bluuebunny/crossref_metadata_2025 huggingface dataset:
Periodontal status among relatives of aggressive periodontitis patients and reliability of family history report
Authors: Llorente M. A. , Griffiths G. S.
Published: January 2006

Objectives: To assess the periodontal status of relatives of Aggressive Periodontitis (AgP) patients, and to evaluate the reliability of the family history report as provided by the proband.

Material and Methods: Data from 54 AgP patients were gathered along with a family history report for each of their relatives. Only 27 patients (probands) had relatives willing to be examined. This yielded a total of 61 relatives from whom the periodontal status was obtained. The family history report for each examined relative was compared with the periodontal diagnosis made at examination to assess reliability.

Results: Eight percentage of the examined relatives, aged between 12–76, were diagnosed with AgP, while chronic periodontitis was present in 39%, gingivitis in 38% and 15% were healthy. If the report provided by the proband was positive, the likelihood of finding any type of periodontitis in that relative was 85.7%, whereas if the report was negative the likelihood of the absence of periodontitis was 70.6%.

Conclusion: The percentage of examined relatives who were affected with AgP (8%), although lower than percentages reported in other AgP family studies, was still higher than the prevalence of the condition in random populations. Reliability of periodontal family history was considered good and more reliable when it was positive.
PHYSICOCHEMICAL PROPERTIES OF GLUTEN‐FREE PANCAKES FROM RICE AND SWEET POTATO FLOURS
Authors: SHIH F.F. , TRUONG V.D. , DAIGLE K.W.
Published: January 2006

Gluten‐free pancakes were prepared using rice flour and rice flour replaced with various amounts, at 10, 20 and 40%, of sweet potato flour. Textural properties of the cooked pancakes, such as hardness and chewiness generally increased with time after cooking, whereas they decreased with increased sweet potato flour replacement. On the other hand, cohesiveness decreased with time, but increased with increased sweet potato flour in the pancake. Nutritional properties of the rice–sweet potato pancakes, such as protein content, dietary fiber, total carbohydrate and calories were generally comparable with those of their wheat counterpart. The only significant difference was in the beta‐carotene content, which increased from 5.2 to 236.1 μg/g when sweet potato flour was incorporated, from 0 to 40%, into the rice pancake formulation.
COMPARISON OF HEADSPACE SOLID PHASE MICROEXTRACTION AND XAD‐2 METHODS TO EXTRACT VOLATILE COMPOUNDS PRODUCED BYSACCHAROMYCESDURING WINE FERMENTATIONS
Authors: BOHLSCHEID JEFFRI C. , WANG XIAO‐DONG , MATTINSON D. SCOTT , EDWARDS CHARLES G.
Published: January 2006

A modified headspace solid phase microextraction (HS‐SPME) method was compared with Amberlite® XAD‐2 resin for the extraction of volatile compounds. In the HS‐SPME method, volatiles were extracted using an 85 μm polyacrylate fiber from wines that contained a standardized amount of ethanol (10% v/v), NaCl (0.325 g/mL) and internal standards (dodecanol and nonanoic acid). Both extraction procedures yielded high relative recoveries (>92%) and reproducibilities (coefficient of variations ≤ 11%) for the different higher alcohols, esters and medium‐chain fatty acids. Overall, limits of detection for the HS‐SPME and XAD‐2 methods were below sensory threshold concentrations. HS‐SPME and XAD‐2 performed similarly in the analysis of a Riesling wine; however, the HS‐SPME method did not require organic solvents and was generally quicker to perform. In applying the HS‐SPME method, differences in concentrations of volatile compounds produced in Riesling and Chenin blanc wines by 11 different yeast strains were noted.
EFFECTS OF VARIETY AND GROWTH SEASON ON THE ORGANOLEPTIC AND NUTRITIONAL QUALITY OF HYDROPONICALLY GROWN TOMATO
Authors: ANZA MIKEL , RIGA PATRICK , GARBISU CARLOS
Published: January 2006

The effects of variety and season on several organoleptic and nutritional quality parameters (i.e., dry weight (dw), total sugars, soluble solid compounds, titratable acidity (TA), electrical conductivity (EC), juiciness, firmness, vitamin C (vit C), total phenolic compounds, hydrophilic antioxidant capacity and minerals) of five different varieties of tomatoes (i.e., Jack, Cabrales, Jaguar, Iker and Nevada) grown in two crop cycles (spring and autumn) were studied. Each variety presented its own specific characteristics regarding the chosen parameters. Firmness, TA and EC were season dependent, whereas soluble solids content did not change between cycles. In some varieties, the dw, juiciness and total sugars were affected by climatic conditions. The total phenolic compounds and the hydrophilic antioxidant capacity were variety dependent in both cycles. By contrast, the vit C content was variety dependent only in the autumn cycle. Similarly, these latter parameters (phenolic compounds, hydrophilic antioxidant capacity and vit C) were also season dependent, showing higher values in the spring than in the autumn cycle. The effect of tomato variety and season on mineral contents is also discussed. Those tomatoes grown in the spring cycle had better quality according to the organoleptic parameters studied here as well as to a higher antioxidant capacity. The percentages of the recommended dietary allowances supplied by the studied tomatoes were not significantly affected by variety or season, despite differences in their physicochemical compositions.
SENSORY EVALUATION OF HOME DRIED FRUIT PREPARED USING TREATMENTS THAT ENHANCE DESTRUCTION OF PATHOGENIC BACTERIA
Authors: DIPERSIO PATRICIA A. , KENDALL PATRICIA A. , SOFOS JOHN N.
Published: January 2006

