bluuebunny/crossref_metadata_2025 huggingface dataset:
Tolosa–Hunt Syndrome: Critical Literature Review Based on IHS 2004 Criteria
Authors: Mantia L La , Curone M , Rapoport AM , Bussone G
Published: May 2006

In 2004, the International Headache Society (IHS) re-defined the diagnostic criteria of Tolosa–Hunt syndrome (THS) specifying that granuloma, demonstrated by magnetic resonance imaging (MRI) or biopsy, is required for diagnosis. We reviewed the literature on THS published from 1988 (year of publication of first IHS criteria) to 2002, analysing individual cases in relation to the new IHS criteria. One hundred and twenty-four cases were identified. As far as it was possible to discern, clinical presentation was similar in all, but 44 (35±) were reported to have inflammation on MRI or bioptic evidence of granuloma, 41/124 (33±) had normal neuroimaging findings and 39 (31±) had a specific lesion, so the THS was secondary. These data confirm that clinical criteria for THS are common to several conditions and their application alone does not guarantee a correct diagnosis. The requirement for inflammation on MRI will result in better classification of painful ophthalmoplegias; nevertheless, an MRI protocol that best defines inflammation should be specified. The status of cases which fulfil the clinical criteria but have normal MRI remains to be clarified.
Enhancement of insulin‐induced PI3K/Akt/GSK‐3β and ERK signaling by neuronal nicotinic receptor/PKC‐α/ERK pathway: up‐regulation of IRS‐1/‐2 mRNA and protein in adrenal chromaffin cells
Authors: Sugano Takashi , Yanagita Toshihiko , Yokoo Hiroki , Satoh Shinya , Kobayashi Hideyuki , Wada Akihiko
Published: May 2006

In cultured bovine adrenal chromaffin cells treated with nicotine (10 µmfor 24 h), phosphorylation of Akt, glycogen synthase kinase‐3β (GSK‐3β) and extracellular signal‐regulated kinase (ERK)1/2 induced by insulin (100 nmfor 10 min) was enhanced by ∼ 62%, without altering levels of these protein kinases. Nicotine produced time (> 12 h)‐ and concentration (EC50 3.6 and 13 µm)‐dependent increases in insulin receptor substrate (IRS)‐1 and IRS‐2 levels by ∼ 125 and 105%, without altering cell surface density of insulin receptors. In these cells, insulin‐induced tyrosine phosphorylation of IRS‐1/IRS‐2 and recruitment of phosphoinositide 3‐kinase (PI3K) to IRS‐1/IRS‐2 were augmented by ∼ 63%. The increase in IRS‐1/IRS‐2 levels induced by nicotine was prevented by nicotinic acetylcholine receptor (nAChR) antagonists, the Ca2+chelator 1,2‐bis(2‐aminophenoxy)‐ethane‐N,N,N′,N′‐tetra‐acetic acid tetrakis‐acetoxymethyl ester, cycloheximide or actinomycin D. Nicotine increased IRS‐1 and IRS‐2 mRNA levels by ∼ 57 and ∼ 50%, and this was prevented by conventional protein kinase C (cPKC) inhibitor Gö6976, or ERK kinase inhibitors PD98059 and U0126. Nicotine phosphorylated cPKC‐α, thereby increasing phosphorylation of ERK1/ERK2, as demonstrated by using Gö6976, PD98059 or U0126. Selective activation of cPKC‐α by thymeleatoxin mimicked these effects of nicotine. Thus, stimulation of nAChRs up‐regulated expression of IRS‐1/IRS‐2 via Ca2+‐dependent sequential activation of cPKC‐α and ERK, and enhanced insulin‐induced PI3K/Akt/GSK‐3β and ERK signaling pathways.
Social isolation‐induced increase in α4and δ subunit gene expression is associated with a greater efficacy of ethanol on steroidogenesis and GABAAreceptor function
Authors: Serra Mariangela , Mostallino Maria Cristina , Talani Giuseppe , Pisu Maria Giuseppina , Carta Mario , Mura Maria Luisa , Floris Ivan , Maciocco Elisabetta , Sanna Enrico , Biggio Giovanni
Published: May 2006

Previously we have demonstrated that social isolation of rats reduces both the cerebrocortical and plasma concentrations of 3α‐hydroxy‐5α‐pregnan‐20‐one (3α,5α‐TH PROG), and potentiates the positive effects of acute ethanol administration on the concentrations of this neurosteroid. We now show that the ethanol‐induced increase in 3α,5α‐TH PROG is more pronounced in the brain than in the plasma of isolated rats. The ability of ethanol to inhibit isoniazid‐induced convulsions is greater in isolated rats than in group‐housed animals and this effect is prevented by treatment with finasteride. Social isolation modified the effects of ethanol on the amounts of steroidogenic regulatory protein mRNA and protein in the brain. Moreover, ethanol increased the amplitude of GABAAreceptor‐mediated miniature inhibitory postsynaptic currents recorded from CA1 pyramidal neurones with greater potency in hippocampal slices prepared from socially isolated rats than in those from group‐housed rats, an effect inhibited by finasteride. The amounts of the α4and δ subunits of the GABAAreceptor in the hippocampus were increased in isolated rats as were GABAAreceptor‐mediated tonic inhibitory currents in granule cells of the dentate gyrus. These results suggest that social isolation results in changes in GABAAreceptor expression in the brain, and in an enhancement of the stimulatory effect of ethanol on brain steroidogenesis, GABAAreceptor function and associated behaviour.
Identity of SMCT1 (SLC5A8) as a neuron‐specific Na+‐coupled transporter for active uptake ofl‐lactate and ketone bodies in the brain
Authors: Martin Pamela M. , Gopal Elangovan , Ananth Sudha , Zhuang Lina , Itagaki Shiro , Prasad Balakrishna M. , Smith Sylvia B. , Prasad Puttur D. , Ganapathy Vadivel
Published: May 2006

