bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Pharmacokinetics of the PDT Photosensitizers Porfimer Sodium (Photofrin), 2‐[1‐Hexyloxyethyl]‐2‐Devinyl Pyropheophorbide‐a (Photochlor) and 5‐ALA‐Induced Protoporphyrin IX
Authors: Bellnier David A. , Greco William R. , Loewen Gregory M. , Nava Hector , Oseroff Allan R. , Dougherty Thomas J. 
Published: April 2006

AbstractBackground and ObjectivesPhotodynamic therapy (PDT) uses a photosensitizer activated by light, in an oxygen‐rich environment, to destroy malignant tumors. Clinical trials of PDT at Roswell Park Cancer Institute (RPCI) use the photosensitizers Photofrin, Photochlor, and 5‐ALA‐induced protoporphyrin IX (PpIX). In some studies the concentrations of photosensitizer in blood, and occasionally in tumor tissue, were obtained. Pharmacokinetic (PK) data from these individual studies were pooled and analyzed. This is the first published review to compare head‐to‐head the PK of Photofrin and Photochlor.Study Design/Materials and MethodsBlood and tissue specimens were obtained from patients undergoing PDT at RPCI. Concentrations of Photofrin, Photochlor, and PpIX were measured using fluorescence analysis. A non‐linear mixed effects modeling approach was used to analyze the PK data for Photochlor (up to 4 days post‐infusion; two‐compartment model) and a simpler multipatient‐data‐pooling approach was used to model PK data for both Photofrin and Photochlor (at least 150 days post‐infusion; three‐compartment models). Physiological parameters were standardized to correspond to a standard (70 kg; 1.818 m2 surface area) man to facilitate comparisons between Photofrin and Photochlor.ResultsSerum concentration‐time profiles obtained for Photofrin and Photochlor showed long circulating half‐lives, where both sensitizers could be found more than 3 months after intravenous infusion; however, estimated plasma clearances (standard man) were markedly smaller for Photofrin (25.8 ml/hour) than for Photochlor (84.2 ml/hour). Volumes of distribution of the central compartment (standard man) for both Photofrin and Photochlor were about the size (3.14 L, 4.29 L, respectively) of plasma volume, implying that both photosensitizers are almost 100% bound to serum components. Circulating levels of PpIX were generally quite low, falling below the level of instrument sensitivity within a few days after topical application of 5‐ALA.ConclusionWe have modeled the PK of Photochlor and Photofrin. PK parameter estimates may, in part, explain the relatively long skin photosensitivity attributed to Photofrin but not Photochlor. Due to the potential impact and limited experimental PK data in the PDT field further clinical studies of photosensitizer kinetics in tumor and normal tissues are warranted. Lasers Surg. Med. © 2006 Wiley‐Liss, Inc.
Clinical and histological healing pattern of peri‐implantitis lesions following non‐surgical treatment with an Er:YAG laser
Authors: Schwarz Frank , Bieling Katrin , Nuesry Enaas , Sculean Anton , Becker Jürgen 
Published: April 2006

AbstractBackground and ObjectivesThe aim of the present study was to assess clinical and histo‐pathological healing pattern of peri‐implantitis lesions following non‐surgical treatment with an Er:YAG laser (ERL).Study Design/Materials and MethodsTwelve patients suffering from peri‐implantitis (n = 12 implants) received a single episode of non‐surgical instrumentation using ERL (12.7 J/cm2). Assessment of clinical parameters (plaque index (PI), bleeding on probing (BOP), probing pocket depth, gingival recession (GR), and clinical attachment level (CAL)), surgical defect examination, and histo‐pathological examination of peri‐implant tissue biopsies was performed after 1, 3, 6, 9, 12, and 24 months.ResultsAll patients exhibited improvements of all clinical parameters investigated. However, histo‐pathological examination of tissue biopsies revealed a mixed chronic inflammatory cell infiltrate (macrophages, lymphocytes, and plasma cells) which seemed to be encapsulated by deposition of irregular bundles of fibrous connective tissue showing increased proliferation of vascular structures.ConclusionIt was concluded that a single course of non‐surgical treatment of peri‐implantitis using ERL may not be sufficient for the maintenance of failing implants. Lasers Surg. Med. © 2006 Wiley‐Liss, Inc.
Simulation of flow between concentric rotating spheres. Part 2. Transitions
Authors: Marcus Philip S. , Tuckerman Laurette S. 
Published: April 2006