Foodborne illness associated with dried foods has prompted research in the area of home‐food preservation. We assessed consumer responses to dehydrated fruits prepared using treatments shown to enhance pathogen destruction. Peach, pear, cantaloupe, apple, tomato and banana samples were left untreated or immersed (10 min, 25C) in 3.4% ascorbic acid or 1.7% citric acid before dehydration (60C). Untrained consumers (n = 280) participated in four sensory panels conducted over an 8‐month period. Panelists were primarily female students (21–34 years of age). Acid treatments maintained or improved the appearance and overall acceptability of dehydrated fruit pieces. Citric acid was more effective than ascorbic acid at inhibiting browning in dried peach, banana and tomato samples. Results suggest differences among fruits necessitate the careful evaluation of treatments to maximize the quality of dried fruits. Guidelines for the safe and palatable preparation of dehydrated fruits are available through Cooperative Extension Services (CES).
DIFFERENTIATION OF ACTIVITY PATTERNS IN THE SUPRAHYOID MUSCLES DURING SWALLOWING OF FOODS WITH FIVE TASTE QUALITIES
Authors: MIYAOKA YOZO , ASHIDA ICHIRO , INAGAKI DAIGO , KAWAKAMI SHIN‐YA
Published: January 2006

Activity patterns of the suprahyoid muscles were examined using a new analytical technique. The suprahyoid activities were recorded during swallowing of tasteless foods and foods with taste qualities (sweet, salty, sour, bitter and umami). The technique involved: (1) division of cumulative integrated suprahyoid activities from each swallow into 10 equal sections and (2) assignment of individually sectioned activities to a standardized timescale as TP (from T10To T100; relative time for P% of the cumulative electromyogram) to enable comparison of data from different trials. Three significant differences were found in T

p

between the following foods: tasteless and sour, tasteless and bitter, and sour and umami. However, the differences were not repeatedly confirmed. These results suggest that gustatory signals from food tastes affect differentially the activity patterns of the suprahyoid muscles during pharyngeal swallowing, although the effect is not permanent. This method may be used to measure taste impressions in infants and in certain disabled subjects.
TWO TYPES OF SENSORY PANELS OR ARE THERE MORE?
Authors: SCRIVEN FRANCES
Published: January 2006

The purpose of this article is to discuss the issues associated with selecting assessors for sensory panels. It develops the argument that although there are many variations in the detail of how assessors are selected, all panels can be considered as either (1) selecting respondents to measure ingredient concentrations via perceptions or (2) selecting respondents to represent the response that would be obtained from a wider consumer population. The validity of the data collected, i.e., the extent to which the data collected measures what was originally intended, depends on the detail of how assessors were selected as well as a number of other factors.
THE IMPACT OF GEOGRAPHIC ORIGIN ON SENSORY PROPERTIES OF VITIS VINIFERA CV. MENCÍA
Authors: VILANOVA MAR , SOTO BEATRIZ
Published: January 2006

The objective of this study was to establish the aromatic descriptors that identify the aroma of young Mencía wines from different geographic areas of Ribeira Sacra Appellation of Origin Controlled in Galicia (NW Spain). Initially, 36 attributes were identified. A multivariate analysis was carried out to evaluate this possible differentiation between the Mencía wines according to production area. Principal component analysis of sensory data permitted the differentiation among geographic areas. The wines differed significantly for seven sensory attributes. The wines from Chantada and Ribeira do Miño were characterized by higher intensities of metallic and bread odors, while Amandi and Quiroga‐Bibei by balsamic, apple and phenolic characters. The wines from Ribeira do Sil exhibited a toasting character and the lactic character was present in all wines except those from Ribeira do Sil.
The Role of the Oculomotor Vermis in the Control of Saccadic Eye Movements
Authors: THIER PETER , DICKE PETER W. , HAAS ROMAN , THIELERT CLAUS‐DIETER , CATZ NICOLAS
Published: January 2006

Abstract: The oculomotor vermis is a part of the posterior cerebellum, characterized by a low threshold (<10 μA) for evoked saccades. It comprises vermal lobuli VIc and VIIA. Many Purkinje cells in this area show eye position or saccade‐related responses or combinations of the two and usually lack responses to the presentation of visual targets, guiding the oculomotor behavior. The saccade‐related responses are directionally selective and show preferences for saccade amplitude or duration, which differ widely between cells. However, at the population level, these saccade‐related Purkinje cells give a very precise account of the timing of the saccadic eye movement and, specifically, of the time it ends. This population signal might therefore contribute to determining the end of the saccadic eye movement. Furthermore, by changing the duration of the population response, the amplitude of the saccade could be changed. In other words, saccadic adaptation could be a consequence of changing a representation of time in the cerebellum.
Role of the Fastigial Nucleus in Controlling Horizontal Saccades during Adaptation
Authors: SCUDDER CHARLES A.
Published: January 2006

