bluuebunny/crossref_metadata_2025 huggingface dataset:
Anxiety sensitivity as predictor of pain in patients undergoing restorative dental procedures
Authors: Klages Ulrich , Kianifard Simin , Ulusoy Özlem , Wehrbein Heinrich
Published: March 2006

Abstract –  Objectives:  The personality disposition to anxiety sensitivity refers to beliefs about negative consequences of bodily arousal. The concept has recently been successfully applied in research on chronic pain conditions. The present study investigated whether anxiety sensitivity interacts with dental fear to increase expected and experienced pain during routine dental treatment.

Methods:  Subjects were 97 patients undergoing dental procedures of excavation and filling. Anxiety dispositions were measured by the Anxiety Sensitivity Index and the Dental Anxiety Scale. Expected and experienced pain were assessed by affective and sensory verbal descriptor scales and a numerical rating scale measuring pain intensity.

Results:  Dentally fearful patients scoring high in anxiety sensitivity both expected and experienced more pain than low scorers did. Significant interactions were found predicting expected affective and intense pain and experienced pain intensity.

Conclusion:  The results lend support to the assumption that dentally fearful patients with a disposition to high anxiety sensitivity amplify pain anticipations when exposed to the critical situation. When dentally fearful patients are under treatment, their beliefs about negative consequences of bodily arousal may negatively influence their evaluation of treatment related pain.
Application of nonhomogenous Markov models for analyzing longitudinal caries risk
Authors: Kopycka‐Kędzierawski D. T. , Billings R. J.
Published: March 2006

Abstract –  Objectives:  Markov modeling is a useful mathematical procedure for calculating probabilities of disease prognosis. Increasingly, Markov models are being applied in medical and health services research and also in social sciences research. The purpose of our study was to use the Markov process to determine time‐dependent transition probabilities for caries‐free children to convert to a caries‐active state and to assess the impact of salivary mutans streptococci (MS) levels on caries status.

Methods:  Our analysis was based on data obtained from a 6‐year longitudinal study of risk factors associated with caries onset in children.

Results:  Based on a two‐state Markov model, the probability that a caries‐free child would convert to a caries‐active state during the study ranged between 0.0046 and 0.0471. The highest probability of converting from a caries‐free state to a caries‐active state was 0.0471 at age 8.5 years.

Conclusions:  In addition to standard statistical methods of analyzing longitudinal caries data, Markov models show promise for use in the analysis of caries risk.
Multilevel assessment of determinants of dental caries experience in Brazil
Authors: Antunes José Leopoldo Ferreira , Peres Marco Aurélio , Mello Tatiana Ribeiro de Campos , Waldman Eliseu Alves
Published: March 2006

Abstract –  Objective:  To examine contextual and individual determinants of dental caries experience, documenting levels of the disease in Brazil.

Methods:  The dental status of 34 550 12‐year‐old schoolchildren was informed by a country‐wide survey of oral health comprising 250 towns and performed in 2002–2003. Indices assessing dental caries experience were compared by sociodemographic characteristics of examined children (gender, ethnic group, localization and type of school), and geographic characteristics of participating towns [the human development index (HDI), and access to fluoridated tap water]. A multilevel model fitted the adjustment of untreated caries to individual and contextual covariates.

Results:  Better‐off Brazilian regions presented an improved profile of dental health, besides having a less unequal distribution of restorative dental treatments between blacks and whites, rural and urban areas, and public and private schools. Girls [odds ratio (OR) = 1.1; 95% confidence interval (CI): 1.0–1.1], blacks (OR = 1.6; 95% CI: 1.5–1.7), and children studying in rural areas (OR = 1.9; 95% CI: 1.7–2.0) and public schools (OR = 1.7; 95% CI: 1.6–1.9) presented higher odds of having untreated decayed teeth. The multilevel model identified the fluoride status of tap water (β = −0.3), the proportion of households linked to the water network (β = −0.3), and the HDI (β = −0.2), as town‐level variables associated with caries levels.

Conclusion:  Dental caries experience is prone to sociodemographic and geographic inequalities. The monitoring of contrasts in dental health outcomes is relevant for programming socially appropriate interventions aimed both at overall improvements and at the targeting of resources for groups of population presenting higher levels of needs.
Fibroblast growth factor‐2 expression during experimental oral carcinogenesis. Its possible role in the induction of pre‐malignant fibrosis
Authors: Raimondi A. R. , Molinolo A. A. , Itoiz M. E.
Published: March 2006

Background:  The fibroblastic growth factor (FGF)‐2 has been shown to induce angiogenesis in several tumor types. To date, the activity of FGF during the development of oral pre‐cancerous lesions has not been analyzed. We herein evaluated the role of FGF‐2 in the pre‐cancerous and cancerous lesions in the hamster cheek pouch oral cancer model.

Methods:  Expression of FGF‐2 and its receptors FGFR‐2 and FGFR‐3 was assessed by immunohistochemistry at different stages of the carcinogenesis protocol. Activity of FGF‐2 isoforms was analyzed by Western blots.

Results:  Increase and abnormal localization of FGF‐2 expression was evident in cancerized epithelium before it was possible to detect morphologic alterations. The changes in FGF‐2 are concomitant with the evolution of subepithelial fibrosis. Immunolabeling of carcinomas was faint or completely negative. Increases of FGF‐2 activity are mainly due to the increase in the 18 kDa isoform. Receptors 2 and 3 of FGF are present in epithelium, fibroblasts, and vascular endothelia of control samples and in all stages of malignant transformation.

