bluuebunny/crossref_metadata_2025 huggingface dataset:
Endogenously activated mGlu5 metabotropic glutamate receptors sustain the increase in c‐Myc expression induced by leukaemia inhibitory factor in cultured mouse embryonic stem cells
Authors: Spinsanti Paola , De Vita Teresa , Di Castro Sara , Storto Marianna , Formisano Pietro , Nicoletti Ferdinando , Melchiorri Daniela
Published: September 2006

We have shown that endogenous activation of type 5 metabotropic glutamate (mGlu5) receptors supports the maintenance of a pluripotent, undifferentiated state in D3 mouse embryonic stem cells cultured in the presence of leukaemia inhibitory factor (LIF). Here, we examined the interaction between LIF and mGlu5 receptors using as a read‐out the immediate early gene, c‐Myc. The selective mGlu5 receptor antagonist, 2‐methyl‐6‐(phenylenthynyl)pyridine (MPEP; 1 μm), reduced the increase in c‐Myc protein levels induced by LIF by enhancing c‐Myc ubiquitination. A reduction in c‐Myc levels was also observed following small interfering RNA‐mediated mGlu5 receptor gene silencing. MPEP reduced glycogen synthase kinase‐3β phosphorylation on Ser9, but increased phosphorylation of the phosphatidylinositol‐3‐kinase (PI‐3‐K) substrate, AKT. In our hands, activated PI‐3‐K reduced the stability of c‐Myc, because (i) the PI‐3‐K inhibitor, LY294002, prevented the reduction in c‐Myc levels induced by MPEP; and (ii) over‐expression of AKT promoted c‐Myc ubiquitination. All effects of MPEP were mimicked by protein kinase C (PKC) inhibitors and reversed by the PKC activator, tetradecanoylphorbol‐13‐acetate. We conclude that endogenous activation of mGlu5 receptors sustains the increase in c‐Myc induced by LIF in embryonic stem cells by inhibiting both glycogen synthase kinase‐3β and PI‐3‐K, both effects resulting from the activation of PKC.
Copper‐dependent inhibition of cytochrome c oxidase by Aβ1−42 requires reduced methionine at residue 35 of the Aβ peptide
Authors: Crouch Peter J. , Barnham Kevin J. , Duce James A. , Blake Rachel E. , Masters Colin L. , Trounce Ian A.
Published: September 2006

By altering key amino acid residues of the Alzheimer's disease‐associated amyloid‐β peptide, we investigated the mechanism through which amyloid‐β inhibits cytochrome c oxidase (EC 1.9.3.1). Native amyloid‐β inhibited cytochrome oxidase by up to 65%, and the level of inhibition was determined by the period of amyloid‐β ageing before the cytochrome oxidase assay. Substituting tyrosine‐10 with alanine did not affect maximal enzyme inhibition, but the altered peptide required a longer period of ageing. By contrast, oxidizing the sulfur of methionine‐35 to a sulfoxide, or substituting methionine‐35 with valine, completely abrogated the peptide's inhibitory potential towards cytochrome oxidase. Sodium dodecyl sulfate–polyacrylamide gel electrophoresis analysis revealed that the loss of inhibitory potential towards cytochrome oxidase with the methionine‐35‐altered peptides did not correlate with a substantially different distribution of amyloid‐β oligomeric species. Although the amyloid‐β‐mediated inhibition of cytochrome oxidase was completely dependent on the presence of divalent Cu2+, it was not supported by monovalent Cu+, and experiments with catalase and H2O2 indicated that the mechanism of cytochrome oxidase inhibition does not involve amyloid‐β‐mediated H2O2 production. We propose that amyloid‐β‐mediated inhibition of cytochrome oxidase is dependent on the peptide's capacity to bind, then reduce Cu2+, and that it may involve the formation of a redox active amyloid‐β‐methionine radical.
Quantitative assessment of liver fibrosis: a novel automated image analysis method
Authors: Matalka Ismail I. , Al‐Jarrah Omar M. , Manasrah Toqa M.
Published: September 2006

Abstract: Background:Semiquantitative staging of liver fibrosis is a highly subjective procedure and may lead to an uncertainty in judgment regarding the degree of severity and hence the progression of the disease.

Aim:In this work, we present an automated quantification system (AQS) for evaluating the degree of severity of fibrosis in liver biopsies based on Ishak et al.'s classification. Accordingly, liver fibrosis is classified into six classes depending on its severity and progression. The described system is of special value in accurately assessing the prognosis of chronic liver disease.

Methods:In our method, we tried to approximate the architecture of the fibrosis in the subject sample using texture features and shape representation of the fibrosis structural expansion with an overall accuracy of about 98%.

Results and conclusion:The presented AQS is considered to be a novel approach in the domain of automatic liver fibrosis quantification. It is a true quantification and intelligent approach that attempts to utilize the current semiquantitative methods of liver fibrosis assessment to turn them into real quantitative ones with significant reduction in variability and subjectivity. We propose that our method can be adopted by a panel of expert liver pathologists and software to be developed and used on a wide scale.
Psychological Reaction to Potential Malfunctioning of Implantable Defibrillators
Authors: VAN DEN BROEK KRISTA C. , DENOLLET JOHAN , NYKLÍČEK IVAN , VAN DER VOORT PEPIJN H.
Published: September 2006

Background: Psychological problems following implantable cardioverter defibrillators (ICD) implantation are diverse and include increased levels of anxiety. Anxiety may even rise further when possible malfunctioning of an ICD is announced, with a higher risk of serious ventricular arrhythmias and death as a consequence. Following the public statement of Medtronic, all patients in the Netherlands with the specific Medtronic ICD were contacted for extra device evaluation. The aim of this exploratory study was to determine whether the proportion of ICD patients with high levels of anxiety would increase after this extra device evaluation.

