Probabilistic anatomical labeling of brain structures using statistical probabilistic anatomical maps

International Nuclear Information System (INIS)

Kim, Jin Su; Lee, Dong Soo; Lee, Byung Il; Lee, Jae Sung; Shin, Hee Won; Chung, June Key; Lee, Myung Chul

2002-01-01

The use of statistical parametric mapping (SPM) program has increased for the analysis of brain PET and SPECT images. Montreal neurological institute (MNI) coordinate is used in SPM program as a standard anatomical framework. While the most researchers look up Talairach atlas to report the localization of the activations detected in SPM program, there is significant disparity between MNI templates and Talairach atlas. That disparity between Talairach and MNI coordinates makes the interpretation of SPM result time consuming, subjective and inaccurate. The purpose of this study was to develop a program to provide objective anatomical information of each x-y-z position in ICBM coordinate. Program was designed to provide the anatomical information for the given x-y-z position in MNI coordinate based on the statistical probabilistic anatomical map (SPAM) images of ICBM. When x-y-z position was given to the program, names of the anatomical structures with non-zero probability and the probabilities that the given position belongs to the structures were tabulated. The program was coded using IDL and JAVA language for the easy transplantation to any operating system or platform. Utility of this program was shown by comparing the results of this program to those of SPM program. Preliminary validation study was performed by applying this program to the analysis of PET brain activation study of human memory in which the anatomical information on the activated areas are previously known. Real time retrieval of probabilistic information with 1 mm spatial resolution was archived using the programs. Validation study showed the relevance of this program: probability that the activated area for memory belonged to hippocampal formation was more than 80%. These programs will be useful for the result interpretation of the image analysis performed on MNI coordinate, as done in SPM program

Nogo receptor 1 limits tactile task performance independent of basal anatomical plasticity.

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Jennifer I Park

Full Text Available The genes that govern how experience refines neural circuitry and alters synaptic structural plasticity are poorly understood. The nogo-66 receptor 1 gene (ngr1 is one candidate that may restrict the rate of learning as well as basal anatomical plasticity in adult cerebral cortex. To investigate if ngr1 limits the rate of learning we tested adult ngr1 null mice on a tactile learning task. Ngr1 mutants display greater overall performance despite a normal rate of improvement on the gap-cross assay, a whisker-dependent learning paradigm. To determine if ngr1 restricts basal anatomical plasticity in the associated sensory cortex, we repeatedly imaged dendritic spines and axonal varicosities of both constitutive and conditional adult ngr1 mutant mice in somatosensory barrel cortex for two weeks through cranial windows with two-photon chronic in vivo imaging. Neither constant nor acute deletion of ngr1 affected turnover or stability of dendritic spines or axonal boutons. The improved performance on the gap-cross task is not attributable to greater motor coordination, as ngr1 mutant mice possess a mild deficit in overall performance and a normal learning rate on the rotarod, a motor task. Mice lacking ngr1 also exhibit normal induction of tone-associated fear conditioning yet accelerated fear extinction and impaired consolidation. Thus, ngr1 alters tactile and motor task performance but does not appear to limit the rate of tactile or motor learning, nor determine the low set point for synaptic turnover in sensory cortex.

Dissection of the Auditory Bulla in Postnatal Mice: Isolation of the Middle Ear Bones and Histological Analysis.

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Sakamoto, Ayako; Kuroda, Yukiko; Kanzaki, Sho; Matsuo, Koichi

2017-01-04

In most mammals, auditory ossicles in the middle ear, including the malleus, incus and stapes, are the smallest bones. In mice, a bony structure called the auditory bulla houses the ossicles, whereas the auditory capsule encloses the inner ear, namely the cochlea and semicircular canals. Murine ossicles are essential for hearing and thus of great interest to researchers in the field of otolaryngology, but their metabolism, development, and evolution are highly relevant to other fields. Altered bone metabolism can affect hearing function in adult mice, and various gene-deficient mice show changes in morphogenesis of auditory ossicles in utero. Although murine auditory ossicles are tiny, their manipulation is feasible if one understands their anatomical orientation and 3D structure. Here, we describe how to dissect the auditory bulla and capsule of postnatal mice and then isolate individual ossicles by removing part of the bulla. We also discuss how to embed the bulla and capsule in different orientations to generate paraffin or frozen sections suitable for preparation of longitudinal, horizontal, or frontal sections of the malleus. Finally, we enumerate anatomical differences between mouse and human auditory ossicles. These methods would be useful in analyzing pathological, developmental and evolutionary aspects of auditory ossicles and the middle ear in mice.

Inner ear dysfunction in caspase-3 deficient mice

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Woo Minna

2011-10-01

Full Text Available Abstract Background Caspase-3 is one of the most downstream enzymes activated in the apoptotic pathway. In caspase-3 deficient mice, loss of cochlear hair cells and spiral ganglion cells coincide closely with hearing loss. In contrast with the auditory system, details of the vestibular phenotype have not been characterized. Here we report the vestibular phenotype and inner ear anatomy in the caspase-3 deficient (Casp3-/- mouse strain. Results Average ABR thresholds of Casp3-/- mice were significantly elevated (P Casp3+/- mice and Casp3+/+ mice at 3 months of age. In DPOAE testing, distortion product 2F1-F2 was significantly decreased (P Casp3-/- mice, whereas Casp3+/- and Casp3+/+ mice showed normal and comparable values to each other. Casp3-/- mice were hyperactive and exhibited circling behavior when excited. In lateral canal VOR testing, Casp3-/- mice had minimal response to any of the stimuli tested, whereas Casp3+/- mice had an intermediate response compared to Casp3+/+ mice. Inner ear anatomical and histological analysis revealed gross hypomorphism of the vestibular organs, in which the main site was the anterior semicircular canal. Hair cell numbers in the anterior- and lateral crista, and utricle were significantly smaller in Casp3-/- mice whereas the Casp3+/- and Casp3+/+ mice had normal hair cell numbers. Conclusions These results indicate that caspase-3 is essential for correct functioning of the cochlea as well as normal development and function of the vestibule.

Mcph1-deficient mice reveal a role for MCPH1 in otitis media.

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Jing Chen

Full Text Available Otitis media is a common reason for hearing loss, especially in children. Otitis media is a multifactorial disease and environmental factors, anatomic dysmorphology and genetic predisposition can all contribute to its pathogenesis. However, the reasons for the variable susceptibility to otitis media are elusive. MCPH1 mutations cause primary microcephaly in humans. So far, no hearing impairment has been reported either in the MCPH1 patients or mouse models with Mcph1 deficiency. In this study, Mcph1-deficient (Mcph1(tm1a (/tm1a mice were produced using embryonic stem cells with a targeted mutation by the Sanger Institute's Mouse Genetics Project. Auditory brainstem response measurements revealed that Mcph1(tm1a (/tm1a mice had mild to moderate hearing impairment with around 70% penetrance. We found otitis media with effusion in the hearing-impaired Mcph1(tm1a (/tm1a mice by anatomic and histological examinations. Expression of Mcph1 in the epithelial cells of middle ear cavities supported its involvement in the development of otitis media. Other defects of Mcph1(tm1a (/tm1a mice included small skull sizes, increased micronuclei in red blood cells, increased B cells and ocular abnormalities. These findings not only recapitulated the defects found in other Mcph1-deficient mice or MCPH1 patients, but also revealed an unexpected phenotype, otitis media with hearing impairment, which suggests Mcph1 is a new gene underlying genetic predisposition to otitis media.

Visual and Motor Deficits in Grown-up Mice with Congenital Zika Virus Infection

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Liyuan Cui

2017-06-01

Full Text Available Human infants with congenital Zika virus (ZIKV infection exhibit a range of symptoms including microcephaly, intracranial calcifications, macular atrophy and arthrogryposis. More importantly, prognosis data have lagged far behind the recent outbreak of ZIKV in 2015. In this work, we allow congenitally ZIKV-infected mice to grow into puberty. These mice exhibited motor incoordination and visual dysfunctions, which can be accounted by anatomical defects in the retina and cerebellar cortex. In contrary, anxiety level of the ZIKV-infected mice is normal. The spectrum of anatomical and behavioral deficits is consistent across different mice. Our data provided evidence that may help predict the public health burden in terms of prognosis of ZIKV-related congenital brain malformations in an animal model. Our study provided behavioral evaluation for the prognosis of congenital ZIKV infection and provides a platform for screening and evaluation of drugs candidates and treatment aiming at improving regeneration of infected neurons to prevent sequelae caused by ZIKV infection of fetus.

Connecting imaging mass spectrometry and magnetic resonance imaging-based anatomical atlases for automated anatomical interpretation and differential analysis.

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Verbeeck, Nico; Spraggins, Jeffrey M; Murphy, Monika J M; Wang, Hui-Dong; Deutch, Ariel Y; Caprioli, Richard M; Van de Plas, Raf

2017-07-01

Imaging mass spectrometry (IMS) is a molecular imaging technology that can measure thousands of biomolecules concurrently without prior tagging, making it particularly suitable for exploratory research. However, the data size and dimensionality often makes thorough extraction of relevant information impractical. To help guide and accelerate IMS data analysis, we recently developed a framework that integrates IMS measurements with anatomical atlases, opening up opportunities for anatomy-driven exploration of IMS data. One example is the automated anatomical interpretation of ion images, where empirically measured ion distributions are automatically decomposed into their underlying anatomical structures. While offering significant potential, IMS-atlas integration has thus far been restricted to the Allen Mouse Brain Atlas (AMBA) and mouse brain samples. Here, we expand the applicability of this framework by extending towards new animal species and a new set of anatomical atlases retrieved from the Scalable Brain Atlas (SBA). Furthermore, as many SBA atlases are based on magnetic resonance imaging (MRI) data, a new registration pipeline was developed that enables direct non-rigid IMS-to-MRI registration. These developments are demonstrated on protein-focused FTICR IMS measurements from coronal brain sections of a Parkinson's disease (PD) rat model. The measurements are integrated with an MRI-based rat brain atlas from the SBA. The new rat-focused IMS-atlas integration is used to perform automated anatomical interpretation and to find differential ions between healthy and diseased tissue. IMS-atlas integration can serve as an important accelerator in IMS data exploration, and with these new developments it can now be applied to a wider variety of animal species and modalities. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann. Copyright © 2017. Published by Elsevier B.V.

Anatomical and histological profiling of orphan G-protein-coupled receptor expression in gastrointestinal tract of C57BL/6J mice.

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Ito, Junko; Ito, Masahiko; Nambu, Hirohide; Fujikawa, Toru; Tanaka, Kenichi; Iwaasa, Hisashi; Tokita, Shigeru

2009-11-01

G-protein-coupled receptors (GPCRs) constitute the largest family of transmembrane receptors and regulate a variety of physiological and disease processes. Although the roles of many non-odorant GPCRs have been identified in vivo, several GPCRs remain orphans (oGPCRs). The gastrointestinal (GI) tract is the largest endocrine organ and is a promising target for drug discovery. Given their close link to physiological function, the anatomical and histological expression profiles of benchmark GI-related GPCRs, such as the cholecystokinin-1 receptor and GPR120, and 106 oGPCRs were investigated in the mucosal and muscle-myenteric nerve layers in the GI tract of C57BL/6J mice by quantitative real-time polymerase chain reaction. The mRNA expression patterns of these benchmark molecules were consistent with previous in situ hybridization and immunohistochemical studies, validating the experimental protocols in this study. Of 96 oGPCRs with significant mRNA expression in the GI tract, several oGPCRs showed unique expression patterns. GPR85, GPR37, GPR37L1, brain-specific angiogenesis inhibitor (BAI) 1, BAI2, BAI3, and GPRC5B mRNAs were preferentially expressed in the muscle-myenteric nerve layer, similar to GPCRs that are expressed in both the central and enteric nerve systems and that play multiple regulatory roles throughout the gut-brain axis. In contrast, GPR112, trace amine-associated receptor (TAAR) 1, TAAR2, and GPRC5A mRNAs were preferentially expressed in the mucosal layer, suggesting their potential roles in the regulation of secretion, immunity, and epithelial homeostasis. These anatomical and histological mRNA expression profiles of oGPCRs provide useful clues about the physiological roles of oGPCRs in the GI tract.

[Variants of anatomical structure of lower-limb veins as a possible cause of the development of primary varicosity].

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Vakhitov, M Kh; Bol'shakov, O P

2011-01-01

In order to reveal anatomical prerequisites for the development of primary varicose veins we investigated the structure of the venous system on a total of 53 adult human cadaveric lower extremities. Congenital morphological grounds providing the phlebohaemodynemics of the lower limbs are ambiguous in different individual forms. We revealed a total of 18 variants of the structure of deep veins, reflecting various stages of the embryonic development. In 34.1% of cases we saw the forms characteristic of incomplete reduction and unfinished transformation, with 30.2% of cases showing the utmost degree of reduction and transformation. An inadequate outflow along the deep veins conditioned by their anatomical structure is a prerequisite for the development of valvular insufficiency and venous reflux to the superficial veins followed by varicose transformation thereof

Ex-vivo assessment and non-invasive in vivo imaging of internal hemorrhages in Aga2/+ mutant mice

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Ermolayev, Vladimir [Institute for Biological and Medical Imaging, Helmholtz Zentrum München, Building 56, Ingolstädter Landstraße 1, D-85764 Neuherberg (Germany); Cohrs, Christian M. [Institute for Experimental Genetics, Helmholtz Zentrum München, Ingolstädter Landstraße 1, D-85764 Neuherberg (Germany); Mohajerani, Pouyan; Ale, Angelique [Institute for Biological and Medical Imaging, Helmholtz Zentrum München, Building 56, Ingolstädter Landstraße 1, D-85764 Neuherberg (Germany); Hrabé de Angelis, Martin [Institute for Experimental Genetics, Helmholtz Zentrum München, Ingolstädter Landstraße 1, D-85764 Neuherberg (Germany); Ntziachristos, Vasilis, E-mail: v.ntziachristos@tum.de [Institute for Biological and Medical Imaging, Helmholtz Zentrum München, Building 56, Ingolstädter Landstraße 1, D-85764 Neuherberg (Germany)

2013-03-08

Highlights: ► Aga2/+ mice, model for Osteogenesis imperfecta, have type I collagen mutation. ► Aga2/+ mice display both moderate and severe phenotypes lethal 6–11th postnatal. ► Internal hemorrhages studied in Aga2/+ vs. control mice at 6 and 9 days postnatal. ► Anatomical and functional findings in-vivo contrasted to the ex-vivo appearance. -- Abstract: Mutations in type I collagen genes (COL1A1/2) typically lead to Osteogenesis imperfecta, the most common heritable cause of skeletal fractures and bone deformation in humans. Heterozygous Col1a1{sup Aga2/+}, animals with a dominant mutation in the terminal C-propeptide domain of type I collagen develop typical skeletal hallmarks and internal hemorrhages starting from 6 day after birth. The disease progression for Aga2/+ mice, however, is not uniform differing between severe phenotype lethal at the 6–11th day of life, and moderate-to-severe one with survival to adulthood. Herein we investigated whether a new modality that combines X-ray computer tomography with fluorescence tomography in one hybrid system can be employed to study internal bleedings in relation to bone fractures and obtain insights into disease progression. The disease phenotype was characterized on Aga2/+ vs. wild type mice between 6 and 9 days postnatal. Anatomical and functional findings obtained in-vivo were contrasted to the ex-vivo appearance of the same tissues under cryo-slicing.

Ex-vivo assessment and non-invasive in vivo imaging of internal hemorrhages in Aga2/+ mutant mice

International Nuclear Information System (INIS)

Ermolayev, Vladimir; Cohrs, Christian M.; Mohajerani, Pouyan; Ale, Angelique; Hrabé de Angelis, Martin; Ntziachristos, Vasilis

2013-01-01

Highlights: ► Aga2/+ mice, model for Osteogenesis imperfecta, have type I collagen mutation. ► Aga2/+ mice display both moderate and severe phenotypes lethal 6–11th postnatal. ► Internal hemorrhages studied in Aga2/+ vs. control mice at 6 and 9 days postnatal. ► Anatomical and functional findings in-vivo contrasted to the ex-vivo appearance. -- Abstract: Mutations in type I collagen genes (COL1A1/2) typically lead to Osteogenesis imperfecta, the most common heritable cause of skeletal fractures and bone deformation in humans. Heterozygous Col1a1 Aga2/+ , animals with a dominant mutation in the terminal C-propeptide domain of type I collagen develop typical skeletal hallmarks and internal hemorrhages starting from 6 day after birth. The disease progression for Aga2/+ mice, however, is not uniform differing between severe phenotype lethal at the 6–11th day of life, and moderate-to-severe one with survival to adulthood. Herein we investigated whether a new modality that combines X-ray computer tomography with fluorescence tomography in one hybrid system can be employed to study internal bleedings in relation to bone fractures and obtain insights into disease progression. The disease phenotype was characterized on Aga2/+ vs. wild type mice between 6 and 9 days postnatal. Anatomical and functional findings obtained in-vivo were contrasted to the ex-vivo appearance of the same tissues under cryo-slicing

Effects of noise pollution stress during pregnancy on anatomical and functional brain cortex development of the offsprings of NMRI mice

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Sara Bijani

2012-12-01

Full Text Available Introduction: Effects of stress on changes in neural system activity is well defined, which might be because of the changes in brain cortex architecture. In the present study, the effects of maternal noise stress on the morphological and functional changes in brain cortex of off springs of NMRI mice were examined.Materials and Methods: Female pregnant mice divided into two groups. Control group was maintained in their home cages without any invasion but the experimental group was exposed to the noise stress (80 db for 5 min/day from day zero of pregnancy to day 14 (i.e. 15 days. After delivery, six pups from each group were killed and their brains were fixed, sectioned and stained in H&E. These sections were investigated by MOTIC software for both control and experimental groups. Other pups were nursed by their mothers until their adolescence (22 g-8 weeks old. Then they were examined for behavioral side-biased and locomotor activity tests.Results: Decrease in cortex diameter and diameter of each layer for the experimental group was observed. In addition, neuron counting in each layer indicated that the number of the neurons in the middle and outer layers of cortex for the experimental group was reduced than the control group. In contrast, the number of the neurons in the inner layer of the experimental group was increased. From the functional view, in experimental group increases in left-handness especially in female off springs were observed. Furthermore, spontaneous locomotor activity in the new environment was increased in the experimental group.Conclusion: These results indicated that neuronal immigration and network connections in the inner layer of cortex through the middle and outer layers in the experimental group were inhibited. In other word, noise stress was able to inhibit brain cortex development in next generation

Development of a new generation of high-resolution anatomical models for medical device evaluation: the Virtual Population 3.0

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Gosselin, Marie-Christine; Neufeld, Esra; Moser, Heidi; Huber, Eveline; Farcito, Silvia; Gerber, Livia; Jedensjö, Maria; Hilber, Isabel; Di Gennaro, Fabienne; Lloyd, Bryn; Cherubini, Emilio; Szczerba, Dominik; Kainz, Wolfgang; Kuster, Niels

2014-09-01

The Virtual Family computational whole-body anatomical human models were originally developed for electromagnetic (EM) exposure evaluations, in particular to study how absorption of radiofrequency radiation from external sources depends on anatomy. However, the models immediately garnered much broader interest and are now applied by over 300 research groups, many from medical applications research fields. In a first step, the Virtual Family was expanded to the Virtual Population to provide considerably broader population coverage with the inclusion of models of both sexes ranging in age from 5 to 84 years old. Although these models have proven to be invaluable for EM dosimetry, it became evident that significantly enhanced models are needed for reliable effectiveness and safety evaluations of diagnostic and therapeutic applications, including medical implants safety. This paper describes the research and development performed to obtain anatomical models that meet the requirements necessary for medical implant safety assessment applications. These include implementation of quality control procedures, re-segmentation at higher resolution, more-consistent tissue assignments, enhanced surface processing and numerous anatomical refinements. Several tools were developed to enhance the functionality of the models, including discretization tools, posing tools to expand the posture space covered, and multiple morphing tools, e.g., to develop pathological models or variations of existing ones. A comprehensive tissue properties database was compiled to complement the library of models. The results are a set of anatomically independent, accurate, and detailed models with smooth, yet feature-rich and topologically conforming surfaces. The models are therefore suited for the creation of unstructured meshes, and the possible applications of the models are extended to a wider range of solvers and physics. The impact of these improvements is shown for the MRI exposure of an adult

Development of a new generation of high-resolution anatomical models for medical device evaluation: the Virtual Population 3.0

International Nuclear Information System (INIS)

Gosselin, Marie-Christine; Neufeld, Esra; Moser, Heidi; Huber, Eveline; Farcito, Silvia; Gerber, Livia; Jedensjö, Maria; Hilber, Isabel; Gennaro, Fabienne Di; Lloyd, Bryn; Szczerba, Dominik; Kuster, Niels; Cherubini, Emilio; Kainz, Wolfgang

2014-01-01

The Virtual Family computational whole-body anatomical human models were originally developed for electromagnetic (EM) exposure evaluations, in particular to study how absorption of radiofrequency radiation from external sources depends on anatomy. However, the models immediately garnered much broader interest and are now applied by over 300 research groups, many from medical applications research fields. In a first step, the Virtual Family was expanded to the Virtual Population to provide considerably broader population coverage with the inclusion of models of both sexes ranging in age from 5 to 84 years old. Although these models have proven to be invaluable for EM dosimetry, it became evident that significantly enhanced models are needed for reliable effectiveness and safety evaluations of diagnostic and therapeutic applications, including medical implants safety. This paper describes the research and development performed to obtain anatomical models that meet the requirements necessary for medical implant safety assessment applications. These include implementation of quality control procedures, re-segmentation at higher resolution, more-consistent tissue assignments, enhanced surface processing and numerous anatomical refinements. Several tools were developed to enhance the functionality of the models, including discretization tools, posing tools to expand the posture space covered, and multiple morphing tools, e.g., to develop pathological models or variations of existing ones. A comprehensive tissue properties database was compiled to complement the library of models. The results are a set of anatomically independent, accurate, and detailed models with smooth, yet feature-rich and topologically conforming surfaces. The models are therefore suited for the creation of unstructured meshes, and the possible applications of the models are extended to a wider range of solvers and physics. The impact of these improvements is shown for the MRI exposure of an adult

Visual and Motor Deficits in Grown-up Mice with Congenital Zika Virus Infection.

Science.gov (United States)

Cui, Liyuan; Zou, Peng; Chen, Er; Yao, Hao; Zheng, Hao; Wang, Qian; Zhu, Jing-Ning; Jiang, Shibo; Lu, Lu; Zhang, Jiayi

2017-06-01

Human infants with congenital Zika virus (ZIKV) infection exhibit a range of symptoms including microcephaly, intracranial calcifications, macular atrophy and arthrogryposis. More importantly, prognosis data have lagged far behind the recent outbreak of ZIKV in 2015. In this work, we allow congenitally ZIKV-infected mice to grow into puberty. These mice exhibited motor incoordination and visual dysfunctions, which can be accounted by anatomical defects in the retina and cerebellar cortex. In contrary, anxiety level of the ZIKV-infected mice is normal. The spectrum of anatomical and behavioral deficits is consistent across different mice. Our data provided evidence that may help predict the public health burden in terms of prognosis of ZIKV-related congenital brain malformations in an animal model. Our study provided behavioral evaluation for the prognosis of congenital ZIKV infection and provides a platform for screening and evaluation of drugs candidates and treatment aiming at improving regeneration of infected neurons to prevent sequelae caused by ZIKV infection of fetus. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Anatomical eponyms - unloved names in medical terminology.

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Burdan, F; Dworzański, W; Cendrowska-Pinkosz, M; Burdan, M; Dworzańska, A

2016-01-01

Uniform international terminology is a fundamental issue of medicine. Names of various organs or structures have developed since early human history. The first proper anatomical books were written by Hippocrates, Aristotle and Galen. For this reason the modern terms originated from Latin or Greek. In a modern time the terminology was improved in particular by Vasalius, Fabricius and Harvey. Presently each known structure has internationally approved term that is explained in anatomical or histological terminology. However, some elements received eponyms, terms that incorporate the surname of the people that usually describe them for the first time or studied them (e.g., circle of Willis, follicle of Graff, fossa of Sylvious, foramen of Monro, Adamkiewicz artery). Literature and historical hero also influenced medical vocabulary (e.g. Achilles tendon and Atlas). According to various scientists, all the eponyms bring colour to medicine, embed medical traditions and culture to our history but lack accuracy, lead of confusion, and hamper scientific discussion. The current article presents a wide list of the anatomical eponyms with their proper anatomical term or description according to international anatomical terminology. However, since different eponyms are used in various countries, the list could be expanded.

Anatomical Basis for the Cardiac Interventional Electrophysiologist

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Damián Sánchez-Quintana

2015-01-01

Full Text Available The establishment of radiofrequency catheter ablation techniques as the mainstay in the treatment of tachycardia has renewed new interest in cardiac anatomy. The interventional arrhythmologist has drawn attention not only to the gross anatomic details of the heart but also to architectural and histological characteristics of various cardiac regions that are relevant to the development or recurrence of tachyarrhythmias and procedural related complications of catheter ablation. In this review, therefore, we discuss some anatomic landmarks commonly used in catheter ablations including the terminal crest, sinus node region, Koch’s triangle, cavotricuspid isthmus, Eustachian ridge and valve, pulmonary venous orifices, venoatrial junctions, and ventricular outflow tracts. We also discuss the anatomical features of important structures in the vicinity of the atria and pulmonary veins, such as the esophagus and phrenic nerves. This paper provides basic anatomic information to improve understanding of the mapping and ablative procedures for cardiac interventional electrophysiologists.

Development of an Allergic Conjunctivitis Model in Mice

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Tolga Kocatürk

2012-12-01

Full Text Available Pur po se: To develop an animal model that simulates human allergic conjunctivitis to understand the physiopathogenesis of allergic diseases and for developing novel therapeutic interventions. Ma te ri al and Met hod: BALB/c mice (12 males were divided into two groups each comprised of six mice. For sensitization, on the 1st and 8th days, a 0.2 ml mixed solution, adjusted to a concentration to 5mg/ml of ovalbumin (OVA and 15mg/ml of aluminium hydroxide, was administered intraperitoneally to the mice in Group 1 and 0.2 ml saline solution to the mice in Group 2. To induce experimental allergic conjunctivitis, an antigen challenge was made on days 15 and 18, using an OVA solution (5mg/ml instilled into both eyes of the mice in Group 1; while the mice in Group 2 received Human Balanced Salt Solution instead of OVA. For the clinical evaluation, the occurrence of conjunctival and palpebral oedema, conjunctival hyperaemia, and lacrimation were observed. For the histological examination, eyeballs, eyelids, and lacrimal glands were removed and prepared according to the routine processing method of the tissue laboratory. Immunohistochemical examination was made with mast cell tryptase using the labeled streptavidin–biotin amplification method and 3.3´-diaminobenzidine, in addition to hematoxylin-eosin (HE, and toluidine blue (TB staining. Re sults: Evident conjunctival oedema, palpebral oedema, conjunctival hyperaemia, and lacrimation were observed in Group 1. Mean mast cell density in cells/mm2, infiltrating the subconjunctival tissue was significantly high in Group 1 (allergy group, 23.17±7.46, p<0.0001 when compared to Group 2 (5.58±3.12. There was no increase in eosinophil and lymphocyte counts as well as vascular intensity in the subconjunctival tissue in any group. Dis cus si on: The murine model developed is similar to the human allergic conjunctivitis both clinically and histopathologically and can be used as a template for future studies

Early fetal anatomical sonography.

