bluuebunny/crossref_metadata_2025 huggingface dataset:
Caractéristiques vocaliques intrinsèques et co-intrinsèques dans les dysarthries cérébelleuse et parkinsonienne
Authors: Baudelle E. , Vaissière J. , Renard J.L. , Roubeau B. , Chevrie-Müller C.
Published: May 2003

Les caractéristiques intrinsèques et co-intrinsèques des voyelles ont été peu étudiées dans les dysarthries neurologiques. Cette étude évalue ces paramètres, en confrontant à une population de 10 sujets témoins 4 sujets dysarthriques cérébelleux atteints d’un syndrome cérébelleux dégénératif et 4 sujets dysarthriques parkinsoniens atteints de la maladie de Parkinson. Une rééducation intensive de la parole de type Lee Silverman (LSVT) a par ailleurs été appliquée à un sujet parkinsonien appartenant à la population étudiée, avec une évaluation avant et après rééducation. Les mesures acoustiques appréciaient la durée et la fréquence des voyelles [a, i, u] au sein de contextes consonantiques variés, leurs valeurs formantiques ainsi que la durée des phrases. Les résultats montrent des altérations différentes selon le type de dysarthrie, ainsi que des formes de transposition de contrastes. La rééducation du sujet dysarthrique parkinsonien a pour effet de restaurer des contrastes sub-normaux.
A Comparison of Voice Quality Ratings Made by Japanese and American Listeners Using the GRBAS Scale
Authors: Yamaguchi Hiroya , Shrivastav Rahul , Andrews Moya L. , Niimi Seiji
Published: May 2003

The GRBAS scale is a widely used method for perceptual evaluation of voice quality. Two linguistically diverse groups of listeners (Japanese and American) rated 35 voice samples using the GRBAS scale. The ratings obtained from the two groups were compared to determine if the different linguistic background affected the use of the GRBAS scale. Results show that there are no significant differences between the Japanese and American listeners in the use of the Grade, Roughness and Breathiness scales. Ratings on the Asthenia and Strain scales, however, were different between the two groups of listeners. Despite these discrepancies, the GRBAS scale may be an excellent tool for perceptual evaluation of voice quality by linguistically diverse groups.
Endotoxins and Allergy: Lessons from the Murine Model
Authors: Gerhold K. , Blümchen K. , Bock A. , Franke A. , Avagjan A. , Hamelmann E.
Published: May 2003

Exposure early in life to organic dusts containing immunomodulatory components such as endotoxins and immunizing components such as aeroallergens may greatly influence whether subsequent encounters with allergens lead rather to sensitization or unresponsiveness. We investigated the effects of endotoxin in the context of allergen-mediated immune responses in a murine model of allergen sensitization. Systemic sensitization with ovalbumin induced high serum levels of allergen-specific IgE, predominant Th2-type cytokine production, eosinophilic airway inflammation and in vivo airway hyperreactivity. Endotoxins were either applied systemically prior to sensitization, or via the airways prior to airway challenges, or by repeated inhalation during the first weeks of life prior to subsequent sensitization. Different effects of endotoxins on allergen-induced immune responses may be attributed to differences in dosing, route of application, time relationship with allergen sensitization and the concurrent exposure to endotoxin and allergen. The results of these studies may help to define the effects of endotoxin on allergen-mediated immune reactions and to further delineate the important interrelationships between environment and disease development. Finally, this may lead to new strategies in the prevention and treatment of allergic diseases.
Animal Models of Chronic Obstructive Pulmonary Disease: Some Critical Remarks
Authors: Fehrenbach H.
Published: May 2003

A variety of animal models of chronic obstructive pulmonary disease (COPD) are available, comprising elastase instillation or inhalation of noxious agents and genetic models like mouse mutants, gene-targeted and transgenic mice. The present review discusses some critical aspects which should be taken into account when evaluating these animal models of human COPD. Critical aspects related to the human disease itself: (1) diagnosis is largely symptom based, and symptoms cannot be mimicked in animals; (2) COPD is not a well-defined entity, but comprises patients with variable contribution of chronic bronchitis, mucus hypersecretion and emphysema, and (3) various factors contribute to the development of COPD, indicating that different pathways may converge into a single endpoint. Critical aspects related to the animals used: (1) species-, strain- and gender-related differences in lung structure and function preclude mimicking some features of the human disease; (2) genetic models frequently present with air space enlargement as a result of the disturbance of early postnatal alveolization (conditionally controlled transgenic animals are recommended); (3) inhalation models frequently use young animals during lung growth, which may preclude distinguishing effects owing to growth retardation or to loss of existing alveolar walls; (4) inhalation of noxious agents may result in reduction of food intake and loss of body weight, which itself may result in emphysema, and (5) the presence of emphysema cannot be concluded based on measurement of air space enlargement alone, but should include the determination of total alveolar surface area.
High Prevalence of Transfusion-Transmitted Virus Infection in Patients with Chronic Liver Diseases in an Endemic Area of Hepatitis B and C Virus
Authors: Savas M. Cemil , Guney Cakir , Kadayıfcı Abdurrahman , Balkan Ayhan , Koruk Mehmet , Kubar Ayhan , Uygun Ahmet
Published: May 2003