We examine the transitions among the steady-state axisymmetric spherical Couette flows with zero, one, and two vortices per hemisphere. The steady flows are reflection symmetric with respect to the equator, but some of the transitions that we find break this symmetry. This is the first study to reproduce numerically the transitions to the one-vortex flow from the zero- and two-vortex flows. In our study, we use a numerical initial-value code to: (i) compute the bifurcation diagrams of the steady (stable and unstable) states, (ii) solve for the most unstable or least stable linear eigenmode and eigenvalue of a steady state, (iii) calculate the velocity field as a function of time during both the linear and nonlinear stages of the transitions, and (iv) determine the energy transfer mechanism into and out of the antireflection-symmetric components of the flow during the transitions.Our study provides the explanation of the laboratory observation that some transitions occur only when the inner sphere of the Couette-flow apparatus is accelerated or decelerated quickly, whereas other transitions occur only when the acceleration is slow.
Experimental studies of wakes behind circularly capped bubbles
Authors: Bessler W. F. , Littman H. 
Published: April 2006

The wake behind a circularly capped bubble rising in fluids of different viscosity has been experimentally investigated using aspirin powder for flow visualization and high-speed photography synchronized with pressure-time measurements to measure the pressure field. The bubble plus its primary wake with a cusped tail is observed to contain symmetric pressure minima within the primary wake. Adjacent to the boundary wake is a free shear layer which contains large-scale vortices generated near the bubble rim that remain essentially stationary to an observer in the laboratory reference frame. The change in wake geometry and the transition to an ellipsoidal bubble shape as fluid viscosity increases is documented.The airfoil shape of the boundary of the circularly capped bubble and its closed primary wake is modelled using a Joukowski transformation in which the Joukowski constant is adjusted to match the experimental and potential-flow pressures along the bubble cap. The model successfully predicts the frontal pressure field, and the wake size and shape. The Davies & Taylor bubble-cap boundary condition is also verified.
The structure of a shear layer bounding a separation region. Part 2. Effects of free-stream turbulence
Authors: Castro I. P. , Haque A. 
Published: April 2006

Detailed measurements throughout the separated region behind a flat plate placed normal to a turbulent stream are reported. A long, central, downstream splitter plate prevented vortex shedding and led to a relatively extensive reversed flow region. Mean flow and turbulence data are compared with results obtained in the (nominal) absence of free-stream turbulence, and attention is concentrated on the changes in the shear-layer structure resulting from the different nature of the upstream flow.Many aspects of the results confirm those obtained recently by other workers. Free-stream turbulence enhances shear-layer entrainment rates, reduces the distance to reattachment and modifies the relatively low-frequency ‘flapping’ motion of the shear layer. In addition, however, extensive use of pulsed wire anemometry has allowed detailed measurements of the turbulence structure throughout the flow and it is shown that this is also modified significantly by the stream turbulence.
Genetically engineered Bifidobacterium longum for tumor‐targeting enzyme‐prodrug therapy of autochthonous mammary tumors in rats
Authors: Sasaki Takayuki , Fujimori Minoru , Hamaji Yoshinori , Hama Yoshihisa , Ito Ken‐ichi , Amano Jun , Taniguchi Shun’ichiro 
Published: April 2006

A fundamental obstacle in systemic therapy for cancer patients is the specific targeting of therapy directly to solid tumors. A strain of the domestic bacterium Bifidobacterium longum, which is non‐pathogenic and anaerobic, showed selective localization to and proliferation within solid tumors after systemic application. Here, we propose a novel approach to cancer gene therapy in which anaerobic and non‐pathogenic bacteria of the genus B. longum are used to achieve tumor‐specific gene delivery and enzyme‐prodrug therapy. We constructed a plasmid, pBLES100‐S‐eCD, which included eCD. Transfected B. longum produced CD in hypoxic tumors and achieved tumor site‐specific conversion of 5‐FC to 5‐FU. Furthermore, we demonstrated antitumor efficacy in rat bearing autochthonous mammary tumors injected with the transfected B. longum directly or intravenously. This method was confirmed to be effective for enzyme‐prodrug therapy not only by intratumoral injection but also by systemic administration. To estimate the toxicity of this bacterial vector, the systemic immunogenicity was evaluated by ASA reaction and the anaphylactic activity of IgG was evaluated by PCA reaction in guinea pigs. In the ASA reaction, no anaphylaxis symptoms were observed in any immunized guinea pigs injected with transfected B. longum. In the PCA reaction, B. longum/S‐eCD specific‐PCA‐induced antibody was not detected. Thus, we proposed that anaerobic bacteria of the genus B. longum were an attractive and safe tumor‐targeting vector and transfected B. longum was a potential anticancer agent that could effectively and specifically treat solid tumors. (Cancer Sci 2006; 97: 649–657)
Effects of menthol on the triggering of the swallowing reflex in elderly patients with dysphagia
Authors: Ebihara Takae , Ebihara Satoru , Watando Aya , Okazaki Tatsuma , Asada Masanori , Ohrui Takashi , Yamaya Mutsuo , Arai Hiroyuki 
Published: April 2006