Conclusions:  Our results would suggest a role for FGF‐2 in the epithelium–connective interactions and a deregulation of its expression in the early stages of oral cancerization. In pre‐cancerous tissue FGF‐2 would play a central role in the development of fibrosis and a more collateral role in the induction of angiogenesis. The data would indicate its involvement in the process via the 18 kDa isoform.
Solitary angiokeratoma of the tongue
Authors: Siponen Maria , Penna Tomi , Apaja‐Sarkkinen Meeri , Palatsi Riitta , Salo Tuula
Published: March 2006

Angiokeratoma is a rare, cutaneous vascular disorder that can occur in several clinically distinct conditions. It usually presents as multiple, red to blue or black, asymptomatic papules on the skin. Oral mucosal involvement is common in the systemic form, but very rare in the localized forms of angiokeratomas. We report the second case of a solitary papular angiokeratoma of the oral cavity.
Salivary interleukin‐6 and tumor necrosis factor‐α in patients with recurrent aphthous ulceration
Authors: Boras V. Vučićević , Lukač J. , Brailo V. , Picek P. , Kordić D. , Žilić I. Alajbeg
Published: March 2006

Background:  Recurrent apthous ulceration (RAU) is a well known oral disease which seems to be mediated principally by the immune system. However, it is still a matter of debate which part of the immune system is implicated in its pathogenesis as a reaction to the still unknown antigen. The aim of this study was to evaluate salivary cytokines, interleukin (IL)‐6, and tumor necrosis factor (TNF)‐α.

Methods:  In 26 patients with minor RAU, age range of 23–49 years (mean 27.3 years), during both the acute phase and remission and in 26 healthy controls, age range of 22–64 years (mean 30.1 years), salivary IL‐6 and TNF‐α levels were determined by use of enzyme‐linked immunosorbent assay (ELISA). Statistical analysis was performed by use of descriptive statistics.

Results:  Significant differences in salivary TNF‐α between healthy controls and patients with acute RAU and during the remission period were found (P < 0.001) as well as between patients with acute RAU and those during the remission period (P < 0.001). No differences in salivary IL‐6 between all three groups could be found.

Conclusions:  We might conclude that elevated salivary TNF‐α levels during acute RAU and especially during the remission period are of importance in RAU, whereas salivary IL‐6 levels seem not to play a role in the RAU disease.
GSTM1 polymorphism and oral leukoplakia
Authors: Duarte Eliza Carla Barroso , da Silva Marina Sena Lopes , Gomez Marcus Vinícius , Gomez Ricardo Santiago
Published: March 2006

Background:  Molecular epidemiological studies have now provided evidence that an individual susceptibility to cancer is mediated by genetic and environmental factors. Genetic polymorphisms have been described for enzymes involved in the metabolism of tobacco carcinogens and cancer risk is determined by the degree of expression and/or activity of enzymes involved in carcinogen activation or deactivation. The objective of this study was to investigate the GSTM1 null polymorphism and the risk for oral leukoplakia in individuals with tobacco‐smoking habit in a Brazilian population.

Methods:  A total of 52 tobacco‐smoking patients with oral leukoplakia and 52 tobacco‐smoking controls were recruited in a Brazilian population. The GSTM1 genotypes were studied by polymerase chain reaction‐based methods.

Results:  The frequency of the GSTM1 null genotype in the group with oral leukoplakia (57.7%) was statistically different from the controls (34.6%; OR: 2.57, 95% CI: 1.16–5.69, P < 0.05). The stratification of the samples according to the level of dysplasia showed increased prevalence of GSTM1 null genotype on lesions with moderate/severe histological dysplasia (68.2%) compared with the control group (31.9%). This difference was statistically significant (OR: 4.59, 95% CI: 1.29–16.33, P < 0.05).

Conclusion:  In conclusion, the GSTM1 null genotype may increase the risk for oral leukoplakia development.
The role of histopathological characteristics in distinguishing amalgam‐associated oral lichenoid reactions and oral lichen planus
Authors: Thornhill Martin H. , Sankar Vidya , Xu Xiao‐Jun , Barrett A. William , High Alec S. , Odell Edward W. , Speight Paul M. , Farthing Paula M.
Published: March 2006

Objectives:  To identify histological features that distinguish amalgam‐associated oral lichenoid reactions (AAOLR) from oral lichen planus (OLP).

Methods:  Oral pathologists provided their opinion as to the possibility of distinguishing AAOLR and OLP histologically, the features important in distinguishing AAOLR from OLP and the diagnosis of 12 AAOLR and 12 OLP cases including the features that drew them to their conclusion.

Results:  There was considerable variation between pathologists in their ability to distinguish the AAOLR and OLP cases. The sensitivity and specificity for histological diagnosis were 40% and 32% respectively. There were four features that were used most commonly to discriminate between AAOLR and OLP: an inflammatory infiltrate located deep to superficial infiltrate in some or all areas; a focal perivascular infiltrate; plasma cells in the connective tissue and neutrophils in the connective tissue. Each was independently predictive of AAOLR or OLP (P < 0.028).