LENUS (Irish Health Repository)

Donnelly, Jennifer C

2012-10-01

Over the past decade, prenatal screening and diagnosis has moved from the second into the first trimester, with aneuploidy screening becoming both feasible and effective. With vast improvements in ultrasound technology, sonologists can now image the fetus in greater detail at all gestational ages. In the hands of experienced sonographers, anatomic surveys between 11 and 14 weeks can be carried out with good visualisation rates of many structures. It is important to be familiar with the normal development of the embryo and fetus, and to be aware of the major anatomical landmarks whose absence or presence may be deemed normal or abnormal depending on the gestational age. Some structural abnormalities will nearly always be detected, some will never be and some are potentially detectable depending on a number of factors.

Development and preliminary evaluation of a new anatomically based prosthetic alignment method for below-knee prosthesis.

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Tafti, Nahid; Karimlou, Masoud; Mardani, Mohammad Ali; Jafarpisheh, Amir Salar; Aminian, Gholam Reza; Safari, Reza

2018-04-20

The objectives of current study were to a) assess similarities and relationships between anatomical landmark-based angles and distances of lower limbs in unilateral transtibial amputees and b) develop and evaluate a new anatomically based static prosthetic alignment method. First sub-study assessed the anthropometrical differences and relationships between the lower limbs in the photographs taken from amputees. Data were analysed via paired t-test and regression analysis. Results show no significant differences in frontal and transverse planes. In the sagittal plane, the anthropometric parameters of the amputated limb were significantly correlated to the corresponding variables of the sound limb. The results served as bases for the development of a new prosthetic alignment method. The method was evaluated on a single subject study. Prosthetic alignment carried out by an experienced prosthetist was compared with such alignment adjusted by an inexperienced prosthetist but with the use of the developed method. In sagittal and frontal planes, the socket angle was tuned with respect to the shin angle, and the position of the prosthetic foot was tuned in relation to the pelvic landmarks. Further study is needed to assess the proposed method on a larger sample of amputees and prosthetists.

Recent advances in standards for collaborative Digital Anatomic Pathology

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2011-01-01

reports that are interoperable at an international level. The use of machine-readable format of APSR supports the development of decision support as well as secondary use of Anatomic Pathology information for epidemiology or clinical research. PMID:21489187

In Vivo Evaluation of Fracture Callus Development During Bone Healing in Mice Using an MRI-compatible Osteosynthesis Device for the Mouse Femur.

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Haffner-Luntzer, Melanie; Müller-Graf, Fabian; Matthys, Romano; Abaei, Alireza; Jonas, René; Gebhard, Florian; Rasche, Volker; Ignatius, Anita

2017-11-14

Endochondral fracture healing is a complex process involving the development of fibrous, cartilaginous, and osseous tissue in the fracture callus. The amount of the different tissues in the callus provides important information on the fracture healing progress. Available in vivo techniques to longitudinally monitor the callus tissue development in preclinical fracture-healing studies using small animals include digital radiography and µCT imaging. However, both techniques are only able to distinguish between mineralized and non-mineralized tissue. Consequently, it is impossible to discriminate cartilage from fibrous tissue. In contrast, magnetic resonance imaging (MRI) visualizes anatomical structures based on their water content and might therefore be able to noninvasively identify soft tissue and cartilage in the fracture callus. Here, we report the use of an MRI-compatible external fixator for the mouse femur to allow MRI scans during bone regeneration in mice. The experiments demonstrated that the fixator and a custom-made mounting device allow repetitive MRI scans, thus enabling longitudinal analysis of fracture-callus tissue development.

Transcranial magnetic stimulation of mouse brain using high-resolution anatomical models

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Crowther, L. J.; Hadimani, R. L.; Kanthasamy, A. G.; Jiles, D. C.

2014-05-01

Transcranial magnetic stimulation (TMS) offers the possibility of non-invasive treatment of brain disorders in humans. Studies on animals can allow rapid progress of the research including exploring a variety of different treatment conditions. Numerical calculations using animal models are needed to help design suitable TMS coils for use in animal experiments, in particular, to estimate the electric field induced in animal brains. In this paper, we have implemented a high-resolution anatomical MRI-derived mouse model consisting of 50 tissue types to accurately calculate induced electric field in the mouse brain. Magnetic field measurements have been performed on the surface of the coil and compared with the calculations in order to validate the calculated magnetic and induced electric fields in the brain. Results show how the induced electric field is distributed in a mouse brain and allow investigation of how this could be improved for TMS studies using mice. The findings have important implications in further preclinical development of TMS for treatment of human diseases.

Mistakes in the usage of anatomical terminology in clinical practice.

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Kachlik, David; Bozdechova, Ivana; Cech, Pavel; Musil, Vladimir; Baca, Vaclav

2009-06-01

Anatomical terminology serves as a basic communication tool in all the medical fields. Therefore Latin anatomical nomenclature has been repetitively issued and revised from 1895 (Basiliensia Nomina Anatomica) until 1998, when the last version was approved and published as the Terminologia Anatomica (International Anatomical Terminology) by the Federative Committee on Anatomical Terminology. A brief history of the terminology and nomenclature development is mentioned, along with the concept and contributions of the Terminologia Anatomica including the employed abbreviations. Examples of obsolete anatomical terms and their current synonyms are listed. Clinicians entered the process of the nomenclature revision and this aspect is demonstrated with several examples of terms used in clinical fields only, some already incorporated in the Terminologia Anatomica and a few obsolete terms still alive in non-theoretical communication. Frequent mistakes in grammar and orthography are stated as well. Authors of the article strongly recommend the use of the recent revision of the Latin anatomical nomenclature both in theoretical and clinical medicine.

Polyuria-associated hydronephrosis induced by xenobiotic chemical exposure in mice.

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Yoshioka, Wataru; Kawaguchi, Tatsuya; Nishimura, Noriko; Akagi, Toshiya; Fujisawa, Nozomi; Yanagisawa, Hiroyuki; Matsumura, Fumio; Tohyama, Chiharu

2016-10-01

Hydronephrosis is a commonly found disease state characterized by the dilation of renal calices and pelvis, resulting in the loss of kidney function in the severest cases. A generally accepted etiology of hydronephrosis involves the obstruction of urine flow along the urinary tract. In the recent years, we have developed a mouse model of hydronephrosis induced by lactational exposure to dioxin and demonstrated a lack of anatomical obstruction in this model. We also showed that prostaglandin E 2 synthesis system plays a critical role in the onset of hydronephrosis. In the present study, we found that neonatal hydronephrosis was not likely to be associated with functional obstruction (impaired peristalsis) but was found to be associated with polyuria and low urine osmolality with the downregulation of proteins involved in the urine concentrating process. The administration of an antidiuretic hormone analog to the dioxin-exposed pups not only suppressed the increased urine output but also decreased the incidence and severity of hydronephrosis. In contrast to the case in pups, administration of dioxin to adult mice failed to induce polyuria and upregulation of prostaglandin E 2 synthesis system, and the adult mice were resistant to develop hydronephrosis. These findings suggest the possibility that polyuria could induce hydronephrosis in the absence of anatomical or functional obstruction of the ureter. It is concluded that the present animal model provides a unique example of polyuria-associated type of hydronephrosis, suggesting a need to redefine this disease state. Copyright © 2016 the American Physiological Society.

Effects of prenatal cocaine exposure on social development in mice.

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Kabir, Zeeba D; Kennedy, Bruce; Katzman, Aaron; Lahvis, Garet P; Kosofsky, Barry E

2014-01-01

Prenatal cocaine exposure (PCE) in humans and animals has been shown to impair social development. Molecules that mediate synaptic plasticity and learning in the medial prefrontal cortex (mPFC), specifically brain-derived neurotrophic factor (BDNF) and its downstream signaling molecule, early growth response protein 1 (egr1), have been shown to affect the regulation of social interactions (SI). In this study we determined the effects of PCE on SI and the corresponding ultrasonic vocalizations (USVs) in developing mice. Furthermore, we studied the PCE-induced changes in the constitutive expression of BDNF, egr1 and their transcriptional regulators in the mPFC as a possible molecular mechanism mediating the altered SI. In prenatal cocaine-exposed (PCOC) mice we identified increased SI and USV production at postnatal day (PD) 25, and increased SI but not USVs at PD35. By PD45 the expression of both social behaviors normalized in PCOC mice. At the molecular level, we found increased BDNF exon IV and egr1 mRNA in the mPFC of PCOC mice at PD30 that normalized by PD45. This was concurrent with increased EGR1 protein in the mPFC of PCOC mice at PD30, suggesting a role of egr1 in the enhanced SI observed in juvenile PCOC mice. Additionally, by measuring the association of acetylation of histone 3 at lysine residues 9 and 14 (acH3K9,14) and MeCP2 at the promoters of BDNF exons I and IV and egr1, our results provide evidence of promoter-specific alterations in the mPFC of PCOC juvenile mice, with increased association of acH3K9,14 only at the BDNF exon IV promoter. These results identify a potential PCE-induced molecular alteration as the underlying neurobiological mechanism mediating the altered social development in juvenile mice. © 2014 S. Karger AG, Basel.

The development of lower respiratory tract microbiome in mice.

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Singh, Nisha; Vats, Asheema; Sharma, Aditi; Arora, Amit; Kumar, Ashwani

2017-06-21

Although culture-independent methods have paved the way for characterization of the lung microbiome, the dynamic changes in the lung microbiome from neonatal stage to adult age have not been investigated. In this study, we tracked changes in composition and diversity of the lung microbiome in C57BL/6N mice, starting from 1-week-old neonates to 8-week-old mice. Towards this, the lungs were sterilely excised from mice of different ages from 1 to 8 weeks. High-throughput DNA sequencing of the 16S rRNA gene followed by composition and diversity analysis was utilized to decipher the microbiome in these samples. Microbiome analysis suggests that the changes in the lung microbiome correlated with age. The lung microbiome was primarily dominated by phyla Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria in all the stages from week 1 to week 8 after birth. Although Defluvibacter was the predominant genus in 1-week-old neonatal mice, Streptococcus became the dominant genus at the age of 2 weeks. Lactobacillus, Defluvibacter, Streptococcus, and Achromobacter were the dominant genera in 3-week-old mice, while Lactobacillus and Achromobacter were the most abundant genera in 4-week-old mice. Interestingly, relatively greater diversity (at the genus level) during the age of 5 to 6 weeks was observed as compared to the earlier weeks. The diversity of the lung microbiome remained stable between 6 and 8 weeks of age. In summary, we have tracked the development of the lung microbiome in mice from an early age of 1 week to adulthood. The lung microbiome is dominated by the phyla Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria. However, dynamic changes were observed at the genus level. Relatively higher richness in the microbial diversity was achieved by age of 6 weeks and then maintained at later ages. We believe that this study improves our understanding of the development of the mice lung microbiome and will facilitate further analyses of the role of

Meal parameters and vagal gastrointestinal afferents in mice that experienced early postnatal overnutrition.

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Biddinger, Jessica E; Fox, Edward A

2010-08-04

Early postnatal overnutrition results in a predisposition to develop obesity due in part to hypothalamic and sympathetic dysfunction. Potential involvement of another major regulatory system component--the vagus nerve--has not been examined. Moreover, feeding disturbances have rarely been investigated prior to development of obesity when confounds due to obesity are minimized. To examine these issues, litters were culled on the day of birth to create small litters (SL; overnutrition), or normal size litters (NL; normal nutrition). Body weight, fat pad weight, meal patterns, and vagal sensory duodenal innervation were compared between SL and NL adult mice prior to development of obesity. Meal patterns were studied 18 h/day for 3 weeks using a balanced diet. Then vagal mechanoreceptors were labeled using anterograde transport of wheatgerm agglutinin-horseradish peroxidase injected into the nodose ganglion and their density and morphology were examined. Between postnatal day 1 and weaning, body weight of SL mice was greater than for NL mice. By young adulthood it was similar in both groups, whereas SL fat pad weight was greater in males, suggesting postnatal overnutrition produced a predisposition to obesity. SL mice exhibited increased food intake, decreased satiety ratio, and increased first meal rate (following mild food deprivation) compared to NL mice, suggesting postnatal overnutrition disrupted satiety. The density and structure of intestinal IGLEs appeared similar in SL and NL mice. Thus, although a vagal role cannot be excluded, our meal parameter and anatomical findings provided no evidence for significant postnatal overnutrition effects on vagal gastrointestinal afferents. Copyright 2010 Elsevier Inc. All rights reserved.

Automatic anatomically selective image enhancement in digital chest radiography

International Nuclear Information System (INIS)

Sezan, M.I.; Minerbo, G.N.; Schaetzing, R.

1989-01-01

The authors develop a technique for automatic anatomically selective enhancement of digital chest radiographs. Anatomically selective enhancement is motivated by the desire to simultaneously meet the different enhancement requirements of the lung field and the mediastinum. A recent peak detection algorithm and a set of rules are applied to the image histogram to determine automatically a gray-level threshold between the lung field and mediastinum. The gray-level threshold facilitates anatomically selective gray-scale modification and/or unsharp masking. Further, in an attempt to suppress possible white-band or black-band artifacts due to unsharp masking at sharp edges, local-contrast adaptivity is incorporated into anatomically selective unsharp masking by designing an anatomy-sensitive emphasis parameter which varies asymmetrically with positive and negative values of the local image contrast

Development of mice without Cip/Kip CDK inhibitors

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Tateishi, Yuki; Matsumoto, Akinobu; Kanie, Tomoharu [Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582 (Japan); CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012 (Japan); Hara, Eiji [Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Nakayama, Keiko [Department of Developmental Genetics, Center for Translational and Advanced Animal Research, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575 (Japan); Nakayama, Keiichi I., E-mail: nakayak1@bioreg.kyushu-u.ac.jp [Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582 (Japan); CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012 (Japan)

2012-10-19

Highlights: Black-Right-Pointing-Pointer Mice lacking Cip/Kip CKIs (p21, p27, and p57) survive until embryonic day 13.5. Black-Right-Pointing-Pointer Proliferation of MEFs lacking all three Cip/Kip CKIs appears unexpectedly normal. Black-Right-Pointing-Pointer CDK2 kinase activity of the triple mutant MEFs is increased in G0 phase. -- Abstract: Timely exit of cells from the cell cycle is essential for proper cell differentiation during embryogenesis. Cyclin-dependent kinase (CDK) inhibitors (CKIs) of the Cip/Kip family (p21, p27, and p57) are negative regulators of cell cycle progression and are thought to be essential for development. However, the extent of functional redundancy among Cip/Kip family members has remained largely unknown. We have now generated mice that lack all three Cip/Kip CKIs (TKO mice) and compared them with those lacking each possible pair of these proteins (DKO mice). We found that the TKO embryos develop normally until midgestation but die around embryonic day (E) 13.5, slightly earlier than p27/p57 DKO embryos. The TKO embryos manifested morphological abnormalities as well as increased rates of cell proliferation and apoptosis in the placenta and lens that were essentially indistinguishable from those of p27/p57 DKO mice. Unexpectedly, the proliferation rate and cell cycle profile of mouse embryonic fibroblasts (MEFs) lacking all three Cip/Kip CKIs did not differ substantially from those of control MEFs. The abundance and kinase activity of CDK2 were markedly increased, whereas CDK4 activity and cyclin D1 abundance were decreased, in both p27/p57 DKO and TKO MEFs during progression from G{sub 0} to S phase compared with those in control MEFs. The extents of the increase in CDK2 activity and the decrease in CDK4 activity and cyclin D1 abundance were greater in TKO MEFs than in p27/p57 DKO MEFs. These results suggest that p27 and p57 play an essential role in mouse development after midgestation, and that p21 plays only an auxiliary role in

Reproductive phase determination in male meagre (Argyrosomus regius, Sciaenidae: testis development and histologic corroboration of a gross anatomical scale

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Nuno Prista

2014-03-01

Full Text Available Reproductive stage determination of male gonads has received sparse attention in fish biology literature with few studies detailing the building of gross anatomical- and histologic scales. The meagre (Argyrosomus regius is one of the world’s largest sciaenids and supports a significant regional fishery in European and North African waters whose reproductive patterns are yet to be fully investigated. In the present study, we derive a macroscopic grading system for meagre testis using semi-quantitative graphs that feature the testis variability along the species size range and time of the year. We then describe the histological stages and reproductive phases of male testes and determine the extent to which they corroborate the anatomical scale. Our results indicate that gross anatomical analyses are accurate in assessments of the meagre spawning season but may not precisely distinguish the testes of well-mature fish and first spawning virgins. Furthermore, we show that milt expression varies widely with size and misclassifies as immature many smaller fish in spawning-capable condition. We discuss these findings in terms of their contribution to the understanding of testes development and the uncertainties involved in determining the size-at-maturity of male fish using gross anatomical scales.

Food restriction affects Y-maze spatial recognition memory in developing mice.

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Fu, Yu; Chen, Yanmei; Li, Liane; Wang, Yumei; Kong, Xiangyang; Wang, Jianhong

2017-08-01

The ambiguous effects of food restriction (FR) on cognition in rodents have been mostly explored in the aged brain by a variety of paradigms, in which either rewards or punishments are involved. This study aims to examine the effects of chronic and acute FR with varying intensities on spatial recognition memory in developing mice. We have used a Y-maze task that is based on the innate tendency of rodents to explore novel environments. In chronic FR, mice had 70-30% chow of control for seven weeks. In acute FR, mice were food restricted for 12-48h before the tests. We found that chronic FR had no effect on the preference of mice for novelty in the Y-maze, but severe FR (50-30% of control) caused impairment on spatial recognition memory. The impairment significantly correlated with the slow weight growth induced by FR. Acute FR also did not affect the novelty preference of mice, but either improved or impaired the memory retention. These data suggest chronic FR impairs Y-maze spatial recognition memory in developing mice depending on FR intensity and individual tolerability of the FR. Moreover, acute FR exerts diverse effects on the memory, either positive or negative. Our findings have revealed new insights on the effects of FR on spatial recognition memory in developing animals. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

TAP1-deficiency does not alter atherosclerosis development in Apoe-/- mice.

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Daniel Kolbus

Full Text Available Antigen presenting cells (APC have the ability to present both extra-cellular and intra-cellular antigens via MHC class I molecules to CD8(+ T cells. The cross presentation of extra-cellular antigens is reduced in mice with deficient Antigen Peptide Transporter 1 (TAP1-dependent MHC class I antigen presentation, and these mice are characterized by a diminished CD8(+ T cell population. We have recently reported an increased activation of CD8(+ T cells in hypercholesterolemic Apoe(-/- mice. Therefore, this study included TAP1-deficient Apoe(-/- mice (Apoe(-/-Tap1(-/- to test the atherogenicity of CD8(+ T cells and TAP1-dependent cross presentation in a hypercholesterolemic environment. As expected the CD8(+ T cell numbers were low in Apoe(-/-Tap1(-/- mice in comparison to Apoe(-/- mice, constituting ~1% of the lymphocyte population. In spite of this there were no differences in the extent of atherosclerosis as assessed by en face Oil Red O staining of the aorta and cross-sections of the aortic root between Apoe(-/-Tap1(-/- and Apoe(-/- mice. Moreover, no differences were detected in lesion infiltration of macrophages or CD3(+ T cells in Apoe(-/-Tap1(-/- compared to Apoe(-/- mice. The CD3(+CD4(+ T cell fraction was increased in Apoe(-/-Tap1(-/- mice, suggesting a compensation for the decreased CD8(+ T cell population. Interestingly, the fraction of CD8(+ effector memory T cells was increased but this appeared to have little impact on the atherosclerosis development.In conclusion, Apoe(-/-Tap1(-/- mice develop atherosclerosis equal to Apoe(-/- mice, indicating a minor role for CD8(+ T cells and TAP1-dependent antigen presentation in the disease process.

[Project HRANAFINA--Croatian anatomical and physiological terminology].

Science.gov (United States)

Vodanović, Marin

2012-01-01

HRANAFINA--Croatian Anatomical and Physiological Terminology is a project of the University of Zagreb School of Dental Medicine funded by the Croatian Science Foundation. It is performed in cooperation with other Croatian universities with medical schools. This project has a two-pronged aim: firstly, building of Croatian anatomical and physiological terminology and secondly, Croatian anatomical and physiological terminology usage popularization between health professionals, medical students, scientists and translators. Internationally recognized experts from Croatian universities with medical faculties and linguistics experts are involved in the project. All project activities are coordinated in agreement with the National Coordinator for Development of Croatian Professional Terminology. The project enhances Croatian professional terminology and Croatian language in general, increases competitiveness of Croatian scientists on international level and facilitates the involvement of Croatian scientists, health care providers and medical students in European projects.

Handbook of anatomical models for radiation dosimetry

CERN Document Server

Eckerman, Keith F

2010-01-01

Covering the history of human model development, this title presents the major anatomical and physical models that have been developed for human body radiation protection, diagnostic imaging, and nuclear medicine therapy. It explores how these models have evolved and the role that modern technologies have played in this development.

FTO is a relevant factor for the development of the metabolic syndrome in mice.

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Kathrin Ikels

Full Text Available The metabolic syndrome is a worldwide problem mainly caused by obesity. FTO was found to be a obesity-risk gene in humans and FTO deficiency in mice led to reduction in adipose tissue. Thus, FTO is an important factor for the development of obesity. Leptin-deficient mice are a well characterized model for analysing the metabolic syndrome. To determine the relevance of FTO for the development of the metabolic syndrome we analysed different parameters in combined homozygous deficient mice (Lep(ob/ob;Fto(-/-. Lep(ob/ob;Fto(-/- mice showed an improvement in analysed hallmarks of the metabolic syndrome in comparison to leptin-deficient mice wild type or heterozygous for Fto. Lep(ob/ob;Fto(-/- mice did not develop hyperglycaemia and showed an improved glucose tolerance. Furthermore, extension of beta-cell mass was prevented in Lep(ob/ob;Fto(-/-mice and accumulation of ectopic fat in the liver was reduced. In conclusion this study demonstrates that FTO deficiency has a protective effect not only on the development of obesity but also on the metabolic syndrome. Thus, FTO plays an important role in the development of metabolic disorders and is an interesting target for therapeutic agents.

Posterolateral supporting structures of the knee: findings on anatomic dissection, anatomic slices and MR images

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Maeseneer, M. de; Shahabpour, M.; Vanderdood, K.; Ridder, F. de; Osteaux, M. [Dept. of Radiology, Free Univ. Brussels (Belgium); Roy, F. van [Dept. of Experimental Anatomy, Free Univ. Brussels (Belgium)

2001-11-01

In this article we study the ligaments and tendons of the posterolateral corner of the knee by anatomic dissection, MR-anatomic correlation, and MR imaging. The posterolateral aspect of two fresh cadaveric knee specimens was dissected. The MR-anatomic correlation was performed in three other specimens. The MR images of 122 patients were reviewed and assessed for the visualization of different posterolateral structures. Anatomic dissection and MR-anatomic correlation demonstrated the lateral collateral, fabellofibular, and arcuate ligaments, as well as the biceps and popliteus tendons. On MR images of patients the lateral collateral ligament was depicted in all cases. The fabellofibular, arcuate, and popliteofibular ligaments were visualized in 33, 25, and 38% of patients, respectively. Magnetic resonance imaging allows a detailed appreciation of the posterolateral corner of the knee. (orig.)

Rufus of Ephesus and his contribution to the development of anatomical nomenclature.

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Bujalkova, Maria

2011-01-01

Rufus of Ephesus, a famous ancient physician, lived about the years 80 - 150 CE. His theories stressed the importance of anatomy and he preferred pragmatic approach to diagnosis and treatment. In his work "On the Names of the Parts of the Human Body", he put in pragmatic effort to make a lexicon of anatomy for his pupils. In the introduction, he described it as a manual for the students of medical art which relied on demonstration in teaching; visible (outer) parts of the body were shown on a demonstrator and invisible (inner) parts were shown on a dissected monkey. The brief explanation of the anatomical terms includes position, shape, and functions of organs, and this is what makes his work a pioneering effort to explain the anatomy clearly, systematically, and using consistent terminology. Rufus stressed the importance of exact nomenclature to prevent misunderstandings in medical practice. This anatomy manual had a major influence on the development of anatomical terminology. It is an important contribution to the history of teaching. The other essential contribution of Rufus' lexicon (also known for its briefer title Onomastikon) is that the author recognised and critically reviewed the knowledge and views of his predecessors, physicians of the pre-Galenic period. No less important was his teaching to anatomists and physicians who followed, as they often cited or paraphrased Rufus in their own works (Galen, Oribasius). Many fragments of Rufus' work have been preserved by medieval Arabic medical writers, especially by Rhazes.

Sex differences in obesity development in pair-fed neuronal lipoprotein lipase deficient mice

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Hong Wang

2016-10-01

Full Text Available Objective: Compared to men, postmenopausal women suffer from a disproportionate burden of many co-morbidities associated with obesity, e.g. cardiovascular disease, cancer, and dementia. The underlying mechanism for this sex difference is not well understood but is believed to relate to absence of the protective effect of estrogen through the action of estrogen receptor alpha (ERα in the central nervous system. With the recently developed neuron-specific lipoprotein lipase deficient mice (NEXLPL−/− (Wang et al., Cell Metabolism, 2011 [15], we set to explore the possible role of lipid sensing in sex differences in obesity development. Methods: Both male and female NEXLPL−/− mice and littermate WT controls were subjected to pair feeding (pf where daily food amount given was adjusted according to body weight to match the food intake of ad libitum (ad fed control WT mice. Food intake and body weight were measured daily, and pair feeding was maintained to 42 wk in male mice and to 38 wk in female mice. Various brain regions of the mice were harvested, and ERα gene expression was examined in both male and female NEXLPL−/− and WT control mice under both ad- and pf-fed conditions. Results: Although both male and female NEXLPL−/− mice developed obesity similarly on standard chow, male NEXLPL−/− mice still developed obesity under with pair feeding, but on a much delayed time course, while female NEXLPL−/− mice were protected from extra body weight and fat mass gain compared to pair-fed WT control mice. Pair feeding alone induced extra fat mass gain in both male and female WT mice, and this was mostly driven by the reduction in physical activity. LPL deficiency resulted in an increase in ERα mRNA in the hypothalamus of ad-fed female mice, while pair feeding alone also resulted in an increase of ERα in both female WT control and NEXLPL−/− mice. The effect on increasing ERα by pair feeding and LPL deficiency was additive in

Aldose Reductase-Deficient Mice Develop Nephrogenic Diabetes Insipidus

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Ho, Horace T. B.; Chung, Sookja K.; Law, Janice W. S.; Ko, Ben C. B.; Tam, Sidney C. F.; Brooks, Heddwen L.; Knepper, Mark A.; Chung, Stephen S. M.