Abstract: Saccade size was adapted in rhesus monkeys using surgical weakening of the muscles of one eye combined with monocular viewing. Neurons in the caudal fastigial nucleus were recorded during the adaptation. Neuronal discharges changed in a way that could be interpreted as causing the changes in saccade size given our current knowledge of the projections of these neurons to the saccadic burst generator in the brain stem.
The Olivocerebellar System as a Generator of Temporal Patterns
Authors: YAROM Y. , COHEN D.
Published: January 2006

Abstract: The large number of diverse functions attributed to the cerebellum appears to be inconsistent with its simple, homogeneous and evolutionary preserved structure. A homogeneous structure that participates in a variety of functions implies that a common denominator underlies all of them. Since the concept of precise timing can be recognized in almost all cerebellar functions, it is likely, therefore, that the basic cerebellar circuit is capable of generating temporal patterns. Of the different mechanisms that can generate temporal patterns, two are suggested by the functional anatomy of the cerbellum: transmission lines or oscillators. Our recent experimental observations indicate that the olivary oscillatory property is more likely to serve this function. We propose that interactions between the cerebellum and the inferior olive endow the system with the ability to generate complex temporal patterns. These temporal patterns can be used for fine adjustment of motor output, sensory expectation, or shifting attentions.
The Organization of Cerebellar Cortical Circuitry Revisited
Authors: BOWER JAMES M.
Published: January 2006

Abstract: For more than 35 years there has been experimental evidence that parallel fiber activity does not generate the beams of activated Purkinje cells hypothesized on the basis of cortical anatomy and assumed by most theories of cerebellar cortical function. This paper first reviews the evidence for and against the parallel fiber beam hypothesis, and then discusses the findings of our recent experimental and model‐based investigations intended to better understand parallel fiber effects on Purkinje cells. A principal conclusion of these studies is that the excitatory effects of parallel fibers on Purkinje cell dendrites are modulating and must be considered in the context of a balancing inhibitory influence provided by molecular layer interneurons to these same dendrites. It is proposed that this association of excitation and inhibition can account for the lack of beam‐like effects on Purkinje cells. The paper concludes by considering the consequences of this new interpretation of cerebellar cortical circuitry for current theories of cerebellar function.
In Defense of the Cerebellum
Authors: BRAITENBERG VALENTINO
Published: January 2006

Abstract: The very special intrinsic connectivity of the cerebellar cortex plays but a minor role in present‐day theories of cerebellar function, and it is hardly used as a source of inspiration for experiments. It is argued here that a direct translation of structure into physiological relations inescapably leads to some propositions about cerebellar function that could be tested experimentally.
What Do Complex Spikes Signal about Limb Movements?
Authors: EBNER TIMOTHY J. , JOHNSON MICHAEL T. V. , ROITMAN ALEXANDER , FU QINGGONG
Published: January 2006

Abstract: Deciphering the information or signals carried by the complex spike discharge of Purkinje cells has proven to be problematic, primarily because of low frequency discharge and lack of adequate analytical techniques. This problem is particularly acute for studies of limb movements. To this end the relationship of cerebellar Purkinje cell complex spike discharge to direction and speed were studied in a manual‐tracking task. Two monkeys were trained to pursue track targets moving in one of eight directions and at one of four speeds. An analysis based on Poisson regression modeling fitted the complex spike counts during single movement trials to target direction and/or speed. Using single trial data, the Poisson modeling demonstrated that the complex spike discharge for a majority of the Purkinje cells was significantly fit to tracking direction and speed. A second analysis based on the directional distribution of position and speed errors and a Poisson regression model of complex spike discharge to tracking position and speed errors found little relationship to movement error. Comparison of the preferred direction of the complex spike discharge with that of the simple spike activity revealed a reciprocal relationship for many cells. Thus, the complex spike discharge signals both tracking direction and speed but not movement errors. Furthermore, treating complex spike counts as a Poisson process provides a powerful tool for analyzing these events in single trials, without the need for extensive averaging.
On the Amazing Olivocerebellar System
Authors: LLINÁS R. , LEZNIK E. , MAKARENKO V. I.
Published: January 2006

Abstract: Over the last four decades elegant sets of a single‐cell studies, originating from various research groups, have contributed significantly to our understanding of olivary and cerebellar physiology. Nevertheless questions relating to the dynamic properties of olivocerebellar network, as a system, remain unsolved. We may be reaching the limits of what can be learned using the single‐cell recordings. Further research on this subject may require study of the spatiotemporal activity profiles of ensemble neuronal activity. This paper summarizes results obtained using voltage‐sensitive dye imaging in inferior olive slices, and the use of mathematical modeling to address such activity profiles.
Motor and Nonmotor Domains in the Monkey Dentate
Authors: DUM RICHARD P. , LI CHEN , STRICK PETER L.
Published: January 2006