SMCT1 is a sodium‐coupled (Na+‐coupled) transporter forl‐lactate and short‐chain fatty acids. Here, we show that the ketone bodies, β‐d‐hydroxybutyrate and acetoacetate, and the branched‐chain ketoacid, α‐ketoisocaproate, are also substrates for the transporter. The transport of these compounds via human SMCT1 is Na+‐coupled and electrogenic. The Michaelis constant is 1.4 ± 0.1 mmfor β‐d‐hydroxybutyrate, 0.21 ± 0.04 mmfor acetoacetate and 0.21 ± 0.03 mmfor α‐ketoisocaproate. The Na+ : substrate stoichiometry is 2 : 1. Asl‐lactate and ketone bodies constitute primary energy substrates for neurons, we investigated the expression pattern of this transporter in the brain.In situhybridization studies demonstrate widespread expression of SMCT1 mRNA in mouse brain. Immunofluorescence analysis shows that SMCT1 protein is expressed exclusively in neurons. SMCT1 protein co‐localizes with MCT2, a neuron‐specific Na+‐independent monocarboxylate transporter. In contrast, there was no overlap of signals for SMCT1 and MCT1, the latter being expressed only in non‐neuronal cells. We also demonstrate the neuron‐specific expression of SMCT1 in mixed cultures of rat cortical neurons and astrocytes. This represents the first report of an Na+‐coupled transport system for a major group of energy substrates in neurons. These findings suggest that SMCT1 may play a critical role in the entry ofl‐lactate and ketone bodies into neurons by a process driven by an electrochemical Na+gradient and hence, contribute to the maintenance of the energy status and function of neurons.
Association Between Blood Pressure and Survival over 9 Years in a General Population Aged 85 and Older
Authors: Rastas Sari , Pirttilä Tuula , Viramo Petteri , Verkkoniemi Auli , Halonen Pirjo , Juva Kati , Niinistö Leena , Mattila Kimmo , Länsimies Esko , Sulkava Raimo
Published: May 2006

OBJECTIVES: To investigate the association between blood pressure and mortality in people aged 85 and older.

DESIGN: Population‐based prospective study with 9‐year follow‐up.

SETTING: Department of Neuroscience and Neurology and Department of Public Health and General Practice, University of Kuopio, and Department of Clinical Neurosciences, Helsinki University Hospital.

PARTICIPANTS: Of all 601 people living in the city of Vantaa born before the April 1, 1906, whether living at home or in institutions and alive on April 1, 1991, 521 were clinically examined and underwent blood pressure measurement.

MEASUREMENTS: Blood pressure was measured using a standardized method in the right arm of the subject after resting for at least 5 minutes. Information on medical history for each participant was verified from a computerized database containing all primary care health records. Death certificates were obtained from the National Register; the collection of death certificates was complete.

RESULTS: After adjusting for age, sex, functional status, and coexisting diseases (earlier‐diagnosed myocardial infarction, congestive heart failure, dementia, cancer, stroke, or hypertension), low systolic blood pressure (BP) was associated with risk of death.

CONCLUSION: Low systolic BP may be partially related to poor general health and poor vitality, but the very old may represent a select group of individuals, and the use of BP‐lowering medications needs to be evaluated in this group.
Research Agenda for Frailty in Older Adults: Toward a Better Understanding of Physiology and Etiology: Summary from the American Geriatrics Society/National Institute on Aging Research Conference on Frailty in Older Adults
Authors: Walston Jeremy , Hadley Evan C. , Ferrucci Luigi , Guralnik Jack M. , Newman Anne B. , Studenski Stephanie A. , Ershler William B. , Harris Tamara , Fried Linda P.
Published: May 2006

Evolving definitions of frailty, and improved understanding of molecular and physiological declines in multiple systems that may increase vulnerability in frail, older adults has encouraged investigators from many disciplines to contribute to this emerging field of research. This article reports on the results of the 2004 American Geriatrics Society/National Institute on Aging conference on a Research Agenda on Frailty in Older Adults, which brought together a diverse group of clinical and basic scientists to encourage further investigation in this area. This conference was primarily focused on physical and physiological aspects of frailty. Although social and psychological aspects of frailty are critically important and merit future research, these topics were largely beyond the scope of this meeting. Included in this article are sections on the evolving conceptualization and definitions of frailty; physiological underpinnings of frailty, including the potential contributions of inflammatory, endocrine, skeletal muscle, and neurologic system changes; potential molecular and genetic contributors; proposed animal models; and integrative, system biology approaches that may help to facilitate future frailty research. In addition, several specific recommendations as to future directions were developed from suggestions put forth by participants, including recommendations on definition and phenotype development, methodological development to perform clinical studies of individual‐system and multiple‐system vulnerability to stressors, development of animal and cellular models, application of population‐based studies to frailty research, and the development of large collaborative networks in which populations and resources can be shared. This meeting and subsequent article were not meant to be a comprehensive review of frailty research; instead, they were and are meant to provide a more‐targeted research agenda‐setting process.
Immigration, Labor Market Mobility, and the Earnings of Native‐Born Workers
Authors: Pedace Roberto
Published: May 2006