2000-01-01

Aldose reductase (ALR2) is thought to be involved in the pathogenesis of various diseases associated with diabetes mellitus, such as cataract, retinopathy, neuropathy, and nephropathy. However, its physiological functions are not well understood. We developed mice deficient in this enzyme and found that they had no apparent developmental or reproductive abnormality except that they drank and urinated significantly more than their wild-type littermates. These ALR2-deficient mice exhibited a partially defective urine-concentrating ability, having a phenotype resembling that of nephrogenic diabetes insipidus. PMID:10913167

Development of electrocardiogram intervals during growth of FVB/N neonate mice

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2010-01-01

Background Electrocardiography remains the best diagnostic tool and therapeutic biomarker for a spectrum of pediatric diseases involving cardiac or autonomic nervous system defects. As genetic links to these disorders are established and transgenic mouse models produced in efforts to understand and treat them, there is a surprising lack of information on electrocardiograms (ECGs) and ECG abnormalities in neonate mice. This is likely due to the trauma and anaesthesia required of many legacy approaches to ECG recording in mice, exacerbated by the fragility of many mutant neonates. Here, we use a non-invasive system to characterize development of the heart rate and electrocardiogram throughout the growth of conscious neonate FVB/N mice. Results We examine ECG waveforms as early as two days after birth. At this point males and females demonstrate comparable heart rates that are 50% lower than adult mice. Neonatal mice exhibit very low heart rate variability. Within 12 days of birth PR, QRS and QTc interval durations are near adult values while heart rate continues to increase until weaning. Upon weaning FVB/N females quickly develop slower heart rates than males, though PR intervals are comparable between sexes until a later age. This suggests separate developmental events may contribute to these gender differences in electrocardiography. Conclusions We provide insight with a new level of detail to the natural course of heart rate establishment in neonate mice. ECG can now be conveniently and repeatedly used in neonatal mice. This should serve to be of broad utility, facilitating further investigations into development of a diverse group of diseases and therapeutics in preclinical mouse studies. PMID:20735846

[The anatomical revolution and the transition of anatomical conception in late imperial china].

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Sihn, Kyu Hwan

2012-04-30

This paper aimed to examine the anatomical revolution from Yilingaicuo (Correcting the Errors of Medicine) and Quantixinlun(Outline of Anatomy and Physiology) in late imperial China. As the cephalocentrism which the brain superintend human operation of the mind was diffused in China since 16th century, the cephalocentrism and the cardiocentrism had competed for the hegemony of anatomical conception. Because of the advent of Yilingaicuo and Quantixinlun, the cephalocentrism became the main stream in the anatomical conception. The supporters of the Wang Yangming's Xinxue(the Learning of Heart and Mind) argued that the heart was the central organ of perception, sensitivity, and morality of the human body in medicine since 16th century. Even reformist and revolutionary intellectuals like Tan sitong and Mao zedong who had supported the Wang Yangming's Xinxue embraced the cephalocentrism in the late 19th century and the early 20th century. May Fourth intellectuals had not obsessed metaphysical interpretation of human body any more in the New Culture Movement in 1910s. They regarded human body as the object of research and writing. The anatomy was transformed into the instrumental knowledge for mutilation of the body. Yilingaicuo challenged the traditional conception of body, and Chinese intellectuals drew interest in the anatomy knowledge based on real mutilation. Quantixinlun based on Western medicine fueled a controversy about anatomy. Though new knowledge of anatomy was criticized by traditional Chinese medical doctors from the usefulness and morality of anatomy, nobody disavowed new knowledge of anatomy from the institutionalization of Western medicine in medical school. The internal development of cephalocentrism and positivism had influence on anatomy in China since 16th century. The advent of Yilingaicuo and Quantixinlun provided the milestone of new anatomy, though both sides represented traditional Chinese medicine and Western medicine respectively. They

Morphological study of tooth development in podoplanin-deficient mice.

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Kenyo Takara

Full Text Available Podoplanin is a mucin-type highly O-glycosylated glycoprotein identified in several somatyic cells: podocytes, alveolar epithelial cells, lymphatic endothelial cells, lymph node stromal fibroblastic reticular cells, osteocytes, odontoblasts, mesothelial cells, glia cells, and others. It has been reported that podoplanin-RhoA interaction induces cytoskeleton relaxation and cell process stretching in fibroblastic cells and osteocytes, and that podoplanin plays a critical role in type I alveolar cell differentiation. It appears that podoplanin plays a number of different roles in contributing to cell functioning and growth by signaling. However, little is known about the functions of podoplanin in the somatic cells of the adult organism because an absence of podoplanin is lethal at birth by the respiratory failure. In this report, we investigated the tooth germ development in podoplanin-knockout mice, and the dentin formation in podoplanin-conditional knockout mice having neural crest-derived cells with deficiency in podoplanin by the Wnt1 promoter and enhancer-driven Cre recombinase: Wnt1-Cre;PdpnΔ/Δmice. In the Wnt1-Cre;PdpnΔ/Δmice, the tooth and alveolar bone showed no morphological abnormalities and grow normally, indicating that podoplanin is not critical in the development of the tooth and bone.

Morphological study of tooth development in podoplanin-deficient mice.

Science.gov (United States)

Takara, Kenyo; Maruo, Naoki; Oka, Kyoko; Kaji, Chiaki; Hatakeyama, Yuji; Sawa, Naruhiko; Kato, Yukinari; Yamashita, Junro; Kojima, Hiroshi; Sawa, Yoshihiko

2017-01-01

Podoplanin is a mucin-type highly O-glycosylated glycoprotein identified in several somatyic cells: podocytes, alveolar epithelial cells, lymphatic endothelial cells, lymph node stromal fibroblastic reticular cells, osteocytes, odontoblasts, mesothelial cells, glia cells, and others. It has been reported that podoplanin-RhoA interaction induces cytoskeleton relaxation and cell process stretching in fibroblastic cells and osteocytes, and that podoplanin plays a critical role in type I alveolar cell differentiation. It appears that podoplanin plays a number of different roles in contributing to cell functioning and growth by signaling. However, little is known about the functions of podoplanin in the somatic cells of the adult organism because an absence of podoplanin is lethal at birth by the respiratory failure. In this report, we investigated the tooth germ development in podoplanin-knockout mice, and the dentin formation in podoplanin-conditional knockout mice having neural crest-derived cells with deficiency in podoplanin by the Wnt1 promoter and enhancer-driven Cre recombinase: Wnt1-Cre;PdpnΔ/Δmice. In the Wnt1-Cre;PdpnΔ/Δmice, the tooth and alveolar bone showed no morphological abnormalities and grow normally, indicating that podoplanin is not critical in the development of the tooth and bone.

An Anatomically Validated Brachial Plexus Contouring Method for Intensity Modulated Radiation Therapy Planning

International Nuclear Information System (INIS)

Van de Velde, Joris; Audenaert, Emmanuel; Speleers, Bruno; Vercauteren, Tom; Mulliez, Thomas; Vandemaele, Pieter; Achten, Eric; Kerckaert, Ingrid; D'Herde, Katharina; De Neve, Wilfried; Van Hoof, Tom

2013-01-01

Purpose: To develop contouring guidelines for the brachial plexus (BP) using anatomically validated cadaver datasets. Magnetic resonance imaging (MRI) and computed tomography (CT) were used to obtain detailed visualizations of the BP region, with the goal of achieving maximal inclusion of the actual BP in a small contoured volume while also accommodating for anatomic variations. Methods and Materials: CT and MRI were obtained for 8 cadavers positioned for intensity modulated radiation therapy. 3-dimensional reconstructions of soft tissue (from MRI) and bone (from CT) were combined to create 8 separate enhanced CT project files. Dissection of the corresponding cadavers anatomically validated the reconstructions created. Seven enhanced CT project files were then automatically fitted, separately in different regions, to obtain a single dataset of superimposed BP regions that incorporated anatomic variations. From this dataset, improved BP contouring guidelines were developed. These guidelines were then applied to the 7 original CT project files and also to 1 additional file, left out from the superimposing procedure. The percentage of BP inclusion was compared with the published guidelines. Results: The anatomic validation procedure showed a high level of conformity for the BP regions examined between the 3-dimensional reconstructions generated and the dissected counterparts. Accurate and detailed BP contouring guidelines were developed, which provided corresponding guidance for each level in a clinical dataset. An average margin of 4.7 mm around the anatomically validated BP contour is sufficient to accommodate for anatomic variations. Using the new guidelines, 100% inclusion of the BP was achieved, compared with a mean inclusion of 37.75% when published guidelines were applied. Conclusion: Improved guidelines for BP delineation were developed using combined MRI and CT imaging with validation by anatomic dissection

Standardized anatomic space for abdominal fat quantification

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Tong, Yubing; Udupa, Jayaram K.; Torigian, Drew A.

2014-03-01

The ability to accurately measure subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from images is important for improved assessment and management of patients with various conditions such as obesity, diabetes mellitus, obstructive sleep apnea, cardiovascular disease, kidney disease, and degenerative disease. Although imaging and analysis methods to measure the volume of these tissue components have been developed [1, 2], in clinical practice, an estimate of the amount of fat is obtained from just one transverse abdominal CT slice typically acquired at the level of the L4-L5 vertebrae for various reasons including decreased radiation exposure and cost [3-5]. It is generally assumed that such an estimate reliably depicts the burden of fat in the body. This paper sets out to answer two questions related to this issue which have not been addressed in the literature. How does one ensure that the slices used for correlation calculation from different subjects are at the same anatomic location? At what anatomic location do the volumes of SAT and VAT correlate maximally with the corresponding single-slice area measures? To answer these questions, we propose two approaches for slice localization: linear mapping and non-linear mapping which is a novel learning based strategy for mapping slice locations to a standardized anatomic space so that same anatomic slice locations are identified in different subjects. We then study the volume-to-area correlations and determine where they become maximal. We demonstrate on 50 abdominal CT data sets that this mapping achieves significantly improved consistency of anatomic localization compared to current practice. Our results also indicate that maximum correlations are achieved at different anatomic locations for SAT and VAT which are both different from the L4-L5 junction commonly utilized.

Mice deficient in PAPP-A show resistance to the development of diabetic nephropathy.

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Mader, Jessica R; Resch, Zachary T; McLean, Gary R; Mikkelsen, Jakob H; Oxvig, Claus; Marler, Ronald J; Conover, Cheryl A

2013-10-01

We investigated pregnancy-associated plasma protein-A (PAPP-A) in diabetic nephropathy. Normal human kidney showed specific staining for PAPP-A in glomeruli, and this staining was markedly increased in diabetic kidney. To assess the possible contribution of PAPP-A in the development of diabetic nephropathy, we induced diabetes with streptozotocin in 14-month-old WT and Papp-A knockout (KO) mice. Renal histopathology was evaluated after 4 months of stable hyperglycemia. Kidneys from diabetic WT mice showed multiple abnormalities including thickening of Bowman's capsule (100% of mice), increased glomerular size (80% of mice), tubule dilation (80% of mice), and mononuclear cell infiltration (90% of mice). Kidneys of age-matched non-diabetic WT mice had similar evidence of tubule dilation and mononuclear cell infiltration to those of diabetic WT mice, indicating that these changes were predominantly age-related. However, thickened Bowman's capsule and increased glomerular size appeared specific for the experimental diabetes. Kidneys from diabetic Papp-A KO mice had significantly reduced or no evidence of changes in Bowman's capsule thickening and glomerular size. There was also a shift to larger mesangial area and increased macrophage staining in diabetic WT mice compared with Papp-A KO mice. In summary, elevated PAPP-A expression in glomeruli is associated with diabetic nephropathy in humans and absence of PAPP-A is associated with resistance to the development of indicators of diabetic nephropathy in mice. These data suggest PAPP-A as a potential therapeutic target for diabetic nephropathy.

Anatomical imaging for radiotherapy

International Nuclear Information System (INIS)

Evans, Philip M

2008-01-01

The goal of radiation therapy is to achieve maximal therapeutic benefit expressed in terms of a high probability of local control of disease with minimal side effects. Physically this often equates to the delivery of a high dose of radiation to the tumour or target region whilst maintaining an acceptably low dose to other tissues, particularly those adjacent to the target. Techniques such as intensity modulated radiotherapy (IMRT), stereotactic radiosurgery and computer planned brachytherapy provide the means to calculate the radiation dose delivery to achieve the desired dose distribution. Imaging is an essential tool in all state of the art planning and delivery techniques: (i) to enable planning of the desired treatment, (ii) to verify the treatment is delivered as planned and (iii) to follow-up treatment outcome to monitor that the treatment has had the desired effect. Clinical imaging techniques can be loosely classified into anatomic methods which measure the basic physical characteristics of tissue such as their density and biological imaging techniques which measure functional characteristics such as metabolism. In this review we consider anatomical imaging techniques. Biological imaging is considered in another article. Anatomical imaging is generally used for goals (i) and (ii) above. Computed tomography (CT) has been the mainstay of anatomical treatment planning for many years, enabling some delineation of soft tissue as well as radiation attenuation estimation for dose prediction. Magnetic resonance imaging is fast becoming widespread alongside CT, enabling superior soft-tissue visualization. Traditionally scanning for treatment planning has relied on the use of a single snapshot scan. Recent years have seen the development of techniques such as 4D CT and adaptive radiotherapy (ART). In 4D CT raw data are encoded with phase information and reconstructed to yield a set of scans detailing motion through the breathing, or cardiac, cycle. In ART a set of

Anatomical curve identification

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Bowman, Adrian W.; Katina, Stanislav; Smith, Joanna; Brown, Denise

2015-01-01

Methods for capturing images in three dimensions are now widely available, with stereo-photogrammetry and laser scanning being two common approaches. In anatomical studies, a number of landmarks are usually identified manually from each of these images and these form the basis of subsequent statistical analysis. However, landmarks express only a very small proportion of the information available from the images. Anatomically defined curves have the advantage of providing a much richer expression of shape. This is explored in the context of identifying the boundary of breasts from an image of the female torso and the boundary of the lips from a facial image. The curves of interest are characterised by ridges or valleys. Key issues in estimation are the ability to navigate across the anatomical surface in three-dimensions, the ability to recognise the relevant boundary and the need to assess the evidence for the presence of the surface feature of interest. The first issue is addressed by the use of principal curves, as an extension of principal components, the second by suitable assessment of curvature and the third by change-point detection. P-spline smoothing is used as an integral part of the methods but adaptations are made to the specific anatomical features of interest. After estimation of the boundary curves, the intermediate surfaces of the anatomical feature of interest can be characterised by surface interpolation. This allows shape variation to be explored using standard methods such as principal components. These tools are applied to a collection of images of women where one breast has been reconstructed after mastectomy and where interest lies in shape differences between the reconstructed and unreconstructed breasts. They are also applied to a collection of lip images where possible differences in shape between males and females are of interest. PMID:26041943

Anatomic variations of the cerebral arteries and their embryology: a pictorial review

International Nuclear Information System (INIS)

Okahara, Mika; Kiyosue, Hiro; Mori, Hiromu; Tanoue, Shuichi; Sainou, Michihumi; Nagatomi, Hirohumi

2002-01-01

In the embryonic period, several developmental anomalies of the cerebral arteries occur. The knowledge of these anatomic variations of the cerebral artery is important to avoid the unnecessary surgery and to undergo surgery or interventional radiology with safety. We reviewed 3000 MR angiographies and 700 cerebral angiographies of the previous 5 years to assess cerebral arterial system, and to illustrate the embryological development, imaging findings, occurrence, and clinical significance of the anatomic variation of the cerebral arteries. The normal development and variations of the cerebral arteries are depicted. Knowledge of the anatomic variations is important since it can influence surgical and interventional procedure. (orig.)

Unification of Sinonasal Anatomical Terminology

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Voegels, Richard Louis

2015-07-01

Full Text Available The advent of endoscopy and computed tomography at the beginning of the 1980s brought to rhinology a revival of anatomy and physiology study. In 1994, the International Conference of Sinus Disease was conceived because the official “Terminologia Anatomica”[1] had little information on the detailed sinonasal anatomy. In addition, there was a lack of uniformity of terminology and definitions. After 20 years, a new conference has been held. The need to use the same terminology led to the publication by the European Society of Rhinology of the “European Position Paper on the Anatomical Terminology of the Internal Nose and Paranasal Sinuses,” that can be accessed freely at www.rhinologyjournal.com. Professor Valerie Lund et al[2] wrote this document reviewing the anatomical terms, comparing to the “Terminology Anatomica” official order to define the structures without eponyms, while respecting the embryological development and especially universalizing and simplifying the terms. A must-read! The text's purpose lies beyond the review of anatomical terminology to universalize the language used to refer to structures of the nasal and paranasal cavities. Information about the anatomy, based on extensive review of the current literature, is arranged in just over 50 pages, which are direct and to the point. The publication may be pleasant reading for learners and teachers of rhinology. This text can be a starting point and enables searching the universal terminology used in Brazil, seeking to converge with this new European proposal for a nomenclature to help us communicate with our peers in Brazil and the rest of the world. The original text of the European Society of Rhinology provides English terms that avoided the use of Latin, and thus fall beyond several national personal translations. It would be admirable if we created our own cross-cultural adaptation of this new suggested anatomical terminology.

Anatomical, functional, physiological and behavioural aspects of the development of mastication in early childhood.

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Le Révérend, Benjamin J D; Edelson, Lisa R; Loret, Chrystel

2014-02-01

Mastication efficiency is defined as the efficiency of crushing food between the teeth and manipulating the resulting particles to form a swallowable food bolus. It is dependent on the orofacial anatomical features of the subject, the coordination of these anatomical features and the consistency of the food used during testing. Different measures have been used to indirectly quantify mastication efficiency as a function of children's age such as observations, food bolus characterisation, muscle activity measurement and jaw movement tracking. In the present review, we aim to describe the changes in the oral physiology (e.g. bone and muscle structure, teeth and soft tissues) of children and how these changes are associated with mastication abilities. We also review previous work on the effect of food consistency on children's mastication abilities and on their level of texture acceptance. The lack of reference foods and differences in testing methodologies across different studies do not allow us to draw conclusions about (1) the age at which mastication efficiency reaches maturity and (2) the effect of food consistency on the establishment of mature mastication efficiency. The effect of food consistency on the development of children's mastication efficiency has not been tested widely. However, both human and animal studies have reported the effect of food consistency on orofacial development, suggesting that a diet with harder textures enhances bone and muscle growth, which could indirectly lead to better mastication efficiency. Finally, it was also reported that (1) children are more likely to accept textures that they are able to manipulate and (2) early exposure to a range of textures facilitates the acceptance of foods of various textures later on. Recommending products well adapted to children's mastication during weaning could facilitate their acceptance of new textures and support the development of healthy eating habits.

A reusable anatomically segmented digital mannequin for public health communication.

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Fujieda, Kaori; Okubo, Kosaku

2016-01-01

The ongoing development of world wide web technologies has facilitated a change in health communication, which has now become bi-directional and encompasses people with diverse backgrounds. To enable an even greater role for medical illustrations, a data set, BodyParts3D, has been generated and its data set can be used by anyone to create and exchange customised three-dimensional (3D) anatomical images. BP3D comprises more than 3000 3D object files created by segmenting a digital mannequin in accordance with anatomical naming conventions. This paper describes the methodologies and features used to generate an anatomically correct male mannequin.

Histopathological Defects in Intestine in Severe Spinal Muscular Atrophy Mice Are Improved by Systemic Antisense Oligonucleotide Treatment.

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Palittiya Sintusek

Full Text Available Gastrointestinal (GI defects, including gastroesophageal reflux, constipation and delayed gastric emptying, are common in patients with spinal muscular atrophy (SMA. Similar GI dysmotility has been identified in mouse models with survival of motor neuron (SMN protein deficiency. We previously described vascular defects in skeletal muscle and spinal cord of SMA mice and we hypothesized that similar defects could be involved in the GI pathology observed in these mice. We therefore investigated the gross anatomical structure, enteric vasculature and neurons in the small intestine in a severe mouse model of SMA. We also assessed the therapeutic response of GI histopathology to systemic administration of morpholino antisense oligonucleotide (AON designed to increase SMN protein expression. Significant anatomical and histopathological abnormalities, with striking reduction of vascular density, overabundance of enteric neurons and increased macrophage infiltration, were detected in the small intestine in SMA mice. After systemic AON treatment in neonatal mice, all the abnormalities observed were significantly restored to near-normal levels. We conclude that the observed GI histopathological phenotypes and functional defects observed in these SMA mice are strongly linked to SMN deficiency which can be rescued by systemic administration of AON. This study on the histopathological changes in the gastrointestinal system in severe SMA mice provides further indication of the complex role that SMN plays in multiple tissues and suggests that at least in SMA mice restoration of SMN production in peripheral tissues is essential for optimal outcome.

Histopathological Defects in Intestine in Severe Spinal Muscular Atrophy Mice Are Improved by Systemic Antisense Oligonucleotide Treatment

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Sintusek, Palittiya; Catapano, Francesco; Angkathunkayul, Napat; Marrosu, Elena; Parson, Simon H.; Morgan, Jennifer E.; Muntoni, Francesco; Zhou, Haiyan

2016-01-01

Gastrointestinal (GI) defects, including gastroesophageal reflux, constipation and delayed gastric emptying, are common in patients with spinal muscular atrophy (SMA). Similar GI dysmotility has been identified in mouse models with survival of motor neuron (SMN) protein deficiency. We previously described vascular defects in skeletal muscle and spinal cord of SMA mice and we hypothesized that similar defects could be involved in the GI pathology observed in these mice. We therefore investigated the gross anatomical structure, enteric vasculature and neurons in the small intestine in a severe mouse model of SMA. We also assessed the therapeutic response of GI histopathology to systemic administration of morpholino antisense oligonucleotide (AON) designed to increase SMN protein expression. Significant anatomical and histopathological abnormalities, with striking reduction of vascular density, overabundance of enteric neurons and increased macrophage infiltration, were detected in the small intestine in SMA mice. After systemic AON treatment in neonatal mice, all the abnormalities observed were significantly restored to near-normal levels. We conclude that the observed GI histopathological phenotypes and functional defects observed in these SMA mice are strongly linked to SMN deficiency which can be rescued by systemic administration of AON. This study on the histopathological changes in the gastrointestinal system in severe SMA mice provides further indication of the complex role that SMN plays in multiple tissues and suggests that at least in SMA mice restoration of SMN production in peripheral tissues is essential for optimal outcome. PMID:27163330

[Effect of Huanglian Jiedu Decoction on Monocyte Development in apoE Gene Knockout Mice].

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Chen, Bing; Kong, Ya-xian; Ll, Yu-mei; Xue, Xin; Zhang, Jian-ping; Zeng, Hui; Hu, Jing- qing; Ma, Ya-luan

2016-01-01

To observe monocyte (Mo) development in wild type C57BL/6 mice and apoE gene knockout (apoE(-/-)) mice, and to evaluate the immuno-regulatory effect of Huanglian Jiedu Decoction (HJD) on peripheral Mo development in apoE(-/-) mice. Four, 8, 12, and 16 weeks old female C57BL/6 mice were set up as control groups of different ages, while 4, 8, 12, and 16 weeks old female apoE(-/-) mice were set up as hyperlipidemia groups of different ages. Four-week old female C57BL/6 mice were recruited as a blank group. Four-week old female apoE(-/-) mice were randomly divided into the control group, the Western medicine group, and the Chinese medicine group by paired comparison, 5 in each group. Equivalent clinical dose was administered to mice according to body weight. Mice in the Western medicine group were administered with Atrovastatin at the daily dose of 10 mg/kg by gastrogavage, while those in the Chinese medicine group were administered with HJD at the daily dose of 5 g/kg by gastrogavage. Body weight was detected each week. After 4 weeks blood lipids levels (such as TG, TC, LDL-C, and HDL-C), and the proportions of Mo and Ly6c(hi) were detected. Compared with 4-week-old homogenic mice, the proportion of Mo decreased in 16-week-old C57BL/6 mice (P < 0.05). Levels of TC and TG, and the proportion of Ly6c(hi) subtype increased, but the proportion of Mo de- creased in 8-week-old apoE(-/-) mice (P <0. 05). Levels of TC, TG, and LDL-C increased in 12-week-old apoE(-/-) mice (P < 0.05). Levels of TC, TG, LDL-C, and HDL-C increased in 16-week-old apoE(-/-) mice (P < 0.05, P < 0.01). Compared with 8-week-old homogenic mice, the proportion of Mo decreased in 16-week-old C57BL/6 mice (P < 0.05); levels of TC and LDL-C increased in 12-week-old apoE(-/-) mice (P < 0.05); levels of TC and HDL-C increased in 16-week-old apoE(-/-) mice (P < 0.05, P < 0.01). Compared with C57BL/6 mice of the same age, TC and TG increased, HDL-C decreased (P < 0.01) in 4-and 8-week-old apoE(-/-) mice (P

Development of resistance to serotonin-induced itch in bile duct ligated mice.

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Ostadhadi, Sattar; Haddadi, Nazgol-Sadat; Foroutan, Arash; Azimi, Ehsan; Elmariah, Sarina; Dehpour, Ahmad-Reza

2017-06-01

Cholestatic itch can be severe and significantly impair the quality of life of patients. The serotonin system is implicated in cholestatic itch; however, the pruritogenic properties of serotonin have not been evaluated in cholestatic mice. Here, we investigated the serotonin-induced itch in cholestatic mice which was induced by bile duct ligation (BDL). Serotonin, sertraline or saline were administered intradermally to the rostral back area in BDL and sham operated (SHAM) mice, and the scratching behaviour was videotaped for 1 hour. Bile duct ligated mice had significantly increased scratching responses to saline injection on the seventh day after surgery. Additionally, serotonin or sertraline significantly induced scratching behaviour in BDL mice compared to saline at day 7 after surgery, while it did not induce itch at day 5. The scratching behaviour induced by serotonin or sertraline was significantly less in BDL mice compared to SHAM mice. Likewise, the locomotor activity of BDL or SHAM mice was not significantly different from unoperated (UNOP) mice on the fifth and seventh day, suggesting that the scratching behaviour was not affected by motor dysfunctions. Our data suggest that despite the potentiation of evoked itch, a resistance to serotonin-induced itch is developed in cholestatic mice. © 2017 John Wiley & Sons Australia, Ltd.

Asic3(-/- female mice with hearing deficit affects social development of pups.

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Wei-Li Wu

Full Text Available BACKGROUND: Infant crying is an important cue for mothers to respond adequately. Inappropriate response to infant crying can hinder social development in infants. In rodents, the pup-mother interaction largely depends on pup's calls. Mouse pups emit high frequency to ultrasonic vocalization (2-90 kHz to communicate with their dam for maternal care. However, little is known about how the maternal response to infant crying or pup calls affects social development over the long term. METHODOLOGY/PRINCIPAL FINDINGS: Here we used mice lacking acid-sensing ion channel 3 (Asic3(-/- to create a hearing deficit to probe the effect of caregiver hearing on maternal care and adolescent social development. Female Asic3(-/- mice showed elevated hearing thresholds for low to ultrasonic frequency (4-32 kHz on auditory brain stem response, which thus hindered their response to their pups' wriggling calls and ultrasonic vocalization, as well as their retrieval of pups. In adolescence, pups reared by Asic3(-/- mice showed a social deficit in juvenile social behaviors as compared with those reared by wild-type or heterozygous dams. The social-deficit phenotype in juvenile mice reared by Asic3(-/- mice was associated with the reduced serotonin transmission of the brain. However, Asic3(-/- pups cross-fostered to wild-type dams showed rescued social deficit. CONCLUSIONS/SIGNIFICANCE: Inadequate response to pups' calls as a result of ASIC3-dependent hearing loss confers maternal deficits in caregivers and social development deficits in their young.