Methods: Patients were recruited from an ongoing prospective study on psychological effects of ICD implantation. Thirty‐three patients completed the State subscale of the State‐Trait Anxiety Inventory (STAI) before and after extra device evaluation. The STAI can identify patients with high levels of anxiety.

Results: A high level of anxiety was experienced by two patients (6.1%) at baseline and eight patients (24.2%) at follow‐up (P = 0.031). Hence, ICD patients were significantly more likely to experience high levels of anxiety following the public statement of potential malfunctioning of their device.

Conclusion: A public statement regarding device safety may increase levels of anxiety among ICD patients. Given the potential triggering effect of high levels of anxiety on arrhythmias, psychological support may be considered for some of the ICD patients after such public statement.
Pulmonary Vein Vestibule Ablation for the Control of Atrial Fibrillation in Patients with Impaired Left Ventricular Function
Authors: TONDO CLAUDIO , MANTICA MASSIMO , RUSSO GIOVANNI , AVELLA ANDREA , DE LUCA LUCIA , PAPPALARDO AUGUSTO , FAGUNDES RAFAEL LOPES , PICCHIO EDO , LAURENZI FRANCESCO , PIAZZA VITO , BISCEGLIA IRMA
Published: September 2006

Introduction: Congestive heart failure (CHF) and atrial fibrillation (AF) are frequently linked, and when associated produce additive deleterious effects. In this prospective study, the effects of catheter ablation for AF in patients with impaired left ventricular (LV) function are presented.

Methods: Baseline data and clinical outcome have been prospectively collected in 105 consecutive patients who underwent pulmonary vein ablation for the control of AF. We evaluated 40 patients affected by LV dysfunction with ejection fraction (EF) <40% and compared them to the remaining 65 patients with normal ventricular function in terms of changes in LV function, maintenance of sinus rhythm, and quality of life during follow‐up.

Results: After a mean follow‐up of 14 ± 2 months, 87% of patients with impaired LV function and 92% of patients with normal ventricular function were in sinus rhythm, with or without antiarrhythmic therapy (P = NS). A significant improvement in LVEF and fractional shortening was documented in patients with CHF (33 ± 2% vs 47 ± 3%, and 19 ± 4% vs 30 ± 3%, P < 0.01 for both comparisons). Evaluation of exercise capacity and quality of life documented better improvements in patients with CHF compared to patients without CHF.

Conclusions: Catheter ablation in patients with LV dysfunction is feasible, not associated with higher procedural complications, and provides a significant improvement in LV performance, symptoms, and quality of life during follow‐up.
Nonfluoroscopic Catheter Navigation for Radiofrequency Catheter Ablation of Supraventricular Tachycardia in Children
Authors: PAPAGIANNIS JOHN , TSOUTSINOS ALEXANDROS , KIRVASSILIS GEORGE , SOFIANIDOU IOANNA , KOUSSI THEOFILI , LASKARI CLEO , KIAFFAS MARIA , APOSTOLOPOULOU SOTIRIA , RAMMOS SPYRIDON
Published: September 2006

Background: Radiofrequency catheter ablation (RCA) of supraventricular tachycardia (SVT) in children is highly successful but requires exposure to radiation. Nonfluoroscopic mapping systems may significantly reduce fluoroscopy time.

Methods: Forty consecutive pediatric patients who underwent RCA for accessory pathways (AP) or AV nodal reentrant tachycardia (AVNRT) with use of a nonfluoroscopic navigation system (Ensite® NavX™) (group A) were compared retrospectively to 40 consecutive patients with similar diagnoses who underwent RCA with fluoroscopic guidance only (group B).

Results: Group A (mean age 12.1 ± 2.9 years, mean weight 47 ± 13.9 kg) consisted of 11 patients (27.7%) with AVNRT and 29 (72.5%) with AP. Group B (mean age 10.9 ± 3.1 years, mean weight 47.1 ± 17.1 kg) consisted of 7 patients (17.5%) with AVNRT and 33 (82.5%) with AP. There were no significant differences in AP location, patients with congenital heart disease, and number of radiofrequency lesions. Fluoroscopy time was significantly shorter in group A than in group B (10.4 ± 6.1, range 3.1–28.8 minutes, vs 24.9 ± 16.0, range 4.4–82.0 minutes, P < 0.0001). Procedure duration was also significantly shorter in group A than in group B (170 ± 68.5, range 90–420 minutes, vs 218 ± 69.3, range 90–360 minutes, P < 0.0001). Initial success was 95% in group A and 100% in group B. Tachycardia recurrences occurred in two patients in group A (5%) and six patients in group B (15%). Final success, including repeat ablations for recurrences or failures, was 100% in both groups.