Conclusions:  This study confirms the uncertainty of the diagnostic histological differences between AAOLR and OLP. Distinguishing these conditions should not rely on histology alone, but should be based on a synthesis of all available information including history, examination, histopathology and skin patch testing.
Gene expression analysis by cDNA microarray in oral squamous cell carcinoma
Authors: Tomioka Hirofumi , Morita Kei‐ichi , Hasegawa Shogo , Omura Ken
Published: March 2006

Background:  Oral squamous cell carcinoma (OSCC) is common type of human cancer, but little is known about the molecular mechanisms deciding on this malignancy. Comprehensive gene expression profiling is essential for understanding OSCC.

Methods:  cDNA microarray was used to analyze expression patterns of 16 617 genes in nine OSCC patients.

Results:  Forty‐seven genes with altered expression among all cases were extracted. The ontology of these 47 genes was classified into 10 categories. To validate the microarray data, the expression of genes, including TGFBI, FADD and DUSP1 was analyzed by reverse transcriptase‐polymerase chain reaction (RT‐PCR). By hierarchical clustering analysis, the nine cases were divided into two clusters.

Conclusions:  The 47 genes are suggested as having a functional significance in oral squamous cell carcinogenesis. It is also suggested that the gene expression patterns by hierarchical clustering analysis can represent degrees of differentiation. The postoperative recovery was uneventful and patients free from tumor after surgery. In the future, on the occasion when the time comes that the number of cases accumulated for microarray increases and each case is observed more over a long‐term, these data of 5‐year survival rate will be added. Thereby, it will become possible to represent the malignancy of OSCC by these gene expression patterns.
A simple test for salivary gland hypofunction using Oral Schirmer's test
Authors: López‐Jornet Pia , Camacho‐Alonso Fabio , Bermejo‐Fenoll Ambrosio
Published: March 2006

Objective: The objective of this study was to develop a test for detecting salivary gland hypofunction.

Study Design: Oral Schirmer's test was performed by placing a strip of filter paper on the floor of the mouth and measuring the wetted length after 5 min. The control group consisted of 70 healthy patients, while another group consisted of 61 patients with Sjögren's Syndrome (SS) and a third group of 31 patients who suffered from xerostomia caused by other pathologies.

Results: The mean saliva flow was 40.92 ± 22.28 mm/5 min in the control group, 27.25 ± 24.11 mm/5 min in patients with SS and 36.847 ± 23.4 mm/5 min in the third group. The differences between the control group and the other two groups were statistically different (P > 0.001).

Conclusions: The whole saliva test was used to distinguish between healthy adults and subjects with hyposalivation.
Histological evaluation of a replanted tooth retained for 49 years
Authors: Keklikoglu Nurullah , Asci Selmin Kaan
Published: March 2006

Abstract –  A maxillary incisor that had been replanted immediately after avulsion 49 years previously was evaluated histologically after extraction. The histological evaluation revealed resorption of the apical root surface, depositions in cement with different phases and mineral density, and histological changes in the periodontal ligament.
Orofacial injury in a Brazilian professional basketball player: case report
Authors: Dos Santos Ana Paula Pires , Monte Alto Luciane A.
Published: March 2006

Abstract –  The frequency of dental trauma has increased among children and athletes of all ages who play contact sports. This kind of trauma may result in irreversible damage to the patient. The aim of this report is to present a case of an orofacial trauma involving a professional basketball player who was elbowed by another player. The athlete reported loss of sensitivity in three teeth and computerized tomography showed fractures in three points of the malar bone. After the incident and dental follow‐up, the player was made aware of the need to wear a mouthguard.
Genetic and environmental interactions determine seizure susceptibility in epileptic EL mice
Authors: Todorova M. T. , Mantis J. G. , Le M. , Kim C. Y. , Seyfried T. N.
Published: March 2006

Gene identification has progressed rapidly for monogenic epilepsies, but complex gene–environmental interactions have hindered progress in gene identification for multifactorial epilepsies. We analyzed the role of environmental risk factors in the inheritance of multifactorial idiopathic generalized epilepsy in the EL mouse. Seizure susceptibility was evaluated in the EL (E) and seizure‐resistant ABP/LeJ (A) parental mouse strains and in their AEF1 and AEF2 hybrid offspring using a handling‐induced seizure test. The seizure test was administered in three environments (environments I, II and III) that differed with respect to the number of seizure tests administered (one test or four tests) and the age of the mice when tested (young or old). The inheritance of seizure susceptibility appeared dominant after repetitive seizure testing in young or old mice, but recessive after a single test in old mice. Heritability was high (0.67–0.77) in each environment. Significant quantitative trait loci (QTL) that were associated with environments I and III (repetitive testing) were found on chromosomes 2 and 9 and colocalized with previously mapped El2 and El4, respectively. The El2 QTL found in environment I associated only with female susceptibility. A novel QTL, El‐N, for age‐dependent predisposition to seizures was found on proximal chromosome 9 only in environment II. The findings indicate that environmental risk factors determine the genetic architecture of seizure susceptibility in EL mice and suggest that QTL for complex epilepsies should be defined in terms of the environment in which they are expressed.
Association between the CHRM2 gene and intelligence in a sample of 304 Dutch families
Authors: Gosso M. F. , Van Belzen M. , De Geus E. J. C. , Polderman J. C. , Heutink P. , Boomsma D. I. , Posthuma D.
Published: March 2006