Overactivation of Hedgehog Signaling Alters Development of the Ovarian Vasculature in Mice1

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Ren, Yi; Cowan, Robert G.; Migone, Fernando F.; Quirk, Susan M.

2012-01-01

ABSTRACT The hedgehog (HH) signaling pathway is critical for ovarian function in Drosophila, but its role in the mammalian ovary has not been defined. Previously, expression of a dominant active allele of the HH signal transducer protein smoothened (SMO) in Amhr2cre/+SmoM2 mice caused anovulation in association with a lack of smooth muscle in the theca of developing follicles. The current study examined events during the first 2 wk of life in Amhr2cre/+SmoM2 mice to gain insight into the cause of anovulation. Expression of transcriptional targets of HH signaling, Gli1, Ptch1, and Hhip, which are used as measures of pathway activity, were elevated during the first several days of life in Amhr2cre/+SmoM2 mice compared to controls but were similar to controls in older mice. Microarray analysis showed that genes with increased expression in 2-day-old mutants compared to controls were enriched for the processes of vascular and tube development and steroidogenesis. The density of platelet endothelial cell adhesion molecule (PECAM)-labeled endothelial tubes was increased in the cortex of newborn ovaries of mutant mice. Costaining of preovulatory follicles for PECAM and smooth muscle actin showed that muscle-type vascular support cells are deficient in theca of mutant mice. Expression of genes for steroidogenic enzymes that are normally expressed in the fetal adrenal gland were elevated in newborn ovaries of mutant mice. In summary, overactivation of HH signaling during early life alters gene expression and vascular development and this is associated with the lifelong development of anovulatory follicles in which the thecal vasculature fails to mature appropriately. PMID:22402963

Ultrastructural analysis of development of myocardium in calreticulin-deficient mice

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Michalak Marek

2006-11-01

Full Text Available Abstract Background Calreticulin is a Ca2+ binding chaperone of the endoplasmic reticulum which influences gene expression and cell adhesion. The levels of both vinculin and N-cadherin are induced by calreticulin expression, which play important roles in cell adhesiveness. Cardiac development is strictly dependent upon the ability of cells to adhere to their substratum and to communicate with their neighbours. Results We show here that the levels of N-cadherin are downregulated in calreticulin-deficient mouse embryonic hearts, which may lead to the disarray and wavy appearance of myofibrils in these mice, which we detected at all investigated stages of cardiac development. Calreticulin wild type mice exhibited straight, thick and abundant myofibrils, which were in stark contrast to the thin, less numerous, disorganized myofibrils of the calreticulin-deficient hearts. Interestingly, these major differences were only detected in the developing ventricles while the atria of both calreticulin phenotypes were similar in appearance at all developmental stages. Glycogen also accumulated in the ventricles of calreticulin-deficient mice, indicating an abnormality in cardiomyocyte metabolism. Conclusion Calreticulin is temporarily expressed during heart development where it is required for proper myofibrillogenesis. We postulate that calreticulin be considered as a novel cardiac fetal gene.

NFC Evaluation in the Development of Mobile Applications for MICE in Tourism

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David Silva-Pedroza

2017-10-01

Full Text Available This paper presents an analysis and implementation of a service for the deployment of events in the Meetings, Incentives, Conferences, and Exhibitions (MICE category, to answer the question: how can Near Field Communication (NFC and mobile applications contribute to the development of tourism in the MICE category? First is an analysis of the applications that are currently on the market and an extraction of the features of greater relevance; later, we define the functionalities for our service, and finally we provide a performance test in a MICE-type event, the seventh Seminar on Emerging Technologies in Telecommunications “TET 2016” developed in Popayán, Colombia and the results of the experience are analyzed. The use of NFC technology with a mobile application allows the experience to be improved when a MICE event was made, for both the user and the organizer.

Changes in Otx2 and Parvalbumin Immunoreactivity in the Superior Colliculus in the Platelet-Derived Growth Factor Receptor-β Knockout Mice

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Juanjuan Zhao

2013-01-01

Full Text Available The superior colliculus (SC, a relay nucleus in the subcortical visual pathways, is implicated in socioemotional behaviors. Homeoprotein Otx2 and β subunit of receptors of platelet-derived growth factor (PDGFR-β have been suggested to play an important role in development of the visual system and development and maturation of GABAergic neurons. Although PDGFR-β-knockout (KO mice displayed socio-emotional deficits associated with parvalbumin (PV-immunoreactive (IR neurons, their anatomical bases in the SC were unknown. In the present study, Otx2 and PV-immunolabeling in the adult mouse SC were investigated in the PDGFR-β KO mice. Although there were no differences in distribution patterns of Otx2 and PV-IR cells between the wild type and PDGFR-β KO mice, the mean numbers of both of the Otx2- and PV-IR cells were significantly reduced in the PDGFR-β KO mice. Furthermore, average diameters of Otx2- and PV-IR cells were significantly reduced in the PDGFR-β KO mice. These findings suggest that PDGFR-β plays a critical role in the functional development of the SC through its effects on Otx2- and PV-IR cells, provided specific roles of Otx2 protein and PV-IR cells in the development of SC neurons and visual information processing, respectively.

The Virtual Family-development of surface-based anatomical models of two adults and two children for dosimetric simulations

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Christ, Andreas; Honegger, Katharina; Zefferer, Marcel; Neufeld, Esra; Oberle, Michael; Szczerba, Dominik; Kuster, Niels [Foundation for Research on Information Technologies in Society (IT' IS), Zeughausstr. 43, 8004 Zuerich (Switzerland); Kainz, Wolfgang; Guag, Joshua W [US Food and Drug Administration (FDA), Center for Devices and Radiological Health (CDRH), Silver Spring, MD 20993 (United States); Hahn, Eckhart G; Rascher, Wolfgang; Janka, Rolf; Bautz, Werner [Universitaetsklinikum Erlangen, Friedrich-Alexander Universitaet Erlangen-Nuernberg, 91054 Erlangen (Germany); Chen, Ji; Shen, Jianxiang [Department of Electrical and Computer Engineering, The University of Houston, Houston, TX 77204 (United States); Kiefer, Berthold; Schmitt, Peter; Hollenbach, Hans-Peter [Siemens Healthcare, MR-Application Development, 91052 Erlangen (Germany); Kam, Anthony [Department of Imaging, Johns Hopkins Bayview Medical Center, Baltimore, MD 21224 (United States)], E-mail: christ@itis.ethz.ch

2010-01-21

The objective of this study was to develop anatomically correct whole body human models of an adult male (34 years old), an adult female (26 years old) and two children (an 11-year-old girl and a six-year-old boy) for the optimized evaluation of electromagnetic exposure. These four models are referred to as the Virtual Family. They are based on high resolution magnetic resonance (MR) images of healthy volunteers. More than 80 different tissue types were distinguished during the segmentation. To improve the accuracy and the effectiveness of the segmentation, a novel semi-automated tool was used to analyze and segment the data. All tissues and organs were reconstructed as three-dimensional (3D) unstructured triangulated surface objects, yielding high precision images of individual features of the body. This greatly enhances the meshing flexibility and the accuracy with respect to thin tissue layers and small organs in comparison with the traditional voxel-based representation of anatomical models. Conformal computational techniques were also applied. The techniques and tools developed in this study can be used to more effectively develop future models and further improve the accuracy of the models for various applications. For research purposes, the four models are provided for free to the scientific community. (note)

The Virtual Family-development of surface-based anatomical models of two adults and two children for dosimetric simulations

International Nuclear Information System (INIS)

Christ, Andreas; Honegger, Katharina; Zefferer, Marcel; Neufeld, Esra; Oberle, Michael; Szczerba, Dominik; Kuster, Niels; Kainz, Wolfgang; Guag, Joshua W; Hahn, Eckhart G; Rascher, Wolfgang; Janka, Rolf; Bautz, Werner; Chen, Ji; Shen, Jianxiang; Kiefer, Berthold; Schmitt, Peter; Hollenbach, Hans-Peter; Kam, Anthony

2010-01-01

The objective of this study was to develop anatomically correct whole body human models of an adult male (34 years old), an adult female (26 years old) and two children (an 11-year-old girl and a six-year-old boy) for the optimized evaluation of electromagnetic exposure. These four models are referred to as the Virtual Family. They are based on high resolution magnetic resonance (MR) images of healthy volunteers. More than 80 different tissue types were distinguished during the segmentation. To improve the accuracy and the effectiveness of the segmentation, a novel semi-automated tool was used to analyze and segment the data. All tissues and organs were reconstructed as three-dimensional (3D) unstructured triangulated surface objects, yielding high precision images of individual features of the body. This greatly enhances the meshing flexibility and the accuracy with respect to thin tissue layers and small organs in comparison with the traditional voxel-based representation of anatomical models. Conformal computational techniques were also applied. The techniques and tools developed in this study can be used to more effectively develop future models and further improve the accuracy of the models for various applications. For research purposes, the four models are provided for free to the scientific community. (note)

Construction of a 3-D anatomical model for teaching temporal lobectomy.

Science.gov (United States)

de Ribaupierre, Sandrine; Wilson, Timothy D

2012-06-01

Although we live and work in 3 dimensional space, most of the anatomical teaching during medical school is done on 2-D (books, TV and computer screens, etc). 3-D spatial abilities are essential for a surgeon but teaching spatial skills in a non-threatening and safe educational environment is a much more difficult pedagogical task. Currently, initial anatomical knowledge formation or specific surgical anatomy techniques, are taught either in the OR itself, or in cadaveric labs; which means that the trainee has only limited exposure. 3-D computer models incorporated into virtual learning environments may provide an intermediate and key step in a blended learning approach for spatially challenging anatomical knowledge formation. Specific anatomical structures and their spatial orientation can be further clinically contextualized through demonstrations of surgical procedures in the 3-D digital environments. Recordings of digital models enable learner reviews, taking as much time as they want, stopping the demonstration, and/or exploring the model to understand the anatomical relation of each structure. We present here how a temporal lobectomy virtual model has been developed to aid residents and fellows conceptualization of the anatomical relationships between different cerebral structures during that procedure. We suggest in comparison to cadaveric dissection, such virtual models represent a cost effective pedagogical methodology providing excellent support for anatomical learning and surgical technique training. Copyright © 2012 Elsevier Ltd. All rights reserved.

Growth hormone modulates hypothalamic inflammation in long-lived pituitary dwarf mice.

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Sadagurski, Marianna; Landeryou, Taylor; Cady, Gillian; Kopchick, John J; List, Edward O; Berryman, Darlene E; Bartke, Andrzej; Miller, Richard A

2015-12-01

Mice in which the genes for growth hormone (GH) or GH receptor (GHR(-/-) ) are disrupted from conception are dwarfs, possess low levels of IGF-1 and insulin, have low rates of cancer and diabetes, and are extremely long-lived. Median longevity is also increased in mice with deletion of hypothalamic GH-releasing hormone (GHRH), which leads to isolated GH deficiency. The remarkable extension of longevity in hypopituitary Ames dwarf mice can be reversed by a 6-week course of GH injections started at the age of 2 weeks. Here, we demonstrate that mutations that interfere with GH production or response, in the Snell dwarf, Ames dwarf, or GHR(-/-) mice lead to reduced formation of both orexigenic agouti-related peptide (AgRP) and anorexigenic proopiomelanocortin (POMC) projections to the main hypothalamic projection areas: the arcuate nucleus (ARH), paraventricular nucleus (PVH), and dorsomedial nucleus (DMH). These mutations also reduce hypothalamic inflammation in 18-month-old mice. GH injections, between 2 and 8 weeks of age, reversed both effects in Ames dwarf mice. Disruption of GHR specifically in liver (LiGHRKO), a mutation that reduces circulating IGF-1 but does not lead to lifespan extension, had no effect on hypothalamic projections or inflammation, suggesting an effect of GH, rather than peripheral IGF-1, on hypothalamic development. Hypothalamic leptin signaling, as monitored by induction of pStat3, is not impaired by GHR deficiency. Together, these results suggest that early-life disruption of GH signaling produces long-term hypothalamic changes that may contribute to the longevity of GH-deficient and GH-resistant mice. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

ANATOMIC STRUCTURE OF CAMPANULA ROTUNDIFOLIA L. GRASS

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V. N. Bubenchikova

2017-01-01

Full Text Available The article present results of the study for a anatomic structure of Campanula rotundifolia grass from Campanulaceae family. Despite its dispersion and application in folk medicine, there are no data about its anatomic structure, therefore to estimate the indices of authenticity and quality of raw materials it is necessary to develop microdiagnostical features in the first place, which could help introducing of thisplant in a medical practice. The purpose of this work is to study anatomical structureof Campanula rotundifolia grass to determine its diagnostic features. Methods. Thestudy for anatomic structure was carried out in accordance with the requirements of State Pharmacopoeia, edition XIII. Micromed laboratory microscope with digital adjutage was used to create microphotoes, Photoshop CC was used for their processing. Result. We have established that stalk epidermis is prosenchymal, slightly winding with straight of splayed end cells. After study for the epidermis cells we established that upper epidermis cells had straight walls and are slightly winding. The cells of lower epidermishave more winding walls with prolong wrinkled cuticule. Presence of simple one-cell, thin wall, rough papillose hair on leaf and stalk epidermis. Cells of epidermis in fauces of corolla are prosenchymal, with winding walls, straight or winding walls in a cup. Papillary excrescences can be found along the cup edges. Stomatal apparatus is anomocytic. Conclusion. As the result of the study we have carried out the research for Campanula rotundifolia grass anatomic structure, and determined microdiagnostic features for determination of raw materials authenticity, which included presence of simple, one-cell, thin-walled, rough papillose hair on both epidermises of a leaf, along the veins, leaf edge, and stalk epidermis, as well as the presence of epidermis cells with papillary excrescences along the edges of leaves and cups. Intercellular canals are situatedalong the

Mice do not develop conditioned taste aversion because of immunity loss.

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Vidal, Jose

2011-01-01

This study intends to test the generation of conditioned taste aversion and conditioned immunodepression by daily paired administration of saccharin solution with cyclophosphamide, 15 mg/kg, for 4 days. One group of male mice of the outbred CD1 strain drank 0.15% saccharin and received 1 injection of cyclophosphamide, 15 mg/kg, for 4 days (paired group), another group (unpaired group) received the same doses of saccharin and cyclophosphamide noncontingently, the third group (cy60) received saccharin paired with cyclophosphamide, 60 mg/kg, and the fourth group (placebo) received saccharin in the absence of cyclophosphamide. All mice were immunized with keyhole limpet hemocyanin (KLH), 0.2 mg, 1 day before the treatments. Mice of the paired, unpaired and cy60 groups displayed a similarly decreased antibody response to KLH, but mice of the paired group did not develop an aversion to saccharin while mice of the cy60 group did. Besides, repeat presentation of saccharin to mice of the paired group did not alter their antibody response to ovalbumin compared with mice of the unpaired or placebo group. Taste aversion was not elicited in response to impaired immunity and the conditioned stimulus (saccharin) did not impair the antibody response. 2011 S. Karger AG, Basel.

A practical workflow for making anatomical atlases for biological research.

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Wan, Yong; Lewis, A Kelsey; Colasanto, Mary; van Langeveld, Mark; Kardon, Gabrielle; Hansen, Charles

2012-01-01

The anatomical atlas has been at the intersection of science and art for centuries. These atlases are essential to biological research, but high-quality atlases are often scarce. Recent advances in imaging technology have made high-quality 3D atlases possible. However, until now there has been a lack of practical workflows using standard tools to generate atlases from images of biological samples. With certain adaptations, CG artists' workflow and tools, traditionally used in the film industry, are practical for building high-quality biological atlases. Researchers have developed a workflow for generating a 3D anatomical atlas using accessible artists' tools. They used this workflow to build a mouse limb atlas for studying the musculoskeletal system's development. This research aims to raise the awareness of using artists' tools in scientific research and promote interdisciplinary collaborations between artists and scientists. This video (http://youtu.be/g61C-nia9ms) demonstrates a workflow for creating an anatomical atlas.

Types and rate of cataract development in mice irradiated at different ages

International Nuclear Information System (INIS)

Gajewski, A.K.; Majewska, K.; Slowikowska, M.G.; Chomiczewski, K.; Kulig, A.

1977-01-01

The effect of age on the development of radiation cataract has been investigated in an inbred A strain of mice and, as a result, the patterns of age dependence and senile mice cataract development were obtained. In general, the lenses of mice 1 to 3 days old were the most sensitive to radiation; the maximum resistance was noted in 5-day-old mice, and from this age up to 3 to 7 weeks of life there was a period of increasing sensitivity. In older animals the lens sensitivity tends to level off. The early stages of cataract occurred in all irradiated groups at a younger age than in the control group, but the late stages occurred in irradiated groups at the same age as the senile cataract occurred in the control group. Two types of cataract were observed. One was typical for young irradiated mice 1 to 5 days of age and the other was typical for all remaining irradiated groups and for a control group. Also, an attempt was made to correlate the obtained results with the cell kinetics in normal lens epithelium

EFFECTS OF VITEX AGNUS CASTUS ON MICE FETUS DEVELOPMENT

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M. Azarnia; S. Ejtemaee-Mehr; A. Shakoor A. Ansari

2007-07-01

Full Text Available Vitex agnus castus (chasteberry is a popular treatment for the management of female reproductive disorders including corpus luteum insufficiency, premenstrual syndrome (PMS, menopausal symptoms, and insufficient milk production. According to developing situation of complementary medicine, and frequent use of this herb, it is important to examine its effects during pregnancy. In this research we studied its effects on mice development, and we focused on macroscopic parameters, such as CRL (Crown-Rump length and the weight of embryos, and diameter and the weight of placenta, and microscopic parameters such as the diameters of eye and lens of embryos. We found that Vitex has special effects during different stages of mice development, for example it can improve the growth of embryos in 8th and 9th day of pregnancy (it causes significant increase in CRL and weight of embryos. Also, it may changes some microscopic parameters. These founding suggest that it should be used more cautiously during pregnancy.

Learning-based stochastic object models for characterizing anatomical variations

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Dolly, Steven R.; Lou, Yang; Anastasio, Mark A.; Li, Hua

2018-03-01

It is widely known that the optimization of imaging systems based on objective, task-based measures of image quality via computer-simulation requires the use of a stochastic object model (SOM). However, the development of computationally tractable SOMs that can accurately model the statistical variations in human anatomy within a specified ensemble of patients remains a challenging task. Previously reported numerical anatomic models lack the ability to accurately model inter-patient and inter-organ variations in human anatomy among a broad patient population, mainly because they are established on image data corresponding to a few of patients and individual anatomic organs. This may introduce phantom-specific bias into computer-simulation studies, where the study result is heavily dependent on which phantom is used. In certain applications, however, databases of high-quality volumetric images and organ contours are available that can facilitate this SOM development. In this work, a novel and tractable methodology for learning a SOM and generating numerical phantoms from a set of volumetric training images is developed. The proposed methodology learns geometric attribute distributions (GAD) of human anatomic organs from a broad patient population, which characterize both centroid relationships between neighboring organs and anatomic shape similarity of individual organs among patients. By randomly sampling the learned centroid and shape GADs with the constraints of the respective principal attribute variations learned from the training data, an ensemble of stochastic objects can be created. The randomness in organ shape and position reflects the learned variability of human anatomy. To demonstrate the methodology, a SOM of an adult male pelvis is computed and examples of corresponding numerical phantoms are created.

The anatomical diaspora: evidence of early American anatomical traditions in North Dakota.

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Stubblefield, Phoebe R

2011-09-01

The current focus in forensic anthropology on increasing scientific certainty in ancestry determination reinforces the need to examine the ancestry of skeletal remains used for osteology instruction. Human skeletal remains were discovered on the University of North Dakota campus in 2007. After recovery, the osteological examination resulted in a profile for a 33- to 46-year-old woman of African descent with stature ranging from 56.3 to 61.0 in. The pattern of postmortem damage indicated that the remains had been prepared for use as an anatomical teaching specimen. Review of the American history of anatomical teaching revealed a preference for Black subjects, which apparently extended to states like North Dakota despite extremely low resident populations of people of African descent. This study emphasizes the need to examine the ancestry of older teaching specimens that lack provenience, rather than assuming they are derived from typical (i.e., Indian) sources of anatomical material. © 2011 American Academy of Forensic Sciences.

Early-Onset Diabetic E1-DN Mice Develop Albuminuria and Glomerular Injury Typical of Diabetic Nephropathy

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Mervi E. Hyvönen

2015-01-01

Full Text Available The transgenic E1-DN mice express a kinase-negative epidermal growth factor receptor in their pancreatic islets and are diabetic from two weeks of age due to impaired postnatal growth of β-cell mass. Here, we characterize the development of hyperglycaemia-induced renal injury in the E1-DN mice. Homozygous mice showed increased albumin excretion rate (AER at the age of 10 weeks; the albuminuria increased over time and correlated with blood glucose. Morphometric analysis of PAS-stained histological sections and electron microscopy images revealed mesangial expansion in homozygous E1-DN mice, and glomerular sclerosis was observed in the most hyperglycaemic mice. The albuminuric homozygous mice developed also other structural changes in the glomeruli, including thickening of the glomerular basement membrane and widening of podocyte foot processes that are typical for diabetic nephropathy. Increased apoptosis of podocytes was identified as one mechanism contributing to glomerular injury. In addition, nephrin expression was reduced in the podocytes of albuminuric homozygous E1-DN mice. Tubular changes included altered epithelial cell morphology and increased proliferation. In conclusion, hyperglycaemic E1-DN mice develop albuminuria and glomerular and tubular injury typical of human diabetic nephropathy and can serve as a new model to study the mechanisms leading to the development of diabetic nephropathy.

Why can't rodents vomit? A comparative behavioral, anatomical, and physiological study.

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Charles C Horn

Full Text Available The vomiting (emetic reflex is documented in numerous mammalian species, including primates and carnivores, yet laboratory rats and mice appear to lack this response. It is unclear whether these rodents do not vomit because of anatomical constraints (e.g., a relatively long abdominal esophagus or lack of key neural circuits. Moreover, it is unknown whether laboratory rodents are representative of Rodentia with regards to this reflex. Here we conducted behavioral testing of members of all three major groups of Rodentia; mouse-related (rat, mouse, vole, beaver, Ctenohystrica (guinea pig, nutria, and squirrel-related (mountain beaver species. Prototypical emetic agents, apomorphine (sc, veratrine (sc, and copper sulfate (ig, failed to produce either retching or vomiting in these species (although other behavioral effects, e.g., locomotion, were noted. These rodents also had anatomical constraints, which could limit the efficiency of vomiting should it be attempted, including reduced muscularity of the diaphragm and stomach geometry that is not well structured for moving contents towards the esophagus compared to species that can vomit (cat, ferret, and musk shrew. Lastly, an in situ brainstem preparation was used to make sensitive measures of mouth, esophagus, and shoulder muscular movements, and phrenic nerve activity-key features of emetic episodes. Laboratory mice and rats failed to display any of the common coordinated actions of these indices after typical emetic stimulation (resiniferatoxin and vagal afferent stimulation compared to musk shrews. Overall the results suggest that the inability to vomit is a general property of Rodentia and that an absent brainstem neurological component is the most likely cause. The implications of these findings for the utility of rodents as models in the area of emesis research are discussed.

A distinctive patchy osteomalacia characterises Phospho1-deficient mice.

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Boyde, Alan; Staines, Katherine A; Javaheri, Behzad; Millan, Jose Luis; Pitsillides, Andrew A; Farquharson, Colin

2017-08-01

The phosphatase PHOSPHO1 is involved in the initiation of biomineralisation. Bones in Phospho1 knockout (KO) mice show histological osteomalacia with frequent bowing of long bones and spontaneous fractures: they contain less mineral, with smaller mineral crystals. However, the consequences of Phospho1 ablation on the microscale structure of bone are not yet fully elucidated. Tibias and femurs obtained from wild-type and Phospho1 null (KO) mice (25-32 weeks old) were embedded in PMMA, cut and polished to produce near longitudinal sections. Block surfaces were studied using 20 kV backscattered-electron (BSE) imaging, and again after iodine staining to reveal non-mineralised matrix and cellular components. For 3D characterisation, we used X-ray micro-tomography. Bones opened with carbide milling tools to expose endosteal surfaces were macerated using an alkaline bacterial pronase enzyme detergent, 5% hydrogen peroxide and 7% sodium hypochlorite solutions to produce 3D surfaces for study with 3D BSE scanning electron microscopy (SEM). Extensive regions of both compact cortical and trabecular bone matrix in Phospho1 KO mice contained no significant mineral and/or showed arrested mineralisation fronts, characterised by a failure in the fusion of the calcospherite-like, separately mineralising, individual micro-volumes within bone. Osteoclastic resorption of the uncalcified matrix in Phospho1 KO mice was attenuated compared with surrounding normally mineralised bone. The extent and position of this aberrant biomineralisation varied considerably between animals, contralateral limbs and anatomical sites. The most frequent manifestation lay, however, in the nearly complete failure of mineralisation in the bone surrounding the numerous transverse blood vessel canals in the cortices. In conclusion, SEM disclosed defective mineralising fronts and extensive patchy osteomalacia, which has previously not been recognised. These data further confirm the role of this phosphatase

Development of Murine Cyp3a Knockout Chimeric Mice with Humanized Liver.

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Kato, Kota; Ohbuchi, Masato; Hamamura, Satoko; Ohshita, Hiroki; Kazuki, Yasuhiro; Oshimura, Mitsuo; Sato, Koya; Nakada, Naoyuki; Kawamura, Akio; Usui, Takashi; Kamimura, Hidetaka; Tateno, Chise

2015-08-01

We developed murine CYP3A knockout ko chimeric mice with humanized liver expressing human P450S similar to those in humans and whose livers and small intestines do not express murine CYP3A this: approach may overcome effects of residual mouse metabolic enzymes like Cyp3a in conventional chimeric mice with humanized liver, such as PXB-mice [urokinase plasminogen activator/severe combined immunodeficiency (uPA/SCID) mice repopulated with over 70% human hepatocytes] to improve the prediction of drug metabolism and pharmacokinetics in humans. After human hepatocytes were transplanted into Cyp3a KO/uPA/SCID host mice, human albumin levels logarithmically increased until approximately 60 days after transplantation, findings similar to those in PXB-mice. Quantitative real-time-polymerase chain reaction analyses showed that hepatic human P450s, UGTs, SULTs, and transporters mRNA expression levels in Cyp3a KO chimeric mice were also similar to those in PXB-mice and confirmed the absence of Cyp3a11 mRNA expression in mouse liver and intestine. Findings for midazolam and triazolam metabolic activities in liver microsomes were comparable between Cyp3a KO chimeric mice and PXB-mice. In contrast, these activities in the intestine of Cyp3a KO chimeric mice were attenuated compared with PXB-mice. Owing to the knockout of murine Cyp3a, hepatic Cyp2b10 and 2c55 mRNA levels in Cyp3a KO/uPA/SCID mice (without hepatocyte transplants) were 8.4- and 61-fold upregulated compared with PXB-mice, respectively. However, human hepatocyte transplantation successfully restored Cyp2b10 level nearly fully and Cyp2c55 level partly (still 13-fold upregulated) compared with those in PXB-mice. Intestinal Cyp2b10 and 2c55 were also repressed by human hepatocyte transplantation in Cyp3a KO chimeric mice. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Renal Tumor Anatomic Complexity: Clinical Implications for Urologists.