Conclusions: The use of a nonfluoroscopic system for catheter navigation significantly reduced fluoroscopy exposure and total procedure duration of RCA of common SVT substrates in children.
The Renin‐Angiotensin System: A Therapeutic Target in Atrial Fibrillation
Authors: PATLOLLA VISHNU , ALSHEIKH‐ALI ALAWI A. , AL‐AHMAD AMIN M.
Published: September 2006

There is growing evidence to suggest a role for the renin‐angiotensin system (RAS) in the pathogenesis of atrial fibrillation (AF). Experimental animal data suggest RAS‐dependent mechanisms for the development of a structural and electrophysiologic substrate for AF. This is consistent with clinical data demonstrating the effectiveness of RAS blockade in preventing new‐onset or recurrent AF in a variety of patient populations including patients with hypertension and left ventricular hypertrophy, congestive heart failure, and those undergoing electrical cardioversion for AF. This review summarizes experimental and clinical evidence to date relating to the role of RAS in the pathogenesis of AF, and the efficacy of its inhibition in managing this common arrhythmia.
The Homozygous KCNQ1 Gene Mutation Associated with Recessive Romano–Ward Syndrome
Authors: NOVOTNY TOMAS , KADLECOVA JITKA , JANOUSEK JAN , GAILLYOVA RENATA , BITTNEROVA ALEXANDRA , FLORIANOVA ALENA , SISAKOVA MARTINA , TOMAN ONDREJ , CHROUST KAREL , PAPOUSEK IVO , SPINAR JINDRICH
Published: September 2006

In a 7‐year‐old boy with normal hearing suffering from repeated syncope an extremely prolonged QTc interval (up to 700 ms) was found. The mother was completely asymptomatic and the father had an intermittently borderline QTc interval (maximum 470 ms) but no symptoms. In the proband a mutation analysis of KCNQ1 gene revealed a homozygous 1893insC mutation. The parents were heterozygous for this mutation. There was no consanguineous marriage in the family. The clinical relevance of these findings is that apparently normal individuals may have a latent reduction of repolarizing currents, a “reduced repolarization reserve,” because they are carriers of latent ion channel genes mutations.
Electrocardiographic Manifestations of Cardiac Metastasis in Lung Cancer
Authors: LIM HONG EUY , PAK HUI‐NAM , JUNG HYE CHEOL , KIM JIN SEOK , SHIM WAN JOO , KIM YOUNG‐HOON
Published: September 2006

We describe a case of primary lung cancer with myocardial metastasis, documented with electrocardiogram (ECG) mimicking myocardial ischemia and manifesting VT. Metastatic tumor to the myocardium proper is uncommon
and difficult to diagnose because of nonspecific signs and symptoms. We observed such ECG changes in this case were initially misinterpreted as acute coronary syndrome. The diagnosis of cardiac metastasis was confirmed by contrast‐enhanced magnetic resonance imaging and computed tomography.
Quantification of Right Ventricular Volumes and Function by Real Time Three‐Dimensional Echocardiographic Longitudinal Axial Plane Method: Validation in the Clinical Setting
Authors: Endo Yuka , Maddukuri Prasad V. , Vieira Marcelo L.C. , Pandian Natesa G. , Patel Ayan R.
Published: September 2006

Background: Measurement of right ventricular (RV) volumes and right ventricular ejection fraction (RVEF) by three‐dimensional echocardiographic (3DE) short‐axis disc summation method has been validated in multiple studies. However, in some patients, short‐axis images are of insufficient quality for accurate tracing of the RV endocardial border. This study examined the accuracy of long‐axis analysis in multiple planes (longitudinal axial plane method) for assessment of RV volumes and RVEF. Methods: 3DE images were analyzed in 40 subjects with a broad range of RV function. RV end‐diastolic (RVEDV) and end‐systolic volumes (RVESV) and RVEF were calculated by both short‐axis disc summation method and longitudinal axial plane method. Results: Excellent correlation was obtained between the two methods for RVEDV, RVESV, and RVEF (r = 0.99, 0.99, 0.94, respectively; P < 0.0001 for all comparisons). Conclusion: 3DE longitudinal‐axis analysis is a promising technique for the evaluation of RV function, and may provide an alternative method of assessment in patients with suboptimal short‐axis images.
Feasibility and Utility of Three‐Dimensional Color Flow Echocardiography of the Aortic Arch: The “Echocardiographic Angiogram”
Authors: Hlavacek Anthony , Lucas Jon , Baker Hamilton , Chessa Karen , Shirali Girish
Published: September 2006

Two‐dimensional transthoracic echocardiography (2DE) is the most commonly used diagnostic modality to evaluate congenital and acquired abnormalities of the aortic arch. However, 2DE is frequently limited in this ability due to the three‐dimensional character of the arch and its interrelationships with other vascular structures. Recently, three‐dimensional echocardiography (3DE) with 3D color flow Doppler became commercially available. We examined the feasibility and utility of 3DE with 3D color Doppler in the evaluation of patients with congenital (native and postoperative) abnormalities of the aortic arch. We found that 3DE color flow provides important diagnostic information in patients with aortic arch anomalies, in a manner that is quick and user‐friendly. In addition, 17 of the 26 patients had their 3DE findings confirmed by additional modalities, providing reasonably significant validation for our findings with 3DE.
Validity of Revised Doppler Echocardiographic Algorithms and Composite Clinical and Angiographic Data in Diagnosis of Diastolic Dysfunction
Authors: Ogunyankin Kofo O. , Burggraf Gary W. , Abiose Ademola K. , Malik Paul G.
Published: September 2006