Abstract.  This article seeks to improve on previous estimates of the impact of immigration on native wages by using an occupational segmentation approach that directly controls for regional migration and other shifts in the native‐born U.S. labor supply. The U.S. labor market is segmented by occupation in order to determine which, if any, native workers tend to be vulnerable to increased immigrant competition for jobs. The results suggest that native‐born workers in the primary sector are the main beneficiaries of increased immigration, while native‐born Hispanic females in the secondary sector are the most susceptible to downward wage pressures.
Employers’ Flexibility and Employment Volatility
Authors: Wenger Jeffrey B. , Kalleberg Arne L.
Published: May 2006

Abstract. Previous analyses of the strong secular growth in personnel supply employment have focused primarily on the relative impacts of demand and supply factors. This industry’s dramatic growth has tended to mask its high degree of volatility, which may be more useful in understanding employers’ motivations for hiring temporary employees. This article examines alternative explanations for the volatility of employment in the temporary supply industry from 1972 to 2000. Using a seemingly unrelated time‐series estimator, we compare the volatility of temporary employment to that of regular full‐time employment. We find that quarterly changes in temporary employment are more sensitive to the business cycle than regular full‐time employment are and argue that temporary employment is likely to have a number of disadvantages as a reemployment strategy during a recession, since temporary employment typically declines during that time. Additionally, employment growth during this period is better explained by employers’ efforts to achieve numerical rather than wage flexibility.
Risk Determinants of Suicide Attempts Among Adolescents
Authors: Molina José‐Alberto , Duarte Rosa
Published: May 2006

Abstract.  In this article we present evidence about the factors that determine four gradual decisions on the part of adolescents to attempt suicide. To that end, we estimate a series of binary choice models by using data drawn from the U.S. National Youth Risk Behavior Surveys corresponding to 1991, 1993, 1995, and 1997. Our results show that the decisions to attempt suicide are motivated by both demographic and psychosocial variables, such as gender, age, ethnicity, education failure, possession of a gun, habitual participation in sporting activities, individual weight perception, and taking pills or provoking vomiting to lose weight. Moreover, we also find that a significant degree of influence is exerted by another group of factors, such as the consumption of drugs, sexual relationships, and, finally, pregnancy.
How I approach a thrombotic thrombocytopenia purpura patient
Authors: Brecher Mark E.
Published: May 2006

In the past few years, advances in the understanding of the pathophysiology of thrombotic thrombocytopenic purpura (TTP) has made great strides; however, this has yet to significantly impact the clinical care of patients. Although the use of daily plasma exchange is evidence‐based and well established, many of the facets of clinical care remain largely empiric. Our laboratory has had a sustained interest in studying and optimizing the use of plasma exchange in TTP patients. This article presents a summary of how our clinical service approaches TTP patients and manages commonly occurring problems.
Low‐Rank Scale‐Invariant Tensor Product Smooths for Generalized Additive Mixed Models
Authors: Wood Simon N.
Published: May 2006

SummaryA general method for constructing low‐rank tensor product smooths for use as components of generalized additive models or generalized additive mixed models is presented. A penalized regression approach is adopted in which tensor product smooths of several variables are constructed from smooths of each variable separately, these “marginal” smooths being represented using a low‐rank basis with an associated quadratic wiggliness penalty. The smooths offer several advantages: (i) they have one wiggliness penalty per covariate and are hence invariant to linear rescaling of covariates, making them useful when there is no “natural” way to scale covariates relative to each other; (ii) they have a useful tuneable range of smoothness, unlike single‐penalty tensor product smooths that are scale invariant; (iii) the relatively low rank of the smooths means that they are computationally efficient; (iv) the penalties on the smooths are easily interpretable in terms of function shape; (v) the smooths can be generated completely automatically from any marginal smoothing bases and associated quadratic penalties, giving the modeler considerable flexibility to choose the basis penalty combination most appropriate to each modeling task; and (vi) the smooths can easily be written as components of a standard linear or generalized linear mixed model, allowing them to be used as components of the rich family of such models implemented in standard software, and to take advantage of the efficient and stable computational methods that have been developed for such models. A small simulation study shows that the methods can compare favorably with recently developed smoothing spline ANOVA methods.
Neural tube defects and associated anomalies in a fetal and perinatal autopsy series
Authors: NIELSEN LJUDMILLA A. G. , MAROUN LISA LETH , BROHOLM HELLE , LAURSEN HENNING , GRAEM NIELS
Published: May 2006

Neural tube defects (NTDs) are congenital malformations of the central nervous system (CNS) secondary to abnormal closure of the neural tube during embryonic development. This study provides information on NTD rate, distribution, associated morphologic anomalies and organ weights in a Danish fetal and perinatal autopsy series during a 16 year period. The data were extracted from the autopsy reports of a consecutive series of 1984 fetal and perinatal autopsies from the Copenhagen area performed in the period 1989–2004. Registered parameters included: The location and morphology of the NTD, associated morphological anomalies, and organ weights. Organ weights were evaluated according to new fetal autopsy standards and grouped as low, normal or high. Ninety‐seven NTD cases were found (4.9%): Spina bifida (38 cases), cephalocele (17 cases) and anencephaly (42 cases). 63% of NTD cases had associated morphologic anomalies. Among the most common were hydrocephalus, NTD in another region, and anomalies in the urogenital system. 58% of the NTD cases had abnormal weight of one or more organs. Most notable was low adrenal weight not only in anencephalic fetuses but also in cases with cephalocele, suggesting a possible association.
Lawsonia intracellularisinfection in the large intestines of pigs
Authors: JENSEN T. K. , CHRISTENSEN B. B. , BOYE M.
Published: May 2006