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Joshi, Shreyas S; Uzzo, Robert G

2017-05-01

Anatomic tumor complexity can be objectively measured and reported using nephrometry. Various scoring systems have been developed in an attempt to correlate tumor complexity with intraoperative and postoperative outcomes. Nephrometry may also predict tumor biology in a noninvasive, reproducible manner. Other scoring systems can help predict surgical complexity and the likelihood of complications, independent of tumor characteristics. The accumulated data in this new field provide provocative evidence that objectifying anatomic complexity can consolidate reporting mechanisms and improve metrics of comparisons. Further prospective validation is needed to understand the full descriptive and predictive ability of the various nephrometry scores. Copyright © 2017 Elsevier Inc. All rights reserved.

A comprehensive analysis of the physiological and anatomical components involved in higher water loss rates after leaf development at high humidity

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Fanourakis, D.; Heuvelink, E.; Pinto De Carvalho, S.M.

2013-01-01

To better understand the poor regulation of water loss after leaf development at high relative air humidity (RH), the relative importance of the physiological and anatomical components was analyzed focusing on cultivars with a contrasting sensitivity to elevated RH. The stomatal responsiveness to

Heterozygous Che-1 KO mice show deficiencies in object recognition memory persistence.

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Zalcman, Gisela; Corbi, Nicoletta; Di Certo, Maria Grazia; Mattei, Elisabetta; Federman, Noel; Romano, Arturo

2016-10-06

Transcriptional regulation is a key process in the formation of long-term memories. Che-1 is a protein involved in the regulation of gene transcription that has recently been proved to bind the transcription factor NF-κB, which is known to be involved in many memory-related molecular events. This evidence prompted us to investigate the putative role of Che-1 in memory processes. For this study we newly generated a line of Che-1(+/-) heterozygous mice. Che-1 homozygous KO mouse is lethal during development, but Che-1(+/-) heterozygous mouse is normal in its general anatomical and physiological characteristics. We analyzed the behavioral characteristic and memory performance of Che-1(+/-) mice in two NF-κB dependent types of memory. We found that Che-1(+/-) mice show similar locomotor activity and thigmotactic behavior than wild type (WT) mice in an open field. In a similar way, no differences were found in anxiety-like behavior between Che-1(+/-) and WT mice in an elevated plus maze as well as in fear response in a contextual fear conditioning (CFC) and object exploration in a novel object recognition (NOR) task. No differences were found between WT and Che-1(+/-) mice performance in CFC training and when tested at 24h or 7days after training. Similar performance was found between groups in NOR task, both in training and 24h testing performance. However, we found that object recognition memory persistence at 7days was impaired in Che-1(+/-) heterozygous mice. This is the first evidence showing that Che-1 is involved in memory processes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

In vitro development of embryos from experimentally Kerack-addicted Mice

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Elham Mohammadzadeh

2017-08-01

Full Text Available Background: Prenatal drug exposure, as a common public health concern, is associated with an increased risk of adverse effects on early embryo development. Objective: To investigate the in vitro development of - embryo from experimentally Kerack-addicted mice. Materials and Methods: Twenty-five female mice were studied in five groups: control, vehicle, and three experimental groups of Kerack-dependent mice (I, II, and III which received different doses of Kerack for 14 days. After the establishment of addiction model (7 days, experimental groups I, II, and III were given Kerack intraperitoneally at the doses of 5, 35, and 70 mg/kg, twice a day for a period of 7 days, respectively. The vehicle group received normal saline and lemon juice whilst the control group just received water and food. Morulae were obtained through oviduct flashing. The survived embryos were cultured in T6+ 5mg/ml bovine serum albumin. The developmental rates up to hatched stage daily and embryo quality (differential staining and Tunnel staining were also assessed Results: The developmental potential of embryos obtained from the addicted mother was significantly decreased in comparison with control group. There was a significant reduction in the rate of blastocyst formation in the high dose Kerack dependent group. However, in addicted mice there was reduction in the total cell number (40.92% vs. 65.08% in control and, inner cell mass percentage (17.17% vs. 26.15% in control while apoptotic cells numbers were increased (7.17 vs. 1.46 in control (p<0.05. Conclusion: The Kerack addiction during pregnancy retards preimplantation development and induces apoptosis.

Persistent Salmonella enterica serovar Typhimurium Infection Increases the Susceptibility of Mice to Develop Intestinal Inflammation

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Bárbara M. Schultz

2018-05-01

Full Text Available Chronic intestinal inflammations are triggered by genetic and environmental components. However, it remains unclear how specific changes in the microbiota, host immunity, or pathogen exposure could promote the onset and exacerbation of these diseases. Here, we evaluated whether Salmonella enterica serovar Typhimurium (S. Typhimurium infection increases the susceptibility to develop intestinal inflammation in mice. Two mouse models were used to evaluate the impact of S. Typhimurium infection: the chemical induction of colitis by dextran sulfate sodium (DSS and interleukin (IL-10−/− mice, which develop spontaneous intestinal inflammation. We observed that S. Typhimurium infection makes DSS-treated and IL-10−/− mice more susceptible to develop intestinal inflammation. Importantly, this increased susceptibility is associated to the ability of S. Typhimurium to persist in liver and spleen of infected mice, which depends on the virulence proteins secreted by Salmonella Pathogenicity Island 2-encoded type three secretion system (TTSS-2. Although immunization with a live attenuated vaccine resulted in a moderate reduction of the IL-10−/− mice susceptibility to develop intestinal inflammation due to previous S. Typhimurium infection, it did not prevent bacterial persistence. Our results suggest that persistent S. Typhimurium infection may increase the susceptibility of mice to develop inflammation in the intestine, which could be associated with virulence proteins secreted by TTSS-2.

Mitochondrial DNA mutations in mutator mice confer respiration defects and B-cell lymphoma development.

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Takayuki Mito

Full Text Available Mitochondrial DNA (mtDNA mutator mice are proposed to express premature aging phenotypes including kyphosis and hair loss (alopecia due to their carrying a nuclear-encoded mtDNA polymerase with a defective proofreading function, which causes accelerated accumulation of random mutations in mtDNA, resulting in expression of respiration defects. On the contrary, transmitochondrial mito-miceΔ carrying mtDNA with a large-scale deletion mutation (ΔmtDNA also express respiration defects, but not express premature aging phenotypes. Here, we resolved this discrepancy by generating mtDNA mutator mice sharing the same C57BL/6J (B6J nuclear background with that of mito-miceΔ. Expression patterns of premature aging phenotypes are very close, when we compared between homozygous mtDNA mutator mice carrying a B6J nuclear background and selected mito-miceΔ only carrying predominant amounts of ΔmtDNA, in their expression of significant respiration defects, kyphosis, and a short lifespan, but not the alopecia. Therefore, the apparent discrepancy in the presence and absence of premature aging phenotypes in mtDNA mutator mice and mito-miceΔ, respectively, is partly the result of differences in the nuclear background of mtDNA mutator mice and of the broad range of ΔmtDNA proportions of mito-miceΔ used in previous studies. We also provided direct evidence that mtDNA abnormalities in homozygous mtDNA mutator mice are responsible for respiration defects by demonstrating the co-transfer of mtDNA and respiration defects from mtDNA mutator mice into mtDNA-less (ρ(0 mouse cells. Moreover, heterozygous mtDNA mutator mice had a normal lifespan, but frequently developed B-cell lymphoma, suggesting that the mtDNA abnormalities in heterozygous mutator mice are not sufficient to induce a short lifespan and aging phenotypes, but are able to contribute to the B-cell lymphoma development during their prolonged lifespan.

Testicular development in mice lacking receptors for follicle stimulating hormone and androgen.

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Peter J O'Shaughnessy

Full Text Available Post-natal testicular development is dependent on gonadotrophin and androgen stimulation. Follicle stimulating hormone (FSH acts through receptors (FSHR on the Sertoli cell to stimulate spermatogenesis while androgens promote testis growth through receptors (AR on the Sertoli cells, Leydig cells and peritubular myoid cells. In this study we have examined the effects on testis development of ablating FSHRs (FSHRKO mice and/or ARs ubiquitously (ARKO mice or specifically on the Sertoli cells (SCARKO mice. Cell numbers were measured using stereological methods. In ARKO mice Sertoli cell numbers were reduced at all ages from birth until adulthood. FSHR ablation also caused small reductions in Sertoli cell numbers up to day 20 with more marked effects seen in the adult. Germ cell numbers were unaffected by FSHR and/or AR ablation at birth. By day 20 ubiquitous AR or FSHR ablation caused a marked reduction in germ cell numbers with a synergistic effect of losing both receptors (germ cell numbers in FSHRKO.ARKO mice were 3% of control. Germ cell numbers in SCARKO mice were less affected. By adulthood, in contrast, clear synergistic control of germ cell numbers had become established between the actions of FSH and androgen through the Sertoli cells. Leydig cell numbers were normal on day 1 and day 5 in all groups. By day 20 and in adult animals total AR or FSHR ablation significantly reduced Leydig cell numbers but Sertoli cell specific AR ablation had no effect. Results show that, prior to puberty, development of most testicular parameters is more dependent on FSH action than androgen action mediated through the Sertoli cells although androgen action through other cells types is crucial. Post-pubertally, germ cell numbers and spermatogenesis are dependent on FSH and androgen action through the Sertoli cells.

The dual role of scavenger receptor class A in development of diabetes in autoimmune NOD mice.

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Mami Shimizu

Full Text Available Human type 1 diabetes is an autoimmune disease that results from the autoreactive destruction of pancreatic β cells by T cells. Antigen presenting cells including dendritic cells and macrophages are required to activate and suppress antigen-specific T cells. It has been suggested that antigen uptake from live cells by dendritic cells via scavenger receptor class A (SR-A may be important. However, the role of SR-A in autoimmune disease is unknown. In this study, SR-A-/- nonobese diabetic (NOD mice showed significant attenuation of insulitis, lower levels of insulin autoantibodies, and suppression of diabetes development compared with NOD mice. We also found that diabetes progression in SR-A-/- NOD mice treated with low-dose polyinosinic-polycytidylic acid (poly(I:C was significantly accelerated compared with that in disease-resistant NOD mice treated with low-dose poly(I:C. In addition, injection of high-dose poly(I: C to mimic an acute RNA virus infection significantly accelerated diabetes development in young SR-A-/- NOD mice compared with untreated SR-A-/- NOD mice. Pathogenic cells including CD4+CD25+ activated T cells were increased more in SR-A-/- NOD mice treated with poly(I:C than in untreated SR-A-/- NOD mice. These results suggested that viral infection might accelerate diabetes development even in diabetes-resistant subjects. In conclusion, our studies demonstrated that diabetes progression was suppressed in SR-A-/- NOD mice and that acceleration of diabetes development could be induced in young mice by poly(I:C treatment even in SR-A-/- NOD mice. These results suggest that SR-A on antigen presenting cells such as dendritic cells may play an unfavorable role in the steady state and a protective role in a mild infection. Our findings imply that SR-A may be an important target for improving therapeutic strategies for type 1 diabetes.

[Development and clinical application of a new type of anatomical locking plate for sternoclavicular joint fracture and dislocation].

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Sun, Yuanlin; Yang, Yunkang; Ge, Jianhua; Yang, Kun; Xiang, Feifan; Zhou, Ju; Liang, Jie

2018-03-01

To report a new type of anatomical locking plate for sternocalvicular joint, and investigate its effectiveness in treatment of sternoclavicular joint fracture and dislocation. A new type of anatomical locking plate for sternoclavicular joint was developed, which accorded with the anatomical features and biomechanical characteristics of Chinese sternoclavicular joint. By adopting the method of clinical randomized controlled study, 32 patients with the sternoclavicular joint fracture and dislocation who met the selection criteria between June 2008 and May 2015 were randomly divided into groups A and B ( n =16), and the patients were treated with new anatomic locking plate and distal radial T locking plate internal fixation, respectively. There was no significant difference between 2 groups in gender, age, injured side, body mass index, cause of injury, type of injury, the time from injury to operation, and preoperative Rockwood grading score ( P >0.05). The operation time, intraoperative blood loss, incision length, hospitalization time, and postoperative complications in 2 groups were recorded, and the effectiveness was evaluated by Rockwood grading score. The operations of 2 groups completed successfully. The operation time, intraoperative blood loss, and hospitalization time in group A were significantly less than those in group B ( P case of sternoclavicular joint pain and 2 cases of wound infection; in group B, there were 1 case of sternoclavicular joint pain, 1 case of internal fixation loosening, and 1 case of sternoclavicular joint re-dislocation; there was no significant difference in complication incidence between 2 groups ( P =1.000). The Rockwood grading scores at each time point after operation in 2 groups were significantly higher than those before operation. At 1 month after operation, the Rockwood grading score in group A was significantly higher than that in group B ( t= 2.270, P =0.031); but there was no significant difference in the Rockwood

Development of a model for marburgvirus based on severe-combined immunodeficiency mice

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Kalina Warren V

2007-10-01

Full Text Available Abstract The filoviruses, Ebola (EBOV and Marburg (MARV, cause a lethal hemorrhagic fever. Human isolates of MARV are not lethal to immmunocompetent adult mice and, to date, there are no reports of a mouse-adapted MARV model. Previously, a uniformly lethal EBOV-Zaire mouse-adapted virus was developed by performing 9 sequential passages in progressively older mice (suckling to adult. Evaluation of this model identified many similarities between infection in mice and nonhuman primates, including viral tropism for antigen-presenting cells, high viral titers in the spleen and liver, and an equivalent mean time to death. Existence of the EBOV mouse model has increased our understanding of host responses to filovirus infections and likely has accelerated the development of countermeasures, as it is one of the only hemorrhagic fever viruses that has multiple candidate vaccines and therapeutics. Here, we demonstrate that serially passaging liver homogenates from MARV-infected severe combined immunodeficient (scid mice was highly successful in reducing the time to death in scid mice from 50–70 days to 7–10 days after MARV-Ci67, -Musoke, or -Ravn challenge. We performed serial sampling studies to characterize the pathology of these scid mouse-adapted MARV strains. These scid mouse-adapted MARV models appear to have many similar properties as the MARV models previously developed in guinea pigs and nonhuman primates. Also, as shown here, the scid-adapted MARV mouse models can be used to evaluate the efficacy of candidate antiviral therapeutic molecules, such as phosphorodiamidate morpholino oligomers or antibodies.

Antidepressant-like behavioral, anatomical, and biochemical effects of petroleum ether extract from maca (Lepidium meyenii) in mice exposed to chronic unpredictable mild stress.

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Ai, Zhong; Cheng, Ai-Fang; Yu, Yuan-Tao; Yu, Long-Jiang; Jin, Wenwen

2014-05-01

Maca has been consumed as a medical food in Peru for thousands of years, and exerts anxiolytic and antidepressant effects. Our present study aimed to evaluate the behavior and anatomical and biochemical effects of petroleum ether extract from maca (ME) in the chronic unpredictable mild stress (CUMS) model of depression in mice. Three different doses of maca extract (125, 250, and 500 mg/kg) were orally administrated in the six-week CUMS procedure. Fluoxetine (10 mg/kg) was used as a positive control drug. Maca extract (250 and 500 mg/kg) significantly decreased the duration of immobility time in the tail suspension test. After treatment with maca extract (250 and 500 mg/kg), the granule cell layer in the dentate gyrus appeared thicker. Maca extract (250 and 500 mg/kg) also induced a significant reduction in corticosterone levels in mouse serum. In mouse brain tissue, after six weeks of treatment, noradrenaline and dopamine levels were increased by maca extract, and the activity of reactive oxygen species was significantly inhibited. Serotonin levels were not significantly altered. These results demonstrated that maca extract (250 and 500 mg/kg) showed antidepressant-like effects and was related to the activation of both noradrenergic and dopaminergic systems, as well as attenuation of oxidative stress in mouse brain.

Sdhd and SDHD/H19 knockout mice do not develop paraganglioma or pheochromocytoma.

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Jean-Pierre Bayley

Full Text Available BACKGROUND: Mitochondrial succinate dehydrogenase (SDH is a component of both the tricarboxylic acid cycle and the electron transport chain. Mutations of SDHD, the first protein of intermediary metabolism shown to be involved in tumorigenesis, lead to the human tumors paraganglioma (PGL and pheochromocytoma (PC. SDHD is remarkable in showing an 'imprinted' tumor suppressor phenotype. Mutations of SDHD show a very high penetrance in man and we postulated that knockout of Sdhd would lead to the development of PGL/PC, probably in aged mice. METHODOLOGY/PRINCIPAL FINDINGS: We generated a conventional knockout of Sdhd in the mouse, removing the entire third exon. We also crossed this mouse with a knockout of H19, a postulated imprinted modifier gene of Sdhd tumorigenesis, to evaluate if loss of these genes together would lead to the initiation or enhancement of tumor development. Homozygous knockout of Sdhd results in embryonic lethality. No paraganglioma or other tumor development was seen in Sdhd KO mice followed for their entire lifespan, in sharp contrast to the highly penetrant phenotype in humans. Heterozygous Sdhd KO mice did not show hyperplasia of paraganglioma-related tissues such as the carotid body or of the adrenal medulla, or any genotype-related pathology, with similar body and organ weights to wildtype mice. A cohort of Sdhd/H19 KO mice developed several cases of profound cardiac hypertrophy, but showed no evidence of PGL/PC. CONCLUSIONS: Knockout of Sdhd in the mouse does not result in a disease phenotype. H19 may not be an initiator of PGL/PC tumorigenesis.

Rate of lens lesion development and the age of mice at time of irradiation

International Nuclear Information System (INIS)

Gajewski, A.K.; Majewska, K.; Slowikowska, M.G.

1976-01-01

The rate of lens lesion development has been studied in mice irradiated at different age ranging from one day up to one year old mice. The time needed for the first appearance of lens lesion was shortest in groups of mice irradiated at the age of one, two and three days of life, and longest in groups of mice irradiated at the age of 5 days, 1 week and 2 weeks of life. The time needed for the first appearance of lens lesion for mice irradiated between the third week and one year of life was constant. It was longer than for mice irradiated during the first three days of life and shorter than for mice irradiated at 5 up to 14 days of life. In all but one irradiated groups the age at which the first lens lesion occurred differed significantly from the age at which the first senile changes occurred in the lens of control mice. The one exception was the group of mice irradiated at the age of one year. (author)

Junctional Adhesion Molecule (JAM)-C Deficient C57BL/6 Mice Develop a Severe Hydrocephalus

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Liebner, Stefan; Mittelbronn, Michel; Deutsch, Urban; Enzmann, Gaby; Adams, Ralf H.; Aurrand-Lions, Michel; Plate, Karl H.; Imhof, Beat A.; Engelhardt, Britta

2012-01-01

The junctional adhesion molecule (JAM)-C is a widely expressed adhesion molecule regulating cell adhesion, cell polarity and inflammation. JAM-C expression and function in the central nervous system (CNS) has been poorly characterized to date. Here we show that JAM-C−/− mice backcrossed onto the C57BL/6 genetic background developed a severe hydrocephalus. An in depth immunohistochemical study revealed specific immunostaining for JAM-C in vascular endothelial cells in the CNS parenchyma, the meninges and in the choroid plexus of healthy C57BL/6 mice. Additional JAM-C immunostaining was detected on ependymal cells lining the ventricles and on choroid plexus epithelial cells. Despite the presence of hemorrhages in the brains of JAM-C−/− mice, our study demonstrates that development of the hydrocephalus was not due to a vascular function of JAM-C as endothelial re-expression of JAM-C failed to rescue the hydrocephalus phenotype of JAM-C−/− C57BL/6 mice. Evaluation of cerebrospinal fluid (CSF) circulation within the ventricular system of JAM-C−/− mice excluded occlusion of the cerebral aqueduct as the cause of hydrocephalus development but showed the acquisition of a block or reduction of CSF drainage from the lateral to the 3rd ventricle in JAM-C−/− C57BL/6 mice. Taken together, our study suggests that JAM-C−/− C57BL/6 mice model the important role for JAM-C in brain development and CSF homeostasis as recently observed in humans with a loss-of-function mutation in JAM-C. PMID:23029139

Critical role of IFN-gamma in CFA-mediated protection of NOD mice from diabetes development.

Science.gov (United States)

Mori, Yoshiko; Kodaka, Tetsuro; Kato, Takako; Kanagawa, Edith M; Kanagawa, Osami

2009-11-01

IFN-gamma signaling-deficient non-obese diabetic (NOD) mice develop diabetes with similar kinetics to those of wild-type NOD mice. However, the immunization of IFN-gamma signaling-deficient NOD mice with CFA failed to induce long-term protection, whereas wild-type NOD mice receiving CFA remained diabetes-free. CFA also failed to protect IFN-gamma receptor-deficient (IFN-gammaR(-/-)) NOD mice from the autoimmune rejection of transplanted islets, as it does in diabetic NOD mice, and from disease transfer by spleen cells from diabetic NOD mice. These data clearly show that the pro-inflammatory cytokine IFN-gamma is necessary for the CFA-mediated protection of NOD mice from diabetes. There is no difference in the T(h)1/T(h)17 balance between IFN-gammaR(-/-) NOD and wild-type NOD mice. There is also no difference in the total numbers and percentages of regulatory T (Treg) cells in the lymph node CD4(+) T-cell populations between IFN-gammaR(-/-) NOD and wild-type NOD mice. However, pathogenic T cells lacking IFN-gammaR are resistant to the suppressive effect of Treg cells, both in vivo and in vitro. Therefore, it is likely that CFA-mediated protection against diabetes development depends on a change in the balance between Treg cells and pathogenic T cells, and IFN-gamma signaling seems to control the susceptibility of pathogenic T cells to the inhibitory activity of Treg cells.

Development of a quantitative multivariable radiographic method to evaluate anatomic changes associated with laminitis in the forefeet of donkeys.

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Collins, Simon N; Dyson, Sue J; Murray, Rachel C; Newton, J Richard; Burden, Faith; Trawford, Andrew F

2012-08-01

To establish and validate an objective method of radiographic diagnosis of anatomic changes in laminitic forefeet of donkeys on the basis of data from a comprehensive series of radiographic measurements. 85 donkeys with and 85 without forelimb laminitis for baseline data determination; a cohort of 44 donkeys with and 18 without forelimb laminitis was used for validation analyses. For each donkey, lateromedial radiographic views of 1 weight-bearing forelimb were obtained; images from 11 laminitic and 2 nonlaminitic donkeys were excluded (motion artifact) from baseline data determination. Data from an a priori selection of 19 measurements of anatomic features of laminitic and nonlaminitic donkey feet were analyzed by use of a novel application of multivariate statistical techniques. The resultant diagnostic models were validated in a blinded manner with data from the separate cohort of laminitic and nonlaminitic donkeys. Data were modeled, and robust statistical rules were established for the diagnosis of anatomic changes within laminitic donkey forefeet. Component 1 scores ≤ -3.5 were indicative of extreme anatomic change, and scores from -2.0 to 0.0 denoted modest change. Nonlaminitic donkeys with a score from 0.5 to 1.0 should be considered as at risk for laminitis. Results indicated that the radiographic procedures evaluated can be used for the identification, assessment, and monitoring of anatomic changes associated with laminitis. Screening assessments by use of this method may enable early detection of mild anatomic change and identification of at-risk donkeys.

Sodium meta-arsenite prevents the development of autoimmune diabetes in NOD mice

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Lee, Y.S.; Kim, D.; Lee, E.K. [Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840 (Korea, Republic of); Kim, S. [Komipharm International Co. Ltd., 3188, Seongnam-dong, Jungwon-gu, Seongnam-si, Gyeonggi-do 462-827 (Korea, Republic of); Choi, C.S. [Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840 (Korea, Republic of); Endocrinology, Internal Medicine, Gachon University Gil Medical Center, 1198 Guwol-Dong, Namdong-Gu, Incheon 405-760 (Korea, Republic of); Gachon Medical Research Institute, Gil Hospital, 1198 Guwol-Dong, Namdong-Gu, Incheon 405-760 (Korea, Republic of); Jun, H.S., E-mail: hsjun@gachon.ac.kr [Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840 (Korea, Republic of); College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840 (Korea, Republic of); Gachon Medical Research Institute, Gil Hospital, 1198 Guwol-Dong, Namdong-Gu, Incheon 405-760 (Korea, Republic of)

2015-04-15

Sodium meta-arsenite (SA) is an orally available arsenic compound. We investigated the effects of SA on the development of autoimmune type 1 diabetes. Female non-obese diabetic (NOD) mice were orally intubated with SA (5 mg/kg/day) from 8 weeks of age for 8 weeks. The cumulative incidence of diabetes was monitored until 30 weeks of age, islet histology was examined, and lymphocytes including T cells, B cells, CD4+ IFN-γ+ cells, CD8+ IFN-γ+ cells, CD4+ IL-4+ cells, and regulatory T cells were analyzed. We also investigated the diabetogenic ability of splenocytes using an adoptive transfer model and the effect of SA on the proliferation, activation, and expression of glucose transporter 1 (Glut1) in splenocytes treated with SA in vitro and splenocytes isolated from SA-treated mice. SA treatment decreased the incidence of diabetes and delayed disease onset. SA treatment reduced the infiltration of immunocytes in islets, and splenocytes from SA-treated mice showed a reduced ability to transfer diabetes. The number of total splenocytes and T cells and both the number and the proportion of CD4+ IFN-γ+ and CD8+ IFN-γ+ T cells in the spleen were significantly reduced in SA-treated NOD mice compared with controls. The number, but not the proportion, of regulatory T cells was decreased in SA-treated NOD mice. Treatment with SA either in vitro or in vivo inhibited proliferation of splenocytes. In addition, the expression of Glut1 and phosphorylated ERK1/2 was decreased by SA treatment. These results suggest that SA reduces proliferation and activation of T cells, thus preventing autoimmune diabetes in NOD mice. - Highlights: • SA prevents the development of diabetes and delays the age of onset in NOD mice. • SA decreases the number but not the proportion of T lymphocytes in NOD mice. • SA reduces IFN-γ-producing T lymphocytes in NOD mice. • SA reduces proliferation and activation of T lymphocytes in vitro and in vivo. • SA reduces the expression of glucose

Sodium meta-arsenite prevents the development of autoimmune diabetes in NOD mice

International Nuclear Information System (INIS)

Lee, Y.S.; Kim, D.; Lee, E.K.; Kim, S.; Choi, C.S.; Jun, H.S.