Objective: To determine the prevalence and clinical impact of transfusion-transmitted virus (TTV) DNA in patients with chronic liver diseases in the Southeast Anatolia region of Turkey where hepatitis B and C viral infections are endemic. Subjects and Methods: Patients diagnosed with chronic liver disease by clinical, biochemical and histologic means were enrolled in the study. Serum samples of 60 patients (19 males, 41 females) with chronic liver diseases, and of 45 healthy volunteer blood donors as a control group were collected. The chronic liver disease group consisted of 11 patients with hepatitis B, 44 with hepatitis C and 5 with chronic liver disease of unknown etiology. Presence of TTV DNA was investigated by the polymerase chain reaction. Using a scoring system histological grading of inflammation and staging of fibrosis were performed only in the chronic hepatitis C group. Results: TTV DNA was detected in 47 (78%) patients with chronic liver disease and 5 (11%) volunteers in the control group. The difference was statistically significant (p < 0.001). Ten of the 11 (91%) patients with hepatitis B, 32 of 44 (73%) of those with hepatitis C-related chronic liver disease, and 5 of 5 (100%) of the patients with cryptogenic liver disease were positive for TTV DNA. Conclusion: TTV is highly prevalent in patients with chronic liver diseases in Southeast Anatolia, Turkey but no pathogenic effect attributable to TTV infection was detected.
Maxillary Canine-to-First Premolar Bilateral Transposition in a Female with Down Syndrome
Authors: Al-Mutawa Sabiha A. , Shyama Maddi , Honkala Eino
Published: May 2003

Objective and Importance: To report a case of the bilateral transposition of the maxillary canines with the premolars in a 17-year-old female with Down syndrome. Clinical Presentation and Intervention: A 17-year-old female presented with moderate mental retardation; she was short and of small stature, and she had a round cherubic face and a broad forehead. Clinical intraoral examination revealed bilateral malpositions of the maxillary canines and premolars as transposition. She had an open mouth, macroglossia and a protruding tongue. The case required the combined orthodontic and prosthetic treatment to achieve an acceptable morphologic and esthetic occlusion. However, the parents refused to accept the proposed treatment. Extractions of the roots and caries treatment were done as these were considered priority for the patient. Conclusion: This rare and severe positional anomaly represents an orthodontic challenge and its correction involves treatment risk and requires a great deal of control and carefully applied mechanics.
Longitudinal Study of the Three-Dimensional Development of Subsurface Enamel Lesions during in vitro Demineralisation
Authors: Dowker S.E.P. , Dowker S.E.P. , Elliott J.C. , Elliott J.C. , Davis G.R. , Davis G.R. , Wassif H.S. , Wassif H.S.
Published: May 2003

A longitudinal study was made of the 3D development of subsurface enamel lesions in whole human molars. X-ray microtomography (XMT) was used to measure the 3D distribution of linear attenuation coefficients in the tissue at 8–15 stages during cumulative times of 36–107 days demineralisation through ∼1-mm-wide windows. Although lesion morphology was consistent with preferential anisotropic dissolution parallel to enamel prisms at the advancing front, detail (at a scale of ∼100 µm) varied in relation to exposed surface sites separated by <1 mm. The distribution of mineral in the most superficial region varied across the exposed face of each lesion. Within lesions, localised foci of low mineral concentration (at a scale of ∼200 µm) retained their general form through successive stages of demineralisation before coalescing. The most advanced regions within a lesion seemed to correspond with surface regions with lowest mineral concentration. These findings indicate that local variations in fractional pore volume of partially demineralised enamel influence the subsequent spatial development of lesions.
In vivo Cariostatic Effect of Black Copper Cement on Carious Dentine
Authors: Foley Jennifer , Foley Jennifer , Blackwell Alison , Blackwell Alison
Published: May 2003

This study compared the effect of a copper phosphate cement (BCC) and a conventional glass ionomer cement (GIC) on carious dentine that remains under restorations in vivo. Using a split-mouth design, 45 primary molar pairs with dentine caries were sampled microbiologically. Without further removal of carious dentine, the molar pairs were randomly allocated to three restorative groups: (1) one cavity was lined with BCC and restored with GIC and the other was kept under review as an untreated control; (2) one cavity was restored with GIC, whilst the other was kept under review; (3) one cavity was lined with BCC and restored with GIC, whilst the other was filled with GIC. The dentine was re-sampled microbiologically at 1 month (30 pairs) and 6 months (15 pairs). BCC demonstrated a significant effect on the total anaerobic count over 1 month, when paired with both the control and GIC, whereas the antibacterial effects of GIC compared with no treatment were not statistically significant. In addition, BCC performed significantly better than no treatment in reducing mutans streptococci and lactobacilli over 1 month. Over 6 months, BCC caused a significantly greater reduction in mutans streptococci than GIC. In conclusion, BCC demonstrated a significant antibacterial effect on carious dentine in vivo.
Non-Mutans Streptococci in Patients Receiving Radiotherapy in the Head and Neck Area
Authors: Tong H.C. , Gao X.J. , Dong X.Z.
Published: May 2003