The CHRM2 gene is thought to be involved in neuronal excitability, synaptic plasticity and feedback regulation of acetylcholine release and has previously been implicated in higher cognitive processing. In a sample of 667 individuals from 304 families, we genotyped three single‐nucleotide polymorphisms (SNPs) in the CHRM2 gene on 7q31–35. From all individuals, standardized intelligence measures were available. Using a test of within‐family association, which controls for the possible effects of population stratification, a highly significant association was found between the CHRM2 gene and intelligence. The strongest association was between rs324650 and performance IQ (PIQ), where the T allele was associated with an increase of 4.6 PIQ points. In parallel with a large family‐based association, we observed an attenuated – although still significant – population‐based association, illustrating that population stratification may decrease our chances of detecting allele–trait associations. Such a mechanism has been predicted earlier, and this article is one of the first to empirically show that family‐based association methods are not only needed to guard against false positives, but are also invaluable in guarding against false negatives.
Characterization of the dimerization process of a domain‐swapped dimeric variant of human pancreatic ribonuclease
Authors: Rodríguez Montserrat , Benito Antoni , Ribó Marc , Vilanova Maria
Published: March 2006

It has been previously reported that the structure of a human pancreatic ribonuclease variant, namely PM8, constitutes a dimer by the exchange of an N‐terminal domain, although in an aqueous solution it is found mainly as a monomer. First, we investigated the solution conditions that favour the dimerization of this variant. At 29 °C in a 20% (v/v) ethanol buffer, a significant fraction of the protein is found in dimeric form without the appearance of higher oligomers. This dimer was isolated by size‐exclusion chromatography and the dimerization process was studied. The dissociation constant of this dimeric form is 5 mm at 29 °C. Analysis of the dependence of the dimerization process on the temperature shows that unlike bovine pancreatic ribonuclease, a decrease in the temperature shifts the monomer–dimer equilibrium to the latter form. We also show that a previous dissociation of the exchangeable domain from the main protein body does not take place before the dimerization process. Our results suggest a model for the dimerization of PM8 that is different to that postulated for the dimerization of the homologous bovine pancreatic ribonuclease. In this model, an open interface is formed first and then intersubunit interactions stabilize the hinge loop in a conformation that completely displaces the equilibrium between nonswapped and swapped dimers to the latter one.
Site‐specific phosphorylation of MCM4 during the cell cycle in mammalian cells
Authors: Komamura‐Kohno Yuki , Karasawa‐Shimizu Kumiko , Saitoh Takako , Sato Michio , Hanaoka Fumio , Tanaka Shoji , Ishimi Yukio
Published: March 2006

MCM4, a subunit of a putative replicative helicase, is phosphorylated during the cell cycle, at least in part by cyclin‐dependent kinases (CDK), which play a central role in the regulation of DNA replication. However, detailed characterization of the phosphorylation of MCM4 remains to be performed. We examined the phosphorylation of human MCM4 at Ser3, Thr7, Thr19, Ser32, Ser54, Ser88 and Thr110 using anti‐phosphoMCM4 sera. Western blot analysis of HeLa cells indicated that phosphorylation of MCM4 at these seven sites can be classified into two groups: (a) phosphorylation that is greatly enhanced in the G2 and M phases (Thr7, Thr19, Ser32, Ser54, Ser88 and Thr110), and (b) phosphorylation that is firmly detected during interphase (Ser3). We present data indicating that phosphorylation at Thr7, Thr19, Ser32, Ser88 and Thr110 in the M phase requires CDK1, using a temperature‐sensitive mutant of mouse CDK1, and phosphorylation at sites 3 and 32 during interphase requires CDK2, using a dominant‐negative mutant of human CDK2. Based on these results and those from in vitro phosphorylation of MCM4 with CDK2/cyclin A, we discuss the kinases responsible for MCM4 phosphorylation. Phosphorylated MCM4 detected using anti‐phospho sera exhibited different affinities for chromatin. Studies on the nuclear localization of chromatin‐bound MCM4 phosphorylated at sites 3 and 32 suggested that they are not generally colocalized with replicating DNA. Unexpectedly, MCM4 phosphorylated at site 32 was enriched in the nucleolus through the cell cycle. These results suggest that phosphorylation of MCM4 has several distinct and site‐specific roles in the function of MCM during the mammalian cell cycle.
Oxygen binding properties of non‐mammalian nerve globins
Authors: Hundahl Christian , Fago Angela , Dewilde Sylvia , Moens Luc , Hankeln Tom , Burmester Thorsten , Weber Roy E.
Published: March 2006