Background: Commonly used echocardiographic indices for grading diastolic function predicated on mitral inflow Doppler analysis have a poor diagnostic concordance and discriminatory value. Even when combined with other indices, significant overlap prevents a single group assignment for many subjects. We tested the relative validity of echocardiographic and clinical algorithms for grading diastolic function in patients undergoing cardiac catheterization. Method: Patients (n = 115), had echocardiograms immediately prior to measuring left ventricular (LV) diastolic (pre‐A, mean, end‐diastolic) pressures. Diastolic function was classified into the traditional four stages, and into three stages using a new classification that obviates the pseudonormal class. Summative clinical and angiographic data were used in a standardized fashion to classify each patient according to the probability for abnormal diastolic function. Measured LV diastolic pressure in each patient was compared with expected diastolic pressures based on the clinical and echocardiographic classifications. Result: The group means of the diastolic pressures were identical in patients stratified by four‐stage or three‐stage echocardiographic classifications, indicating that both classifications schemes are interchangeable. When severe diastolic dysfunction is diagnosed by the three‐stage classification, 88% and 12%, respectively, were clinically classified as high and intermediate probability, and the mean LV pre‐A pressures was >12 mmHg (P < 0.005). Conversely, the mean LV pre‐A pressure in the clinical low probability or echocardiographic normal groups was <11 mmHg. Conclusion: Use of a standardized clinical algorithm to define the probability of diastolic function identifies patients with elevated LV filing pressure to the same extent as echocardiographic methods.
The impact of gestational stress and prenatal growth on emotional problems in offspring: a review
Authors: Rice F. , Jones I. , Thapar A.
Published: September 2006

Objective:  Events occurring very early in life, even prenatally, may have long‐term effects on future health and behaviour. The influence of poor foetal growth and gestational stress in the mother on the risk of emotional problems in offspring was reviewed.

Method:  A selective review of the literature was undertaken.

Results:  Studies of preterm infants and infants born small for gestational age have shown increased levels of emotional problems across the lifespan. In general, studies examining maternal depression/anxiety during pregnancy and other indices of gestational stress have shown significant associations with emotional problems in children. The results of several studies also point to the importance of psychosocial and genetic factors in moderating associations.

Conclusion:  Future research that focuses on identifying the mechanisms underlying these associations is needed. The moderating role of psychosocial and genetic risk factors is an important area in which future research should be directed. These findings have clinical implications for the provision of antenatal care.
Generalized anxiety disorder: a 40‐year follow‐up study
Authors: Rubio G. , López‐Ibor J. J.
Published: September 2006

Objective:  There is insufficient knowledge of the long‐term course of generalized anxiety disorder (GAD). We studied the course of this disorder in patients who were followed up for 40 years.

Method:  Patients admitted with the diagnosis of anxiety states (‘anxious thymopathy’ ) to the Lopez Ibor Neuropsychiatric Research Institute between 1950 and 1961 were examined between 1984 and 1988 (n = 65). The retrospective diagnosis of GAD was made according to DSM‐III‐R criteria during 1984–1988 (first examination). A re‐examination was performed by the same psychiatrist in the period 1997–2001 (n = 59; second examination).

Results:  At first and second examinations 20% and 17% of subjects were diagnosed as GAD. Improvement was observed in 83%. GAD tended to disappear around age 50, but was replaced by somatization disorders. Lack of regular treatment compliance, female sex, and onset of GAD before age 25 were variables associated with a worse outcome. Undifferentiated somatization disorder was the most prevalent clinical status at follow‐up.

Conclusion:  After several decades, participants improve with regard to GAD, although most continue to present somatizations.
Benefit of “one‐stage full‐mouth disinfection” is explained by disinfection and root planing within 24 hours: a randomized controlled trial
Authors: Quirynen Marc , De Soete Marc , Boschmans Geert , Pauwels Martine , Coucke Wim , Teughels Wim , Van Steenberghe Daniel
Published: September 2006

Objectives: The beneficial effects of the one‐stage, full‐mouth disinfection remain controversial in the scientific literature. This might be due to the fact that an entire mouth disinfection with the use of antiseptics has been confused with a full‐mouth scaling and root planing. This parallel, single blind RCT study aimed to compare several full‐mouth treatment strategies with each other.

Material and methods: Seventy‐one patients with moderate periodontitis were randomly allocated to one of the following treatment strategies: scaling and root planing, quadrant by quadrant, at two‐week intervals (negative control, NC), full‐mouth scaling and root planing within 2 consecutive days (FRP), or three one‐stage, full‐mouth disinfection (FM) protocols within 2 consecutive days applying antiseptics to all intra‐oral niches for periopathogens using as antiseptics: chlorhexidine (FMCHX) for 2 months, amine fluoride/stannous fluoride for 2 months (FMF), or chlorhexidine for 2 months followed by amine fluoride/stannous fluoride for another 6 months (FMCHX+F). At baseline and after 2, 4, and 8 a series of periodontal parameters were recorded.

Results: All treatment strategies resulted in significant (p<0.05) improvements of all clinical parameters over the entire duration of the study. Inter‐treatment differences were often encountered. The NC group nearly always showed significant smaller improvements than the two CHX groups. The differences between the FRP or FM groups, and the two CHX groups only sporadically reached a statistical significance.