AimsTo investigate the effect of menthol on swallowing reflex sensitivity in elderly patients with dysphagia.Methods and resultsThe swallowing reflex sensitivity of institutionalized elderly patients was evaluated as a latent time of swallowing reflex (LTSR), induced by the injection of 1 ml solution into the pharynx. LTSR was significantly shortened in a concentration‐dependent manner, from 13.8 s [95% confidence interval (CI) 11.1, 16.5] by distilled water to 9.4 s (95% CI 7.1. 11.8) by 10−2m menthol.ConclusionUsing menthol with elderly patients with dysphagia may improve the sensitivity of their swallowing reflex, resulting in prevention of aspiration pneumonia.
Expression of Toll-like receptors and their association with cytokine responses in peripheral blood mononuclear cells of children with acute rotavirus diarrhoea
Authors: Xu J , Yang Y , Sun J , Ding Y , Su L , Shao C , Jiang B 
Published: April 2006

SummaryTo understand virus and host interactions and host responses to rotavirus infection in children, we analysed by real-time polymerase chain reaction (PCR) the expression of mRNA for five Toll-like receptors (TLRs) (TLR2, TLR3, TLR4, TLR7 and TLR8) and four T helper (Th)1 and Th2 cytokines [interleukin (IL)-2, IL-12, interferon (IFN)-γ and IL-4) in peripheral blood mononuclear cells (PBMC) of children with acute rotavirus diarrhoea. We observed significantly higher expression of genes encoding TLR2, TLR3, TLR4, TLR7 and TLR8 in PBMC of 41% (31/75) patients within 3 days of illness onset than those in healthy children. After 3 days of illness onset, only TLR3 and TLR8 mRNA expressions were still significantly (P &lt; 0.05) increased in 59% (44/75) children with diarrhoea. We also observed significantly (P &lt; 0.05) elevated expression of IL-12p40 and IFN-γ in PBMC of patients during the entire period of illness and the first 3 days of illness, respectively. We further demonstrated a weak but significant association between elevated levels of gene expression of four TLRs (TLR2, TLR3, TLR4 and TLR8) and IFN-γ. Our results suggest that multiple TLRs may modulate the immune response in the acute phase of rotavirus infection and play a role in the activation of IFN-γ.
Assessment of need for psychosocial interventions in an Asian population of carers of patients with schizophrenia
Authors: Pearce Kenneth , McGovern John , Barrowclough Christine 
Published: April 2006

Aim.  This paper reports on a study to establish the profile of need for psychosocial family interventions and to examine the concurrent validity of the Relatives’ Cardinal Needs Schedule with an Asian population of carers in England, UK.Background.  Although psychosocial interventions for schizophrenia have a strong evidence base, little is known of the needs of Asian families. A cardinal need is indicative of the existence of a problem causing the carer a strain for which the carer is willing to co‐operate if help is offered and for which systematic help has not been provided in the last 12 months.Methods.  The Relatives’ Cardinal Needs Schedule was used to assess needs in a small randomly selected sample of Asian carers in one English locality and to compare the results with independent measures of patient symptoms and carer distress.Results.  Feedback from carers indicated that the Relatives’ Cardinal Needs Schedule was culturally acceptable and appropriate to their needs. There was evidence for the validity of the assessment in that there were large and statistically significant associations between the number of needs detected by the Relatives’ Cardinal Needs Schedule and independent measures of both carer distress (as measured by the 28 item General Health Questionnaire) and patient symptom severity (as reliably assessed from case notes).Conclusion.  The Relatives’ Cardinal Needs Schedule may prove useful for nurses and service managers in establishing the need for psychosocial family interventions amongst Asian families in the United Kingdom.
Impact of follow‐up time and re‐measurement of the electrocardiogram and conventional cardiovascular risk factors on their predictive value for myocardial infarction
Authors: MÖLLER CHRISTINA STRÖM , ZETHELIUS BJÖRN , SUNDSTRÖM JOHAN , LIND LARS 
Published: April 2006

