of the wind input, part of which does not require a Lagrangian mass exchange (theory of dissipative meandering). Herein the intergyre eddy vorticity flux is shown to be a controlling factor in barotropic models at high Reynolds number only with exactly antisymmetric gyres and slip boundary conditions. Almost no intergyre flux occurs when no-slip boundary conditions are used, yet the subtropical gyre is still significantly weaker in multiple-gyre calculations. Sinuous modes of instability present only in multiple gyres are shown here to vastly increase the eddy vorticity transport efficiency. This increase in efficiency reduces the mean circulation necessary for equilibrium. With slip boundary conditions, the intergyre eddy transport is possibly much larger. However, with wind forcing relevant for the ocean—two unequal gyres—a mean flow flux of vorticity rather than an eddy flux between the regions of opposing wind forcing is increasingly important with increasing Reynolds number. A physical rationalization of the differing results is provided by diagnosis of the equilibrium vorticity budget and eddy transport efficiency. Calculations varying 1) boundary conditions, 2) sources and sinks of vorticity, 3) eddy transport efficiency, and 4) the degree of symmetry of the gyres are discussed.
New insights into the tonoplast architecture of plant vacuoles and vacuolar dynamics during osmotic stress
Authors: Reisen Daniel , Marty Francis , Leborgne-Castel Nathalie
Published: August 2005

Background

The vegetative plant vacuole occupies >90% of the volume in mature plant cells. Vacuoles play fundamental roles in adjusting cellular homeostasis and allowing cell growth. The composition of the vacuole and the regulation of its volume depend on the coordinated activities of the transporters and channels localized in the membrane (named tonoplast) surrounding the vacuole. While the tonoplast protein complexes are well studied, the tonoplast itself is less well described. To extend our knowledge of how the vacuole folds inside the plant cell, we present three-dimensional reconstructions of vacuoles from tobacco suspension cells expressing the tonoplast aquaporin fusion gene BobTIP26-1::gfp.

Results

3-D reconstruction of the cell vacuole made possible an accurate analysis of large spanning folds of the vacuolar membrane under both normal and stressed conditions, and suggested interactions between surrounding plastids. Dynamic, high resolution 3-D pictures of the vacuole in tobacco suspension cells monitored under different growth conditions provide additional details about vacuolar architecture. The GFP-decorated vacuole is a single continuous compartment transected by tubular-like transvacuolar strands and large membrane surfaces. Cell culture under osmotic stress led to a complex vacuolar network with an increased tonoplast surface area. In-depth 3-D realistic inspections showed that the unity of the vacuole is maintained during acclimation to osmotic stress. Vacuolar unity exhibited during stress adaptation, coupled with the intimate associations of vacuoles with other organelles, suggests a physiological role for the vacuole in metabolism, and communication between the vacuole and organelles, respectively, in plant cells. Desiccation stress ensuing from PEG treatment generates "double" membrane structures closely linked to the tonoplast within the vacuole. These membrane structures may serve as membrane reservoirs for membrane reversion when cells are reintroduced to normal growth conditions.

Conclusion

3-D processing of a GFP-labeled tonoplast provides compelling visual constructions of the plant cell vacuole and elaborates on the nature of tonoplast folding and architecture. Furthermore, these methods allow real-time determination of membrane rearrangements during stresses.
Trauma-associated growth of suspected dormant micrometastasis
Authors: El Saghir Nagi S , Elhajj Ihab I , Geara Fady B , Hourani Mukbil H
Published: August 2005

Background

Cancer patients may harbor micrometastases that remain dormant, clinically undetectable during a variable period of time. A traumatic event or surgery may trigger the balance towards tumor growth as a result of associated angiogenesis, cytokine and growth factors release.

Case presentation

We describe a patient with non-small lung cancer who had a rapid tumor growth and recurrence at a minor trauma site of his skull bone.

Conclusion

This case is an illustration of the phenomenon of tumor growth after trauma or surgery and its associated cellular mechanisms. This phenomenon deserves further investigation and study.
Effects of alpha fetoprotein on escape of Bel 7402 cells from attack of lymphocytes
Authors: Li Mengsen , Liu Xinhua , Zhou Sheng , Li Pingfeng , Li Gang
Published: August 2005

Background

Involvement of AFP against apoptosis of tumor cell has been implicated in its evasion of immune surveillance. However, the molecular events of immune escape mechanisms are still unknown. The major observations reported here relate to a possible mechanism by which heptoloma Bel 7402 cells escape immune surveillance in vitro.