Objective: To study mutans and non-mutans streptococci in patients after radiotherapy of the head and neck. Methods: Oral rinse samples collected from nasopharyngeal carcinoma patients before and after radiotherapy were diluted and cultured on nonselective and selective media for enumeration of total cultivable plaque flora, mutans and non-mutans streptococci and lactobacilli. Non-mutans streptococci were identified biochemically and by 16S rDNA sequence homology analysis. Results: After irradiation, mutans streptococci were not isolated; the levels of Streptococcus mitis and lactobacilli increased significantly. The level of Streptococcus salivarius increased, but the significance was the borderline. The level of Streptococcus sanguis decreased significantly after irradiation. The abundance of other oral streptococci species showed no significant changes. Conclusions: S. mitis and S. salivarius are the predominant non-mutans streptococci in the high-caries-risk oral flora following radiotherapy.
Cell Differentiation of Gonadotropin-Releasing Hormone Neurons and Alternative RNA Splicing of the Gonadotropin-Releasing Hormone Transcript
Authors: Choe Youngshik , Son Gi Hoon , Lee Sukwon , Park Eonyoung , Moon Younghye , Kim Kyungjin
Published: May 2003

Two different, yet related issues regarding gonadotropin-releasing hormone (GnRH), i.e. the development and differentiation of hypothalamic GnRH neurons and the alternative RNA splicing of GnRH gene transcripts, are addressed in the present review. Using the immortalized GnRH-producing GT1 cell line, we found that activation of protein kinase C (PKC) with 12-O-tetradecanoylphorbol-13-acetate induces morphological and functional differentiation of these neurons. Specific isoforms of PKC are involved in neurite growth, cell migration and synaptic contacts and involve different signaling pathways. Using an in vitro splicing assay with HeLa nuclear extract, we found that excision of the first intron of the GnRH primary transcript is attenuated in non-GnRH-producing cells, but not in GnRH-producing cells such as GT1. This attenuation was relieved by exonic splicing enhancers located in the GnRH exons 3 and 4. Interestingly, addition of nuclear extract derived from GT1 cells further increased the excision rate of intron A, indicating that GnRH neurons contain trans-acting splicing factors. Extensive biochemical analysis indicates that Tra2α, a serine/arginine-rich RNA-binding protein, and other cofactors are likely involved in mediating neuron-specific excision of intron A from the GnRH primary transcript. An understanding of the GnRH neuron-specific splicing machinery provides critical insight into the molecular mechanism of GnRH gene regulation and consequently of mammalian reproductive development.
Hypertension and Dialysis
Authors: Hörl Matthias P. , Hörl Walter H.
Published: May 2003

The high mortality rate seen in dialysis patients is related to long-standing high blood pressure and the presence of other traditional as well as non-traditional risk factors for cardiovascular disease. Hypertension is associated with increased risk for left ventricular hypertrophy, coronary artery disease, congestive heart failure and cerebrovascular complications. High blood pressure is frequent and difficult to control in the dialysis population. Available therapeutic options to normalize blood pressure in these patients include dietary salt and fluid restriction in combination with reduction of dialysate sodium concentration. A possible treatment option for these patients may be long, slow hemodialysis (3 × 8 h per week); short daily hemodialysis (2–3 h 7 times per week); nocturnal hemodialysis (6–7 times overnight per week). Reduction of residual renal function is a major cause of blood pressure increase in the peritoneal dialysis patient population. Therefore, hyperhydration should be avoided. If antihypertensive medication is needed, ACE inhibitors, β-blockers and/or calcium channel blockers are recommended. Optimal blood pressure in dialysis patients is not different from recommendations for the general population.
Cytokine Removal in Septic Patients with Continuous Venovenous Hemofiltration
Authors: Heering P. , Grabensee B. , Brause M.
Published: May 2003

Despite the progress that has been made in intensive care medicine, multiple organ failure is still associated with high mortality. Apart from the prevention of infectious complications, numerous efforts are being made to improve the treatment of sepsis through adequate antibiotic therapy, the development of new respirator therapies, better control of the hemodynamic situation, and adequate renal replacement therapy. Some authors advocate continuous renal replacement therapy not only for acute renal failure but also for the elimination of inflammatory molecules such as cytokines. Continuous renal replacement therapy improves the cardiovascular hemodynamics in patients with multiple organ failure. Therapeutic options such as volume control, clearance of uremic toxins, correction of acid base disturbances and temperature control are improved. Suitable renal replacement therapy improves not only cardiovascular hemodynamics but also patient survival. In current practice, continuous renal replacement therapy is not used to eliminate mediators such as cytokines. In patients with multiple organ failure and compromised cardiovascular hemodynamics, renal replacement therapy should be carried out as early as possible. In the following review, experimental and clinical findings concerning mediator elimination by continuous and intermittent renal replacement therapy are summarized.
A Retrospective Study Comparing the Different Surgical Procedures for the Treatment of Hydatid Disease of the Liver
Authors: Mueller Lars , Broering Dieter C. , Vashist Yogesh , Fischer Lutz , Hillert Christian , Rogiers Xavier
Published: May 2003