Oxygen‐binding globins occur in the nervous systems of both invertebrates and vertebrates. While the function of invertebrate nerve haemoglobins as oxygen stores that extend neural excitability under hypoxia has been convincingly demonstrated, the physiological role of vertebrate neuroglobins is less well understood. Here we provide a detailed analysis of the oxygenation characteristics of nerve haemoglobins from an annelid (Aphrodite aculeata), a nemertean (Cerebratulus lacteus) and a bivalve (Spisula solidissima) and of neuroglobin from zebrafish (Danio rerio). The functional differences have been related to haem coordination: the haem is pentacoordinate (as in human haemoglobin and myoglobin) in A. aculeata and C. lacteus nerve haemoglobins and hexacoordinate in S. solidissima nerve haemoglobin and D. rerio neuroglobin. Whereas pentacoordinate nerve globins lacked Bohr effects at all temperatures investigated and exhibited large enthalpies of oxygenation, the hexacoordinate globins showed reverse Bohr effects (at least at low temperature) and approximately twofold lower oxygenation enthalpies. Only S. solidissima nerve haemoglobin showed apparent cooperativity in oxygen binding, suggesting deoxygenation‐linked self‐association of the monomeric proteins. These results demonstrate a remarkable diversity in oxygenation characteristics of vertebrate and invertebrate nerve haemoglobins that clearly reflect distinct physiological roles.
The decline and fall of GRS 1915+105: the end is nigh?
Authors: Truss Michael , Done Chris
Published: March 2006

The Galactic microquasar GRS 1915+105 has been in a continuous state of outburst since 1992, over 20 times longer than any other black hole X-ray transient. Assuming that the outburst is powered via accretion of an irradiated gaseous disc, we calculate how the predicted outburst duration varies according to the efficiency of the self-irradiation mechanism. At least one current model leads to the conclusion that the end of the outburst is imminent. The timing of the decline of GRS 1915+105, whenever it arrives, will be an excellent discriminator of the self-irradiation mechanism in X-ray transients, allowing us to infer the fraction of the disc that is heated by the incident X-rays and the magnitude of the mass loss rate in the form of a wind.
Fast and Frugal Heuristics1
Authors: Bishop Michael A.
Published: March 2006

A heuristic is a rule of thumb. In psychology, heuristics are relatively simple rules for making judgments. A fast heuristic is easy to use and allows one to make judgments quickly. A frugal heuristic relies on a small fraction of the available evidence in making judgments. Typically, fast and frugal heuristics (FFHs) have, or are claimed to have, a further property: They are very reliable, yielding judgments that are about as accurate in the long run as ideal non‐fast, non‐frugal rules. This paper introduces some well‐known examples of FFHs, raises some objections to the FFH program, and looks at the implications of those parts of the FFH program about which we can have some reasonable degree of confidence.
Renal function in juvenile rats subjected to prenatal malnutrition and chronic salt overload
Authors: Magalhães João Carlos G. , Da Silveira Alex B. , Mota Diogenes L. , Paixão Ana Durce O.
Published: March 2006

Dietary sodium may contribute to hypertension and to cardiovascular and renal disease if a primary deficiency of the kidney to excrete sodium exists. In order to investigate whether chronic 1% NaCl in the drinking water changes blood pressure and renal haemodynamics in juvenile Wistar rats subjected to prenatal malnutrition, an evaluation of plasma volume, oxidative stress in the kidney, proteinuria and renal haemodynamics was carried out. Malnutrition was induced by a multideficient diet. Mean arterial pressure, renal blood flow and glomerular filtration rate (GFR) were measured using a blood pressure transducer, a flow probe and inulin clearance, respectively. Plasma volume and oxidative stress were measured by means of the Evans Blue method and by monitoring thiobarbituric acid reactive substances (TBARS) in the kidneys, respectively. Urinary protein was measured by precipitation with 3% sulphosalicylic acid. It was observed that prenatally malnourished rats presented higher values of plasma volume (26%, P < 0.05), kidney TBARS (43%, P < 0.01) and blood pressure (10%, P < 0.01) when compared with the control group. However, they showed no change in renal haemodynamics or proteinuria. Neither prenatally malnourished nor control rats treated with sodium overload presented plasma volume or blood pressure values different from their respective control groups, but both groups presented elevated proteinuria (P < 0.01). The prenatally malnourished group treated with sodium overload presented higher values of kidney TBARS, GFR and filtration fraction (58, 87 and 72% higher, respectively, P < 0.01) than its respective control group. In summary, sodium overload did not exacerbate the hypertension in juvenile prenatally malnourished rats, but induced renal haemodynamic adjustments compatible with the development of renal disease.
Histamine mediates osteoclastic resorption only during the acute phase of bone loss in ovariectomized rats
Authors: Lesclous Ph. , Schramm F. , Gallina S. , Baroukh B. , Guez D. , Saffar J. L.
Published: March 2006

Short‐term studies have shown that histamine is involved, via its H2 receptors (H2R), in the mediator network regulating trabecular bone loss in long bones of ovariectomized (OVX) rats. It is not known whether this effect of histamine persists over time or involves other skeletal sites. In this study, rats were maintained for 6 months postOVX and treated daily with saline or famotidine (10 mg kg−1), an H2R antagonist. At the end of the experimental period, femur trabecular bone mass was markedly decreased in OVX rats, whether or not they were treated with famotidine. In contrast, in the fourth lumbar vertebra, where bone loss starts later than in the femur, famotidine treatment attenuated the decline in trabecular bone volume, protected the trabecular architecture, maintained the thickness of the cortices and reduced the numbers of osteoclasts and tartrate‐resistant acid phosphatase‐positive preosteoclasts, whereas it had no influence on bone formation parameters. In vertebral bone marrow of OVX rats, the numbers of mast cells (MCs) and non‐MC histamine‐producing cells increased, while famotidine treatment significantly diminished both cell populations. These data show that H2R antagonism does not protect trabecular bone mass in the long term, and that short‐term protection involves all bones. Histamine is involved during the early phase of strong osteoclastic resorption but not during the late phase of slower resorption, suggesting that different mediator networks control the two phases of destruction. Histamine would be part of the network mediating the early phase.
Characterization of voltage‐dependent sodium and calcium channels in mouse pancreatic A‐ and B‐cells
Authors: Vignali Sheila , Leiss Veronika , Karl Rosi , Hofmann Franz , Welling Andrea
Published: March 2006