Methods

Western blotting and a well-characterized cofocal scanning image were performed to analyze the expression of Fas/FasL and caspase-3 in co-cultured Bel 7402 and Jurkat cells.

Results

After co-culture with Jurkat cells, up-regulated Fas and reduced FasL expression could be observed. Treatment with AFP could remarkably inhibit the elevated Fas and, whereas, induce the FasL expression in co-cultured Bel 7402 cells. Cells co-culture could induce the expression of caspase-3 in both cells line. The elevated caspase-3 in Bel 7402 cells was abolished following the treatment of AFP. The expression of caspase-3 was elevated in co-cultured Jurkat cells treated with AFP. No detectable change on the expression of survivin was examined in both cells line. Monoclonal antibody against AFP treatment alone did not obviously influence the growth of cells, as well as the expression of Fas/FasL and caspase-3. However, the effect of AFP could be blocked by antibody.

Conclusions

our results provide evidence that AFP could promote the escape of liver cancer cells from immune surveillance through blocking the caspase signal pathway of tumor cells and triggering the Fas/FasL interaction between tumor cells and lymphocytes.
Iron absorption and oxidant stress during erythropoietin therapy in very low birth weight premature infants: a cohort study
Authors: Friel James K , Aziz Khalid , Andrews Wayne L , Serfass Robert E
Published: August 2005

Background

Iron supplementation may be associated with oxidative stress particularly in premature infants. Our purpose was to examine 1) early supplemental iron during treatment with erythropoietin (EPO) and oxidative stress; 2) enhanced iron absorption during EPO in those infants receiving human milk. Therefore, we determined the effect of erythropoietin plus supplemental iron intakes (4 mg/kg/d) on antioxidant status and iron incorporation.

Methods

Ten very-low-birth-weight infants who were enterally fed and receiving either human milk or formula were followed for 4 weeks during erythropoietin therapy; blood and urine were collected at 3 times; baseline, 2 and 4 weeks later. Once oral feeds commenced the study protocol was initiated. After baseline blood collection, a dose of Fe57 was administered. Two weeks later, a dose of Fe58 was administered as ferrous chloride to determine the effect of human-milk or formula on iron incorporation into RBCs.

Results

Infants started the study at 35 ± 13 days. Incorporation of isotope into RBCs did not differ between formula fed for Fe57 (mean incorporation 8 ± 2.9 n = 3) compared to human-milk fed infants (8.7 ± 5 n = 7) nor for Fe58 (6 ± 2.7 n = 3 vs. 8.6 ± 5 n = 7). Tissue damage measured by malondialdehyde in plasma and F-2 – isoprostanes in urine, did not differ by feed or over time. Neither ability to resist oxidative stress/nor RBC superoxide dismutase differed according to feed or over time.

Conclusion

Data suggest that during erythropoietin therapy antioxidant defence in VLBW infants are capable of dealing with early supplemental iron during treatment with EPO.
Osteopathic manipulative treatment for low back pain: a systematic review and meta-analysis of randomized controlled trials
Authors: Licciardone John C , Brimhall Angela K , King Linda N
Published: August 2005

Background

Osteopathic manipulative treatment (OMT) is a distinctive modality commonly used by osteopathic physicians to complement their conventional treatment of musculoskeletal disorders. Previous reviews and meta-analyses of spinal manipulation for low back pain have not specifically addressed OMT and generally have focused on spinal manipulation as an alternative to conventional treatment. The purpose of this study was to assess the efficacy of OMT as a complementary treatment for low back pain.

Methods

Computerized bibliographic searches of MEDLINE, EMBASE, MANTIS, OSTMED, and the Cochrane Central Register of Controlled Trials were supplemented with additional database and manual searches of the literature.

Six trials, involving eight OMT vs control treatment comparisons, were included because they were randomized controlled trials of OMT that involved blinded assessment of low back pain in ambulatory settings. Data on trial methodology, OMT and control treatments, and low back pain outcomes were abstracted by two independent reviewers. Effect sizes were computed using Cohen's d statistic and meta-analysis results were weighted by the inverse variance of individual comparisons. In addition to the overall meta-analysis, stratified meta-analyses were performed according to control treatment, country where the trial was conducted, and duration of follow-up. Sensitivity analyses were performed for both the overall and stratified meta-analyses.