Background/Aims: The purpose of this study was to compare the security and effectiveness of the different surgical procedures used for treatment of the liver infestations with larvae of the dog tapeworm (Echinoocccus granulosus). Methods: 55 patients with echinococcal cysts in the liver were treated surgically at our department between 1987 and 1999. The patients were grouped according to the mode of surgical technique and comprised 16 anatomical liver resections, 26 pericystectomies and 13 endocystectomies. The results of the different procedures have been analyzed statistically. Results: The decision which procedure was to be performed was based on the severity of the disease. Complications requiring relaparotomy occurred in 5% of all cases, not showing any predisposition to a certain technique. Blood loss and duration of hospitalization was lowest in the endocystectomy group; however, the differences were not statistically significant. At a median follow-up period of 84 months, recurrences were noted in 2 cases (4%), 1 after pericystectomy and 1 after resection. Conclusion: There was no substantial evidence that the more radical procedure carries a lower risk of recurrence, and there was convincing evidence that endocystectomy is the most careful procedure in regard to blood loss and duration of hospitalization.
Randomized Clinical Trial of Postoperative Subfascial Infusion with Bupivacaine following Ambulatory Open Mesh Repair of Inguinal Hernia
Authors: Lau Hung , Patil Nivritti G. , Lee Francis
Published: May 2003

Background: Wound pain remains the commonest problem after ambulatory open repair of inguinal hernia. Postoperative subfascial infusion of the wound with bupivacaine extends local analgesia at home and may achieve superior analgesia compared with oral analgesics alone. The objective of the present trial was to evaluate the efficacy of postoperative subfascial infusion of the wound with 0.5% bupicavaine at 2 ml per hour for 48 h after operation. Methods: Forty-four patients who underwent ambulatory open tension-free mesh hernioplasties were randomized to two arms of treatment. The pump group had an infusion pump containing 100 ml 0.5% bupivacaine being placed between the external oblique aponeurosis and the Prolene mesh, whereas the nonpump group was treated with oral analgesics alone. Assuming that an observed difference of 2.0 existed between the mean pain scores of the two groups, the estimated sample size would be at least 20 patients in each group. Results: Postoperative pain scores at rest and on coughing were significantly lower in the pump group than in the nonpump group on days 0 and 1 after surgery (p < 0.01). Before being discharged, none of the pump group patients requested analgesics, but 6 patients of the nonpump group required analgesic supplement (p = 0.025). Ten patients (50%) of the pump group experienced no pain during the period of bupivacaine infusion. Recovery variables, including time taken to resume ambulation and micturition, were comparable between the two groups. The pump and nonpump group patients returned to their normal activities after a median of 3 and 4 days, respectively (p = 0.217). The postoperative morbidity rates of the two groups were similar. Conclusion: Postoperative subfascial infusion of the wound with 0.5% bupivacaine achieved superior analgesia compared with oral analgesics alone. Portable infusion pump is a safe technique to continue local analgesia at home after ambulatory open repair of inguinal hernia. The drawbacks of the ON-Q Pain Management System included its high cost and frequent seepage of blood-stained anesthetic fluid into the wound dressing.
Angiotensin-Converting Enzyme Inhibition Induces Death Receptor Apoptotic Pathways in Erythroid Precursors following Renal Transplantation
Authors: Glezerman Ilya , Patel Hiren , Glicklich Daniel , Croizat Helena , Devarajan Prasad
Published: May 2003

Background: Posttransplant erythrocytosis (PTE) is a condition that occurs in kidney transplant patients and is characterized by increase in hematocrit above 51%. While its pathogenesis remains unclear, angiotensin-converting enzyme inhibitors (ACEI) have been used successfully in the treatment of PTE. We have previously shown that ACEI induce apoptosis in the peripheral erythroid precursors from patients with PTE. In the current study we elucidate the molecular mechanisms of ACEI-induced apoptosis. Methods: Peripheral CD34+ cells were obtained from four normal controls, five normal kidney transplants, and six kidney transplants with PTE, before and after treatment with ACEI. We evaluated the expression of a variety of apoptotic factors by quantitative reverse transcription-multiplex polymerase chain reaction, Western blot and immunocytochemistry. Results: ACEI resulted in a significant induction of Fas, FADD, and TRADD mRNAs in renal transplant patients with or without PTE. No changes were noted in the expression of mRNAs encoding Bcl-2, Bcl-xL, Bax, caspase 8, caspase 3, or GAPDH. ACEI also resulted in a significant upregulation of Fas, FADD and TRADD protein expression, and their localization predominantly at the plasma membrane. Conclusions: Our results suggest that ACEI therapy induces apoptosis in erythrocyte progenitor cells of renal transplant patients at least in part via induction of death receptor apoptotic cascades.
Nondisposable materials, chronic inflammation, and adjuvant action
Authors: Hamilton John A
Published: May 2003