In this study we examined the proliferative enteropathy, caused by the obligate intracellular bacteriumLawsonia intracellularis,in colon of naturally infected pigs, using immunohistochemistry,in situhybridisation and scanning confocal laser microscopy. When 396 pigs submitted for routine laboratory examination were investigated, large intestinal gross lesions were seen in 93, including 74 cases ofL. intracellulariscolitis (proliferative enteropathy). Fifty‐one pigs without recorded colonic gross lesions revealedL. intracellulariscolitis microscopically. In four cases,L. intracellulariswas only revealed in colon. Fifty‐seven pigs were positive forL. intracellularisin the small intestines only. Thus, the overall prevalence of colonic infection inL. intracellularis‐positive animals was as high as 69% (125 out of 182). In comparison, the large intestinal pathogensBrachyspira hyodysenteriaeandSalmonella entericawere only isolated from 5 and 4 of the 93 cases, respectively. Morphologically, an unforeseen severe involvement of the subepithelial mucosa with multipleL. intracellularisfound free and within large macrophages was observed in areas with acute infection. The distribution of wholeL. intracellularisorganisms was confirmed byin situhybridisation and scanning confocal laser microscopy. The significance and possible role of subepithelial infection in the proliferative enteropathy is discussed. In conclusion, the study shows thatL. intracellularisis a prevalent cause of naturally acquired colitis in pigs.
The concept of positive health: a review and commentary on its application in oral health research
Authors: Locker David , Gibson Barry
Published: May 2006

Abstract –  Although the concept of positive health has been around for more than 60 years, acceptable measures of this construct have yet to emerge. Potential explanations are that there is no consensus on how it is to be defined and its ambiguous status with respect to medical and socioenvironmental models of health. In this paper we review definitions of positive health, the origins of these definitions, the way the concept of positive outcomes has been used in research on the outcomes of oral and orofacial conditions and assess whether the concept of positive health has any merit in terms of applied oral health research. This literature reveals many competing and imprecise definitions, many of which are similar to other constructs, such as well‐being. Most are lacking empirical referents or indicators. In examining the literature on oral health we found five distinct, although overlapping, ways in which the concept of positive health has been framed: (i) positive health as the absence of negative health states; (ii) positive health as positively worded items; (iii) the positive outcomes of oral health; (iv) positive oral health as a set of psychological and social attributes, and (v) the positive outcomes of chronic conditions such as oro‐ and craniofacial differences. Each of these ways can be challenged on conceptual or methodological grounds. For example, the states that comprise the upper end of the negative–positive health continuum have not been defined and health states and determinants of health are often confused. Moreover, the meaning of responses to health status questionnaires and the interpretation of accounts of the illness experience is often unclear. Nevertheless, the notion of positive health, irrespective of its merits and public policy implications, provides a context for methodological and theoretical debate that can only serve to enrich theory and practice with respect to measures of health and quality of life and therapeutic interventions at the individual and population.
Can the development of new dental caries in Danish schoolchildren be predicted from surveillance data in the School Dental Service?
Authors: Jeppesen Berit Anna , Foldspang Anders
Published: May 2006

Abstract –  Background:  Dental screening programmes for Danish children generally target all children, irrespective of their individual caries risk. The standard screening interval is approximately 12 months. A valid systematic screening tool based on routine information sources is however indispensable, if more selective screening strategies should be developed to target the children at highest risk.

Objective:  To estimate the precision with which Danish schoolchildren at high risk for developing dental caries within 1 year can be identified based on information from routine registers.

Methods:  Based on data from the Danish National Board of Health's Recording System for the Danish Child Dental Services and from the Central Office of Civil Registration, 3705 schoolchildren aged 7–12 years were followed through 1994–1996. Dental health information as of 1994 and changes 1994–1995 were applied in multiple logistic regressions together with social data as of 1995 to estimate the individual 1‐year (1995–1996) risk of developing caries.

Results:  In 1995, 37.4% of the children had a DMFS index above 0, and during the following year 21.8% of all children developed new caries. The individual child's 1‐year caries risk could be estimated relatively accurately at baseline as indicated by the area (76%) under the receiver operating characteristic curve. About 40% of children with an estimated risk of 20% and above developed new caries, whereas 90% of the rest of the children did not do so.