Abstract:Our concepts about the organization and functions of the cerebellum have changed substantially in the last 10 years. In recent studies, we used transneuronal virus tracing techniques to demonstrate that the output of the cerebellum of primates projects via the thalamus not only to its classical motor target, the primary motor cortex, but also to “nonmotor” cortical areas in the prefrontal and posterior parietal cortex. We found that dentate neurons projecting to different cortical areas originated from localized regions of the nucleus which we termed “output channels.” To compare the locations of the output channels projecting to different cortical targets, we have created an unfolded map of the dentate. This unfolded map revealed that dentate output channels were segregated into spatially separate “motor” and “nonmotor” domains. The output channels in the motor domain exclusively targeted primary motor and premotor areas of the cerebral cortex. These channels were localized in the dorsal portion of the dentate. The output channels in the nonmotor domain projected to prefrontal and posterior parietal cortical areas. The nonmotor domain was confined to the ventral portion of the dentate. In recent studies, we defined a unique molecular marker, monoclonal antibody 8B3, which appears to differentially “recognize” these two domains. Taken together, our results suggest that dentate output is organized according to the functional capabilities of its cortical targets. This organization provides the dentate nucleus with the anatomical substrate to influence not only the control of movement, but also cognitive, higher‐order executive and visuospatial functions.
Role of the Cerebellum in Motor Cognition
Authors: Van MIER HANNEKE I. , PETERSEN STEVE E.
Published: January 2006

Abstract: Cerebellar data from five experiments using different groups of subjects performing the same motor learning task are presented. Positron emission tomography (PET) as well as functional magnetic resonance imaging (fMRI) was used to study changes in cerebellar activations as an effect of learning. Cerebellar brain activations obtained during the performance of a new motor task were compared to activations during the performance of the same task after as well as during practice. To account for changes in velocity and somatosensory processing as an effect of practice, two control conditions were included. Behavioral data showed that as an effect of practice performance speed as well as accuracy increased in all five experiments and groups. Neuroimaging data from adults as well as children showed differential changes in brain activations in different cerebellar areas. In all experiments an area in the left lateral cerebellum showed practice‐related decreases, which were most likely related to a decrease in errors. In two experiments a highly significant correlation was found between the decrease in errors and the decrease in left cerebellar activation. An area in the right lateral cerebellum and one in the ipsilateral anterior vermis showed activations that seemed related to the level of capacity at which the subjects were performing and might refer to timing‐related aspects of the task.
Roles of Inhibitory Interneurons in the Cerebellar Cortex
Authors: HIRANO TOMOO , WATANABE DAI , KAWAGUCHI SHIN‐YA , PASTAN IRA , NAKANISHI SHIGETADA
Published: January 2006

Abstract: The roles of inhibitory interneurons in the cerebellar cortex were investigated. First, Golgi cells were specifically eliminated in transgenic mice in which Golgi cells expressed human interleukin‐2 receptor α subunit (IL2Rα). Injection of exotoxin coupled to anti‐IL2Rα antibody in the cerebellum of the transgenic mouse eliminated Golgi cells and abolished GABA and synaptic inhibition in the granular layer. After elimination of Golgi cells, acute severe ataxia and subsequent mild motor discoordination were observed. In the latter chronic phase, NMDA receptor‐mediated synaptic response was reduced in granule cells. Our findings indicate that elimination of GABAergic inhibition in the granular layer caused overexcitation of granule cells resulting in severe ataxia, and then NMDA receptors in granule cells were downregulated, compensating for the reduction of GABAergic inhibition and improving motor control. In the second part, we report on the regulation mechanism of synaptic plasticity at inhibitory synapses on Purkinje cells (PCs). Inhibitory synaptic transmission on a PC is potentiated after repetitive PC depolarization. This synaptic plasticity (rebound potentiation, RP) was suppressed when a presynaptic neuron was activated during the PC depolarization. This synaptic regulation is unique in the sense that the homosynaptic activity suppresses the induction of synaptic plasticity. The mechanism of how presynaptic activity suppresses RP was examined. GABA released from the presynaptic terminal activated not only GABAA receptor but also GABAB receptor. The latter was coupled to Gi/o proteins, which downregulated adenylyl cyclase reducing cAMP and inactivated cAMP‐dependent protein kinase (PKA). Downregulation of PKA suppressed RP induction.
Trying to Understand the Cerebellum Well Enough to Build One
Authors: OHYAMA TATSUYA , MEDINA JAVIER F. , NORES WILLIAM L. , MAUK MICHAEL D.
Published: January 2006

Abstract: The development of an increasingly detailed computer simulation of the cerebellum is briefly described. Specific and relatively direct evaluation of the performance of this simulation is made possible by the straightforward way in which pavlovian eyelid conditioning engages the cerebellum. Inputs to the simulation are based on recordings of mossy fiber and climbing fiber responses to the stimuli used in eyelid conditioning, and the output of the simulation can be evaluated with respect to the extensively characterized behavioral properties of eyelid conditioning. Because construction of the simulation has been guided by a strong aversion to errors of commission, both failures and successes of the simulation have proven informative. The behavior of the simulation related to the inhibitory nucleo‐olivary feedback connection and spontaneous activity of climbing fibers is described. A prediction of the simulation concerning extinction is confirmed by experiment.
Surface‐Based Atlases of Cerebellar Cortex in the Human, Macaque, and Mouse
Authors: Van ESSEN DAVID C.
Published: January 2006