Why inflammatory responses become chronic and how adjuvants work remain unanswered. Macrophage-lineage cells are key components of chronic inflammatory reactions and in the actions of immunologic adjuvants. One explanation for the increased numbers of macrophages long term at sites of chronic inflammation could be enhanced cell survival or even local proliferation. The evidence supporting a unifying hypothesis for one way in which this macrophage survival and proliferation may be promoted is presented. Many materials, often particulate, of which macrophages have difficulty disposing, can promote monocyte/macrophage survival and even proliferation. Materials active in this regard and which can initiate chronic inflammatory reactions include oxidized low-density lipoprotein, inflammatory microcrystals (calcium phosphate, monosodium urate, talc, calcium pyrophosphate), amyloidogenic peptides (amyloid β and prion protein), and joint implant biomaterials. Additional, similar materials, which have been shown to have adjuvant activity (alum, oil-in-water emulsions, heat-killed bacteria, CpG oligonucleotides, methylated bovine serum albumin, silica), induce similar responses. Cell proliferation can be striking, following uptake of some of the materials, when macrophage-colony stimulating factor is included at low concentrations, which normally promote mainly survival. It is proposed that if such responses were occurring in vivo, there would be a shift in the normal balance between cell survival and cell death, which maintains steady-state, macrophage-lineage numbers in tissues. Thus, there would be more cells in an inflammatory lesion or at a site of adjuvant action with the potential, following activation and/or differentiation, to perpetuate inflammatory or antigen-specific, immune responses, respectively.
Role of Rho-family GTPase Cdc42 in polarized expression of lymphocyte appendages
Authors: Ratner Stuart , Piechocki Marie P , Galy Anne
Published: May 2003

Lymphocytes polarize for motility by developing a broad anterior, where lamellipodia arise, and a simple stalk-like posterior appendage, the uropod. Through time-lapse analysis of normal and leukemic human T cells, it was found that this polarized form is maintained by a mechanism that excludes lamellipodia from the uropod. Lamellipodia regularly traveled rearward to encroach upon the uropod but disassembled abruptly at the uropod border. This exclusion of lamellipodia from the uropod required the Rho-family guanosine triphosphatase Cdc42. Reduction of Cdc42 activity by expression of dominant-negative Cdc42 resulted in “two headed” cells in which lamellipodia persisted at the distal end of the uropod. Random and chemotactic motility were impaired. Increased Cdc42 activity, induced by expression of activated, mutant Cdc42, was accompanied by a general loss of lamellipodia. The results suggest that one role of Cdc42 in lymphocyte motility is to preserve polarity by concentrating lamellipodial disassembly signals in the uropod.
IgD-receptor (IgD-R) cross-linking partially protects murine T cells from dexamethasone-induced apoptosis
Authors: Tamma Seetha M Lakshmi , Coico Richard F
Published: May 2003

Based on our previous findings that immunoglobulin D (IgD) receptor (IgD-R) cross-linking with oligomeric IgD (IgD-R-xL) led to T cell activation, we examined the effect of IgD-R-xL on the expression of Fas antigen and apoptosis induction. In splenic T cells, IgD-R-xL followed by dexamethasone (dex) treatment resulted in a decreased percentage of Fas-positive cells as well as a decreased mean fluorescence intensity (P<0.05) when compared with cells treated with dex alone. There are significant differences in annexin–fluorescein isothiocyanate (FITC) and phosphatidylinositol (PI) staining between samples treated with dex alone and IgD-R-xL followed by dex-treated samples (P<0.05), suggesting a protective role for IgD-R-xL. No significant differences are seen in Fas antigen expression, annexin–FITC staining, and/or PI staining in murine T hybridoma (7C5) cells cultured under similar conditions (P<0.07). We hypothesize that ligation of IgD-R may predispose antigen-specific T lymphocytes for survival during primary immune responses when IgD-positive B cells serve as antigen-presenting cells.
p53 deficiency and defective mitotic checkpoint in proliferating T lymphocytes increase chromosomal instability through aberrant exit from mitotic arrest
Authors: Baek Kwan-Hyuck , Shin Hyun-Jin , Yoo Jae-Kwang , Cho Jae-Ho , Choi Yo-Han , Sung Young-Chul , McKeon Frank , Lee Chang-Woo
Published: May 2003

During the proliferation of T cells for successful immune responses against pathogens, the fine regulation of cell cycle is important to the maintenance of T cell homeostasis and the prevention of lymphoproliferative disorders. However, it remains to be elucidated how the cell cycle is controlled at the mitotic phase in proliferating T cells. Here, we show that during the proliferation of primary T cells, the disruption of the mitotic spindle leads to cell-cycle arrest at mitosis and that prolonged mitotic arrest results in not only apoptosis but also the form of chromosomal instability observed in human cancers. It is interesting that in response to spindle damage, the phosphorylation of BubR1, a mitotic checkpoint kinase, was significantly induced in proliferating T cells, and the expression of the dominant-negative mutant of BubR1 compromised mitotic arrest and subsequent apoptosis and thus led to the augmentation of polyploidy formation. We also show that in response to prolonged spindle damage, the expression of p53 but not of p73 was significantly induced. In addition, following sustained mitotic arrest, p53-deficient T cells were found to be more susceptible to polyploidy formation than the wild type. These results suggest that during flourishing immune response, mitotic checkpoint and p53 play important roles in the prevention of chromosomal instability and in the maintenance of the genomic integrity of proliferating T cells.
Histone acetylation and chromatin conformation are regulated separately at the TNF-α promoter in monocytes and macrophages
Authors: Lee Julia Y , Kim Nahmah A , Sanford Amy , Sullivan Kathleen E
Published: May 2003

Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine, which participates in a wide range of immunoregulatory activities. It is generally produced at highest levels by cells of the myeloid lineage in response to activation of pathogen recognition receptors such as Toll-like receptors. Impaired production predisposes to infection with intracellular organisms, and overproduction results in systemic or organ-specific inflammation. Control of expression is essential to maintain homeostasis, and this control is mediated via multiple strategies. We examined two separate aspects of chromatin accessibility in this study of the human TNF-α promoter. We examined the role of histone acetylation and chromatin remodeling in cell lines and primary cells and identified two individual steps associated with activation of TNF-α production. Histone H3 and H4 acetylation was found to be strongly dependent on the developmental stage of human monocytes. It did not appear to be regulated by acute stimuli, and instead, chromatin remodeling was found to occur after acute stimuli in a cell line competent to produce TNF-α. These data suggest that there is a hierarchy of controls regulating expression of TNF-α. Acetylation of histones is a prerequisite but is insufficient on its own for TNF-α production.
Decisions on life and death: FOXO Forkhead transcription factors are in command when PKB/Akt is off duty
Authors: Burgering Boudewijn M T , Medema René H
Published: May 2003

Forkhead transcription factors of the FOXO family are important downstream targets of protein kinase B (PKB)/Akt, a kinase shown to play a decisive role in cell proliferation and cell survival. Direct phosphorylation by PKB/Akt inhibits transcriptional activation by FOXO factors, causing their displacement from the nucleus into the cytoplasm. Work from recent years has shown that this family of transcription factors regulates the expression of a number of genes that are crucial for the proliferative status of a cell, as well as a number of genes involved in programmed cell death. As such, these transcription factors appear to play an essential role in many of the effects of PKB/Akt on cell proliferation and survival. Indeed, in cells of the hematopoietic system, mere activation of a FOXO factor is sufficient to activate a variety of proapoptotic genes and to trigger apoptosis. In contrast, in most other cell types, activation of FOXO blocks cellular proliferation and drives cells into a quiescent state. In such cell types, FOXO factors also provide the protective mechanisms that are required to adapt to the altered metabolic state of quiescent cells. Thus, as PKB/Akt signaling is switched off, FOXO factors take over to determine the fate of a cell, long-term survival in a quiescent state, or programmed cell death. This review summarizes our current understanding of the mechanisms by which PKB/Akt and FOXO factors regulate these decisions.
Wind data for natural ventilation design in Hong Kong
Authors: Yik F WH , Lo T Y , Burnett J
Published: May 2003

The paper discusses what kind of wind data are required for natural ventilation design for residential buildings and the results of a statistical analysis on the wind data records measured from 1984 to 1998 at a weather station within an urban area in Hong Kong. In addition to the general patterns of wind speeds and directions, the study analysed the durations of stagnant periods. It was found that most stagnant periods lasted for only 1–2 h; the total duration of stagnant periods accounted only for 0.14% of the time in the 15 years; the durations between two consecutive stagnant periods were predominantly over 24 h; and the most frequent time of occurrence of stagnant periods was before dawn in the winter months.
Model-based condition monitoring of a HVAC cooling coil sub-system in a real building
Authors: Buswell R A , Haves P , Wright J A
Published: May 2003

A comparison of the performance of two fault detection and diagnosis methods applied to a cooling coil subsystem in an air-handling unit installed in a real building is presented. Both methods employ a first principles based reference model of the target system. One scheme carries out diagnosis using expert rules and the other recursively re-estimates selected parameters of the system model that correspond to particular faults. The procedures and information required to configure the schemes for condition monitoring are discussed. The results of testing the methods on an HVAC cooling coil subsystem in a commercial office building in the UK over an entire cooling season are reported. Both methods were able to both detect faults and provide some diagnosis. The expert rule method, however, appears to be more robust. Issues associated with the con” guration and implementation of both methods are discussed in terms of performance and cost.
Building Energy and Environment Performance System (BEEPS): a programme for building energy certification in Italy
Authors: de Santoli Livio , Di Matteo Umberto
Published: May 2003

This paper deals with the Kyoto protocol implication for the built environment. This work relates to a research study undertaken by the Ministry for the Environment in Italy and the Department of Fisica Tecnica at the University La Sapienza of Rome aimed at defining an instrument to use in the calculation of the energy performance in existing buildings in Italy. This instrument would make allowances for climactic conditions, indoor comfort conditions and associated costs as established by the European Union (Working Party on National Environmental Policy, Policy Instruments for Environmentally Sustainable Buildings, ENV/EPOC/WPNEP (2001)6). It was established that the European Community would promote actions in the sustainable building sector with the intent to: · reduce CO2 emissions; · minimize waste; · prevent pollution in indoor environments. Following the acknowledgement of official directives regarding the operational strategies of high energy consumption buildings (Directive of the European Parliament and of the Council on the energy performance of buildings, 2002/91/CE), a program for the energy certification of buildings and the calculation of the building and its building services was begun in Italy (BEEPS, Building Energy and Environment Performance System). This program is divided into two phases: the first phase deals with an individual evaluation of the existing buildings, available on the Internet, aimed at providing an initial, simplified calculation, while the next phase is a more in-depth study of the buildings that have not met the minimum standards from the individual evaluation. The code that has been developed will use parameters such as: resource consumption, environmental impact, indoor environment quality, materials used, and economic costs. The software will be implemented through three distinct calculation sections: the building envelope, the installed equipment and the indoor environmental quality (IEQ). The three sections will be calculated using an analytical life-cycle technique that supplies a balance of matter and energy and takes into consideration the entire life-cycle of the materials, products or services. Data collection will be carried out via the Internet.
Short-term projections for variant Creutzfeldt-Jakob disease onsets
Authors: Ghani Azra C , Ferguson Neil M , Donnelly Christl A , Anderson Roy M
Published: May 2003