Conclusion:  Based on information from Danish routine registers children at low caries risk may be identified relatively precisely. This may form the basis for the continuous development and targeting of high‐risk strategies, in which the screening for caries among children of estimated low risk may be postponed at least 1 year.
Challenges to dental access – England as a case study*
Authors: Bedi Raman
Published: May 2006

Abstract –  Access to dental services because of an insufficient workforce is a historic challenge faced by many developing countries. In recent years, however, it has become a major issue for many industrialized countries. The growing demand for cosmetic dentistry, an increase in patients’ willingness to pay for dental treatment, and growing numbers of older dentate patients have all put pressure on dental systems. Ways of meeting these challenges and ensuring reasonable dental access will vary from country to country, but the solutions often lie in how the dental workforce is regulated. This case study of the dental reforms currently being implemented in England highlights progress at a particular point in time (Summer 2005). It is clear that it will take a number of years to find a new national dental payment system (the National Health Service) to replace the system which has changed little since 1948. However, the political pressure to address poor access to state‐funded dental services calls for more immediate actions. The initial approach was to increase the dental workforce via international recruitment, and in the medium term to increase the number of dental students in training and to expand the numbers of other members of the dental team. An additional stratagem is to retain those already providing dental care under the National Health Service by the introduction of a new method of remuneration. England is trying to improve both access to care and the oral health of the population by creating a workforce more suitable to public demands and changing oral health needs.
Evidence by signal peptide trap technology for the expression of carbonic anhydrase 6 in rat incisor enamel organs
Authors: Smith Charles E. , Nanci Antonio , Moffatt Pierre
Published: May 2006

During screening of a rat incisor enamel organ cDNA library by signal peptide trap technology, we identified a DNA fragment matching a predicted translation sequence for rat carbonic anhydrase 6 (CA6). This result was unexpected because CA6, to date, has been associated primarily with secretions from glandular tissues. To further characterize this observation, reverse transcription–polymerase chain reaction (RT–PCR) amplifications were carried out on total RNA extracted from freeze‐dried secretory and maturation‐stage rat incisor enamel organs. A cDNA fragment of the expected size was detected in control samples from rat salivary glands as well as within maturation‐stage enamel organ samples. This CA6 RT–PCR fragment was further cloned and sequenced and found to match the nucleotide sequence 770–1079 from clone XM_216584 of GenBank. Northern blot analyses with the rat CA6 cDNA fragment confirmed its expression relative to maturation‐stage enamel organ samples. It is at present unclear whether the CA6 expressed by enamel organ cells is secreted into the enamel layer or into the intercellular spaces of the enamel organ itself to assist in neutralizing excess protons arising from the growth of apatite crystals during the maturation stage of amelogenesis.
How do enamelysin and kallikrein 4 process the 32‐kDa enamelin?
Authors: Yamakoshi Yasuo , Hu Jan C.‐C. , Fukae Makoto , Yamakoshi Fumiko , Simmer James P.
Published: May 2006

The activities of two proteases – enamelysin (MMP‐20) and kallikrein 4 (KLK4) – are necessary for dental enamel to achieve its high degree of mineralization. We hypothesize that the selected enamel protein cleavage products which accumulate in the secretory‐stage enamel matrix do so because they are resistant to further cleavage by MMP‐20. Later, they are degraded by KLK4. The 32‐kDa enamelin is the only domain of the parent protein that accumulates in the deeper enamel. Our objective was to identify the cleavage sites of 32‐kDa enamelin that are generated by proteolysis with MMP‐20 and KLK4. Enamelysin, KLK4, the major amelogenin isoform (P173), and the 32‐kDa enamelin were isolated from developing porcine enamel. P173 and the 32‐kDa enamelin were incubated with MMP‐20 or KLK4 for up to 48 h. Then, the 32‐kDa enamelin digestion products were fractionated by reverse‐phase high‐performance liquid chromatography (RP‐HPLC) and characterized by Edman sequencing, amino acid analysis, and mass spectrometry. Enamelysin cleaved the 32‐kDa enamelin only after it was deglycosylated. Kallikrein 4 digestion of the 32‐kDa enamelin generated nine major cleavage products, six of which were successfully characterized. After 12 h of digestion with KLK4, all of the 32‐kDa enamelin had been cleaved, but some cleavage products persisted after 48 h of digestion.
Human enamel phenotype associated with amelogenesis imperfecta and a kallikrein‐4 (g.2142G>A) proteinase mutation
Authors: Wright J. Tim , Daly Bill , Simmons Darrin , Hong Sung , Hart Suzanne P. , Hart Tom C. , Atsawasuwan Phimon , Yamauchi Mitsuo
Published: May 2006

Kallikrein‐4 is known to be highly expressed during the maturation stage of enamel formation and is thought to be critical for the final phase of crystallite growth. The purpose of this study was to evaluate the enamel phenotype in humans with a known KLK‐4 mutation (g.2142G>A). Primary teeth from two individuals with a known KLK‐4 mutation were evaluated using amino acid analysis and light and electron microscopy. Light microscopy showed the enamel was of normal thickness but opaque throughout its width compared with normal enamel. Electron microscopy showed enamel affected by the KLK‐4 mutation had a normal prismatic structure and generally had a well‐organized and discernable crystallite composition. In some areas, globular structures were present where crystallites were not discernable or appeared to have an altered morphology. The KLK‐4 mutant enamel had an increased protein content compared with normal enamel. Human enamel formed with a lack of functioning KLK‐4 proteinase is altered primarily in the completeness of crystallite growth, while enamel thickness and prism structure remains essentially normal. Collectively, these studies suggest that the KLK‐4 proteinase is essential for the final crystallite growth of enamel but is not critical for crystallite orientation, prism formation or enamel thickness.
Comparative calcium binding of leucine‐rich amelogenin peptide and full‐length amelogenin
Authors: Le Thuan Q. , Gochin Miriam , Featherstone John D. B. , Li Wu , DenBesten Pamela K.
Published: May 2006