Abstract: This study describes surface reconstructions and associated flat maps that represent the highly convoluted shape of cerebellar cortex in three species: human, macaque, and mouse. The reconstructions were based on high‐resolution structural MRI data obtained from other laboratories. The surface areas determined for the fiducial reconstructions are about 600 cm2 for the human, 60 cm2 for the macaque, and 0.8 cm2 for the mouse. As expected from the ribbon‐like pattern of cerebellar folding, the cerebellar flat maps are elongated along the axis parallel to the midline. However, the degree of elongation varies markedly across species. The macaque flat map is many times longer than its mean width, whereas the mouse flat map is only slightly elongated and the human map is intermediate in its aspect ratio. These cerebellar atlases, along with associated software for visualization and for mapping experimental data onto the atlas, are freely available to the neuroscience community (see http://brainmap.wustl.edu).
Plasticity of the Vertical VOR
Authors: HIRATA YUTAKA , HIGHSTEIN STEPHEN M.
Published: January 2006

Abstract: The vestibulo‐ocular reflex (VOR) stabilizes the visual image on the retina during head movement by counter‐rotating the eyes in the head. The VOR is under adaptive control and has been extensively used to investigate sensorimotor transformations and motor learning. The cerebellar flocculus (FL) is intimately involved in VOR motor control and learning, because its sole output, the Purkinje cell firing pattern, modulates during visual‐vestibular interaction paradigms that induce motor learning, and flocculectomy impairs the ability to modify the VOR. However, the role of the FL in VOR motor learning and the possibility of another neuronal site responsible for learning have been controversial. Currently, we performed single unit recordings of FL Purkinje cells during adaptation of the vertical (V) VOR in squirrel monkeys and used a system identification approach to localize the adaptable neuronal sites responsible for VVOR motor learning. We demonstrated that there are multiple adaptive sites: one upstream or in the FL, another in the non‐FL pathway; change in the former site is in the wrong direction to cause the observed VVOR gain change, whereas that in the latter site is in the correct direction. The possibility that FL Purkinje cells convey an error signal to their target neurons that can be used to aid learning is discussed.
Synaptic vesicles in rat hippocampal boutons recycle to different pools in a use‐dependent fashion
Authors: Vanden Berghe Pieter , Klingauf Jürgen
Published: January 2006

Efficient vesicle membrane recycling at presynaptic terminals is pivotal for preventing depletion and maintaining high firing rates in neuronal networks. We used a new approach, based on the combination of spectrally different optical probes, to investigate how stimulation determines the fate of synaptic vesicles after endocytosis. We found that in the small central synapses of rat hippocampal neurones low frequency stimulation (40 action potentials at 2 Hz) targets vesicles preferentially to vesicle pools that were kinetically faster. Vesicles taken up during endocytosis triggered by high frequency stimulation (400 action potentials, 20 Hz) were also placed in the back of the release queue. We performed a spatial analysis of the recycled vesicles in living hippocampal boutons using two spectrally different FM‐dyes (FM1‐43 and FM5‐95). By using these consecutively, vesicles endocytosed by either stimulation protocol were labelled with a different colour. This revealed that the kinetic arrangement was also reflected in the spatial organization of vesicles within the bouton. Next, we identified the postsynaptic site of the active zone by transfecting the neurones with postsynaptic density protein PSD‐95‐CFP. The data from these triple colour experiments suggest that retrieval after low frequency stimulation keeps vesicles in a more confined region closer to the active zone as identified by PSD‐95‐CFP expression at the postsynaptic site.
Effect of satellite cell ablation on low‐frequency‐stimulated fast‐to‐slow fibre‐type transitions in rat skeletal muscle
Authors: Martins Karen J. B. , Gordon Tessa , Pette Dirk , Dixon Walter T. , Foxcroft George R. , MacLean Ian M. , Putman Charles T.
Published: January 2006

The purpose of this study was to determine whether satellite cell ablation within rat fast‐twitch muscles exposed to chronic low‐frequency stimulation (CLFS) would limit fast‐to‐slow fibre‐type transitions. Twenty‐nine male Wistar rats were randomly assigned to one of three groups. Satellite cells of the left tibialis anterior were ablated by weekly exposure to a 25 Gy dose of γ‐irradiation during 21 days of CLFS (IRR‐Stim), whilst a second group received only 21 days of CLFS (Stim). A third group received weekly doses of γ‐irradiation (IRR). Non‐irradiated right legs served as internal controls. Continuous infusion of 5‐bromo‐2′‐deoxyuridine (BrdU) revealed that CLFS induced an 8.0‐fold increase in satellite cell proliferation over control (mean ±s.e.m.: 23.9 ± 1.7 versus 3.0 ± 0.5 mm−2, P < 0.0001) that was abolished by γ‐irradiation. M‐cadherin and myogenin staining were also elevated 7.7‐ and 3.8‐fold (P < 0.0001), respectively, in Stim compared with control, indicating increases in quiescent and terminally differentiating satellite cells; these increases were abolished by γ‐irradiation. Myonuclear content was elevated 3.3‐fold (P < 0.0001) in Stim, but remained unchanged in IRR‐Stim. Immunohistochemical analyses revealed attenuation of fast‐to‐slow fibre‐type transitions in IRR‐Stim compared with Stim. Comparable changes were observed at the protein level by SDS‐PAGE. It is concluded that although considerable adaptive potential exists within myonuclei, satellite cells play a role in facilitating fast‐to‐slow fibre‐type transitions.
Ca2+‐desensitizing hypoxic vasorelaxation: pivotal role for the myosin binding subunit of myosin phosphatase (MYPT1) in porcine coronary artery
Authors: Wardle Robert L. , Gu Min , Ishida Yukisato , Paul Richard J.
Published: January 2006