Results

Overall, OMT significantly reduced low back pain (effect size, -0.30; 95% confidence interval, -0.47 – -0.13; P = .001). Stratified analyses demonstrated significant pain reductions in trials of OMT vs active treatment or placebo control and OMT vs no treatment control. There were significant pain reductions with OMT regardless of whether trials were performed in the United Kingdom or the United States. Significant pain reductions were also observed during short-, intermediate-, and long-term follow-up.

Conclusion

OMT significantly reduces low back pain. The level of pain reduction is greater than expected from placebo effects alone and persists for at least three months. Additional research is warranted to elucidate mechanistically how OMT exerts its effects, to determine if OMT benefits are long lasting, and to assess the cost-effectiveness of OMT as a complementary treatment for low back pain.
Tumor suppressor in lung cancer 1 (TSLC1) alters tumorigenic growth properties and gene expression
Authors: Sussan Thomas E , Pletcher Mathew T , Murakami Yoshinori , Reeves Roger H
Published: August 2005

Background

Introduction of cDNA or genomic clones of the tumor suppressor in lung cancer 1 (TSLC1) gene into the non-small cell lung cancer line, A549, reverses tumorigenic growth properties of these cells. These results and the observation that TSLC1 is down-regulated in a number of tumors suggest that TSLC1 functions as a critical switch mediating repression of tumorigenesis.

Results

To investigate this mechanism, we compared growth properties of A549 with the TSLC1-containing derivative. We found a G1/S phase transition delay in 12.2. Subtractive hybridization, quantitative PCR, and TranSignal Protein/DNA arrays were used to identify genes whose expression changed when TSLC1 was up-regulated. Members of common G1/S phase regulatory pathways such as TP53, MYC, RB1 and HRAS were not differentially expressed, indicating that TSLC1 may function through an alternative pathway(s). A number of genes involved in cell proliferation and tumorigenesis were differentially expressed, notably genes in the Ras-induced senescence pathway. We examined expression of several of these key genes in human tumors and normal lung tissue, and found similar changes in expression, validating the physiological relevance of the A549 and 12.2 cell lines.

Conclusion

Gene expression and cell cycle differences provide insights into potential downstream pathways of TSLC1 that mediate the suppression of tumor properties in A549 cells.
Clinico-pathological features of bladder carcinoma in women in Pakistan and smokeless tobacco as a possible risk factor
Authors: Rafique Muhammad
Published: August 2005

Background

Bladder carcinoma is one of the common urological malignancies occurring worldwide in both sexes. Use of smokeless tobacco by women is common in rural areas of Pakistan. The clinico-pathological features of bladder carcinoma in women and association of smokeless tobacco as a possible risk factor for bladder carcinoma has not been well described in the literature. The objective of the study was to determine the clinico-pathological features of histologically confirmed bladder carcinoma in women and to investigate the role of smokeless tobacco use as a possible risk factor for its development.

Patients and methods

Of the 204 patients (160 male and 44 female M:F ratio 3.6:1) of newly diagnosed bladder carcinoma treated at Nishtar Medical College Hospital Multan from January 1998 to December 2004, the 44 female patients were evaluated with respect to age, clinical presentation, cystoscopic findings, histopathological reports and possible etiological factors. Data were collected and prospectively updated at the time of discharge from hospital and during follow-up in urology out-patient clinic.

Results

Transitional cell carcinoma accounted for all of the bladder carcinoma in women. Median age of the patients was 55 years and 68% patients were under 60 years of age. Majority of patients (88%) presented with hematuria. Eleven (25%) patients had superficial (pTa/pT1) while 33 (75%) patients had muscle invasive (T2–T4) bladder carcinoma. Most (81%) superficial tumors were papillary while muscle invasive tumors had solid configuration at cystoscopy. Of these, 21 (47%) patients had long history of smokeless tobacco use (chewable or moist snuff).