Insulin and glucagon are the major hormones of the islets of Langerhans that are stored and released from the B‐ and A‐cells, respectively. Both hormones are secreted when the intracellular cytosolic Ca2+ concentration ([Ca2+]i) increases. The [Ca2+]i is modulated by mutual inhibition and activation of different voltage‐gated ion channels. The precise interplay of these ion channels in either glucagon or insulin release is unknown, owing in part to the difficulties in distinguishing A‐ from B‐cells in electrophysiological experiments. We have established a single‐cell RT‐PCR method to identify A‐ and B‐cells from the mouse. A combination of PCR, RT‐PCR, electrophysiology and pharmacology enabled us to characterize the different sodium and calcium channels in mouse islet cells. In both A‐ and B‐cells, 60% of the inward calcium current (ICa) is carried by L‐type calcium channels. In B‐cells, the predominant calcium channel is CaV1.2, whereas CaV1.2 and CaV1.3 were identified in A‐cells. These results were confirmed by using mice carrying A‐ or B‐cell‐specific inactivation of the CaV1.2 gene. In B‐cells, the remaining ICa flows in equal amounts through CaV2.1, CaV2.2 and CaV2.3. In A‐cells, 30 and 15% of ICa is due to CaV2.3 and CaV2.1 activity, respectively, whereas CaV2.2 current was not found in these cells. Low‐voltage‐activated T‐type calcium channels could not be identified in A‐ and B‐cells. Instead, two TTX‐sensitive sodium currents were found: an early inactivating and a residual current. The residual current was only recovered in a subpopulation of B‐cells. A putative genetic background for these currents is NaV1.7.
Vascular adrenergic responsiveness is inversely related to tonic activity of sympathetic vasoconstrictor nerves in humans
Authors: Charkoudian N. , Joyner M. J. , Sokolnicki L. A. , Johnson C. P. , Eisenach J. H. , Dietz N. M. , Curry T. B. , Wallin B. G.
Published: March 2006

In humans, sympathetic nerve activity (SNA) at rest can vary several‐fold among normotensive individuals with similar blood pressures. We recently showed that a balance exists between SNA and cardiac output, which may contribute to the maintenance of normal blood pressures over the range of resting SNA levels. In the present studies, we assessed whether variability in vascular adrenergic responsiveness has a role in this balance. We tested the hypothesis that forearm vascular responses to noradrenaline (NA) and tyramine (TYR) are related to SNA such that individuals with lower resting SNA have greater adrenergic responsiveness, and vice‐versa. We measured multifibre muscle SNA (MSNA; microneurography), arterial pressure (brachial catheter) and forearm blood flow (plethysmography) in 19 healthy subjects at baseline and during intrabrachial infusions of NA and TYR. Resting MSNA ranged from 6 to 34 bursts min−1, and was inversely related to vasoconstrictor responsiveness to both NA (r= 0.61, P= 0.01) and TYR (r= 0.52, P= 0.02), such that subjects with lower resting MSNA were more responsive to NA and TYR. We conclude that interindividual variability in vascular adrenergic responsiveness contributes to the balance of factors that maintain normal blood pressure in individuals with differing levels of sympathetic neural activity. Further understanding of this balance may have important implications for our understanding of the pathophysiology of hypertension.
Dynamic association between α‐actinin and β‐integrin regulates contraction of canine tracheal smooth muscle
Authors: Zhang Wenwu , Gunst Susan J.
Published: March 2006

The adhesion junctions of smooth muscle cells may be dynamically regulated during smooth muscle contraction, and this dynamic regulation may be important for the development of active tension. In the present study, the role of α‐actinin during smooth muscle contraction was evaluated in tracheal smooth muscle tissues and freshly dissociated cells. Stimulation with acetylcholine (ACh) increased the localization of α‐actinin at the membrane of freshly dissociated smooth muscle cells, and increased the amount of β1 integrin that coprecipitated with α‐actinin from muscle tissue homogenates. GFP‐α‐actinin fusion proteins were expressed in muscle tissues and visualized in live freshly dissociated cells. GFP‐α‐actinin translocated to the membrane within seconds of stimulation of the cells with ACh. Expression of the integrin‐binding rod domain of α‐actinin in smooth muscle tissues depressed active contraction in response to ACh. Expression of the α‐actinin rod domain also inhibited the translocation of endogenous α‐actinin to the membrane, and inhibited the association of endogenous α‐actinin with β1‐integrin in α‐actinin immunoprecipitates from tissue extracts. However, the expression of α‐actinin rod domain peptides did not inhibit increases in myosin light chain phosphorylation or actin polymerization in response to stimulation with ACh. Results suggest that contractile stimulation of smooth muscle causes the rapid recruitment of α‐actinin to β‐integrin complexes at the membrane, and that the recruitment of α‐actinin to integrin complexes is necessary for active tension development in smooth muscle.
Effect of 30 per cent maternal nutrient restriction from 0.16 to 0.5 gestation on fetal baboon kidney gene expression
Authors: Cox L. A. , Nijland M. J. , Gilbert J. S. , Schlabritz‐Loutsevitch N. E. , Hubbard G. B. , McDonald T. J. , Shade R. E. , Nathanielsz P. W.
Published: March 2006