Abstract.Objective.  To explore if the predictive power of mid‐life electrocardiogram (ECG) abnormalities and conventional cardiovascular risk factors for future myocardial infarction, change over a 30‐year follow‐up period and if repeated examination improves their predictive power.Design and setting.  Longitudinal population‐based study.Participants.  A total of 2322 men aged 50 years, with a total follow‐up period of 30 years and 1221 subjects were re‐examined at age of 70 years.Main outcome measure.  Risk for fatal and nonfatal myocardial infarction (n = 470) analysed at age 50 and 70 years, and separately for 1–10, 11–20 and 21–30 years after first examination. Investigations included a 12‐lead ECG, blood pressure, body mass index, smoking habits, and glucose and lipid variables.Results.  Whilst high blood pressure and dyslipidaemia variables, such as apolipoprotein B/apolipoprotein A1 ratio, measured at age 50 showed an almost unchanged predictive power during the three decades of follow up, ECG abnormalities, insulin and BMI were only significant predictors during the two first decades of follow up. Despite increased prevalences of ECG abnormalities and obesity with age, they predicted for future myocardial infarction in midlife only whilst fasting insulin and smoking regained their predictive power when re‐measured at age 70.Conclusion.  Whilst hypertension and dyslipidaemia were consistent as risk factors, length of follow‐up period and age at baseline investigations affected the predictive power of ECG abnormalities, fasting insulin, BMI and smoking. In the elderly, ECG abnormalities did not contribute to the prediction of myocardial infarction but smoking and fasting insulin may be important in the pathophysiology leading to MI especially in this age group.
Orchestrating bacterial cell morphogenesis
Authors: Carballido‐López Rut 
Published: April 2006

SummaryMreB proteins are bacterial homologues of actin that directly determine cell shape and are involved in a range of other cellular processes in non‐spherical bacteria. Like F‐actin in eukaryotes, MreBs self‐assemble into dynamic filamentous structures that are essential for cell viability. Recent studies have demonstrated that the MreB cytoskeletal scaffold governs shape determination by controlling functions related to the bacterial cell wall (probably by recruiting and directing peptidoglycan‐synthesizing and modifying proteins). Here I consider general implications for bacterial morphogenesis, and the basis for differences in wall expansion and cylindrical cell shape, based on recent studies aimed to determine the role of MreBs in bacteria with different modes of growth.
Crystal structure of the DNA‐binding domain of BldD, a central regulator of aerial mycelium formation in Streptomyces coelicolor A3(2)
Authors: Kim In‐Kwon , Lee Chang‐Jin , Kim Min‐Kyu , Kim Jeong‐Mok , Kim Ji‐Hye , Yim Hyung‐Soon , Cha Sun‐Shin , Kang Sa‐Ouk 
Published: April 2006

SummaryBldD is a central regulator of the developmental process in Streptomyces coelicolor. The 1.8 Å resolution structure of the DNA‐binding domain of BldD (BldDN) reveals that BldDN forms a compact globular domain composed of four helices (α1–α4) containing a helix‐turn‐helix motif (α2–α3) resembling that of the DNA‐binding domain of lambda repressor. The BldDN/DNA complex model led us to design a series of mutants, which revealed the important role of α3 and the ‘turn’ region between α2 and α3 for DNA recognition. Based on the fact that BldD occupies two operator sites of bldN and whiG and shows significant disparity in the affinity toward the two operator sites when they are disconnected, we propose a model of cooperative binding, which means that the binding of one BldD dimer to the high affinity site facilitates that of the second BldD dimer to the low affinity site. In addition, structural and mutational investigation reveals that the Tyr62Cys mutation, found in the first‐identified bldD mutant, can destabilize BldD structure by disrupting the hydrophobic core.
Antigenic variation by Borrelia hermsii occurs through recombination between extragenic repetitive elements on linear plasmids
Authors: Dai Qiyuan , Restrepo Blanca I. , Porcella Stephen F. , Raffel Sandra J. , Schwan Tom G. , Barbour Alan G. 
Published: April 2006