Leucine‐rich amelogenin peptide (LRAP) is an alternately spliced amelogenin. LRAP is known to bind to hydroxyapatite, and has been shown to signal mesenchymal cells to proliferate, but its function in enamel formation is unclear. The purpose of this study was to determine the calcium‐binding properties and structure of recombinant human LRAP (rLRAP) compared with full‐length amelogenin (rH174). rLRAP and rH174 were synthesized in Escherichia coli and purified by affinity chromatography and reverse‐phase high‐performance liquid chromatography. Calcium binding was measured by isothermal titration calorimetry (ITC) at pH 7.5 and 25°C, and raw data were analyzed by origin7.0 software. The structure of rLRAP was analyzed by nuclear magnetic resonance (NMR) and circular dichroism (CD) in the absence or presence of Ca2+, pH 7.5 and 4.0, at 25°C. Thermodynamic values showed that rLRAP had a Ca2+‐binding affinity ≈ 6.4‐times greater than rH174. NMR and CD data revealed that rLRAP was randomly coiled, and that this structure was not altered by Ca2+, which bound to rLRAP and rH174 via ionic interactions. Unlike r174 (β‐spiral), rLRAP had a random‐coiled structure. The calcium binding and structural differences between rLRAP and rH174 suggest that these proteins have different functions in enamel biomineralization.
Three‐dimensional study of human dental fissure enamel by synchrotron X‐ray microtomography
Authors: Dowker Stephanie E. P. , Elliott James C. , Davis Graham R. , Wilson Rory M. , Cloetens Peter
Published: May 2006

The three‐dimensional morphology of human tooth fissures and the quantification of mineral distribution in fissure enamel are pertinent to the development and diagnosis of caries. Synchrotron X‐ray microtomography was used to measure linear attenuation coefficients (at 25 keV) at high spatial resolution with a volume‐imaging element (cubic voxel) of 4.9 × 4.9 × 4.9 µm3 in a block from a human premolar that included part of a stained fissure. From the linear attenuation coefficient, the mineral concentration, expressed as gHAp cm−3 (where HAp is stoichiometric hydroxyapatite), was calculated. The mean mineral concentration in bulk enamel was 2.84 gHAp cm−3. Well‐defined regions (1.5–2.6 gHAp cm−3), extending up to ≈ 130 µm from the base of some narrower lengths of the fissure and up to ≈ 50 µm deep from the fissure surface, were attributed to hypomineralization. Other regions of low mineral concentration, some (1.4–2.3 gHAp cm−3) lying within the expected course of the fissure base and some (2.2–2.7 gHAp cm−3) deep to the pit, were also considered to be of developmental origin. However, a diffuse distribution of low mineral concentrations (2.2–2.7 gHAp cm−3) in the pit walls was attributed primarily to demineralization from caries. The fissure contained heterogeneous material (≤ 0.5 gHAp cm−3) exhibiting partial mineralization.
Comparison of methods for measurement of hypoplastic lesions
Authors: Elcock Claire , Smith Richard N. , Simpson Joanne , Abdellatif Abeer , Bäckman Birgitta , Brook Alan H.
Published: May 2006

Enamel hypoplasia is a quantitative defect of enamel thickness. Methods previously used for its measurement have limitations in clinical studies. The aim of this study was to investigate new methods of measurement using image analysis. Lesions on 8 teeth affected by enamel hypoplasia were quantified from study models and impression surfaces using an image‐analysis system. The measurements made included lesion area and tooth surface area; from these the proportion of tooth surface area affected was calculated. For comparison, manual measurement was performed on impression surfaces and study models, using digital callipers. Images were also acquired of lesions on 12 exfoliated teeth, and the lesion area and total tooth area were calculated. For assessment of intra‐operator reliability, the +/– repeatability coefficient was calculated. Measurement of the surface of lesions direct from the exfoliated teeth gave the best results overall, followed by direct image analysis of the silicone impression.
Improving esthetically objectionable human enamel fluorosis with a simple microabrasion technique
Authors: Limeback Hardy , Vieira Anya P. G. F. , Lawrence Herenia
Published: May 2006

Mild‐to‐moderately severe enamel fluorosis (EF) is an unsightly maturation‐phase dental disorder. Despite extensive epidemiological studies on EF, little is known about individual treatment options. This study was carried out to determine whether a simple microabrasion technique is effective in improving the esthetics of EF. Patients with a variety of severities were treated using a water‐cooled fine diamond polishing bur at high speed to remove the surface enamel layers. Photographs of the affected teeth before and after treatment were shown by computer to a panel of three judges (two lay and one experienced), who rated the appearance of the teeth using a newly developed visual analog scale. The severity of EF was rated randomly and blind for 52 individual teeth (26 before and 26 after treatment). Reteated‐measures analysis of variance was used to analyze the results. The lay judges rated the appearance of the teeth with EF as significantly more objectionable before treatment. All judges found a significant improvement in the severity of EF after treatment. Using a newly developed visual analog scale, our study indicates that EF of an objectionable nature can be significantly improved with a simple microabrasion technique, thus conserving tooth structure and minimizing the cost of treating EF.
Early in vivo and in vitro effects of amelogenin gene splice products on pulp cells
Authors: Lacerda‐Pinheiro Sally , Jegat Nadege , Septier Dominique , Priam Fabienne , Bonnefoix Mireille , Bitard Juliette , Kellermann Odile , Tompkins Kevin , Veis Arthur , Goldberg Michel , Poliard Anne
Published: May 2006