Previous studies in rodents and sheep show that maternal nutrient restriction during pregnancy alters fetal renal development. To date, no studies using fetal baboon RNA with human Affymetrix gene chips have been published. In the present study we have (1) evaluated the specificity of the Affymetrix human gene array ‘Laboratory on a Chip’ system for use with fetal baboon mRNA and (2) investigated the effects of moderate maternal global nutrient restriction (NR; 70% of ad libitum animals) from early (30 days gestation (dG)) to mid‐gestation (90 dG; term = 184 dG) on the fetal baboon kidney. Morphometric and blood measurements were made on 12 non‐pregnant baboons before they were bred. All baboons were fed ad libitum until 30 days pregnant, at which time six control baboons continued to feed ad libitum (control – C) while six received 70% of the C diet on a weight adjusted basis. Fetal kidneys were collected following caesarean section at 90 dG, with samples flash frozen and fixed for histological assessment. Fetal hip circumference was decreased in the NR group (68 ± 2 versus 75 ± 2 mm), while fetal body weight and all other measurements of fetal size were not different between C and NR at 90 dG. Maternal body weight was decreased in the NR group (12.16 ± 0.34 versus 13.73 ± 0.55 kg). Having established the specificity of the Affymetrix system for fetal baboon mRNA, gene expression profiling of fetal kidneys in the context of our maternal nutrient restriction protocol shows that NR resulted in a down‐regulation of genes in pathways related to RNA, DNA and protein biosynthesis, metabolism and catabolism. In contrast, genes in cell signal transduction, communication and transport pathways were up‐regulated in the NR group. These changes indicate that even a moderate level of maternal global NR impacts fetal renal gene pathways. Our histological assessment of renal structure indicates decreased tubule density within the cortex of NR kidneys compared with controls. The number of glomerular cross‐sections per unit area were unaffected by NR, suggesting that tubule tortuosity and/or tubule length was decreased in the NR kidney. Taken together the changes indicate that NR results in accelerated fetal renal differentiation. The negative impact of poor maternal nutrition on the fetal kidney may therefore be in part due to shortening of critical phases of renal growth resulting in decreased functional capacity in later life. These findings may have important implications for postnatal renal function, thereby contributing to the observed increased predisposition to hypertension and renal disease in the offspring of nutrient restricted mothers.
Neonatal nociceptive somatic stimulation differentially modifies the activity of spinal neurons in rats and results in altered somatic and visceral sensation
Authors: Miranda Adrian , Peles Shachar , Shaker Reza , Rudolph Colin , Sengupta Jyoti N.
Published: March 2006

The role of intramuscular, low pH saline injections during the neonatal period in the development and maintenance of visceral hyperalgesia has not been systematically studied. We aimed to investigate alterations in visceral sensation and neural circuitry that result from noxious stimuli in early life. Neonatal male Sprague–Dawley rats received sterile saline injections of pH 4.0 or 7.4 in the gastrocnemius muscle starting at postnatal day 8. Injections were given unilaterally every other day for 12 days ending on postnatal day 20. A third group received needle prick only on the same shedule as the second group, while a fourth group was left naïve. At 2 months of age, rats underwent assessment of cutaneous and deep somatic sensitivity using von Frey filaments and gastrocnemius muscle pinch, respectively. A visceromotor response (VMR) to graded colorectal distension (CRD; 10–80 mmHg for 30 s with 180 s interstimulus intervals) was recorded. Extracellular single‐unit recordings from the thoracolumbar spinal neurons (T13–L1) were performed in adult pH 4.0 injected and naïve controls. There was no difference in the threshold for response to mechanical stimulation of the paw in rats injected with pH 4.0 saline compared to all other groups. Conversely, rats treated with pH 4.0 saline showed a significant bilateral reduction in withdrawal threshold to muscle pinch as adults (P < 0.05). At colorectal distensions ≥ 20 mmHg, an increase in the VMR was observed in the pH 4.0 injected group compared to all other groups (P < 0.05). Spinal neurons were classified as short latency abrupt (SL‐A) or short latency sustained (SL‐S). Spontaneous firing of SL‐S (20.6 ± 2.2 impulses s−1), but not SL‐A neurons (5.3 ± 0.9 impulses s−1) in the pH 4.0 treated rats was significantly higher than in control rats (SL‐S, 2.6 ± 0.8 impulses s−1; SL‐A, 3.1 ± 0.7 impulses s−1). The response of SL‐S neurons to CRD in the pH 4.0 group was significantly higher at distension pressures ≥ 20 mmHg. Nociceptive somatic stimulation in neonatal rats results in chronic deep somatic and visceral hyperalgesia in adulthood. Colorectal distension‐sensitive SL‐S neurons are primarily sensitized to neonatal somatic stimulation.
Effect of posture on the thermal efficiency of a plastic bag wrapping in neonate: Assessment using a thermal “sweating” mannequin
Authors: Belghazi Khalid , Tourneux Pierre , Elabbassi Elmountacer Billah , Ghyselen Laurent , Delanaud Stephane , Libert Jean‐Pierre
Published: March 2006