Acute hypoxia dilates most systemic arteries leading to increased tissue perfusion. We showed that at high stimulus conditions, porcine coronary artery was relaxed by hypoxia without a change in [Ca2+]i. This ‘Ca2+‐desensitizing hypoxic relaxation’ was validated in permeabilized porcine coronary artery smooth muscle (PCASM) in which hypoxia decreased force and myosin regulatory light chain phosphorylation (p‐MRLC) despite fixed [Ca2+]. Rho kinase‐dependent phosphorylation of MYPT1 (p‐MYPT1) is associated with decreased MRLC phosphatase (MLCP) activity, and increased Ca2+ sensitivity of both p‐MRLC and force. We tested the hypothesis that hypoxia induces Ca2+‐desensitizing hypoxic relaxation via dephosphorylation of p‐MYPT1, consequently increasing MLCP activity and thus decreasing p‐MRLC. α‐Toxin‐permeabilized PCASM pretreated with ATPγS did not relax in response to hypoxia. Moreover, when MRLC but not MYPT1 was protected from ATPγS thiophosphorylation by the MRLC kinase inhibitor ML7 (300 μm), hypoxia remained ineffective. In contrast, hypoxic relaxation was preserved with further addition of the Rho kinase inhibitor Y27632 (1 μm), to attenuate thiophosphorylation of MYPT1. Importantly, measurements of p‐MRLC, and p‐MYPT1 at T696 and T853 (human sequence) paralleled that of force. We conclude that Ca2+‐desensitizing hypoxic relaxation requires dephosphorylation of p‐MYPT1. Moreover, no kinases, other then those inhibited by ML7 and Y27632, nor their associated phosphoproteins can be involved in Ca2+‐desensitizing hypoxic relaxation.
Prions in Skeletal Muscles of Deer with Chronic Wasting Disease
Authors: Angers Rachel C. , Browning Shawn R. , Seward Tanya S. , Sigurdson Christina J. , Miller Michael W. , Hoover Edward A. , Telling Glenn C.
Published: January 2006

The emergence of chronic wasting disease (CWD) in deer and elk in an increasingly wide geographic area, as well as the interspecies transmission of bovine spongiform encephalopathy to humans in the form of variant Creutzfeldt Jakob disease, have raised concerns about the zoonotic potential of CWD. Because meat consumption is the most likely means of exposure, it is important to determine whether skeletal muscle of diseased cervids contains prion infectivity. Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure.
Germline Mutations in Genes Within the MAPK Pathway Cause Cardio-facio-cutaneous Syndrome
Authors: Rodriguez-Viciana Pablo , Tetsu Osamu , Tidyman William E. , Estep Anne L. , Conger Brenda A. , Cruz Molly Santa , McCormick Frank , Rauen Katherine A.
Published: January 2006

Cardio-facio-cutaneous (CFC) syndrome is a sporadic developmental disorder involving characteristic craniofacial features, cardiac defects, ectodermal abnormalities, and developmental delay. We demonstrate that heterogeneous de novo missense mutations in three genes within the mitogen-activated protein kinase (MAPK) pathway cause CFC syndrome. The majority of cases (18 out of 23) are caused by mutations in
BRAF
, a gene frequently mutated in cancer. Of the 11 mutations identified, two result in amino acid substitutions that occur in tumors, but most are unique and suggest previously unknown mechanisms of B-Raf activation. Furthermore, three of five individuals without
BRAF
mutations had missense mutations in either
MEK1
or
MEK2
, downstream effectors of B-Raf. Our findings highlight the involvement of the MAPK pathway in human development and will provide a molecular diagnosis of CFC syndrome.
Detection of venous invasion in surgical specimens of colorectal carcinoma: the efficacy of various types of tissue blocks: Table 1
Authors: Sternberg A , Mizrahi A , Amar M , Groisman G
Published: January 2006

Background:Venous invasion (VI) is an important prognosis predictor after colorectal carcinoma (CRC) resection, enabling more accurate staging and influencing postoperative management.

Aims:To assess/compare various tissue block types (perpendicular, tangential, across mesentery (AM), from major vessels or lymph nodes (LNs)) for VI detection in CRC.

Methods:Fifty two CRCs (51 colectomies, one polypectomy) were studied. Tumours were measured, surface area calculated, and colorectum and bowel wall sites recorded. Weigert’s staining for elastin facilitated VI detection. VI sites, type, and amount were recorded. Ratios of relative yield of tissue block types to their frequency were calculated.