Recombinant amelogenin gene splice products A+4 and A‐4, implanted in the pulp, induce the recruitment, proliferation, and differentiation of reparative cells. Our aim was to investigate the precocious events occurring in the pulp 1 d and 3 d after implantation of agarose beads alone or loaded with A+4 or A‐4. Proliferation and cell recruitment towards an odonto/osteogenic phenotype were visualized by detection of the proliferation cell nuclear antigen (PCNA) and RP59. After implantation of beads alone or loaded with A+4, at day 3, pulp cells were moderately immunopositive for osteopontin (OP), whereas labeling was strongly positive upon treatment with A‐4. Dentin sialoprotein (DSP) labeling was not detectable. Parallel in vitro studies were carried out on odontoblastic and mesenchymal progenitor cells in order to evaluate the effect of the amelogenin peptides on the expression of a series of marker genes involved in the odontoblastic/osteogenic/chondrogenic differentiation pathways. Altogether, our results suggest that the ‘signaling’ effects of the amelogenin peptides A+4 and A‐4 may differ according to the type of target cells, their stage of differentiation, the time of treatment, and the type of amelogenin peptide (A+4 or A‐4).
Three‐dimensional reconstruction of enamel thickness and volume in humans and hominoids
Authors: Gantt David G. , Kappleman John , Ketcham Richard A. , Alder Marden E. , Deahl Thomas H.
Published: May 2006

Enamel thickness is an important diagnostic characteristic in Hominoidea. However, the sample size is extremely small, relying upon mostly fractured specimens and a few sectioned specimens, providing an estimate of enamel thickness only. What is needed to fully understand the significance of enamel thickness is a non‐destructive technique that is able to obtain the thickness, density, and volume of the dental hard tissues of large samples, thereby providing an accurate means of relating thickness, area, volume, and the pattern of distribution of both enamel and dentin. Investigators have attempted to circumvent this problem by developing a variety of indexes. However, we are still left with subjective descriptions, such as ‘thin’, ‘thick’, ‘intermediate thick’, and ‘hyperthick’. The purpose of this investigation was therefore to demonstrate the ability of high‐resolution X‐ray computed microtomography (HRXCT), as a non‐destructive method, to produce, accurately and reliably, contiguous slices revealing the thickness and area of enamel, dentin, and pulp chamber. Using imaging software, three‐dimensional reconstructions were produced, which provided volume data for enamel and dentin. Three‐dimensional reconstruction of HRXCT images provide, for the first time, the capability of accurately quantifying enamel and dentin thickness, distribution and volume, thereby eliminating the necessity of destructive thin‐sectional analysis.
Short exposure to high levels of fluoride induces stage‐dependent structural changes in ameloblasts and enamel mineralization
Authors: Lyaruu D. M. , Bervoets T. J. M. , Bronckers A. L. J. J.
Published: May 2006

We tested the hypothesis that the sensitivity of forming dental enamel to fluoride (F–) is ameloblast developmental stage‐dependent and that enamel mineralization disturbances at the surface of fluorotic enamel are caused by damage to late‐secretory‐ and transitional‐stage ameloblasts. Four‐day‐old hamsters received a single intraperitoneal dose of 2.5–20 mg NaF/kg body weight and were examined, 24 h later, by histology and histochemistry. A single dose of ≥ 5 mg of NaF/kg induced the formation of a hyper‐ followed by a hypomineralized band in the secretory enamel, without changing the ameloblast structure. At 10 mg of NaF/kg, cystic lesions became apparent under isolated populations of distorted late‐secretory‐ and transitional‐stage ameloblasts. Staining with von Kossa stain showed that the enamel under these lesions was hypermineralized. At 20 mg of NaF/kg, cystic lesions containing necrotic cells were also found in the early stages of secretory amelogenesis and were also accompanied with hypermineralization of the enamel surface. We concluded that the sensitivity to F– is ameloblast developmental stage‐dependent. Groups of transitional ameloblasts are most sensitive, followed by those at early secretory stages. These data suggest that a F‐induced increase in cell death in the transitional‐stage ameloblasts accompanies the formation of cystic lesions, which may explain the formation of enamel pits seen clinically in erupted teeth.
Increased IL‐18 Levels in Seminal Plasma of Infertile Men with Genital Tract Infections
Authors: Matalliotakis Ioannis M. , Cakmak Hakan , Fragouli Yvoni , Kourtis Argiris , Arici Aydin , Huszar Gabor
Published: May 2006

Problem

Interleukin (IL)‐18 is a novel cytokine, previously known as interferon (IFN)‐γ inducing factor. We evaluated the levels of IL‐18 and IFN‐γ in seminal plasma (SP) of fertile and infertile men.

Method of study

Semen samples were obtained by masturbation from 80 men, and were examined for the levels of IL‐18 and IFN‐γ by enzyme‐linked immunosorbent assay. Seven groups were included: (i) fertile men (n = 18), (i) infertile men with genital tract infections (n = 17), (iii) with varicocele (n = 15), (iv) with Klinefelter syndrome (n = 6), (v) with cryptorchidism (n = 7), (vi) with mumps orchitis (n = 7), and (vii) with idiopathic testicular lesions (n = 10).

Results

Mean levels of IL‐18 were higher in SP from infertile men with genital tract infections compared with SP from other groups except Klinefelter syndrome (P < 0.05). However, no significant differences could be detected for IFN‐γ. A significant positive correlations was found between IL‐18 and IFN‐γ in total patient population (P < 0.001). Moreover, a negative correlation was observed between IL‐18 and sperm concentrations, and motility (P < 0.01 and <0.03, respectively). Furthermore, there was a positive and statistically significant association between IL‐18 and IFN‐γ levels in SP of infertile men with genital tract infections (P < 0.0001). However, there was no relationship between IL‐18 and IFN‐γ, and semen parameters in the same group.