Conclusion: These observations indicate that the benefits of the “OSFMD” protocol are partially due to the use of the antiseptics and partially to the completion of the therapy in a short time.
Adherence to a daily flossing regimen in university students: effects of planning when, where, how and what to do in the face of barriers
Authors: Schüz Benjamin , Sniehotta Falko F. , Wiedemann Amelie , Seemann Rainer
Published: September 2006

Objectives: Regular (daily) dental flossing is recommended for preventing oral diseases, but adherence is unsatisfactory. Social cognitive theory (SCT) specifies determinants of dental flossing: Cognitions about risk, positive and negative outcome expectations and the perceived ability to perform behaviour predict motivation, which in turn predicts behaviour. Recent research suggests that motivation alone may not suffice to predict behaviour, and proposes if‐then‐planning. This study aims to predict flossing adherence from social cognitive variables and planning.

Material and Methods: Questionnaire data from 157 non‐dental university students on flossing, SCT variables and planning were gathered at three measurement points over 6 weeks. Residual floss was used to validate behaviour self‐reports.

Results: Social cognitive variables and planning correlated significantly with flossing at all times. Discriminant function analysis suggests that after controlling for Time 1 flossing, planning Time 2 (Wilk's λ=0.77; p<0.01) is more important in discriminating between adherent and non‐adherent participants at Time 3 than Time 1 social cognitive measures. Regression analyses confirmed this result with planning as only predictor of flossing change (p<0.05).

Conclusions: These results suggest targeting planning in interventions to increase compliance with flossing recommendations. Implications for such interventions are discussed.
The role of contact allergy to aeroallergens in atopic dermatitis
Authors: de Groot Anton C. , Young E.
Published: September 2006

In some patients with atopic dermatitis (AD), delayed‐type allergy to aeroallergens, such us house dust mite, can be demonstrated by patch testing. Positive patch tests can be expected only in patients with AD and, in them, only to aeroallergens to which type 1 reactions have also been demonstrated. In an as yet unknown number of such cases, aeroallergens appear lo play H role in AD. Studies to dale have varied too widely in experimental method and design to allow more definite conclusions 10 he drawn, It is essential that future studies are standardised with regard lo patch test system and designed to include adequate controls und assessment of relevance.
The murine local lymph node assay for identification of contact allergens: a preliminary evaluation of in situ measurement of lymphocyte proliferation
Authors: Kimber Ian , Hilton Jennifer , Weisenberger Claudia
Published: September 2006

A murine local lymph node assay for the identification of contact allergens has been developed. Contact sensitizing activity is measured as a function of lymphocyte proliferation in the draining lymph node following repeated application of the test agent to the dorsum of the ear. In original studies, lymphocyte proliferative activity was measured in vitro. In an attempt to remove the requirement for tissue culture, and thereby enhance the utility of the local lymph node assay as a predictive screening method, a new protocol has been evaluated in which proliferation in draining nodes is measured following i.v. injection of 3H‐thymidine.
Evaluation of a non‐invasive human and an in vitro cytotoxicity method as alternatives to the skin irritation test on rabbits
Authors: Jacobs Guido A. , Castellazzi Annamaria , Dierickx Paul J.
Published: September 2006

5 substances were investigated for their primary irritant effect by means of different protocols. The cutaneous blood flow values (CBFV) were measured in humans: in a 1st series of experiments 12 h after application of the pure substances for 48 h and in a 2nd series of experiment 1, 24. 48 and 72 after application of the 10% diluted substances (subclinical concentration) for 3 h. Rabbit skin erythema scores were obtained 1, 24, 48 and 72 h after application of the undiluted substances for 4 h. The undine uptake inhibition assay on KB cells was included as a cytotoxicity test. Results obtained for both protocols on humans are compared with each other and with the test data obtained on rabbits, and with the cytotoxicity data. Application of the undiluted substances for 48 h on human skin or for only 3 h at 10% dilution resulted in the same ranking between the substances. The CBFV in the human correlated very well (r = 0.99) with erythema scores obtained on rabbits. A poor correlation was observed between the in vitro and the in vivo results. From this study, it can be concluded that CBFV measurement is a valid method For the detection of erythema at subclinical concentrations.
Nickel dermatitis from cheap earrings
Authors: Santucci B. , Ferrari P. V. , Cristaudo A. , Cannistraci C. , Picardo M.
Published: September 2006

In 1988, 64% of our patients patch test positive to al least I allergen of the ICDRG standard series‐were nickel sensitive. In 70% of 300 patients evaluated, dermatitis started on the earlobes and was related to the regular wearing of cheap earrings. At the same time, 62% of 735 young schoolgirls were found to have dermatitis of their carlobes and all regularly wore cheap earrings. 9 clasps and clips commonly used in earrings released high quantities of nickel ions (between 49 and 103 μg/12 h), having been stored in synthetic sweat. A round piece cut from a clasp was taped U the skin of nickel‐sensitive patients, previously tested with 20 μl of NiSO4 5%, 2.5%, 1% aq. solutions, giving a response similar to that caused by the 5% solution. High daily absorption of Ni ions through the skin follows its repetitive exposure la cheap earring, causing, firstly, a direct inflammatory reaction, then followed, in our opinion, by sensitization.
A vision of cell death: Fas ligand and immune privilege 10 years later
Authors: Ferguson Thomas A. , Griffith Thomas S.
Published: September 2006