SummaryThe relapsing fever agent Borrelia hermsii undergoes multiphasic antigenic variation through gene conversion of a unique expression site on a linear plasmid by an archived variable antigen gene. To further characterize this mechanism we assessed the repertoire and organization of archived variable antigen genes by sequencing ∼85% of plasmids bearing these genes. Most archived genes shared with the expressed gene a ≤ 62 nucleotide (nt) region, the upstream homology sequence (UHS), that surrounded the start codon. The 59 archived variable antigen genes were arrayed in clusters with 13 repetitive, 214 nt long downstream homology sequence (DHS) elements distributed among them. A fourteenth DHS element was downstream of the expression locus. Informative nucleotide polymorphisms in UHS regions and DHS elements were applied to the analysis of the expression site of relapse serotypes from 60 infected mice in a prospective study. For most recombinations, the upstream crossover occurred in the UHS’s second half, and the downstream crossover was in the DHS’s second half. Usually the closest archival DHS element was used, but occasionally a more distant DHS was employed. The downstream extragenic crossover site in B. hermsii contrasts with the downstream extragenic crossover site for antigenic variation in African trypanosomes.
Period–colour and amplitude–colour relations in classical Cepheid variables – IV. The multiphase relations
Authors: Ngeow Chow-Choong , Kanbur Shashi M. 
Published: April 2006

Abstract
The superb phase resolution and quality of the Optical Gravitational Lensing Experiment (OGLE) data on the Large Magellanic Cloud (LMC) and Small Magellanic Cloud (SMC) Cepheids, together with existing data on Galactic Cepheids, are combined to study the period–colour (PC) and amplitude–colour (AC) relations as a function of pulsation phase. Our results confirm earlier work that the LMC PC relation (at mean light) is more consistent with two lines of differing slopes, separated at a period of 10 d. However, our multiphase PC relations reveal much new structure which can potentially increase our understanding of Cepheid variables. These multiphase PC relations provide insight into why the Galactic PC relation is linear but the LMC PC relation is non-linear. This is because the LMC PC relation is shallower for short (log P &lt; 1) and steeper for long (log P &gt; 1) period Cepheids than the corresponding Galactic PC relation. Both of the short- and long-period Cepheids in all three galaxies exhibit the steepest and shallowest slopes at phases around 0.75–0.85, respectively. A consequence is that the PC relation at phase ∼ 0.8 is highly non-linear. Further, the Galactic and LMC Cepheids with log P &gt; 1 display a flat slope in the PC plane at phases close to the maximum light. When the LMC period–luminosity (PL) relation is studied as a function of phase, we confirm that it changes with the PC relation. The LMC PL relation in V and I band near the phase of 0.8 provides compelling evidence that this relation is also consistent with two lines of differing slopes joined at a period close to 10 d.
Evidence that differential gene expression between the halophyte, Thellungiella halophila, and Arabidopsis thaliana is responsible for higher levels of the compatible osmolyte proline and tight control of Na+ uptake in T. halophila
Authors: KANT SURYA , KANT PRAGYA , RAVEH ERAN , BARAK SIMON 
Published: April 2006

ABSTRACTSalt‐sensitive glycophytes and salt‐tolerant halophytes employ common mechanisms to cope with salinity, and it is hypothesized that differences in salt tolerance arise because of changes in the regulation of a basic set of salt tolerance genes. We explored the expression of genes involved in two key salt tolerance mechanisms in Arabidopsis thaliana and the halophytic A. thaliana relative model system (ARMS), Thellungiella halophila. Salt overly sensitive 1 (SOS1) is a plasma membrane Na+/H+ antiporter that retrieves and loads Na+ ions from and into the xylem. Shoot SOS1 transcript was more strongly induced by salt in T. halophila while root SOS1 was constitutively higher in unstressed T. halophila. This is consistent with a lower salt‐induced rise in T. halophila xylem sap Na+ concentration than in A. thaliana. Thellungiella halophila contained higher unstressed levels of the compatible osmolyte proline than A. thaliana, while under salt stress, T. halophila accumulated more proline mainly in shoots. Expression of the A. thaliana ortholog of proline dehydrogenase (PDH), involved in proline catabolism, was undetectable in T. halophila shoots. The PDH enzyme activity was lower and T. halophila seedlings were hypersensitive to exogenous proline, indicating repression of proline catabolism in T. halophila. Our results suggest that differential gene expression between glycophytes and halophytes contributes to the salt tolerance of halophytes.