Conclusion

SP IL‐18 levels were increased in men with urogenital infections. Thus, the elevated expression of IL‐18 in SP may be used as a diagnostic marker in the male genital tract infections.
1141105802 Lymphoid neogenesis occurs within fallopian tubes after infection with Chlamydia
Authors: King M , Kok S , Chan AM , Kelly KA
Published: May 2006

Inflammation induces lymphoid aggregates suggestive of lymphoid neogenesis in both murine and human genital tracts after infection with Chlamydia. Lymphoid neogenesis refers to the accumulation of mononuclear cells which organize into distinct regions forming structures which resemble secondary lymphoid tissue. The regulation of lymphoid neogenesis has been implicated in tissue dysfunction. In particular, CXCL13, a homeostatic chemokine necessary in formation of secondary lymphoid tissue in utero, was expressed in both in vitro and in vivo models. In the in vitro model, we used organ cultures of human fallopian tissue (HFT) which was infected with C. trachomatis serovar E. We noted a 30‐fold increase in mRNA for CXCL13 and found expression of CXCL13 in endothelium and stromal cells. Using the murine model for in vivo studies, we found CXCL13 induced in oviducts of Chlamydia‐infected mice. An alteration in the level or duration of bacterial burden in the genital tract was not observed in treated mice. Surprisingly, anti‐CXCL13 treatment significantly extended oviduct diameters, a measure of inflammation, 3 weeks after resolution of genital infection (7.5 + 1.2 goat IgG versus 43.7 + 8.7 anti‐CXCL13; n = 3–4/grp, P = 0.038, n = 4, t‐test). Lastly, ectopic lymphoid tissue in known cases of human salpingitis was found to express CXCL13 and other characteristics of lymphoid neogenesis. This data indicates that CXCL13 plays a role in immune‐mediated fallopian tube dysfunction. (NIH‐AI‐26328, AI‐148146 & Iris‐Cantor‐UCLA fund).
1141681087 An animal model for maternal and fetal infection with Porphyromonas gingivalis
Authors: Brown M , Reyes L , Von Deneen K , Belanger M , Progulske‐Fox A
Published: May 2006

In recent years, a growing body of epidemiological evidence strongly suggests that Porphyromonas gingivalis (Pg) a causative agent of periodontitis, may have an important role in prematurity and low birth weight. This study was designed to evaluate the effect of intravenous inoculation of Pg on intrauterine infection in rats. Pregnant SD rats were intravenously inoculated with sterile PBS or 105, 106, or 109 CFU of Pg strains ATCC33277, W83 or A7436 at gestation day (GD) 14. Animals were sacrificed at GD 18, and dam uterus, vagina and fetal‐placental units (placenta, amniotic fluid, and fetus) were cultured for Pg. Placental sections were also evaluated by histopathology. Of the three strains, Pg A7436 produced the highest rates of infection in the maternal genital tract as well as in fetal tissues (P < 0.0001). For all three strains, 109 CFU produced the highest degree of placental and fetal infection (Pg A7436 at 90%, ATCC33277 at 30%, and W83 at 8.3%). Endometritis with extensive infiltration of degenerated polymorphonuclear cells with vasculitis and hyaline degeneration of maternal vessel were observed in uteroplacental tissues from dams infected with Pg A7436. The inflammatory infiltrate and cellular necrosis was also present at the placental edge, and hemorrhage and necrosis extended into the labyrinth layer. An unexpected finding was the epithelial hyperplasia, cellular necrosis and inflammatory infiltrate present in the chorioallantois. Based on our studies intravenously administered Pg could induce intrauterine infection, chorioamnionitis, and fetal infection in SD rats. Taken together, this data supports the use of the SD rat as an animal model to elucidate the mechanisms by which Pg can induce adverse pregnancy outcome.
Law and the demoralisation of medicine
Authors: Montgomery Jonathan
Published: May 2006

In his Dimbleby Lecture in December 2002, the Archbishop of Canterbury examined the effect of the emergence of the market state on the legitimacy of government activity in areas of morality. He suggested that, while this is becoming limited, the continuing need to provide a moral context for social life provided an opportunity for religious communities to play a crucial role. This paper suggests that the increasing significance of market concepts in healthcare law poses a similar challenge to the moral basis of medical practice, threatening to drive moral argument outside the scope of the discipline, with the consequent effect of undermining the values that drive good healthcare. Thus, the de-moralisation of medicine is also demoralising for those within the health professions. To counteract this tendency, a strong sense of a common moral community needs to be maintained amongst those engaged with the discipline of healthcare law. This paper also examines the role of law in this area. Traditionally, legal scholars have attacked the reluctance of legislators and the judiciary to wrestle from the grip of doctors the authority to determine ethical issues. The dominant view has been that this was a failure to recognise the fact that society has a stake in these matters and that legal non-intervention was an abdication of responsibility that undermines the rule of law. However, the integration of medical and moral decision making into a collaborative enterprise can also be seen as a more effective defence against the forces of demoralisation than the separation that the orthodox approach implies. If this is correct, then a key task for healthcare lawyers, as yet undeveloped, is to consider how to establish a legitimate common moral community, and what role the law might have to play in that process.