2015-01-01

Sodium meta-arsenite (SA) is an orally available arsenic compound. We investigated the effects of SA on the development of autoimmune type 1 diabetes. Female non-obese diabetic (NOD) mice were orally intubated with SA (5 mg/kg/day) from 8 weeks of age for 8 weeks. The cumulative incidence of diabetes was monitored until 30 weeks of age, islet histology was examined, and lymphocytes including T cells, B cells, CD4+ IFN-γ+ cells, CD8+ IFN-γ+ cells, CD4+ IL-4+ cells, and regulatory T cells were analyzed. We also investigated the diabetogenic ability of splenocytes using an adoptive transfer model and the effect of SA on the proliferation, activation, and expression of glucose transporter 1 (Glut1) in splenocytes treated with SA in vitro and splenocytes isolated from SA-treated mice. SA treatment decreased the incidence of diabetes and delayed disease onset. SA treatment reduced the infiltration of immunocytes in islets, and splenocytes from SA-treated mice showed a reduced ability to transfer diabetes. The number of total splenocytes and T cells and both the number and the proportion of CD4+ IFN-γ+ and CD8+ IFN-γ+ T cells in the spleen were significantly reduced in SA-treated NOD mice compared with controls. The number, but not the proportion, of regulatory T cells was decreased in SA-treated NOD mice. Treatment with SA either in vitro or in vivo inhibited proliferation of splenocytes. In addition, the expression of Glut1 and phosphorylated ERK1/2 was decreased by SA treatment. These results suggest that SA reduces proliferation and activation of T cells, thus preventing autoimmune diabetes in NOD mice. - Highlights: • SA prevents the development of diabetes and delays the age of onset in NOD mice. • SA decreases the number but not the proportion of T lymphocytes in NOD mice. • SA reduces IFN-γ-producing T lymphocytes in NOD mice. • SA reduces proliferation and activation of T lymphocytes in vitro and in vivo. • SA reduces the expression of glucose

Embryotoxic effect of gamma radiation in mice and their modulation by vitamins

International Nuclear Information System (INIS)

Goyal, P.K.; Singh, N.; Gajawat, S.; Pareek, T.K.; Dev, P.K.

1999-01-01

Ionizing radiations severely interfere with normal embryonic or fetal development, although period of late fetal development in mammals is considered to be the somewhat radioresistant. Here, an attempt is made to check the radiation induced developmental anomalies by vitamins during fetal development period. For this purpose, pregnant Swiss albino mice were exposed to 0.50 Gy gamma radiation during fetal growth period (day 14.25 post-coitus) in the presence (experimental) or absence (control) of vitamin B complex (20 mg/kg b.w.) till term. All dams were sacrificed on day 18 post-coitus and their uteri were examined to study reproductive status and anatomical abnormalities of each conceptus. About 48% pregnant females of the control group showed a complete embryonic resorption while in the experimental group the number of females showing resorption was only 33%. Resorption of embryos, fetal mortality and reduction in placental weight were significantly increased in mice irradiated in the absence of vitamin B complex. Various gross malformations including skeletal anomalies were significantly reduced in 18 days old fetuses given vitamin B complex therapy. Further, such fetuses had better ossification of skull and vertebrae. Sex-ratio of the fetuses, however, remained unaltered in both groups as compared to normal. (orig.)

EFFECTS OF VITEX AGNUS CASTUS ON MICE FETUS DEVELOPMENT

OpenAIRE

M. Azarnia; S. Ejtemaee-Mehr; A. Shakoor A. Ansari

2007-01-01

Vitex agnus castus (chasteberry) is a popular treatment for the management of female reproductive disorders including corpus luteum insufficiency, premenstrual syndrome (PMS), menopausal symptoms, and insufficient milk production. According to developing situation of complementary medicine, and frequent use of this herb, it is important to examine its effects during pregnancy. In this research we studied its effects on mice development, and we focused on macroscopic parameters, such as CRL (C...

Introducing 3-Dimensional Printing of a Human Anatomic Pathology Specimen: Potential Benefits for Undergraduate and Postgraduate Education and Anatomic Pathology Practice.

Science.gov (United States)

Mahmoud, Amr; Bennett, Michael

2015-08-01

Three-dimensional (3D) printing, a rapidly advancing technology, is widely applied in fields such as mechanical engineering and architecture. Three-dimensional printing has been introduced recently into medical practice in areas such as reconstructive surgery, as well as in clinical research. Three-dimensionally printed models of anatomic and autopsy pathology specimens can be used for demonstrating pathology entities to undergraduate medical, dental, and biomedical students, as well as for postgraduate training in examination of gross specimens for anatomic pathology residents and pathology assistants, aiding clinicopathological correlation at multidisciplinary team meetings, and guiding reconstructive surgical procedures. To apply 3D printing in anatomic pathology for teaching, training, and clinical correlation purposes. Multicolored 3D printing of human anatomic pathology specimens was achieved using a ZCorp 510 3D printer (3D Systems, Rock Hill, South Carolina) following creation of a 3D model using Autodesk 123D Catch software (Autodesk, Inc, San Francisco, California). Three-dimensionally printed models of anatomic pathology specimens created included pancreatoduodenectomy (Whipple operation) and radical nephrectomy specimens. The models accurately depicted the topographic anatomy of selected specimens and illustrated the anatomic relation of excised lesions to adjacent normal tissues. Three-dimensional printing of human anatomic pathology specimens is achievable. Advances in 3D printing technology may further improve the quality of 3D printable anatomic pathology specimens.

TIBIAL LANDMARKS IN ACL ANATOMIC REPAIR

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M. V. Demesсhenko

2016-01-01

Full Text Available Purpose: to identify anatomical landmarks on tibial articular surface to serve as reference in preparing tibial canal with respect to the center of ACL footprint during single bundle arthroscopic repair.Materials and methods. Twelve frozen knee joint specimens and 68 unpaired macerated human tibia were studied using anatomical, morphometric, statistical methods as well as graphic simulation.Results. Center of the tibial ACL footprint was located 13,1±1,7 mm anteriorly from posterior border of intercondylar eminence, at 1/3 of the distance along the line connecting apexes of internal and external tubercles and 6,1±0,5 mm anteriorly along the perpendicular raised to this point.Conclusion. Internal and external tubercles, as well as posterior border of intercondylar eminence can be considered as anatomical references to determine the center of the tibial ACL footprint and to prepare bone canals for anatomic ligament repair.

Development of hepatocellular adenomas and carcinomas in mice with liver-specific G6Pase-α deficiency

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Roberta Resaz

2014-09-01

Full Text Available Glycogen storage disease type 1a (GSD-1a is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α, and is characterized by impaired glucose homeostasis and a high risk of developing hepatocellular adenomas (HCAs. A globally G6Pase-α-deficient (G6pc−/− mouse model that shows pathological features similar to those of humans with GSD-1a has been developed. These mice show a very severe phenotype of disturbed glucose homeostasis and rarely live beyond weaning. We generated liver-specific G6Pase-α-deficient (LS‑G6pc−/− mice as an alternative animal model for studying the long-term pathophysiology of the liver and the potential treatment strategies, such as cell therapy. LS‑G6pc−/− mice were viable and exhibited normal glucose profiles in the fed state, but showed significantly lower blood glucose levels than their control littermates after 6 hours of fasting. LS‑G6pc−/− mice developed hepatomegaly with glycogen accumulation and hepatic steatosis, and progressive hepatic degeneration. Ninety percent of the mice analyzed developed amyloidosis by 12 months of age. Finally, 25% of the mice sacrificed at age 10–20 months showed the presence of multiple HCAs and in one case late development of hepatocellular carcinoma (HCC. In conclusion, LS‑G6pc−/− mice manifest hepatic symptoms similar to those of human GSD-1a and, therefore, represent a valid model to evaluate long-term liver pathogenesis of GSD-1a.

Consensus guidelines for the uniform reporting of study ethics in anatomical research within the framework of the anatomical quality assurance (AQUA) checklist.

Science.gov (United States)

Henry, Brandon Michael; Vikse, Jens; Pekala, Przemyslaw; Loukas, Marios; Tubbs, R Shane; Walocha, Jerzy A; Jones, D Gareth; Tomaszewski, Krzysztof A

2018-05-01

Unambiguous reporting of a study's compliance with ethical guidelines in anatomical research is imperative. As such, clear, universal, and uniform reporting guidelines for study ethics are essential. In 2016, the International Evidence-Based Anatomy Working group in collaboration with international partners established reporting guidelines for anatomical studies, the Anatomical Quality Assurance (AQUA) Checklist. In this elaboration of the AQUA Checklist, consensus guidelines for reporting study ethics in anatomical studies are provided with in the framework of the AQUA Checklist. The new guidelines are aimed to be applicable to research across the spectrum of the anatomical sciences, including studies on both living and deceased donors. The authors hope the established guidelines will improve ethical compliance and reporting in anatomical research. Clin. Anat. 31:521-524, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Hydrolyzed whey protein prevents the development of food allergy to β-lactoglobulin in sensitized mice.

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Gomes-Santos, Ana Cristina; Fonseca, Roberta Cristelli; Lemos, Luisa; Reis, Daniela Silva; Moreira, Thaís Garcias; Souza, Adna Luciana; Silva, Mauro Ramalho; Silvestre, Marialice Pinto Coelho; Cara, Denise Carmona; Faria, Ana Maria Caetano

2015-01-01

Food allergy is an adverse immune response to dietary proteins. Hydrolysates are frequently used for children with milk allergy. However, hydrolysates effects afterwards are poorly studied. The aim of this study was to investigate the immunological consequences of hydrolyzed whey protein in allergic mice. For that, we developed a novel model of food allergy in BALB/c mice sensitized with alum-adsorbed β-lactoglobulin. These mice were orally challenged with either whey protein or whey hydrolysate. Whey-challenged mice had elevated levels of specific IgE and lost weight. They also presented gut inflammation, enhanced levels of SIgA and IL-5 as well as decreased production of IL-4 and IL-10 in the intestinal mucosa. Conversely, mice challenged with hydrolyzate maintained normal levels of IgE, IL-4 and IL-5 and showed no sign of gut inflammation probably due to increased IL-12 production in the gut. Thus, consumption of hydrolysate prevented the development of clinical signs of food allergy in mice. Copyright © 2015 Elsevier Inc. All rights reserved.

RIPK3 Mediates Necroptosis during Embryonic Development and Postnatal Inflammation in Fadd-Deficient Mice

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Qun Zhao

2017-04-01

Full Text Available RIPK3 mediates cell death and regulates inflammatory responses. Although genetic studies have suggested that RIPK3-MLKL-mediated necroptosis leads to embryonic lethality in Fadd or Caspase-8-deficient mice, the exact mechanisms are not fully understood. Here, we generated Ripk3 mutant mice by altering the RIPK3 kinase domain (Ripk3Δ/Δ mice, thus abolishing its kinase activity. Ripk3Δ/Δ cells were resistant to necroptosis stimulation in vitro, and Ripk3Δ/Δ mice were protected from necroptotic diseases. Although the Ripk3Δ/Δ mutation rescued embryonic lethality in Fadd−/− embryos, Fadd−/− Ripk3Δ/Δ mice died within 1 day after birth due to massive inflammation. These results indicate that Ripk3 ablation rescues embryonic lethality in Fadd-deficient mice by suppressing two RIPK3-mediating processes: necroptosis during embryogenesis and inflammation during postnatal development in Fadd−/− mice.

Designing learning spaces for interprofessional education in the anatomical sciences.

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Cleveland, Benjamin; Kvan, Thomas

2015-01-01

This article explores connections between interprofessional education (IPE) models and the design of learning spaces for undergraduate and graduate education in the anatomical sciences and other professional preparation. The authors argue that for IPE models to be successful and sustained they must be embodied in the environment in which interprofessional learning occurs. To elaborate these arguments, two exemplar tertiary education facilities are discussed: the Charles Perkins Centre at the University of Sydney for science education and research, and Victoria University's Interprofessional Clinic in Wyndham for undergraduate IPE in health care. Backed by well-conceived curriculum and pedagogical models, the architectures of these facilities embody the educational visions, methods, and practices they were designed to support. Subsequently, the article discusses the spatial implications of curriculum and pedagogical change in the teaching of the anatomical sciences and explores how architecture might further the development of IPE models in the field. In conclusion, it is argued that learning spaces should be designed and developed (socially) with the expressed intention of supporting collaborative IPE models in health education settings, including those in the anatomical sciences. © 2015 American Association of Anatomists.

Complete Plasmodium falciparum liver-stage development in liver-chimeric mice

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Vaughan, Ashley M.; Mikolajczak, Sebastian A.; Wilson, Elizabeth M.; Grompe, Markus; Kaushansky, Alexis; Camargo, Nelly; Bial, John; Ploss, Alexander; Kappe, Stefan H.I.

2012-01-01

Plasmodium falciparum, which causes the most lethal form of human malaria, replicates in the host liver during the initial stage of infection. However, in vivo malaria liver-stage (LS) studies in humans are virtually impossible, and in vitro models of LS development do not reconstitute relevant parasite growth conditions. To overcome these obstacles, we have adopted a robust mouse model for the study of P. falciparum LS in vivo: the immunocompromised and fumarylacetoacetate hydrolase–deficient mouse (Fah–/–, Rag2–/–, Il2rg–/–, termed the FRG mouse) engrafted with human hepatocytes (FRG huHep). FRG huHep mice supported vigorous, quantifiable P. falciparum LS development that culminated in complete maturation of LS at approximately 7 days after infection, providing a relevant model for LS development in humans. The infections allowed observations of previously unknown expression of proteins in LS, including P. falciparum translocon of exported proteins 150 (PTEX150) and exported protein-2 (EXP-2), components of a known parasite protein export machinery. LS schizonts exhibited exoerythrocytic merozoite formation and merosome release. Furthermore, FRG mice backcrossed to the NOD background and repopulated with huHeps and human red blood cells supported reproducible transition from LS infection to blood-stage infection. Thus, these mice constitute reliable models to study human LS directly in vivo and demonstrate utility for studies of LS–to–blood-stage transition of a human malaria parasite. PMID:22996664

Lgl1 Is Required for Olfaction and Development of Olfactory Bulb in Mice

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Li, Zhenzu; Zhang, Tingting; Lin, Zhuchun; Hou, Congzhe; Zhang, Jian; Men, Yuqin; Li, Huashun

2016-01-01

Lethal giant larvae 1 (Lgl1) was initially identified as a tumor suppressor in Drosophila and functioned as a key regulator of epithelial polarity and asymmetric cell division. In this study, we generated Lgl1 conditional knockout mice mediated by Pax2-Cre, which is expressed in olfactory bulb (OB). Next, we examined the effects of Lgl1 loss in the OB. First, we determined the expression patterns of Lgl1 in the neurogenic regions of the embryonic dorsal region of the LGE (dLGE) and postnatal OB. Furthermore, the Lgl1 conditional mutants exhibited abnormal morphological characteristics of the OB. Our behavioral analysis exhibited greatly impaired olfaction in Lgl1 mutant mice. To elucidate the possible mechanisms of impaired olfaction in Lgl1 mutant mice, we investigated the development of the OB. Interestingly, reduced thickness of the MCL and decreased density of mitral cells (MCs) were observed in Lgl1 mutant mice. Additionally, we observed a dramatic loss in SP8+ interneurons (e.g. calretinin and GABAergic/non-dopaminergic interneurons) in the GL of the OB. Our results demonstrate that Lgl1 is required for the development of the OB and the deletion of Lgl1 results in impaired olfaction in mice. PMID:27603780

Developing a cumulative anatomic scoring system for military perineal and pelvic blast injuries.

Science.gov (United States)

Mossadegh, Somayyeh; Midwinter, M; Parker, P

2013-03-01

Improvised explosive device (IED) yields in Afghanistan have increased resulting in more proximal injuries. The injury severity score (ISS) is an anatomic aggregate score of the three most severely injured anatomical areas but does not accurately predict severity in IED related pelvi-perineal trauma patients. A scoring system based on abbreviated injury score (AIS) was developed to reflect the severity of these injuries in order to better understand risk factors, develop a tool for future audit and improve performance. Using standard AIS descriptors, injury scales were constructed for the pelvis (1, minor to 6, maximal). The perineum was divided into anterior and posterior zones as relevant to injury patterns and blast direction with each soft tissue structure being allocated a score from its own severity scale. A cumulative score, from 1 to 36 for soft tissue, or a maximum of 42 if a pelvic fracture was involved, was created for all structures injured in the anterior and posterior zones. Using this new scoring system, 77% of patients survived with a pelvi-perineal trauma score (PPTS) below 5. There was a significant increase in mortality, number of pelvic fractures and amputations with increase in score when comparing the first group (score 1-5) to the second group (score 6-10). For scores between 6 and 16 survival was 42% and 22% for scores between 17 and 21. In our cohort of 62 survivors, 1 patient with an IED related pelvi-perineal injury had a 'theoretically un-survivable' maximal ISS of 75 and survived, whereas there were no survivors with a PPTS greater than 22 but this group had no-one with an ISS of 75 suggesting ISS is not an accurate reflection of the true severity of pelvi-perineal blast injury. This scoring system is the initial part of a more complex logistic regression model that will contribute towards a unique trauma scoring system to aid surgical teams in predicting fluid requirements and operative timelines. In austere environments, it may also

Advertising cadavers in the republic of letters: anatomical publications in the early modern Netherlands.

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Margócsy, Dániel

2009-06-01

This paper sketches how late seventeenth-century Dutch anatomists used printed publications to advertise their anatomical preparations, inventions and instructional technologies to an international clientele. It focuses on anatomists Frederik Ruysch (1638-1732) and Lodewijk de Bils (1624-69), inventors of two separate anatomical preparation methods for preserving cadavers and body parts in a lifelike state for decades or centuries. Ruysch's and de Bils's publications functioned as an 'advertisement' for their preparations. These printed volumes informed potential customers that anatomical preparations were aesthetically pleasing and scientifically important but did not divulge the trade secrets of the method of production. Thanks to this strategy of non-disclosure and advertisement, de Bils and Ruysch could create a well-working monopoly market of anatomical preparations. The 'advertising' rhetorics of anatomical publications highlight the potential dangers of equating the growth of print culture with the development of an open system of knowledge exchange.

Anatomical Terms in J. Basanavičius’ Manuscript Anatomijos ir medicinos vardyno medžiaga

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Nijolė Litevkienė

2011-12-01

Full Text Available The historical evolution of anatomical terms dates to antiquity, to the writings of Hippocrates. The historical development of Lithuanian anatomical terminology goes back to the seventeenth century. Anatomical terminology, as a comprehensive system of the names of human body parts is being compiled gradually. The originator of Lithuanian medical terminology was J. Basanavičius. The research paper aims to analyze anatomical terms used in J. Basanavičius’ manuscript Anatomijos ir medicinos vardyno medžiaga (further BM and to compare them with the terms in the Dictionary of Medical Terms ( Medicinos terminų žodynas 1980. The research focuses on the analysis of some aspects of differentiation and congruity of simple and multi-word anatomical terms of the manuscript and the dictionary. About 270 Lithuanian anatomical terms with Russian and Latin equivalents were collected by J. Basanavičius. The results show that the major part of the terms are different, the lesser part of the terms are identical.

A novel auditory ossicles membrane and the development of conductive hearing loss in Dmp1-null mice.

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Lv, Kun; Huang, Haiyang; Yi, Xing; Chertoff, Mark E; Li, Chaoyuan; Yuan, Baozhi; Hinton, Robert J; Feng, Jian Q

2017-10-01

Genetic mouse models are widely used for understanding human diseases but we know much less about the anatomical structure of the auditory ossicles in the mouse than we do about human ossicles. Furthermore, current studies have mainly focused on disease conditions such as osteomalacia and rickets in patients with hypophosphatemia rickets, although the reason that these patients develop late-onset hearing loss is unknown. In this study, we first analyzed Dmp1 lac Z knock-in auditory ossicles (in which the blue reporter is used to trace DMP1 expression in osteocytes) using X-gal staining and discovered a novel bony membrane surrounding the mouse malleus. This finding was further confirmed by 3-D micro-CT, X-ray, and alizarin red stained images. We speculate that this unique structure amplifies and facilitates sound wave transmissions in two ways: increasing the contact surface between the eardrum and malleus and accelerating the sound transmission due to its mineral content. Next, we documented a progressive deterioration in the Dmp1-null auditory ossicle structures using multiple imaging techniques. The auditory brainstem response test demonstrated a conductive hearing loss in the adult Dmp1-null mice. This finding may help to explain in part why patients with DMP1 mutations develop late-onset hearing loss, and supports the critical role of DMP1 in maintaining the integrity of the auditory ossicles and its bony membrane. Copyright © 2017 Elsevier Inc. All rights reserved.

Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice

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Zhang, Pengpeng; Shan, Tizhong; Liang, Xinrong; Deng, Changyan; Kuang, Shihuan

2014-01-01

Highlights: • mTOR is a critical regulator of many biological processes yet its function in heart is not well understood. • MCK-Cre/Mtor flox/flox mice were established to delete Mtor in cardiomyocytes. • The mTOR-mKO mice developed normally but die prematurely within 5 weeks after birth due to heart disease. • The mTOR-mKO mice had dilated myocardium and increased cell death. • mTOR-mKO hearts had reduced expression of metabolic genes and activation of mTOR target proteins. - Abstract: Mammalian target of rapamycin (mTOR) is a critical regulator of protein synthesis, cell proliferation and energy metabolism. As constitutive knockout of Mtor leads to embryonic lethality, the in vivo function of mTOR in perinatal development and postnatal growth of heart is not well defined. In this study, we established a muscle-specific mTOR conditional knockout mouse model (mTOR-mKO) by crossing MCK-Cre and Mtor flox/flox mice. Although the mTOR-mKO mice survived embryonic and perinatal development, they exhibited severe postnatal growth retardation, cardiac muscle pathology and premature death. At the cellular level, the cardiac muscle of mTOR-mKO mice had fewer cardiomyocytes due to apoptosis and necrosis, leading to dilated cardiomyopathy. At the molecular level, the cardiac muscle of mTOR-mKO mice expressed lower levels of fatty acid oxidation and glycolysis related genes compared to the WT littermates. In addition, the mTOR-mKO cardiac muscle had reduced Myh6 but elevated Myh7 expression, indicating cardiac muscle degeneration. Furthermore, deletion of Mtor dramatically decreased the phosphorylation of S6 and AKT, two key targets downstream of mTORC1 and mTORC2 mediating the normal function of mTOR. These results demonstrate that mTOR is essential for cardiomyocyte survival and cardiac muscle function

Comparison of Coil Designs for Transcranial Magnetic Stimulation on Mice

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Rastogi, Priyam; Hadimani, Ravi; Jiles, David

2015-03-01

Transcranial magnetic stimulation (TMS) is a non-invasive treatment for neurological disorders using time varying magnetic field. The electric field generated by the time varying magnetic field is used to depolarize the brain neurons which can lead to measurable effects. TMS provides a surgical free method for the treatment of neurological brain disorders like depression, post-traumatic stress disorder, traumatic brain injury and Parkinson's disease. Before using TMS on human subjects, it is appropriate that its effects are verified on animals such as mice. The magnetic field intensity and stimulated region of the brain can be controlled by the shape, position and current in the coils. There are few reports on the designs of the coils for mice. In this paper, different types of coils are developed and compared using an anatomically realistic mouse model derived from MRI images. Parameters such as focality, depth of the stimulation, electric field strength on the scalp and in the deep brain regions, are taken into account. These parameters will help researchers to determine the most suitable coil design according to their need. This should result in improvements in treatment of specific disorders. Carver Charitable Trust.

Prostatome: A combined anatomical and disease based MRI atlas of the prostate

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Rusu, Mirabela; Madabhushi, Anant, E-mail: anant.madabhushi@case.edu [Case Western Reserve University, Cleveland, Ohio 44106 (United States); Bloch, B. Nicolas; Jaffe, Carl C. [Boston University School of Medicine, Boston, Massachusetts 02118 (United States); Genega, Elizabeth M. [Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215 (United States); Lenkinski, Robert E.; Rofsky, Neil M. [UT Southwestern Medical Center, Dallas, Texas 75235 (United States); Feleppa, Ernest [Riverside Research Institute, New York, New York 10038 (United States)

2014-07-15

Purpose: In this work, the authors introduce a novel framework, the anatomically constrained registration (AnCoR) scheme and apply it to create a fused anatomic-disease atlas of the prostate which the authors refer to as the prostatome. The prostatome combines a MRI based anatomic and a histology based disease atlas. Statistical imaging atlases allow for the integration of information across multiple scales and imaging modalities into a single canonical representation, in turn enabling a fused anatomical-disease representation which may facilitate the characterization of disease appearance relative to anatomic structures. While statistical atlases have been extensively developed and studied for the brain, approaches that have attempted to combine pathology and imaging data for study of prostate pathology are not extant. This works seeks to address this gap. Methods: The AnCoR framework optimizes a scoring function composed of two surface (prostate and central gland) misalignment measures and one intensity-based similarity term. This ensures the correct mapping of anatomic regions into the atlas, even when regional MRI intensities are inconsistent or highly variable between subjects. The framework allows for creation of an anatomic imaging and a disease atlas, while enabling their fusion into the anatomic imaging-disease atlas. The atlas presented here was constructed using 83 subjects with biopsy confirmed cancer who had pre-operative MRI (collected at two institutions) followed by radical prostatectomy. The imaging atlas results from mapping thein vivo MRI into the canonical space, while the anatomic regions serve as domain constraints. Elastic co-registration MRI and corresponding ex vivo histology provides “ground truth” mapping of cancer extent on in vivo imaging for 23 subjects. Results: AnCoR was evaluated relative to alternative construction strategies that use either MRI intensities or the prostate surface alone for registration. The AnCoR framework

Prostatome: A combined anatomical and disease based MRI atlas of the prostate

International Nuclear Information System (INIS)

Rusu, Mirabela; Madabhushi, Anant; Bloch, B. Nicolas; Jaffe, Carl C.; Genega, Elizabeth M.; Lenkinski, Robert E.; Rofsky, Neil M.; Feleppa, Ernest

2014-01-01

Purpose: In this work, the authors introduce a novel framework, the anatomically constrained registration (AnCoR) scheme and apply it to create a fused anatomic-disease atlas of the prostate which the authors refer to as the prostatome. The prostatome combines a MRI based anatomic and a histology based disease atlas. Statistical imaging atlases allow for the integration of information across multiple scales and imaging modalities into a single canonical representation, in turn enabling a fused anatomical-disease representation which may facilitate the characterization of disease appearance relative to anatomic structures. While statistical atlases have been extensively developed and studied for the brain, approaches that have attempted to combine pathology and imaging data for study of prostate pathology are not extant. This works seeks to address this gap. Methods: The AnCoR framework optimizes a scoring function composed of two surface (prostate and central gland) misalignment measures and one intensity-based similarity term. This ensures the correct mapping of anatomic regions into the atlas, even when regional MRI intensities are inconsistent or highly variable between subjects. The framework allows for creation of an anatomic imaging and a disease atlas, while enabling their fusion into the anatomic imaging-disease atlas. The atlas presented here was constructed using 83 subjects with biopsy confirmed cancer who had pre-operative MRI (collected at two institutions) followed by radical prostatectomy. The imaging atlas results from mapping thein vivo MRI into the canonical space, while the anatomic regions serve as domain constraints. Elastic co-registration MRI and corresponding ex vivo histology provides “ground truth” mapping of cancer extent on in vivo imaging for 23 subjects. Results: AnCoR was evaluated relative to alternative construction strategies that use either MRI intensities or the prostate surface alone for registration. The AnCoR framework

Utilization management in anatomic pathology.

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Lewandrowski, Kent; Black-Schaffer, Steven

2014-01-01

There is relatively little published literature concerning utilization management in anatomic pathology. Nonetheless there are many utilization management opportunities that currently exist and are well recognized. Some of these impact only the cost structure within the pathology department itself whereas others reduce charges for third party payers. Utilization management may result in medical legal liabilities for breaching the standard of care. For this reason it will be important for pathology professional societies to develop national utilization guidelines to assist individual practices in implementing a medically sound approach to utilization management. © 2013.