Summary:  Immune privilege is a term applied to organs that have a unique relationship with the immune response. These sites prohibit the spread of inflammation, since even minor episodes can threaten organ integrity and function. Once thought to be a passive process relying on physical barriers, immune privilege is now viewed as an active process, which uses multiple mechanisms to maintain organ function. The prototypic organ of immune privilege has been the eye, where the spread of inflammation can threaten vision. Nearly 10 years ago, we discussed the finding that Fas ligand (FasL) was constitutively expressed in the eye and played a major role in immune privilege by inducing apoptosis in inflammatory cells that enter the eye. In this review, we reexamine the original evidence for the role of FasL in immune privilege, update progress on some of the concepts, and discuss some of the issues that remain unresolved.
CNS immune privilege: hiding in plain sight
Authors: Carson Monica J. , Doose Jonathan M. , Melchior Benoit , Schmid Christoph D. , Ploix Corinne C.
Published: September 2006

Summary:  Central nervous system (CNS) immune privilege is an experimentally defined phenomenon. Tissues that are rapidly rejected by the immune system when grafted in sites, such as the skin, show prolonged survival when grafted into the CNS. Initially, CNS immune privilege was construed as CNS isolation from the immune system by the blood–brain barrier (BBB), the lack of draining lymphatics, and the apparent immunoincompetence of microglia, the resident CNS macrophage. CNS autoimmunity and neurodegeneration were presumed automatic consequences of immune cell encounter with CNS antigens. Recent data have dramatically altered this viewpoint by revealing that the CNS is neither isolated nor passive in its interactions with the immune system. Peripheral immune cells can cross the intact BBB, CNS neurons and glia actively regulate macrophage and lymphocyte responses, and microglia are immunocompetent but differ from other macrophage/dendritic cells in their ability to direct neuroprotective lymphocyte responses. This newer view of CNS immune privilege is opening the door for therapies designed to harness autoreactive lymphocyte responses and also implies (i) that CNS autoimmune diseases (i.e. multiple sclerosis) may result as much from neuronal and/or glial dysfunction as from immune system dysfunctions and (ii) that the severe neuronal and glial dysfunction associated with neurodegenerative disorders (i.e. Alzheimer’s disease) likely alters CNS‐specific regulation of lymphocyte responses affecting the utility of immune‐based therapies (i.e. vaccines).
Immune resistance orchestrated by the tumor microenvironment
Authors: Gajewski Thomas F. , Meng Yuru , Blank Christian , Brown Ian , Kacha Aalok , Kline Justin , Harlin Helena
Published: September 2006

Summary:  It is now little disputed that most if not all cancer cells express antigens that can be recognized by specific CD8+ T lymphocytes. However, a central question in the field of anti‐tumor immunity is why such antigen‐expressing tumors are not spontaneously eliminated by the immune system. While in some cases, this lack of rejection may be due to immunologic ignorance, induction of anti‐tumor T‐cell responses in many patients has been detected in the peripheral blood, either spontaneously or in response to vaccination, without accompanying tumor rejection. These observations argue for the importance of barriers downstream from initial T‐cell priming that need to be addressed to translate immune responses into clinical tumor regression. Recent data suggest that the proper trafficking of effector T cells into the tumor microenvironment may not always occur. T cells that do effectively home to tumor metastases are often found to be dysfunctional, pointing toward immunosuppressive mechanisms in the tumor microenvironment. T‐cell anergy due to insufficient B7 costimulation, extrinsic suppression by regulatory cell populations, inhibition by ligands such as programmed death ligand‐1, metabolic dysregulation by enzymes such as indoleamine‐2,3‐dioxygenase, and the action of soluble inhibitory factors such as transforming growth factor‐β have all been clearly implicated in generating this suppressive microenvironment. Identification of these downstream processes points to new therapeutic targets that should be manipulated to facilitate the effector phase of anti‐tumor immune responses in concert with vaccination or T‐cell adoptive transfer.
BRINGING THE OUTSIDE IN
Authors: Rosato Jennifer L.
Published: September 2006

In teaching the law related to child protection, it is important to expose students to policy, theory, and practice. This article suggests a variety of ways to include these perspectives in the traditional classroom, including role‐plays, guest speakers, and a one‐credit externship made available to a limited number of students. These methods are part of an overall classroom experience that is problem oriented and that values student contributions to class discussion.
PRIVATIZATION OF CHILD PROTECTIVE SERVICES
Authors: Freeman Marsha B.
Published: September 2006

Florida is a state in flux in terms of its child protective services organization. The Department of Children and Families has suffered numerous failures in protecting children in its care. Publicity surrounding these defects have led to major overhauls in the agency itself, as well as a concerted effort to move forward toward privatization of virtually all services currently administered by the department. Many of the initial attempts at privatization have already failed; others have had to be revamped to allow for unforseen problems. It is appallingly true that Florida, like any other state with serious issues in child protective services, has an absolute obligation to search for the “miracle cure” for its ailments. But only serious attention to the mistakes of the past and the will to correct them will allow Florida to finally put its children first in its citizens' hearts and minds, where they belong.
PEDOPHILIA
Authors: Bahroo Bhagwan A.
Published: September 2006