Projections of both the short- and long-term course of the variant Creutzfeldt-Jakob disease (vCJD) epidemic in Great Britain have demonstrated great uncertainty due to the lack of knowledge of key aspects of the biology and epidemiology of this new disease. Such projections are sensitive to assumptions made regarding the pattern of exposure to BSE-infected animals, the effectiveness of control measures introduced in 1989 and 1996 in reducing this exposure, the functional form of the incubation period distribution and patterns of age-dependent susceptibility/exposure. This paper provides short-term projections for vCJD onsets using the time- and age-distributed onset data to the end of 2000, with results that are directly comparable to the other papers in this issue. These results demonstrate the continued uncertainty in the future scale of this disease.
Estimation of the exposure of the French population to the BSE agent: comparison of the 1980-95 consumption of beef products containing mechanically recovered meat in France and the UK, by birth cohort and gender
Authors: Chadeau-Hyam Marc , Tard Alexandra , Bird Sheila , Le Guennec Solenn , Bemrah Nawel , Volatier Jean-Luc , Alperovitch Annick
Published: May 2003

Assuming that human exposure to BSE was through beef mechanically recovered meat (MRM) consumed as burgers and other meat products, we estimated the French consumption of different food items containing beef MRM, and compared these consumptions for French and British populations. To estimate consumption of meat products containing bovine MRM, we used dietary data from national individual and household food surveys conducted between 1980 and 1995. After reconciliation of consumption data between the available surveys and calendar year adjustments, we simulated consumption of one-thousandth of the French population. Consumption was estimated by birth cohort and gender, and for the periods 1980-89 and 1990-95 separately. Data showed that burgers (including manufactured minced meat) represented around 75-80% of the individual consumption of meat products containing MRM, and that consumption of burgers increased by 40% over the 1980-95 period. In all age groups, consumption was higher in males than in females. In both genders, the 1940-69 birth cohort had the highest mean consumption of burgers and other beef products containing MRM. Similar findings have been reported for the UK population. Estimated consumption of bovine MRM per calendar year increased markedly over the study period, concomitantly with an increase of bovine carcasses imported from the UK. Comparison of the 1980-1995 pattern of bovine MRM consumption in the UK and France indicated that this consumption peaked later in France than in the UK. This difference might result in different temporal pattern of vCJD incidence.
Extending backcalculation to analyse BSE data
Authors: Donnelly C A , Ferguson N M , Ghani A C , Anderson R M
Published: May 2003

We review the origins of backcalculation (or back projection) methods developed for the analysis of AIDS (acquired immunodeficiencysyndrome) incidence data. These techniques have been used extensivelyfor >15 years to deconvolute clinical case incidence, given knowledge of the incubation period distribution, to obtain estimates of past HIV (human immunodeficiency virus) infection incidence and short-term predictions of future AIDS incidence. Adaptations required for the analysis of bovine spongiform encephalopathy (BSE) incidence included: stratification of BSE incidence by age as well as birth cohort; allowance for incomplete survival between infection and the onset of clinical signs of disease; and decomposition of the age-and time-related infection incidence into a time-dependent feed risk component and an age-dependent exposure/susceptibility function. The most recent methodological developments focus on the incorporation of data from clinically unaffected cattle screened using recently developed tests for preclinical BSE infection. Backcalculation-based predictions of future BSE incidence obtained since 1996 are examined. Finally, future directions of epidemiological analysis of BSE epidemics are discussed taking into account ongoing developments in the science of BSE and possible changes in BSE-related policies.
Forward EphB4 signaling in endothelial cells controls cellular repulsion and segregation from ephrinB2 positive cells
Authors: Füller Tim , Korff Thomas , Kilian Adrienne , Dandekar Gudrun , Augustin Hellmut G.
Published: May 2003

Contact-dependent interactions between endothelial cells (ECs), as well as between ECs and mural cells, play a key role in the formation of a regular vascular system and the assembly of the vessel wall. Recent studies have identified ephrinB2 and EphB4 as markers and makers of arteriovenous differentiation during vascular development. On the basis of these findings,we hypothesized that Ephephrin interactions in the vascular system mediate distinct propulsive and repulsive effector functions that provide guidance signals for the proper spatial organization of the developing vasculature. Utilizing a set of specialized endothelial differentiation and angiogenesis assays, the present study was aimed at studying vascular morphogenic functions of endothelial EphB4 and ephrinB2 activation. EphrinB2-Fc acts anti-adhesively and induces detachment of ECs, as demonstrated by (1) inhibition of adhesion to ephrinB2-Fc-coated culture dishes, (2) detachment of ECs grown as differentiated 3D spheroids, and (3) endothelial denudation of explanted fragments of umbilical vein. Conversely, soluble ephrinB2-Fc inhibits lateral cell migration, vascular endothelial growth factor (VEGF) gradient-driven chemotaxis, capillary-like network formation and sprouting angiogenesis. In turn, soluble EphB4-Fc is pro-adhesive and stimulates EC migration and sprouting angiogenesis. EphrinB2-mediated repulsive signals are transduced by EphB4, as demonstrated by EphrinB2-Fc inhibition of sprouting angiogenesis of constitutively EphB4-overexpressing ECs. Confrontation experiments of EphB4-overexpressing ECs with ECs overexpressing full-length or truncated ephrinB2 that lacks the cytoplasmic catalytic domain demonstrated that forward EphB4 signaling with EphB4 tyrosine phosphorylation restricts intermingling of cells and supports cellular segregation. Taken together, these data identify distinct propulsive and repulsive effector functions of endothelial ephrinB2 and EphB4 that mediate spatial positional signals during angiogenesis and vessel assembly.
WIP participates in actin reorganization and ruffle formation induced by PDGF
Authors: Antón Inés M. , Saville Stephen P. , Byrne Michael J. , Curcio Claudia , Ramesh Narayanaswamy , Hartwig John H. , Geha Raif S.
Published: May 2003