Conclusion

Transitional cell carcinoma is the most common bladder malignancy in women in Pakistan. Many women with bladder carcinoma had long history of use of smokeless tobacco. Majority of patients presented with hematuria and were under 60 years of age. At the time of diagnosis 75% women had muscle invasive bladder carcinoma. In women using smokeless tobacco, the correlation between stage of bladder carcinoma and duration of smokeless tobacco use was significant (p = 0.03). Further studies are needed to clarify the role of smokeless tobacco in the development of bladder carcinoma.
Involvement of a small GTP binding protein in HIV-1 release
Authors: Audoly Gilles , Popoff Michel R , Gluschankof Pablo
Published: August 2005

Background

There is evidence suggesting that actin binding to HIV-1 encoded proteins, or even actin dynamics themselves, might play a key role in virus budding and/or release from the infected cell. A crucial step in the reorganisation of the actin cytoskeleton is the engagement of various different GTP binding proteins. We have thus studied the involvement of GTP-binding proteins in the final steps of the HIV-1 viral replication cycle.

Results

Our results demonstrate that virus production is abolished when cellular GTP binding proteins involved in actin polymerisation are inhibited with specific toxins.

Conclusion

We propose a new HIV budding working model whereby Gag interactions with pre-existing endosomal cellular tracks as well as with a yet non identified element of the actin polymerisation pathway are required in order to allow HIV-1 to be released from the infected cell.
Cough: meeting the needs of a growing field
Authors: Haque Rubaiyat A , Chung Kian Fan
Published: August 2005

There has been a rapidly increasing volume of research undertaken in the field of acute and chronic cough at both basic scientific and clinical levels. However, until now there has been no journal dedicated to publishing work in this field. In this editorial, we introduce the new online, open-access journal entitled Cough which has been founded specifically for this purpose. We also review the clinical problems posed by acute and chronic cough and highlight some of the current issues that are being tackled by cough researchers.
An overview of the sensory receptors regulating cough
Authors: Mazzone Stuart B
Published: August 2005

The cough reflex represents a primary defensive mechanism for airway protection in a variety of mammalian species. However, excessive and inappropriate coughing can emerge as a primary presenting symptom of many airway diseases. Cough disorders are characterized by a reduction in the threshold for reflex initiation and, as a consequence, the occurrence of cough in response to stimuli that are normally innocuous in nature. The current therapeutic strategies for the treatment of cough disorders are only moderately effective. This undoubtedly relates in part to limitations in our understanding of the neural components comprising the cough reflex pathway. The aim of this review is to provide an overview of current concepts relating to the sensory innervation to the mammalian airways, focusing particularly on the sensory receptors that regulate cough. In addition, the review will highlight particular areas and issues relating to cough neurobiology that are creating controversy in the field.
Evaluation of an ambulatory system for the quantification of cough frequency in patients with chronic obstructive pulmonary disease
Authors: Coyle Michael A , Keenan Desmond B , Henderson Linda S , Watkins Michael L , Haumann Brett K , Mayleben David W , Wilson Michael G
Published: August 2005

Background

To date, methods used to assess cough have been primarily subjective, and only broadly reflect the impact of chronic cough and/or chronic cough therapies on quality of life. Objective assessment of cough has been attempted, but early techniques were neither ambulatory nor feasible for long-term data collection. We evaluated a novel ambulatory cardio-respiratory monitoring system with an integrated unidirectional, contact microphone, and report here the results from a study of patients with COPD who were videotaped in a quasi-controlled environment for 24 continuous hours while wearing the ambulatory system.

Methods

Eight patients with a documented history of COPD with ten or more years of smoking (6 women; age 57.4 ± 11.8 yrs.; percent predicted FEV149.6 ± 13.7%) who complained of cough were evaluated in a clinical research unit equipped with video and sound recording capabilities. All patients wore the LifeShirt®system (LS) while undergoing simultaneous video (with sound) surveillance. Video data were visually inspected and annotated to indicate all cough events. Raw physiologic data records were visually inspected by technicians who remained blinded to the video data. Cough events from LS were analyzed quantitatively with a specialized software algorithm to identify cough. The output of the software algorithm was compared to video records on a per event basis in order to determine the validity of the LS system to detect cough in COPD patients.

Results

Video surveillance identified a total of 3,645 coughs, while LS identified 3,363 coughs during the same period. The median cough rate per patient was 21.3 coughs·hr-1(Range: 10.1 cghs·hr-1– 59.9 cghs·hr-1). The overall accuracy of the LS system was 99.0%. Overall sensitivity and specificity of LS, when compared to video surveillance, were 0.781 and 0.996, respectively, while positive- and negative-predictive values were 0.846 and 0.994. There was very good agreement between the LS system and video (kappa = 0.807).