Sex offenses against children are considered the worst of crimes, even among criminals themselves. Attitudes have changed from blaming the victim to holding the perpetrator responsible for the actions. The prevalence of such offenses continues unabated despite the stigma for the offender and the irreparable trauma to the victim. Society and the medical and legal communities have to present a more feasible definition of the problem, addressing specifically the acts that fall under the term of pedophilia. A plan needs to be formulated by various disciplines working together for the common goal of identifying the most effective method to deal with the victims and perpetrator and also to lower the incidence and recidivism rates. Different psychological and biological tests have been devised for investigations but fall short of the desired purpose. Various treatment modalities have been suggested and tried, but much work still needs to be done in that area.
EMBRYO ADOPTION
Authors: Batsedis Olga
Published: September 2006

With the rise of in vitro fertilization, society wrestles with a new dilemma—what is the destiny of all unused embryos? Although some suggest using the embryos for scientific research, others advocate giving them up for adoption. This article therefore explores the moral and legal issues surrounding embryo adoption, its advantages and disadvantages, and its impact on families. In comparing embryo adoption to traditional adoption, this article concludes that embryo adoption is an effective alternative.
THE HAGUE CONVENTION ON INTERNATIONAL CHILD ABDUCTION AND THE GRAVE RISK OF HARM EXCEPTION
Authors: Moskowitz Galit
Published: September 2006

International child abduction is a problem that affects families around the world. The Hague Convention on the Civil Aspects of International Child Abduction was instituted to ensure that abducted children are promptly and safely returned home. Although the goal has been met, recent decisions and their use of Article 13(b) have limited the return of children to Israel on the premise that political turmoil and increased incidences of terrorist attacks constitute war. Although few would dispute that the recent escalation of terrorist attacks in Israel is troublesome, these incidences do not rise to the level of war. Such interpretations of Article 13(b) is too broad and undermines the Convention's policies. Unfortunately, in the global post‐September 11th climate, terror attacks are inevitable throughout the world. In light of this harsh reality, courts must not be quick to declare that a country is a zone of war absent clear and convincing evidence.
THE BOOKSHELF
Authors: Stahl Philip M.
Published: September 2006

Books reviewed in this article:

G. Andrew Benjamin and Jackie Gollan, Family Evaluation in Custody Litigation: Reducing Risks of Ethical Infractions and Malpractice.
Whittaker Chambers's Witness and the Dilemma of a Modern Conservatism
Authors: Kimmage Michael
Published: September 2006

Published in 1952, Witness is the memoir of Whittaker Chambers (1901–61). A former spy for the Soviet Union, Chambers was among the most influential anti‐communists and conservatives of the 1950s. He wrote Witness to further an anti‐communist conservatism. By the objective criterion of influence, Chambers enjoyed unusual success: his book was read by a mass audience and by politicians alike; it was cherished by Ronald Reagan, who brought his own anti‐communist conservatism to the White House in 1980. Yet a careful reading of Witness complicates the story of its influence. Chambers had profound doubts about modernity and modern America. He thought that a secular capitalist modernity had undermined Western culture and America alike. Capitalism and technology may yield great power, but they also corrupt cultural integrity. Witness is as much the record of spiritual anguish within the modern world, of modern conservatism experienced as dilemma, as it is a Cold War call to arms. Chambers's anti‐communist words and energy inspired Reagan and his neoconservative admirers, but by cheerfully embracing modern America they ignored the key dilemma of Chambers's eight‐hundred‐page autobiography. Witness can thus be used to track the intellectual evolution of an increasingly modern American conservatism.
Design of a vapor transport deposition process for thin film materials
Authors: Hanket G. M. , McCandless B. E. , Buchanan W. A. , Fields S. , Birkmire R. W.
Published: September 2006

A vapor transport process for continuous deposition of elemental and compound thin film materials is presented. The process saturates a carrier gas with a vapor from a subliming source. The saturated mixture is directed over a substrate at lower temperature, resulting in a supersaturation condition and subsequent film growth. The process geometry, comprising the dimensions of the saturation and deposition zones, carrier gas pressure and flow rate, and saturation zone temperature are determined by calculating worst-case characteristic times and simply insuring that the residence time of the carrier gas sufficiently exceeds these times. A model was used to design a system, which is currently being used to deposit 1–10μm thick CdTe films on a 10×10cm2 translating substrate. The process produces film thickness uniformity to within ±5% in the translation direction and across the deposition zone, with a material utilization of 50%. Linear translation speed of 12.5cm∕min has been demonstrated in depositing a 4.5μm CdTe film. The vapor transport process has also been used to deposit CdxZn1−xTe alloy films over a wide range of compositions by addition of ZnTe to the source. Photovoltaic conversion efficiencies of >13% for CdTe and >12% for CdxZn1−xTe have been achieved by devices fabricated from vapor transport deposited films deposited on to moving CdS coated substrates. Refinements are suggested for commercial-scale deposition.
Optical diagnostics for plasma-surface interaction in CF4∕Ar radio-frequency inductively coupled plasma during Si and SiO2 etching
Authors: Miyoshi Y. , Miyauchi M. , Oguni A. , Makabe T.
Published: September 2006