Results:Average numbers of tissue blocks/colectomy specimen were: perpendicular, 10.2; tangential, 9.1; AM, 3.3; from major vessels, 2.1. Average number of LNs examined was 16.47. VI was detected in 22 tumours. Overall, VI was detected in 16 perpendicular, seven tangential, five AM, and two LN blocks. VI was detected in eight, two, one, and three tumours in perpendicular, tangential, LN, and AM blocks alone, respectively. In seven tumours, VI was identified in multiple tissue block types. The average number of blocks obtained was 39.7, 42.1, and 38 from all tumours, VI positive, and VI negative tumours, respectively (p = 0.0497). Efficacy to detect VI was 2.151, 2.088, 1.092, 0.172, and 0 for AM, perpendicular, tangential, LN, and mesenteric vessel blocks, respectively.

Conclusions:VI was identified most frequently and in eight cases only in perpendicular blocks. However, extramural VI was detected in six tumours only in blocks cut tangentially, AM, or from harvested LNs. Hence, all these types of blocks should be submitted routinely and scanned for VI.
cDNA microarray analysis of cancer associated gene expression profiles in malignant peripheral nerve sheath tumours
Authors: Karube K , Nabeshima K , Ishiguro M , Harada M , Iwasaki H
Published: January 2006

Background:Malignant peripheral nerve sheath tumour (MPNST) is a highly aggressive malignancy that arises within peripheral nerves, and is associated with poor prognosis. Little is known about the underlying biology of MPNST, especially the mechanisms involved in cell proliferation, invasion, or escape from apoptosis.

Aims:To identify genes differentially expressed in MPNST compared with benign tumours, such as neurofibromas and schwannomas, by means of cDNA microarray analysis.

Methods:Six MPNST cases and five benign cases (three schwannomas and two neurofibromas) were analysed.

Results:Six genes (keratin 18, survivin, tenascin C, adenosine deaminase, collagen type VIa3, and collagen type VIIa1) were significantly upregulated in MPNST, whereas one gene, insulin-like growth factor binding protein 6, was downregulated in MPNST. Survivin and tenascin C expression was validated by reverse transcription polymerase chain reaction. Immunohistochemistry confirmed upregulation of survivin in MPNST at the protein level in six of eight cases compared with benign tumours. Tenascin C was also expressed at the invasive front and tumorous stroma in all MPNST cases. MPNST cells expressed tenascin C in four of nine cases.

Conclusions:Survivin and tenascin C may be associated with the malignant potential of MPNST and could be considered as potential therapeutic targets.
An audit of thrombophilia screens: results from the National Pathology Alliance benchmarking review
Authors: Lyons S , Galloway M J , Osgerby J , Hanley J
Published: January 2006

Aims:The National Pathology Alliance benchmarking review has completed six years of data collection and analysis of the workload and organisation of haematology laboratories in the UK. This study audits national practice of routine thrombophilia screening against the current standards, as set out in the British committee for standards in haematology (BCSH) guidelines on investigation of heritable thrombophilia.

Methods:Each laboratory completed a standard data collection questionnaire about the number of routine thrombophilia assays performed each year. Information was collected on which thrombophilia tests were performed as part of a routine thrombophilia screen. These results were then compared against the BCSH guidelines on investigation of heritable thrombophilia.

Results:Of the 57 National Health Service trusts that submitted data for review in 2002/2003, 47 performed a routine thrombophilia screen. Ten laboratories complied with the guidelines but 37 laboratories did not.

Conclusion:There was variation in practice in the tests used in routine thrombophilia screens. There is evidence that some laboratories deviate from what may be regarded as “evidence based practice”. The lack of compliance with the guidelines was in general associated with the performance of additional tests not recommended in the guideline. In a minority of laboratories, a clinically significant diagnosis would be missed by the failure to include one or more tests in a thrombophilia screen.
An approach to endomyocardial biopsy interpretation
Authors: Cunningham K S , Veinot J P , Butany J
Published: January 2006

The endomyocardial biopsy (EMB) remains the gold standard mode of investigation for diagnosing many primary and secondary cardiac conditions. Through a percutaneous and transvenous route, tissue fragments are generally procured from the right ventricular septum, with very few complications. Widespread use of EMB followed the development of heart transplantation as a means to follow allograft rejection. It has since been useful in helping to diagnose conditions affecting the heart, including cardiomyopathies, myocarditis, infiltrative lesions, arrhythmias, and drug toxicities. The procedure has also been used as a research tool to investigate the natural history of disease and the cardiotoxicity of new medications. This review presents an approach to the evaluation of the EMB, which is particularly directed towards those who may be asked to interpret such biopsies, but are not dedicated cardiovascular pathologists. Through a systematic evaluation of the endocardium, myocardium, interstitium, and intramural vessels, in the context of a complete clinical history, enough information can be deduced to diagnose or exclude specific conditions of clinical value.
Small bowel infarction in a patient with coeliac disease
Authors: McNeill A , Duthie F , Galloway D J
Published: January 2006

A 40 year old man was admitted with a four week history of intractable diarrhoea and abdominal pain. A clinical diagnosis of inflammatory bowel disease was supported by biopsies of colonic mucosa. There was no response to Mesalazine and over 12 days the patient became critically ill with diarrhoea, hypovolaemia, and peritonism. A laparotomy was performed and 130 cm of infarcted ileum was resected. Extensive investigations excluded thrombophilia and echocardiography excluded intracardiac thrombus. Postoperatively the patient continued to have diarrhoea and he was diagnosed with coeliac disease on the basis of positive antiendomysial and antitissue transglutaminase autoantibodies and duodenal histology. Although there is no proof that mesenteric infarction occurred as a direct consequence of coeliac disease, clinicians should be aware of this possibility.
Twenty year review of histopathological findings in enucleated/eviscerated eyes
Authors: Saeed M U , Chang B Y P , Khandwala M , Shivane A G , Chakrabarty A
Published: January 2006

Background/Aims:To evaluate the need for routine histopathological analysis of enucleated/eviscerated eyes and changes in indications for eye removal.