To assess the various heat exchanges with the environment a multisegment, anthropometric, thermal mannequin representing a neonate with a birth weight of has been designed. The mannequin simulates not only dry heat loss (radiative conductive convective body heat exchanges) but also the evaporative skin water loss which can be encountered in low‐birth‐weight neonates. The model was placed in the supine or prone position in a closed incubator (air temperature, ; relative air humidity, 50%; air velocity below ). Experiments were performed with the mannequin either naked or wrapped in a flexible, plastic bag (with the head exposed) used to prevent excessive body water loss at delivery and during the following hours About 30% of the model's total surface was wetted with water. Our results demonstrated that body position does not modify dry and evaporative heat losses, whatever the experimental conditions. The plastic bag acts rapidly and reduces total heat loss by 30% to 34%, primarily through a reduction in evaporative water loss (between 5.4 and ). When the bag is present, the uncovered surface of the head accounts for about 50% of the total heat loss. This simple and inexpensive solution can be used to prevent thermal stress and dehydration in very small premature neonates.
Dose distributions of a proton beam for eye tumor therapy: Hybrid pencil‐beam ray‐tracing calculations
Authors: Rethfeldt Ch. , Fuchs H. , Gardey K.‐U.
Published: March 2006

For the case of eye tumor therapy with protons, improvements are introduced compared to the standard dose calculation which implies straight‐line optics and the constant‐density assumption for the eye and its surrounding. The progress consists of (i) taking account of the lateral scattering of the protons in tissue by folding the entrance fluence distribution with the pencil beam distribution widening with growing depth in the tissue, (ii) rescaling the spread‐out Bragg peak dose distribution in water with the radiological path length calculated voxel by voxel on ray traces through a realistic density matrix for the treatment geometry, yielding a trajectory dependence of the geometrical range. Distributions calculated for some specific situations are compared to measurements and/or standard calculations, and differences to the latter are discussed with respect to the requirements of therapy planning. The most pronounced changes appear for wedges placed in front of the eye, causing additional widening of the lateral falloff. The more accurate prediction of the dose dependence at the field borders is of interest with respect to side effects in the risk organs of the eye.
Calibration of an amorphous‐silicon flat panel portal imager for exit‐beam dosimetry
Authors: Chen Josephine , Chuang Cynthia F. , Morin Olivier , Aubin Michèle , Pouliot Jean
Published: March 2006

Amorphous‐silicon flat panel detectors are currently used to acquire digital portal images with excellent image quality for patient alignment before external beam radiation therapy. As a first step towards interpreting portal images acquired during treatment in terms of the actual dose delivered to the patient, a calibration method is developed to convert flat panel portal images to the equivalent water dose deposited in the detector plane and at a depth of . The method is based on empirical convolution models of dose deposition in the flat panel detector and in water. A series of calibration experiments comparing the response of the flat panel imager and ion chamber measurements of dose in water determines the model parameters. Kernels derived from field size measurements account for the differences in the production and detection of scattered radiation in the two systems. The dissimilar response as a function of beam energy spectrum is characterized from measurements performed at various off‐axis positions and for increasing attenuator thickness in the beam. The flat panel pixel inhomogeneity is corrected by comparing a large open field image with profiles measured in water. To verify the accuracy of the calibration method, calibrated flat panel profiles were compared with measured dose profiles for fields delivered through solid water slabs, a solid water phantom containing an air cavity, and an anthropomorphic head phantom. Open rectangular fields of various sizes and locations as well as a multileaf collimator‐shaped field were delivered. For all but the smallest field centered about the central axis, the calibrated flat panel profiles matched the measured dose profiles with little or no systematic deviation and approximately 3% (two standard deviations) accuracy for the in‐field region. The calibrated flat panel profiles for fields located off the central axis showed a small systematic deviation from the measured profiles for the in‐field region. Out of the field, the differences between the calibrated flat panel and measured profiles continued to be small, approximately 0%–2% of the mean in‐field dose. Further refinement of the calibration model should increase the accuracy of the procedure. This calibration method for flat panel portal imagers may be used as part of a validation scheme to verify the dose delivered to the patient during treatment.
Spatial‐angular compounding for elastography using beam steering on linear array transducers
Authors: Rao Min , Chen Quan , Shi Hairong , Varghese Tomy
Published: March 2006

Spatial‐angular compounding is a new technique that enables the reduction of noise artifacts in ultrasound elastography. Under this method, compounded elastograms are obtained from a spatially weighted average of local strain estimated from radio frequency (rf) echo signals acquired at different insonification angles. In previous work, the acquisition of the rf signals was performed through the lateral translation of a phased‐array transducer. Clinical applications of angular compounding would, however, require the utilization of beam steering on linear‐array transducers to obtain angular data sets, which is more efficient than translating phased‐array transducers. In this article, we investigate the performance of angular compounding for elastography by using beam steering on a linear‐array transducer. Quantitative experimental results demonstrate that spatial angular compounding provides significant improvement in both the elastographic signal‐to‐noise ratio and the contrast‐to‐noise ratio. For the linear array transducer used in this study, the optimum angular increment is around , and the maximum angle that can be used in angular compounding should not exceed .