Highly selective etching of SiO2 over Si is central to the manufacture of ultralarge scale integration devices; the process is generally one of reactive ion etching using polymerizing fluorocarbon chemistry. A number of species including electrons, ions, and radicals are generated by reactions in the gas phase and on the surface in the plasma process. A large number of highly reactive fluorine atoms, fluorocarbon radicals, and ions interact with the substrate and produce etch products. These etch products, primarily SiF4 and SiF2, diffuse back into the bulk plasma where they are dissociated and ionized by interactions with electrons, and the resultant products are transported and redeposited onto the substrate and/or wall surface. That is, the plasma structure may differ depending on whether the Si (or SiO2) surface has been exposed to etching or not. Hence, it is essential to investigate the spatiotemporal characteristics of the plasma structure during etching. In this study, measurements of plasma structure during Si or SiO2 etching in CF4∕Ar radio-frequency inductively coupled plasma (rf-ICP) were performed using computerized tomography of optical emission spectroscopy to investigate plasma-surface interactions. We focused on the characteristics of etch products, their daughter products, and the etchant in the gas phase during Si and SiO2 etching in CF4∕Ar rf-ICP and the disturbance of the plasma structure at high amplitudes of LF bias.
Topography in secondary ion mass spectroscopy images
Authors: Rangarajan Srinath , Tyler Bonnie J.
Published: September 2006

Interpretation of time-of-flight secondary ion mass spectroscopy (TOF-SIMS) images from rough samples such as particles, fibers, or biological specimens can be problematic because the images are influenced not only by the sample chemistry but also by topographical features. In this article we have investigated the influence of spherical and cylindrical features on total ion yields, relative ion yields, and feature shape. TOF-SIMS images of Pluronic coated fibers and polystyrene spheres were collected using both triple focusing time and reflectron geometry instruments and a 25keV Ga+ primary ion source. The fibers and spheres were analyzed on both conducting and insulating substrates to assess the importance of field effects. Trends in the images have been explored using principal components analysis and Poisson and multinomial mixture models. The T2 test was employed to assess the statistical significance of results. The results identify three important topographic effects. The size and shape of features can be distorted as a result of the incidence angle of the primary ion beam. Additionally, both the absolute and relative intensities of ion peaks vary as a result of topography. In regions where the primary ion beam impacted the sample at a glancing angle, the relative intensity of molecular fragments characteristic of the Pluronic surfactant was up to three times higher than in regions where the beam impacted the sample at a normal angle. Comparison of results from conducting and insulating samples suggests that changes in the relative ion yields resulted primarily from differences in the incidence angle of the primary ion beam while changes in the total ion yield are influenced by both the incidence angle and distortion of the electric field by the particle. This study documents that topographic features can influence not only the absolute intensity of ion peaks but can also alter peak ratios in a statistically significant manner. In this light, a greater degree of caution is recommended when interpreting TOF-SIMS images from topographically complex samples.
Sorption and desorption behaviors of hexadecane vapors in plasma deposited fluorocarbon films using a quartz crystal microbalance
Authors: Vaswani Sudeep , Koskinen Jere , Hess Dennis W.
Published: September 2006

Fluorocarbon films can provide barrier properties such as hydrophobicity and oleophobicity to paper- and cellulose-based materials. While qualitative methods such as “oil kit tests” provide information on grease barrier properties, they do not quantify the extent of grease barrier properties. In this study, we report the sorption and desorption behaviors of a grease surrogate (hexadecane) vapor in plasma polymerized fluorocarbon films deposited from pentafluoroethane. Three different film thicknesses (0.5, 0.75, and 1μm) were exposed to varying concentrations of hexadecane vapor and uptake evaluated using a quartz crystal microbalance. The amount of hexadecane sorbed in the fluorocarbon film increased with hexadecane concentration until film saturation occurred, at which point the mass of hexadecane sorbed no longer increased with concentration. While the amount of hexadecane sorbed for a given hexadecane concentration increased with film thickness, the wt % of hexadecane sorbed into the fluorocarbon film was essentially independent of the film thickness reaching ∼0.6% of the maximum hexadecane concentration studied for all film thicknesses. These results indicate that fluorocarbon films have low affinity for hexadecane vapor. Transient sorption and desorption studies were also conducted using hexadecane vapor; both processes followed dual-mode sorption behavior. Diffusivities of hexadecane as determined from sorption and desorption were ∼10−13cm2∕s.
Control of the plasma polymerized acrylic acid film surface chemistry at low electron temperature in low pressure discharge
Authors: Dhayal Marshal
Published: September 2006

A two-stage (primary and processing) [M. Dhayal and J. W. Bradley, Surf. Coat. Technol. 184, 116 (2004)] plasma discharge was used to control the surface chemistry of plasma polymerized acrylic acid (ppAc) films at low ion energy (electron temperature). The discharge conditions in step processing plasma were classified in two regions associated with different distances from the grid separating primary and processing plasmas. The first region showed a steep decrease in electron temperature associated with higher electron collision possibilities with the gas molecules. In the second region a steep decrease in the plasma density that is possibly due to plasma recombination in this region was observed. The analysis of surface chemistry of ppAc films deposited at different positions in these regions was characterized by x-ray photoelectron spectroscopy. In the first region very near the grid results showed that the surface chemistry depends on the neutral or radical diffusing from the primary discharges through the grid. A further increase in the distance from the grid in the first region showed that the energetic electrons’ collisions with the gas molecules can significantly change the surface chemistry. The electrons’ collisions with the gas molecules can dissociate higher masses into smaller masses. Therefore, an increase in the O∕C and –C(O) functionalities at the surface was measured in this region. In the second region, plasma recombination played a significant role to determine the surface chemistry due to creation of highly reactive radicals and fast neutrals. Therefore, an increase in –COX function was seen at the surface of the films.