Methods:Retrospective review of all enucleation/evisceration histopathology reports over 20 years. Clinical history was correlated with pathological findings. Two 10 year periods (1984–93, 1994–2003) were compared to detect changes in indications for eye removal.

Results:In total, 285 histopathology results were traced from 1984 to 2003; 161 and 124 were evisceration and enucleation specimens, respectively. Glaucoma, malignant melanoma, trauma, and retinal detachment were the most frequent diagnoses 1984–1993. Ocular trauma was the most frequent diagnosis 1994–2003, followed by phthisis bulbi and endophthalmitis. Three cases were diagnosed as metastatic carcinoma; all were suspected preoperatively. A fourth case was a diagnostic surprise: adenocarcinoma found in an eye removed for pain and phthisis. Comparison of two 10 year periods showed a decrease in the number of enucleations/eviscerations, perhaps reflecting a decrease in the number of specimens sent. A preference for eviscerations was evident over the 20 years.

Conclusion:The number of eyes removed and histologically analysed decreased in the period 1994 to 2003, perhaps because of better treatment options, allowing globe preservation. There was a significant shift in the diagnosis in the two time periods, and a preference for evisceration in both. Only one diagnostic surprise was discovered (0.35%). This study does not support the need to send all globes/contents for histopathological examination. However, because of the one unexpected finding, it is recommended where the examination is incomplete or the history of visual loss is unclear.
Best practice in primary care pathology: review 2: Figure 1
Authors: Smellie W S , Forth J O , McNulty C A M , Hirschowitz L , Lilic D , Gosling R , Bareford D , Logan E , Kerr K G , Spickett G P , Hoffman J , Galloway A , Bloxham C A
Published: January 2006

This second best practice review examines five series of common primary care questions in laboratory medicine: (1) laboratory testing for allergy, (2) diagnosis and monitoring of menopause, (3) the use of urine cytology, (4) the usefulness of the erythrocyte sedimentation rate, and (5) the investigation of possible urinary tract infection. The review is presented in a question–answer format. The recommendations represent a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents, and evidence based medicine reviews, supplemented by MEDLINE EMBASE searches to identify relevant primary research documents. They are standards but form a guide to be set in the clinical context. Most are consensus rather than evidence based. They will be updated periodically to take account of new information.
Increased apoptosis and accelerated epithelial migration following inhibition of hedgehog signaling in adaptive small bowel postresection
Authors: Tang Yuzhu , Swietlicki Elzbieta A. , Jiang ShuJun , Buhman Kim K. , Davidson Nicholas O. , Burkly Linda C. , Levin Marc S. , Rubin Deborah C.
Published: January 2006

The intestinal epithelium undergoes a marked adaptive response following loss of functional small bowel surface area characterized by increased crypt cell proliferation and increased enterocyte migration from crypt to villus tip, resulting in villus hyperplasia and enhanced nutrient absorption. Hedgehog (Hh) signaling plays a critical role in regulating epithelial-mesenchymal interactions during morphogenesis of the embryonic intestine. Our previous studies showed that blocking Hh signaling in neonatal mice results in increased small intestinal epithelial crypt cell proliferation and altered enterocyte fat absorption and morphology. Hh family members are also expressed in the adult intestine, but their role in the mature small bowel is unclear. With the use of a model of intestinal adaptation following partial small bowel resection, the role of Hh signaling in the adult gut was examined by determining the effects of blocking Hh signaling on the regenerative response following loss of functional surface area. Hh-inactivating monoclonal antibodies or control antibodies were administered to mice that sustained a 50% intestinal resection. mRNA analyses of the preoperative ileum by quantitative real-time PCR revealed that Indian hedgehog was the most abundant Hh family member. The Hh receptor Patched was more abundant than Patched 2. Analyses of downstream targets of Hh signaling demonstrated that Gli3 was twofold more abundant than Gli1 and Gli2 and that bone morphogenetic protein ( BMP) 2 was most highly expressed compared with BMP1, - 4, and - 7. Following intestinal resection, the expression of Hh, Patched, Gli, and most BMP genes was markedly downregulated in the remnant ileum, and, in anti-Hh antibody-treated mice, expression of Patched 2 and Gli 1 was further suppressed. In Hh antibody-treated mice following resection, the enterocyte migration rate from crypt to villus tip was increased, and by 2 wk postoperation, apoptosis was increased in the adaptive gut. However, crypt cell proliferation, villus height, and crypt depth were not augmented. These data indicate that Hh signaling plays a role in adult gut epithelial homeostasis by regulating epithelial cell migration from crypt to villus tip and by enhancing apoptosis.