Platelet-derived growth factor (PDGF) is a chemotactic factor for fibroblasts that triggers actin cytoskeleton reorganization by increasing the level of GTP-Rac, the activated form of a small Rho family GTPase. GTP-Rac induces membrane ruffling and lamellipodium formation that are required for adhesion, migration and macropinocytosis, among other functions. We have shown that WIP interacts with members of the Wiskott-Aldrich syndrome protein family and is essential for filopodium formation regulated by Cdc42 GTPase. In this report, we show that WIP participates in the actin reorganization that leads to ruffle formation. WIP overexpression in murine fibroblasts (3T3 cells)enhances ruffle formation in response to PDGF stimulation, as shown by immunofluorescence and electron and video microscopy. More importantly,microinjection of anti-WIP antibody or absence of WIP in murine fibroblasts results in decreased ruffle formation in response to PDGF treatment. Finally,overexpression of a modified form of WIP lacking the actin-binding site blocks PDGF-induced membrane ruffling. These data suggest a role for WIP in actin reorganization to form PDGF-induced ruffles. This is the first in vivo evidence in mammalian cells for a function of WIP dependent on its ability to bind actin.
Membrane targeting of protein tyrosine phosphatase PTPL1 through its FERM domain via binding to phosphatidylinositol 4,5-biphosphate
Authors: Bompard Guillaume , Martin Marianne , Roy Christian , Vignon Françoise , Freiss Gilles
Published: May 2003

PTPL1 is the largest known cytoplasmic protein tyrosine phosphatase (PTP)containing a FERM (four point-1, ezrin, radixin and moesin) domain. Enzyme localization and PTP-substrate specificity are thought to play crucial roles in the regulation of PTP activity, which determines their functions. Here we report that PTPL1 is predominantly localized at the apical face of plasma membrane enriched in dorsal microvilli when expressed in HeLa cells. By comparing localization of the full-length enzyme with its FERM domain or FERM-deleted PTPL1 construct, we first concluded that PTPL1-FERM domain is necessary and sufficient to address the wild-type enzyme at the membrane. Two potential phosphatidylinositol 4,5-biphosphate[PtdIns(4,5)P2]-binding motifs were identified within the PTPL1-FERM sequence. We further showed that mutation of both sites altered PTPL1 localization similarly to FERM domain deletion, and impaired its subcellular distribution as confirmed biochemically by cell-fractionation experiments. Using protein-lipid overlays, we demonstrated an interaction of the FERM domain of PTPL1 with PtdIns(4,5)P2, which was lost after mutation of potential PtdIns(4,5)P2-binding motifs. Moreover, neomycin, which masks PtdIns(4,5)P2polar heads, was shown to decrease by 50% the association of PTPL1 with the cytoskeletal fraction. These results identify the crucial role of the FERM domain in PTPL1 intracellular targeting and demonstrate that localization of PTPL1 is regulated by phosphoinositide metabolism.
Intracytoplasmic domains of MHC class II molecules are essential for lipid-raft-dependent signaling
Authors: Bécart Stéphane , Setterblad Niclas , Ostrand-Rosenberg Suzanne , Ono Santa J. , Charron Dominique , Mooney Nuala
Published: May 2003

In addition to their role in antigen presentation, major histocompatibility complex (MHC) class II molecules have been widely described as signaling proteins in diverse antigen-presenting cells (APCs) including B cells and dendritic cells. By contrast, little is known of the signaling function of MHC class II molecules expressed in solid tumors. We describe the functional organization and signaling ability of I-Ak expressed in a sarcoma,and report the recruitment of I-Ak to lipid rafts after MHC class II engagement. Lipid raft integrity was required for I-Ak-mediated reorganization of the actin cytoskeleton and translocation of protein kinase C-α(PKC-α) to the precise site of stimulation via I-Ak. Truncation of the intracytoplasmic domains of I-Ak did not perturb I-Ak recruitment to lipid rafts but abrogated PKC-αtranslocation and actin rearrangement. PKC-αwas detected in lipid microdomains and enrichment of activated PKC-αin lipid rafts was induced by I-Ak signaling. Ordering of the molecular events following engagement of the MHC class II molecules revealed that I-Ak recruitment to lipid rafts precedes signaling. This is consistent with the absence of a requirement for the intracytoplasmic tails for localization to lipid rafts. These data reveal that lipid-rich microdomains play a key role in MHC class II-mediated signaling in a solid tumor.