Conclusion

The LS system demonstrated a high level of accuracy and agreement when compared to video surveillance for the measurement of cough in patients with COPD.
Virus overrides the propensity of human CD40L-activated plasmacytoid dendritic cells to produce Th2 mediators through synergistic induction of IFN-γ and Th1 chemokine production
Authors: Bendriss-Vermare Nathalie , Burg Stéphanie , Kanzler Holger , Chaperot Laurence , Duhen Thomas , de Bouteiller Odette , D'agostini Marjorie , Bridon Jean-Michel , Durand Isabelle , Sederstrom Joel M , Chen Wei , Plumas Joël , Jacob Marie-Christine , Liu Yong-Jun , Garrone Pierre , Trinchieri Giorgio , Caux Christophe , Brière Francine
Published: August 2005

Depending on the activation status, plasmacytoid dendritic cells (PDC) and myeloid DC have the ability to induce CD4 T cell development toward T helper cell type 1 (Th1) or Th2 pathways. Thus, we tested whether different activation signals could also have an impact on the profile of chemokines produced by human PDC. Signals that induce human PDC to promote a type 1 response (i.e., viruses) and a type 2 response [i.e., CD40 ligand (CD40L)] also induced PDC isolated from tonsils to secrete chemokines preferentially attracting Th1 cells [such as interferon-γ (IFN-γ)-inducible protein (IP)-10/CXC chemokine ligand 10 (CXCL10) and macrophage inflammatory protein-1β/CC chemokine ligand 4 (CCL4)] or Th2 cells (such as thymus and activation-regulated chemokine/CCL17 and monocyte-derived chemokine/CCL22), respectively. Activated natural killer cells were preferentially recruited by supernatants of virus-activated PDC, and supernatants of CD40L-activated PDC attracted memory CD4+ T cells, particularly the CD4+CD45RO+CD25+ T cells described for their regulatory activities. It is striking that CD40L and virus synergized to trigger the production of IFN-γ by PDC, which induces another Th1-attracting chemokine monokine-induced by IFN-γ/CXCL9 and cooperates with endogenous type I IFN for IP-10/CXCL10 production. In conclusion, our studies reveal that PDC participate in the selective recruitment of effector cells of innate and adaptive immune responses and that virus converts the CD40L-induced Th2 chemokine patterns of PDC into a potent Th1 mediator profile through an autocrine loop of IFN-γ.
Enhanced superoxide release and elevated protein kinase C activity in neutrophils from diabetic patients: association with periodontitis
Authors: Karima M , Kantarci A , Ohira T , Hasturk H , Jones V L , Nam B-H , Malabanan A , Trackman P C , Badwey J A , Van Dyke T E
Published: August 2005

Inflammation and oxidative stress are important factors in the pathogenesis of diabetes and contribute to the pathogenesis of diabetic complications. Periodontitis is an inflammatory disease that is characterized by increased oxidative stress, and the risk for periodontitis is increased significantly in diabetic subjects. In this study, we examined the superoxide (O2−)-generating reduced nicotinamide adenine dinucleotide phosphate-oxidase complex and protein kinase C (PKC) activity in neutrophils. Fifty diabetic patients were grouped according to glycemic control and the severity of periodontitis. Neutrophils from diabetic patients with moderate [amount of glycated hemoglobin (HbA1c) between 7.0% and 8.0%] or poor (HbA1c >8.0%) glycemic control released significantly more O2− than neutrophils from diabetic patients with good glycemic control (HbA1c <7.0%) and neutrophils from nondiabetic, healthy individuals upon stimulation with 4β-phorbol 12-myristate 13-acetate or N-formyl-Met-Leu-Phe. Depending on glycemic status, neutrophils from these patients also exhibited increased activity of the soluble- and membrane-bound forms of PKC, elevated amounts of diglyceride, and enhanced phosphorylation of p47-phox during cell stimulation. In addition, we report a significant correlation between glycemic control (HbA1c levels) and the severity of periodontitis in diabetic patients, suggesting that enhanced oxidative stress and increased inflammation exacerbate both diseases. Thus, hyperglycemia can lead to a novel form of neutrophil priming, where elevated PKC activity results in increased phosphorylation of p47-phox and O2− release.