Mice null for the deubiquitinase USP18 spontaneously develop leiomyosarcomas

International Nuclear Information System (INIS)

Chinyengetere, Fadzai; Sekula, David J.; Lu, Yun; Giustini, Andrew J.; Sanglikar, Aarti; Kawakami, Masanori; Ma, Tian; Burkett, Sandra S.; Eisenberg, Burton L.; Wells, Wendy A.; Hoopes, Paul J.; Demicco, Elizabeth G.; Lazar, Alexander J; Torres, Keila E.; Memoli, Vincent; Freemantle, Sarah J.; Dmitrovsky, Ethan

2015-01-01

USP18 (ubiquitin-specific protease 18) removes ubiquitin-like modifier interferon stimulated gene 15 (ISG15) from conjugated proteins. USP18 null mice in a FVB/N background develop tumors as early as 2 months of age. These tumors are leiomyosarcomas and thus represent a new murine model for this disease. Heterozygous USP18 +/− FVB/N mice were bred to generate wild-type, heterozygous and homozygous cohorts. Tumors were characterized immunohistochemically and two cell lines were derived from independent tumors. Cell lines were karyotyped and their responses to restoration of USP18 activity assessed. Drug testing and tumorigenic assays were also performed. USP18 immunohistochemical staining in a large series of human leiomyosacomas was examined. USP18 −/− FVB/N mice spontaneously develop tumors predominantly on the back of the neck with most tumors evident between 6–12 months (80 % penetrance). Immunohistochemical characterization of the tumors confirmed they were leiomyosarcomas, which originate from smooth muscle. Restoration of USP18 activity in sarcoma-derived cell lines did not reduce anchorage dependent or independent growth or xenograft tumor formation demonstrating that these cells no longer require USP18 suppression for tumorigenesis. Karyotyping revealed that both tumor-derived cell lines were aneuploid with extra copies of chromosomes 3 and 15. Chromosome 15 contains the Myc locus and MYC is also amplified in human leiomyosarcomas. MYC protein levels were elevated in both murine leiomyosarcoma cell lines. Stabilized P53 protein was detected in a subset of these murine tumors, another feature of human leiomyosarcomas. Immunohistochemical analyses of USP18 in human leiomyosarcomas revealed a range of staining intensities with the highest USP18 expression in normal vascular smooth muscle. USP18 tissue array analysis of primary leiomyosarcomas from 89 patients with a clinical database revealed cases with reduced USP18 levels had a significantly

Small heterodimer partner overexpression partially protects against liver tumor development in farnesoid X receptor knockout mice

International Nuclear Information System (INIS)

Li, Guodong; Kong, Bo; Zhu, Yan; Zhan, Le; Williams, Jessica A.; Tawfik, Ossama; Kassel, Karen M.; Luyendyk, James P.; Wang, Li; Guo, Grace L.

2013-01-01

Farnesoid X receptor (FXR, Nr1h4) and small heterodimer partner (SHP, Nr0b2) are nuclear receptors that are critical to liver homeostasis. Induction of SHP serves as a major mechanism of FXR in suppressing gene expression. Both FXR −/− and SHP −/− mice develop spontaneous hepatocellular carcinoma (HCC). SHP is one of the most strongly induced genes by FXR in the liver and is a tumor suppressor, therefore, we hypothesized that deficiency of SHP contributes to HCC development in the livers of FXR −/− mice and therefore, increased SHP expression in FXR −/− mice reduces liver tumorigenesis. To test this hypothesis, we generated FXR −/− mice with overexpression of SHP in hepatocytes (FXR −/− /SHP Tg ) and determined the contribution of SHP in HCC development in FXR −/− mice. Hepatocyte-specific SHP overexpression did not affect liver tumor incidence or size in FXR −/− mice. However, SHP overexpression led to a lower grade of dysplasia, reduced indicator cell proliferation and increased apoptosis. All tumor-bearing mice had increased serum bile acid levels and IL-6 levels, which was associated with activation of hepatic STAT3. In conclusion, SHP partially protects FXR −/− mice from HCC formation by reducing tumor malignancy. However, disrupted bile acid homeostasis by FXR deficiency leads to inflammation and injury, which ultimately results in uncontrolled cell proliferation and tumorigenesis in the liver. - Highlights: • SHP does not prevent HCC incidence nor size in FXR KO mice but reduces malignancy. • Increased SHP promotes apoptosis. • Bile acids and inflammation maybe critical for HCC formation with FXR deficiency

p120-Catenin Is Critical for the Development of Invasive Lobular Carcinoma in Mice.

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Tenhagen, Milou; Klarenbeek, Sjoerd; Braumuller, Tanya M; Hofmann, Ilse; van der Groep, Petra; Ter Hoeve, Natalie; van der Wall, Elsken; Jonkers, Jos; Derksen, Patrick W B

2016-12-01

Loss of E-cadherin expression is causal to the development of invasive lobular breast carcinoma (ILC). E-cadherin loss leads to dismantling of the adherens junction and subsequent translocation of p120-catenin (p120) to the cytosol and nucleus. Although p120 is critical for the metastatic potential of ILC through the regulation of Rock-dependent anoikis resistance, it remains unknown whether p120 also contributes to ILC development. Using genetically engineered mouse models with mammary gland-specific inactivation of E-cadherin, p120 and p53, we demonstrate that ILC formation induced by E-cadherin and p53 loss is severely impaired upon concomitant inactivation of p120. Tumors that developed in the triple-knockout mice were mostly basal sarcomatoid carcinomas that displayed overt nuclear atypia and multinucleation. In line with the strong reduction in ILC incidence in triple-knockout mice compared to E-cadherin and p53 double-knockout mice, no functional redundancy of p120 family members was observed in mouse ILC development, as expression and localization of ARVCF, p0071 or δ-catenin was unaltered in ILCs from triple-knockout mice. In conclusion, we show that loss of p120 in the context of the p53-deficient mouse models is dominant over E-cadherin inactivation and its inactivation promotes the development of basal, epithelial-to-mesenchymal-transition (EMT)-type invasive mammary tumors.

sirt1-null mice develop an autoimmune-like condition

International Nuclear Information System (INIS)

Sequeira, Jedon; Boily, Gino; Bazinet, Stephanie; Saliba, Sarah; He Xiaohong; Jardine, Karen; Kennedy, Christopher; Staines, William; Rousseaux, Colin; Mueller, Rudi; McBurney, Michael W.

2008-01-01

The sirt1 gene encodes a protein deacetylase with a broad spectrum of reported substrates. Mice carrying null alleles for sirt1 are viable on outbred genetic backgrounds so we have examined them in detail to identify the biological processes that are dependent on SIRT1. Sera from adult sirt1-null mice contain antibodies that react with nuclear antigens and immune complexes become deposited in the livers and kidneys of these animals. Some of the sirt1-null animals develop a disease resembling diabetes insipidus when they approach 2 years of age although the relationship to the autoimmunity remains unclear. We interpret these observations as consistent with a role for SIRT1 in sustaining normal immune function and in this way delaying the onset of autoimmune disease

Helicobacter bilis Infection Alters Mucosal Bacteria and Modulates Colitis Development in Defined Microbiota Mice.

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Atherly, Todd; Mosher, Curtis; Wang, Chong; Hostetter, Jesse; Proctor, Alexandra; Brand, Meghan W; Phillips, Gregory J; Wannemuehler, Michael; Jergens, Albert E

2016-11-01

Helicobacter bilis infection of C3H/HeN mice harboring the altered Schaedler flora (ASF) triggers progressive immune responsiveness and the development of colitis. We sought to investigate temporal alterations in community structure of a defined (ASF-colonized) microbiota in normal and inflamed murine intestines and to correlate microbiota changes to histopathologic lesions. The colonic mucosal microbiota of healthy mice and ASF mice colonized with H. bilis for 3, 6, or 12 weeks were investigated by fluorescence in situ hybridization targeting the 16S ribosomal RNA genes of total bacteria, group-specific organisms, and individual ASF bacterial species. Microbial profiling of ASF and H. bilis abundance was performed on cecal contents. Helicobacter bilis-colonized mice developed colitis associated with temporal changes in composition and spatial distribution of the mucosal microbiota. The number of total bacteria, ASF519, and helicobacter-positive bacteria were increased (P attachment, or by invasion, and this interaction is differentially expressed over time.

Analysis of anatomical and micromorphological characteristics of Iva xanthifolia nutt.

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Krstić Lana N.

2007-01-01

Full Text Available Iva xanthifolia is a North American weed species, which was introduced and naturalized in Europe. Anatomical and micromorphological characteristics of this species were investigated, in order to get better knowledge of its biology, which could help in development of strategies for prevention of its spreading. Detailed descriptions of lamina, petiole, stem and inflorescence axis anatomical structures were given, together with micromorphological characteristics of epidermis and indumentum of lamina, petiole, stem, inflorescence axis, involucre and fruit. All vegetative organs had mesomorphic structure, with some xeromorphic adaptations. Mechanical tissue was well developed, which gave those plants additional strength and resistance. Trichomes were the most numerous on lamina and in the region of inflorescence, while rare on petiole and stem epidermis and their distribution varied according to plant organ.

Anatomical characteristics of Turkish steno-endemic Origanum leptocladum Boiss. (Lamiaceae

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Süleyman Doğu

2013-04-01

Full Text Available Origanum leptocladum Boiss. is an endemic East Mediterranean element, naturally growing only in Ermenek district of Karaman province in Turkey. The aim of this study is to determine anatomical features of the species. The study materials were collected from Karaman-Ermenek in 2009 and then preserved in 70 % alcohol. O. leptocladum generally exhibits the anatomical feaures of the family Lamiaceae. Hovewer, herbaceaus stem is weakly-rectangle shaped or tends to be circular, the collenchymatic tissue at the corner of the stem and scleranchymatic pericycle around the vascular tissue are weakly-developed. The most striking anatomical feature is that leaf lamina is dorsiventral in the region near to midvein, but equifacial out of the midvein. According to the results, while the stomata are of mesomorphic type on the leaf surfaces, O. leptocladum has xeromorphic characters such as palisade richness in mesophyll, the occurrence of rich scleranchymatic tissue in midvein and cuticle thickness on leaf surface.

Deletion of the miR-143/145 Cluster Leads to Hydronephrosis in Mice

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Medrano, Silvia; Sequeira-Lopez, Maria Luisa S.; Gomez, R. Ariel

2015-01-01

Obstructive nephropathy, the leading cause of kidney failure in children, can be anatomic or functional. The underlying causes of functional hydronephrosis are not well understood. miRNAs, which are small noncoding RNAs, regulate gene expression at the post-transcriptional level. We found that miR-145-5p, a member of the miR-143/145 cluster that is highly expressed in smooth muscle cells of the renal vasculature, was present in the pelvicalyceal system and the ureter. To evaluate whether the miR-143/145 cluster is involved in urinary tract function we performed morphologic, functional, and gene expression studies in mice carrying a whole-body deletion of miR-143/145. miR-143/145–deficient mice developed hydronephrosis, characterized by severe papillary atrophy and dilatation of the pelvicalyceal system without obvious physical obstruction. Moreover, mutant mice showed abnormal ureteral peristalsis. The number of ureter contractions was significantly higher in miR-143/145–deficient mice. Peristalsis was replaced by incomplete, short, and more frequent contractions that failed to completely propagate in a proximal-distal direction. Microarray analysis showed 108 differentially expressed genes in ureters of miR-143/145–deficient mice. Ninety genes were up-regulated and 18 genes were down-regulated, including genes with potential regulatory roles in smooth muscle contraction and extracellular matrix-receptor interaction. We show that miR-143/145 are important for the normal peristalsis of the ureter and report an association between the expression of these miRNAs and hydronephrosis. PMID:25307343

Isoflurane Damages the Developing Brain of Mice and Induces Subsequent Learning and Memory Deficits through FASL-FAS Signaling

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Xiuwen Yi

2015-01-01

Full Text Available Background. Isoflurane disrupts brain development of neonatal mice, but its mechanism is unclear. We explored whether isoflurane damaged developing hippocampi through FASL-FAS signaling pathway, which is a well-known pathway of apoptosis. Method. Wild type and FAS- or FASL-gene-knockout mice aged 7 days were exposed to either isoflurane or pure oxygen. We used western blotting to study expressions of caspase-3, FAS (CD95, and FAS ligand (FASL or CD95L proteins, TUNEL staining to count apoptotic cells in hippocampus, and Morris water maze (MWM to evaluate learning and memory. Result. Isoflurane increased expression of FAS and FASL proteins in wild type mice. Compared to isoflurane-treated FAS- and FASL-knockout mice, isoflurane-treated wild type mice had higher expression of caspase-3 and more TUNEL-positive hippocampal cells. Expression of caspase-3 in wild isoflurane group, wild control group, FAS/FASL-gene-knockout control group, and FAS/FASL-gene-knockout isoflurane group showed FAS or FASL gene knockout might attenuate increase of caspase-3 caused by isoflurane. MWM showed isoflurane treatment of wild type mice significantly prolonged escape latency and reduced platform crossing times compared with gene-knockout isoflurane-treated groups. Conclusion. Isoflurane induces apoptosis in developing hippocampi of wild type mice but not in FAS- and FASL-knockout mice and damages brain development through FASL-FAS signaling.

TRAF3IP2 mediates atherosclerotic plaque development and vulnerability in ApoE−/− mice

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Prasad, Sakamuri Siva Sankara Vara; Higashi, Yusuke; Sukhanov, Sergiy; Siddesha, Jalahalli M; Delafontaine, Patrice; Siebenlist, Ulrich; Chandrasekar, Bysani

2016-01-01

Background and aims Atherosclerosis is a major cause of heart attack and stroke. Inflammation plays a critical role in the development of atherosclerosis. Since the cytoplasmic adaptor molecule TRAF3IP2 (TRAF3-Interacting Protein 2) plays a causal role in various autoimmune and inflammatory diseases, we hypothesized that TRAF3IP2 mediates atherosclerotic plaque development. Methods TRAF3IP2/ApoE double knockout (DKO) mice were generated by crossing TRAF3IP2−/− and ApoE−/− mice. ApoE−/− mice served as controls. Both DKO and control mice were fed a high-fat diet for 12 weeks. Plasma lipids were measured by ELISA, atherosclerosis by en face analysis of aorta and plaque cross-section measurements at the aortic valve region, plaque necrotic core area, collagen and smooth muscle cell content by histomorphometry, and aortic gene expression by RT-qPCR. Results The plasma lipoprotein profile was not altered by TRAF3IP2 gene deletion in ApoE−/− mice. While total aortic plaque area was decreased in DKO female, but not male mice, the plaque necrotic area was significantly decreased in DKO mice of both genders. Plaque collagen and smooth muscle cell contents were increased significantly in both female and male DKO mice compared to respective controls. Aortic expression of proinflammatory cytokine (Tumor necrosis factor α, TNFα), chemokine (Chemokine (C-X-C motif) Ligand 1, CXCL1) and adhesion molecule (Vascular cell adhesion molecule 1, VCAM1; and Intercellular adhesion molecule 1, ICAM1) gene expression were decreased in both male and female DKO mice. In addition, the male DKO mice showed a markedly reduced expression of extracellular matrix (ECM)-related genes, including TIMP1 (Tissue inhibitor of metalloproteinase 1), RECK (Reversion-Inducing- Cysteine-Rich Protein with Kazal Motifs) and ADAM17 (A Disintegrin And Metalloproteinase 17). Conclusions TRAF3IP2 plays a causal role in atherosclerotic plaque development and vulnerability, possibly by inducing the

Anatomical and Electrophysiological Clustering of Superficial Medial Entorhinal Cortex Interneurons

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2017-01-01

Abstract Local GABAergic interneurons regulate the activity of spatially-modulated principal cells in the medial entorhinal cortex (MEC), mediating stellate-to-stellate connectivity and possibly enabling grid formation via recurrent inhibitory circuitry. Despite the important role interneurons seem to play in the MEC cortical circuit, the combination of low cell counts and functional diversity has made systematic electrophysiological studies of these neurons difficult. For these reasons, there remains a paucity of knowledge on the electrophysiological profiles of superficial MEC interneuron populations. Taking advantage of glutamic acid decarboxylase 2 (GAD2)-IRES-tdTomato and PV-tdTomato transgenic mice, we targeted GABAergic interneurons for whole-cell patch-clamp recordings and characterized their passive membrane features, basic input/output properties and action potential (AP) shape. These electrophysiologically characterized cells were then anatomically reconstructed, with emphasis on axonal projections and pial depth. K-means clustering of interneuron anatomical and electrophysiological data optimally classified a population of 106 interneurons into four distinct clusters. The first cluster is comprised of layer 2- and 3-projecting, slow-firing interneurons. The second cluster is comprised largely of PV+ fast-firing interneurons that project mainly to layers 2 and 3. The third cluster contains layer 1- and 2-projecting interneurons, and the fourth cluster is made up of layer 1-projecting horizontal interneurons. These results, among others, will provide greater understanding of the electrophysiological characteristics of MEC interneurons, help guide future in vivo studies, and may aid in uncovering the mechanism of grid field formation. PMID:29085901

Anatomic and Molecular Development of Corticostriatal Projection Neurons in Mice

OpenAIRE

Sohur, U. Shivraj; Padmanabhan, Hari K.; Kotchetkov, Ivan S.; Menezes, Joao R.L.; Macklis, Jeffrey D.

2012-01-01

Corticostriatal projection neurons (CStrPN) project from the neocortex to ipsilateral and contralateral striata to control and coordinate motor programs and movement. They are clinically important as the predominant cortical population that degenerates in Huntington's disease and corticobasal ganglionic degeneration, and their injury contributes to multiple forms of cerebral palsy. Together with their well-studied functions in motor control, these clinical connections make them a functionally...

A neurorobotic platform for locomotor prosthetic development in rats and mice

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von Zitzewitz, Joachim; Asboth, Leonie; Fumeaux, Nicolas; Hasse, Alexander; Baud, Laetitia; Vallery, Heike; Courtine, Grégoire

2016-04-01

Objectives. We aimed to develop a robotic interface capable of providing finely-tuned, multidirectional trunk assistance adjusted in real-time during unconstrained locomotion in rats and mice. Approach. We interfaced a large-scale robotic structure actuated in four degrees of freedom to exchangeable attachment modules exhibiting selective compliance along distinct directions. This combination allowed high-precision force and torque control in multiple directions over a large workspace. We next designed a neurorobotic platform wherein real-time kinematics and physiological signals directly adjust robotic actuation and prosthetic actions. We tested the performance of this platform in both rats and mice with spinal cord injury. Main Results. Kinematic analyses showed that the robotic interface did not impede locomotor movements of lightweight mice that walked freely along paths with changing directions and height profiles. Personalized trunk assistance instantly enabled coordinated locomotion in mice and rats with severe hindlimb motor deficits. Closed-loop control of robotic actuation based on ongoing movement features enabled real-time control of electromyographic activity in anti-gravity muscles during locomotion. Significance. This neurorobotic platform will support the study of the mechanisms underlying the therapeutic effects of locomotor prosthetics and rehabilitation using high-resolution genetic tools in rodent models.

Sinonasal anatomical variations: their relationship with chronic rhinosinusitis and effect on the severity of disease-a computerized tomography assisted anatomical and clinical study.

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Kaygusuz, Ahmet; Haksever, Mehmet; Akduman, Davut; Aslan, Sündüs; Sayar, Zeynep

2014-09-01

The anatomy of the sinonasal area has a very wide rage of anatomical variations. The significance of these anatomical variations in pathogenesis of rhinosinusitis, which is the commonest disease in the region, is still unclear. The aims of the study were to compare the rate of sinonasal anatomical variations with development and severity of chronic rhinosinusitis patients. CT scan of paranasal sinuses images of 99 individuals were retrospectively reviewed. 65 cases of chronic rhinosinusitis (study group) who had undergone endoscopic sinus surgery were compared with 34 cases without chronic rhinosinusitis (control group). Also in study group Lund-Mackay score of the sinus disease were calculated and compared to the rate of related anatomical variations. There were 74 (74.7 %) males and 25 (25.2 %) females with ages ranging from 13 to 70 years (mean 32.2 years). The anatomical variations recorded were: Septal deviation 47 (72.3) in study and 25 (73.5 %) in control group, concha bullosa 27 (41.5 %) in study and 18 (52.9 %) in control group, overpneumatized ethmoid bulla 17 (26.1 %) in study and 14 (41.1 %) in control group, pneumatized uncinate 3 (4.6 %) in study and 3 (8.8 %) in control group, agger nasi 42 (64.6 %) in study and 19 (55.8 %) in control group, paradoxical middle turbinates 9 (13.8 %) in study and 4 (11.7 %) in control group, Onodi cell 6 (9.2 %) in study and 2 (5.8 %) in control group, Haller's cells (infraorbital ethmoid cell) 9 (13.8 %) in study and 7 (20.5 %) in control group. None of these results were statistically significant between study and control group (p > 0.05). Lund-Mackay score (which was assumed to show the severity of the disease) of the maxillary, ethmoid and frontal sinus were calculated and compared to rate of septal deviation, concha bullosa, agger nasi cells. No significant correlation was conducted (p > 0.05). The results of study showed no statistically significant correlation between sinonasal anatomical

ArthroBroström Lateral Ankle Stabilization Technique: An Anatomic Study.

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Acevedo, Jorge I; Ortiz, Cristian; Golano, Pau; Nery, Caio

2015-10-01

Arthroscopic ankle lateral ligament repair techniques have recently been developed and biomechanically as well as clinically validated. Although there has been 1 anatomic study relating suture and anchor proximity to anatomic structures, none has evaluated the ArthroBroström procedure. To evaluate the proximity of anatomic structures for the ArthroBroström lateral ankle ligament stabilization technique and to define ideal landmarks and "safe zones" for this repair. Descriptive laboratory study. Ten human cadaveric ankle specimens (5 matched pairs) were screened for the study. All specimens underwent arthroscopic lateral ligament repair according to the previously described ArthroBroström technique with 2 suture anchors in the fibula. Three cadaveric specimens were used to test the protocol, and 7 were dissected to determine the proximity of anatomic structures. Several distances were measured, including those of different anatomic structures to the suture knots, to determine the "safe zones." Measurements were obtained by 2 separate observers, and statistical analysis was performed. None of the specimens revealed entrapment by either of the suture knots of the critical anatomic structures, including the superficial peroneal nerve (SPN), sural nerve, peroneus tertius tendon, peroneus brevis tendon, or peroneus longus tendon. The internervous safe zone between the intermediate branch of the SPN and sural nerve was a mean of 51 mm (range, 39-64 mm). The intertendinous safe zone between the peroneus tertius and peroneus brevis was a mean of 43 mm (range, 37-49 mm). On average, a 20-mm (range, 8-36 mm) safe distance was maintained from the most medial suture to the intermediate branch of the SPN. The amount of inferior extensor retinaculum (IER) grasped by either suture knot varied from 0 to 12 mm, with 86% of repairs including the retinaculum. The results indicate that there is a relatively wide internervous and intertendinous safe zone when performing the Arthro

Development of an experimental model of neutrophilic pulmonary response induction in mice

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Leonardo Araújo Pinto

2003-08-01

Full Text Available BACKGROUND: Several lung diseases are characterized by a predominantly neutrophilic inflammation. A better understanding of the mechanisms of action of some drugs on the airway inflammation of such diseases may bring advances to the treatment. OBJECTIVE: To develop a method to induce pulmonary neutrophilic response in mice, without active infection. METHODS: Eight adult Swiss mice were used. The study group (n = 4 received an intranasal challenge with 1 x 10(12 CFU/ml of Pseudomonas aeruginosa (Psa, frozen to death. The control group (n = 4 received an intranasal challenge with saline solution. Two days after the intranasal challenge, a bron­choalveolar lavage (BAL was performed with total cell and differential cellularity counts. RESULTS: The total cell count was significantly higher in the group with Psa, as compared to the control group (median of 1.17 x 10(6 and 0.08 x 10(6, respectively, p = 0.029. In addition to this, an absolute predominance of neutrophils was found in the differential cellularity of the mice that had received the Psa challenge. CONCLUSIONS: The model of inducing a neutrophilic pulmonary disease using frost-dead bacteria was successfully developed. This neutrophilic inflammatory response induction model in Swiss mice lungs may be an important tool for testing the anti-inflammatory effect of some antimicrobial drugs on the inflammation of the lower airways.

SAP Suppresses the Development of Experimental Autoimmune Encephalomyelitis in C57BL6 Mice

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Ji, Zhe; Ke, Zun-Ji; Geng, Jian-Guo

2012-01-01

Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell-mediated disease of the CNS. Serum amyloid P component (SAP) is a highly conserved plasma protein named for its universal presence in amyloid deposits. Here we report SAP transgenic mice had unexpectedly attenuated EAE due to impaired encephalitogenic responses. Following induction with myelin oligodendroglial glycoprotein (MOG) peptide 35–55 in CFA, SAP transgenic mice showed reduced spinal cord inflammation with lower severity of EAE attacks as compared with control C57BL/6 mice. However in SAP-KO mice, the severity of EAE is enhanced. Adoptive transfer of Ag-restimulated T cells from wild-type to SAP transgenic mice or transfer of SAP transgenic Ag-restimulated T cells to control mice induced milder EAE. T cells from MOG-primed SAP transgenic mice showed weak proliferative responses. Furthermore, in SAP transgenic mice, there is little infiltration of CD45-positive cells in the spinal cord. In vitro, SAP suppressed the secretion of IL-2 stimulated by P-selectin, and blocked P-selectin binding to T cells. Moreover, SAP could change the affinity between α4-integrin and T cells. These data suggested that SAP could antagonize the development of the acute phase of inflammation accompanying EAE by modulating the function of P-selectin. PMID:21647172

Abnormal placental development and early embryonic lethality in EpCAM-null mice.

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Keisuke Nagao

Full Text Available BACKGROUND: EpCAM (CD326 is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells. METHODOLOGY/PRINCIPAL FINDINGS: To gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts, eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas. CONCLUSION: EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs.

Abnormal placental development and early embryonic lethality in EpCAM-null mice.

Science.gov (United States)

Nagao, Keisuke; Zhu, Jianjian; Heneghan, Mallorie B; Hanson, Jeffrey C; Morasso, Maria I; Tessarollo, Lino; Mackem, Susan; Udey, Mark C

2009-12-31

EpCAM (CD326) is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells. To gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts), eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas. EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs.

Determining customer satisfaction in anatomic pathology.

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Zarbo, Richard J

2006-05-01

Measurement of physicians' and patients' satisfaction with laboratory services has become a standard practice in the United States, prompted by national accreditation requirements. Unlike other surveys of hospital-, outpatient care-, or physician-related activities, no ongoing, comprehensive customer satisfaction survey of anatomic pathology services is available for subscription that would allow continual benchmarking against peer laboratories. Pathologists, therefore, must often design their own local assessment tools to determine physician satisfaction in anatomic pathology. To describe satisfaction survey design that would elicit specific information from physician customers about key elements of anatomic pathology services. The author shares his experience in biannually assessing customer satisfaction in anatomic pathology with survey tools designed at the Henry Ford Hospital, Detroit, Mich. Benchmarks for physician satisfaction, opportunities for improvement, and characteristics that correlated with a high level of physician satisfaction were identified nationally from a standardized survey tool used by 94 laboratories in the 2001 College of American Pathologists Q-Probes quality improvement program. In general, physicians are most satisfied with professional diagnostic services and least satisfied with pathology services related to poor communication. A well-designed and conducted customer satisfaction survey is an opportunity for pathologists to periodically educate physician customers about services offered, manage unrealistic expectations, and understand the evolving needs of the physician customer. Armed with current information from physician customers, the pathologist is better able to strategically plan for resources that facilitate performance improvements in anatomic pathology laboratory services that align with evolving clinical needs in health care delivery.

Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice

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Zhang, Pengpeng [Key Laboratory of Swine Genetics and Breeding, Ministry of Agriculture, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States); Shan, Tizhong; Liang, Xinrong [Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States); Deng, Changyan [Key Laboratory of Swine Genetics and Breeding, Ministry of Agriculture, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Kuang, Shihuan, E-mail: skuang@purdue.edu [Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States)

2014-09-12

Highlights: • mTOR is a critical regulator of many biological processes yet its function in heart is not well understood. • MCK-Cre/Mtor{sup flox/flox} mice were established to delete Mtor in cardiomyocytes. • The mTOR-mKO mice developed normally but die prematurely within 5 weeks after birth due to heart disease. • The mTOR-mKO mice had dilated myocardium and increased cell death. • mTOR-mKO hearts had reduced expression of metabolic genes and activation of mTOR target proteins. - Abstract: Mammalian target of rapamycin (mTOR) is a critical regulator of protein synthesis, cell proliferation and energy metabolism. As constitutive knockout of Mtor leads to embryonic lethality, the in vivo function of mTOR in perinatal development and postnatal growth of heart is not well defined. In this study, we established a muscle-specific mTOR conditional knockout mouse model (mTOR-mKO) by crossing MCK-Cre and Mtor{sup flox/flox} mice. Although the mTOR-mKO mice survived embryonic and perinatal development, they exhibited severe postnatal growth retardation, cardiac muscle pathology and premature death. At the cellular level, the cardiac muscle of mTOR-mKO mice had fewer cardiomyocytes due to apoptosis and necrosis, leading to dilated cardiomyopathy. At the molecular level, the cardiac muscle of mTOR-mKO mice expressed lower levels of fatty acid oxidation and glycolysis related genes compared to the WT littermates. In addition, the mTOR-mKO cardiac muscle had reduced Myh6 but elevated Myh7 expression, indicating cardiac muscle degeneration. Furthermore, deletion of Mtor dramatically decreased the phosphorylation of S6 and AKT, two key targets downstream of mTORC1 and mTORC2 mediating the normal function of mTOR. These results demonstrate that mTOR is essential for cardiomyocyte survival and cardiac muscle function.

IL-25 inhibits atherosclerosis development in apolipoprotein E deficient mice.

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Polyxeni T Mantani

Full Text Available IL-25 has been implicated in the initiation of type 2 immunity and in the protection against autoimmune inflammatory diseases. Recent studies have identified the novel innate lymphoid type 2 cells (ILC2s as an IL-25 target cell population. The purpose of this study was to evaluate if IL-25 has any influence on atherosclerosis development in mice.Administration of 1 μg IL-25 per day for one week to atherosclerosis-prone apolipoprotein (apoE deficient mice, had limited effect on the frequency of T cell populations, but resulted in a large expansion of ILC2s in the spleen. The expansion was accompanied by increased levels of anti-phosphorylcholine (PC natural IgM antibodies in plasma and elevated levels of IL-5 in plasma and spleen. Transfer of ILC2s to apoE deficient mice elevated the natural antibody-producing B1a cell population in the spleen. Treatment of apoE/Rag-1 deficient mice with IL-25 was also associated with extensive expansion of splenic ILC2s and increased plasma IL-5, suggesting ILC2s to be the source of IL-5. Administration of IL-25 in IL-5 deficient mice resulted in an expanded ILC2 population, but did not stimulate generation of anti-PC IgM, indicating that IL-5 is not required for ILC2 expansion but for the downstream production of natural antibodies. Additionally, administration of 1 μg IL-25 per day for 4 weeks in apoE deficient mice reduced atherosclerosis in the aorta both during initiation and progression of the disease.The present findings demonstrate that IL-25 has a protective role in atherosclerosis mediated by innate responses, including ILC2 expansion, increased IL-5 secretion, B1a expansion and natural anti-PC IgM generation, rather than adaptive Th2 responses.

Variability in coronary artery anatomy affects consistency of cardiac damage after myocardial infarction in mice.

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Chen, Jiqiu; Ceholski, Delaine K; Liang, Lifan; Fish, Kenneth; Hajjar, Roger J

2017-08-01

Low reliability and reproducibility in heart failure models are well established. The purpose of the present study is to explore factors that affect model consistency of myocardial infarction (MI) in mice. MI was induced by left coronary artery (LCA) ligation. The coronary artery was casted with resin and visualized with fluorescent imaging ex vivo. LCA characteristics and MI size were analyzed individually in each animal, and MI size was correlated with left ventricular (LV) function by echocardiography. Coronary anatomy varies widely in mice, posing challenges for surgical ligation and resulting in inconsistent MI size postligation. The length of coronary arterial trunk, level of bifurcation, number of branches, and territory supplied by these branches are unique in each animal. When the main LCA trunk is ligated, this results in a large MI, but when a single branch is ligated, MI size is variable due to differing levels of LCA ligation and area supplied by the branches. During the ligation procedure, nearly 40% of LCAs are not grossly visible to the surgeon. In these situations, the surgeon blindly sutures a wider and deeper area of tissue in an attempt to catch the LCA. Paradoxically, these situations have greater odds of resulting in smaller MIs. In conclusion, variation in MI size and LV function after LCA ligation in mice is difficult to avoid. Anatomic diversity of the LCA in mice leads to inconsistency in MI size and functional parameters, and this is independent of potential technical modifications made by the operator. NEW & NOTEWORTHY In the present study, we demonstrate that left coronary artery diversity in mice is one of the primary causes of variable myocardial infarction size and cardiac functional parameters in the left coronary artery ligation model. Recognition of anatomic diversity is essential to improve reliability and reproducibility in heart failure research. Copyright © 2017 the American Physiological Society.

Retrieving high-resolution images over the Internet from an anatomical image database

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Strupp-Adams, Annette; Henderson, Earl

1999-12-01

The Visible Human Data set is an important contribution to the national collection of anatomical images. To enhance the availability of these images, the National Library of Medicine has supported the design and development of a prototype object-oriented image database which imports, stores, and distributes high resolution anatomical images in both pixel and voxel formats. One of the key database modules is its client-server Internet interface. This Web interface provides a query engine with retrieval access to high-resolution anatomical images that range in size from 100KB for browser viewable rendered images, to 1GB for anatomical structures in voxel file formats. The Web query and retrieval client-server system is composed of applet GUIs, servlets, and RMI application modules which communicate with each other to allow users to query for specific anatomical structures, and retrieve image data as well as associated anatomical images from the database. Selected images can be downloaded individually as single files via HTTP or downloaded in batch-mode over the Internet to the user's machine through an applet that uses Netscape's Object Signing mechanism. The image database uses ObjectDesign's object-oriented DBMS, ObjectStore that has a Java interface. The query and retrieval systems has been tested with a Java-CDE window system, and on the x86 architecture using Windows NT 4.0. This paper describes the Java applet client search engine that queries the database; the Java client module that enables users to view anatomical images online; the Java application server interface to the database which organizes data returned to the user, and its distribution engine that allow users to download image files individually and/or in batch-mode.

Excessive Sensory Stimulation during Development Alters Neural Plasticity and Vulnerability to Cocaine in Mice.

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Ravinder, Shilpa; Donckels, Elizabeth A; Ramirez, Julian S B; Christakis, Dimitri A; Ramirez, Jan-Marino; Ferguson, Susan M

2016-01-01

Early life experiences affect the formation of neuronal networks, which can have a profound impact on brain function and behavior later in life. Previous work has shown that mice exposed to excessive sensory stimulation during development are hyperactive and novelty seeking, and display impaired cognition compared with controls. In this study, we addressed the issue of whether excessive sensory stimulation during development could alter behaviors related to addiction and underlying circuitry in CD-1 mice. We found that the reinforcing properties of cocaine were significantly enhanced in mice exposed to excessive sensory stimulation. Moreover, although these mice displayed hyperactivity that became more pronounced over time, they showed impaired persistence of cocaine-induced locomotor sensitization. These behavioral effects were associated with alterations in glutamatergic transmission in the nucleus accumbens and amygdala. Together, these findings suggest that excessive sensory stimulation in early life significantly alters drug reward and the neural circuits that regulate addiction and attention deficit hyperactivity. These observations highlight the consequences of early life experiences and may have important implications for children growing up in today's complex technological environment.

Nodule detection in digital chest radiography: Effect of anatomical noise

International Nuclear Information System (INIS)

Baath, M.; Haakansson, M.; Boerjesson, S.; Hoeschen, C.; Tischenko, O.; Kheddache, S.; Vikgren, J.; Maansson, L. G.

2005-01-01

The image background resulting from imaged anatomy can be divided into those components that are meaningful to the observers, in the sense that they are recognised as separate structures, and those that are not. These latter components (referred to as anatomical noise) can be removed using a method developed within the RADIUS group. The aim of the present study was to investigate whether the removal of the anatomical noise results in images where lung nodules with lower contrast can be detected. A receiver operating characteristic (ROC) study was therefore conducted using two types of images: clinical chest images and chest images in which the anatomical noise had been removed. Simulated designer nodules with a full-width-at-fifth-maximum of 10 mm but with varying contrast were added to the images. The contrast needed to obtain an area under the ROC curve of 0.80, C0.8, was used as a measure of detectability (a low value of C0.8 represents a high delectability). Five regions of the chest X ray were investigated and it was found that in all regions the removal of anatomical noise led to images with lower C0.8 than the original images. On average, C0.8 was 20% higher in the original images, ranging from 7% (the lateral pulmonary regions) to 41% (the upper mediastinal regions). (authors)

Food restriction by intermittent fasting induces diabetes and obesity and aggravates spontaneous atherosclerosis development in hypercholesterolaemic mice.

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Dorighello, Gabriel G; Rovani, Juliana C; Luhman, Christopher J F; Paim, Bruno A; Raposo, Helena F; Vercesi, Anibal E; Oliveira, Helena C F

2014-03-28

Different regimens of food restriction have been associated with protection against obesity, diabetes and CVD. In the present study, we hypothesised that food restriction would bring benefits to atherosclerosis- and diabetes-prone hypercholesterolaemic LDL-receptor knockout mice. For this purpose, 2-month-old mice were submitted to an intermittent fasting (IF) regimen (fasting every other day) over a 3-month period, which resulted in an overall 20 % reduction in food intake. Contrary to our expectation, epididymal and carcass fat depots and adipocyte size were significantly enlarged by 15, 72 and 68 %, respectively, in the IF mice compared with the ad libitum-fed mice. Accordingly, plasma levels of leptin were 50 % higher in the IF mice than in the ad libitum-fed mice. In addition, the IF mice showed increased plasma levels of total cholesterol (37 %), VLDL-cholesterol (195 %) and LDL-cholesterol (50 %). As expected, in wild-type mice, the IF regimen decreased plasma cholesterol levels and epididymal fat mass. Glucose homeostasis was also disturbed by the IF regimen in LDL-receptor knockout mice. Elevated levels of glycaemia (40 %), insulinaemia (50 %), glucose intolerance and insulin resistance were observed in the IF mice. Systemic inflammatory markers, TNF-α and C-reactive protein, were significantly increased and spontaneous atherosclerosis development were markedly increased (3-fold) in the IF mice. In conclusion, the IF regimen induced obesity and diabetes and worsened the development of spontaneous atherosclerosis in LDL-receptor knockout mice. Although being efficient in a wild-type background, this type of food restriction is not beneficial in the context of genetic hypercholesterolaemia.

Interpreting and Integrating Clinical and Anatomic Pathology Results.

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Ramaiah, Lila; Hinrichs, Mary Jane; Skuba, Elizabeth V; Iverson, William O; Ennulat, Daniela

2017-01-01

The continuing education course on integrating clinical and anatomical pathology data was designed to communicate the importance of using a weight of evidence approach to interpret safety findings in toxicology studies. This approach is necessary, as neither clinical nor anatomic pathology data can be relied upon in isolation to fully understand the relationship between study findings and the test article. Basic principles for correlating anatomic pathology and clinical pathology findings and for integrating these with other study end points were reviewed. To highlight these relationships, a series of case examples, presented jointly by a clinical pathologist and an anatomic pathologist, were used to illustrate the collaborative effort required between clinical and anatomical pathologists. In addition, the diagnostic utility of traditional liver biomarkers was discussed using results from a meta-analysis of rat hepatobiliary marker and histopathology data. This discussion also included examples of traditional and novel liver and renal biomarker data implementation in nonclinical toxicology studies to illustrate the relationship between discrete changes in biochemistry and tissue morphology.

Anatomical and palynological characteristics of Salvia willeana ...

African Journals Online (AJOL)

In this study, anatomical and palynological features of the roots, stems, petiole and leaves of Salvia willeana (Holmboe) Hedge and Salvia veneris Hedge, Salvia species endemic to Cyprus, were investigated. In the anatomical characteristics of stem structures, it was found that the chlorenchyma composed of 6 or 7 rows of ...

Organ specific mapping of in vivo redox state in control and cigarette smoke-exposed mice using EPR/NMR co-imaging

Science.gov (United States)

Caia, George L.; Efimova, Olga V.; Velayutham, Murugesan; El-Mahdy, Mohamed A.; Abdelghany, Tamer M.; Kesselring, Eric; Petryakov, Sergey; Sun, Ziqi; Samouilov, Alexandre; Zweier, Jay L.

2014-01-01

In vivo mapping of alterations in redox status is important for understanding organ specific pathology and disease. While electron paramagnetic resonance imaging (EPRI) enables spatial mapping of free radicals, it does not provide anatomic visualization of the body. Proton MRI is well suited to provide anatomical visualization. We applied EPR/NMR co-imaging instrumentation to map and monitor the redox state of living mice under normal or oxidative stress conditions induced by secondhand cigarette smoke (SHS) exposure. A hybrid co-imaging instrument, EPRI (1.2 GHz) / proton MRI (16.18 MHz), suitable for whole-body co-imaging of mice was utilized with common magnet and gradients along with dual EPR/NMR resonators that enable co-imaging without sample movement. The metabolism of the nitroxide probe, 3–carbamoyl–proxyl (3-CP), was used to map the redox state of control and SHS-exposed mice. Co-imaging allowed precise 3D mapping of radical distribution and reduction in major organs such as the heart, lungs, liver, bladder and kidneys. Reductive metabolism was markedly decreased in SHS-exposed mice and EPR/NMR co-imaging allowed quantitative assessment of this throughout the body. Thus, in vivo EPR/NMR co-imaging enables in vivo organ specific mapping of free radical metabolism and redox stress and the alterations that occur in the pathogenesis of disease. PMID:22296801

Standards to support information systems integration in anatomic pathology.

Science.gov (United States)

Daniel, Christel; García Rojo, Marcial; Bourquard, Karima; Henin, Dominique; Schrader, Thomas; Della Mea, Vincenzo; Gilbertson, John; Beckwith, Bruce A

2009-11-01

Integrating anatomic pathology information- text and images-into electronic health care records is a key challenge for enhancing clinical information exchange between anatomic pathologists and clinicians. The aim of the Integrating the Healthcare Enterprise (IHE) international initiative is precisely to ensure interoperability of clinical information systems by using existing widespread industry standards such as Digital Imaging and Communication in Medicine (DICOM) and Health Level Seven (HL7). To define standard-based informatics transactions to integrate anatomic pathology information to the Healthcare Enterprise. We used the methodology of the IHE initiative. Working groups from IHE, HL7, and DICOM, with special interest in anatomic pathology, defined consensual technical solutions to provide end-users with improved access to consistent information across multiple information systems. The IHE anatomic pathology technical framework describes a first integration profile, "Anatomic Pathology Workflow," dedicated to the diagnostic process including basic image acquisition and reporting solutions. This integration profile relies on 10 transactions based on HL7 or DICOM standards. A common specimen model was defined to consistently identify and describe specimens in both HL7 and DICOM transactions. The IHE anatomic pathology working group has defined standard-based informatics transactions to support the basic diagnostic workflow in anatomic pathology laboratories. In further stages, the technical framework will be completed to manage whole-slide images and semantically rich structured reports in the diagnostic workflow and to integrate systems used for patient care and those used for research activities (such as tissue bank databases or tissue microarrayers).

Development of Schistosoma incognitum in mice upon intraperitoneal inoculation with irradiated schistosomula

International Nuclear Information System (INIS)

Bhilegaonkar, N.G.; Sahasrabudhe, V.K.

1987-01-01

As a prelude to the study of the immunizing potential of gamma-irradiated Schistosoma incognitum schistosomula, experiments were conducted to study the effect of different doses of gamma irradiation (1,3,5 and 10 kr) on the development and survival of S. incognitum in mice, and its attendant pathology. The present experiments suggested that 3 and 5 kr irradiation doses can be safely used for irradiating schistosomula for immunization experiments in mice as the worms will not mature and therefore no harm will be caused which is mainly due to the eggs. (author). 7 refs

Benchmarking Academic Anatomic Pathologists

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Barbara S. Ducatman MD

2016-10-01

Full Text Available The most common benchmarks for faculty productivity are derived from Medical Group Management Association (MGMA or Vizient-AAMC Faculty Practice Solutions Center ® (FPSC databases. The Association of Pathology Chairs has also collected similar survey data for several years. We examined the Association of Pathology Chairs annual faculty productivity data and compared it with MGMA and FPSC data to understand the value, inherent flaws, and limitations of benchmarking data. We hypothesized that the variability in calculated faculty productivity is due to the type of practice model and clinical effort allocation. Data from the Association of Pathology Chairs survey on 629 surgical pathologists and/or anatomic pathologists from 51 programs were analyzed. From review of service assignments, we were able to assign each pathologist to a specific practice model: general anatomic pathologists/surgical pathologists, 1 or more subspecialties, or a hybrid of the 2 models. There were statistically significant differences among academic ranks and practice types. When we analyzed our data using each organization’s methods, the median results for the anatomic pathologists/surgical pathologists general practice model compared to MGMA and FPSC results for anatomic and/or surgical pathology were quite close. Both MGMA and FPSC data exclude a significant proportion of academic pathologists with clinical duties. We used the more inclusive FPSC definition of clinical “full-time faculty” (0.60 clinical full-time equivalent and above. The correlation between clinical full-time equivalent effort allocation, annual days on service, and annual work relative value unit productivity was poor. This study demonstrates that effort allocations are variable across academic departments of pathology and do not correlate well with either work relative value unit effort or reported days on service. Although the Association of Pathology Chairs–reported median work relative

Anatomic partial nephrectomy: technique evolution.

Science.gov (United States)

Azhar, Raed A; Metcalfe, Charles; Gill, Inderbir S

2015-03-01

Partial nephrectomy provides equivalent long-term oncologic and superior functional outcomes as radical nephrectomy for T1a renal masses. Herein, we review the various vascular clamping techniques employed during minimally invasive partial nephrectomy, describe the evolution of our partial nephrectomy technique and provide an update on contemporary thinking about the impact of ischemia on renal function. Recently, partial nephrectomy surgical technique has shifted away from main artery clamping and towards minimizing/eliminating global renal ischemia during partial nephrectomy. Supported by high-fidelity three-dimensional imaging, novel anatomic-based partial nephrectomy techniques have recently been developed, wherein partial nephrectomy can now be performed with segmental, minimal or zero global ischemia to the renal remnant. Sequential innovations have included early unclamping, segmental clamping, super-selective clamping and now culminating in anatomic zero-ischemia surgery. By eliminating 'under-the-gun' time pressure of ischemia for the surgeon, these techniques allow an unhurried, tightly contoured tumour excision with point-specific sutured haemostasis. Recent data indicate that zero-ischemia partial nephrectomy may provide better functional outcomes by minimizing/eliminating global ischemia and preserving greater vascularized kidney volume. Contemporary partial nephrectomy includes a spectrum of surgical techniques ranging from conventional-clamped to novel zero-ischemia approaches. Technique selection should be tailored to each individual case on the basis of tumour characteristics, surgical feasibility, surgeon experience, patient demographics and baseline renal function.

Development of a rabbit's urethral sphincter deficiency animal model for anatomical-functional evaluation

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M. Skaff

2012-02-01

Full Text Available OBJECTIVE: The aim of the study was to develop a new durable animal model (using rabbits for anatomical-functional evaluation of urethral sphincter deficiency. MATERIALS AND METHODS: A total of 40 New Zealand male rabbits, weighting 2.500 kg to 3.100 kg, were evaluated to develop an incontinent animal model. Thirty-two animals underwent urethrolysis and 8 animals received sham operation. Before and at 2, 4, 8 and 12 weeks after urethrolysis or sham operation, it was performed cystometry and leak point pressure (LPP evaluation with different bladder distension volumes (10, 20, 30 mL. In each time point, 10 animals (8 from the study group and 2 from the sham group were sacrificed to harvest the bladder and urethra. The samples were evaluated by H&E and Masson's Trichrome to determine urethral morphology and collagen/smooth muscle density. RESULTS: Twelve weeks after urethrolysis, it was observed a significant decrease in LPP regardless the bladder volume (from 33.7 ± 6.6 to 12.8 ± 2.2 cmH2O. The histological analysis evidenced a decrease of 22% in smooth muscle density with a proportional increase in the collagen, vessels and elastin density (p < 0.01. CONCLUSIONS: Transabdominal urethrolysis develops urethral sphincter insufficiency in rabbits, with significant decrease in LPP associated with decrease of smooth muscle fibers and increase of collagen density. This animal model can be used to test autologous cell therapy for stress urinary incontinence treatment.

Exploring the human body space: A geographical information system based anatomical atlas

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Antonio Barbeito

2016-06-01

Full Text Available Anatomical atlases allow mapping the anatomical structures of the human body. Early versions of these systems consisted of analogical representations with informative text and labeled images of the human body. With computer systems, digital versions emerged and the third and fourth dimensions were introduced. Consequently, these systems increased their efficiency, allowing more realistic visualizations with improved interactivity and functionality. The 4D atlases allow modeling changes over time on the structures represented. The anatomical atlases based on geographic information system (GIS environments allow the creation of platforms with a high degree of interactivity and new tools to explore and analyze the human body. In this study we expand the functions of a human body representation system by creating new vector data, topology, functions, and an improved user interface. The new prototype emulates a 3D GIS with a topological model of the human body, replicates the information provided by anatomical atlases, and provides a higher level of functionality and interactivity. At this stage, the developed system is intended to be used as an educational tool and integrates into the same interface the typical representations of surface and sectional atlases.

Development of anatomically and dielectrically accurate breast phantoms for microwave imaging applications

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O'Halloran, M.; Lohfeld, S.; Ruvio, G.; Browne, J.; Krewer, F.; Ribeiro, C. O.; Inacio Pita, V. C.; Conceicao, R. C.; Jones, E.; Glavin, M.

2014-05-01

Breast cancer is one of the most common cancers in women. In the United States alone, it accounts for 31% of new cancer cases, and is second only to lung cancer as the leading cause of deaths in American women. More than 184,000 new cases of breast cancer are diagnosed each year resulting in approximately 41,000 deaths. Early detection and intervention is one of the most significant factors in improving the survival rates and quality of life experienced by breast cancer sufferers, since this is the time when treatment is most effective. One of the most promising breast imaging modalities is microwave imaging. The physical basis of active microwave imaging is the dielectric contrast between normal and malignant breast tissue that exists at microwave frequencies. The dielectric contrast is mainly due to the increased water content present in the cancerous tissue. Microwave imaging is non-ionizing, does not require breast compression, is less invasive than X-ray mammography, and is potentially low cost. While several prototype microwave breast imaging systems are currently in various stages of development, the design and fabrication of anatomically and dielectrically representative breast phantoms to evaluate these systems is often problematic. While some existing phantoms are composed of dielectrically representative materials, they rarely accurately represent the shape and size of a typical breast. Conversely, several phantoms have been developed to accurately model the shape of the human breast, but have inappropriate dielectric properties. This study will brie y review existing phantoms before describing the development of a more accurate and practical breast phantom for the evaluation of microwave breast imaging systems.

Increased cortical-limbic anatomical network connectivity in major depression revealed by diffusion tensor imaging.

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Peng Fang

Full Text Available Magnetic resonance imaging studies have reported significant functional and structural differences between depressed patients and controls. Little attention has been given, however, to the abnormalities in anatomical connectivity in depressed patients. In the present study, we aim to investigate the alterations in connectivity of whole-brain anatomical networks in those suffering from major depression by using machine learning approaches. Brain anatomical networks were extracted from diffusion magnetic resonance images obtained from both 22 first-episode, treatment-naive adults with major depressive disorder and 26 matched healthy controls. Using machine learning approaches, we differentiated depressed patients from healthy controls based on their whole-brain anatomical connectivity patterns and identified the most discriminating features that represent between-group differences. Classification results showed that 91.7% (patients=86.4%, controls=96.2%; permutation test, p<0.0001 of subjects were correctly classified via leave-one-out cross-validation. Moreover, the strengths of all the most discriminating connections were increased in depressed patients relative to the controls, and these connections were primarily located within the cortical-limbic network, especially the frontal-limbic network. These results not only provide initial steps toward the development of neurobiological diagnostic markers for major depressive disorder, but also suggest that abnormal cortical-limbic anatomical networks may contribute to the anatomical basis of emotional dysregulation and cognitive impairments associated with this disease.

The linguistic roots of Modern English anatomical terminology.

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Turmezei, Tom D

2012-11-01

Previous research focusing on Classical Latin and Greek roots has shown that understanding the etymology of English anatomical terms may be beneficial for students of human anatomy. However, not all anatomical terms are derived from Classical origins. This study aims to explore the linguistic roots of the Modern English terminology used in human gross anatomy. By reference to the Oxford English Dictionary, etymologies were determined for a lexicon of 798 Modern English gross anatomical terms from the 40(th) edition of Gray's Anatomy. Earliest traceable language of origin was determined for all 798 terms; language of acquisition was determined for 747 terms. Earliest traceable languages of origin were: Classical Latin (62%), Classical Greek (24%), Old English (7%), Post-Classical Latin (3%), and other (4%). Languages of acquisition were: Classical Latin (42%), Post-Classical Latin (29%), Old English (8%), Modern French (6%), Classical Greek (5%), Middle English (3%), and other (7%). While the roots of Modern English anatomical terminology mostly lie in Classical languages (accounting for the origin of 86% of terms), the anatomical lexicon of Modern English is actually much more diverse. Interesting and perhaps less familiar examples from these languages and the methods by which such terms have been created and absorbed are discussed. The author suggests that awareness of anatomical etymologies may enhance the enjoyment and understanding of human anatomy for students and teachers alike. Copyright © 2012 Wiley Periodicals, Inc.

Prenatal exposure to fenugreek impairs sensorimotor development and the operation of spinal cord networks in mice.

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Loubna Khalki

Full Text Available Fenugreek is a medicinal plant whose seeds are widely used in traditional medicine, mainly for its laxative, galactagogue and antidiabetic effects. However, consumption of fenugreek seeds during pregnancy has been associated with a range of congenital malformations, including hydrocephalus, anencephaly and spina bifida in humans. The present study was conducted to evaluate the effects of prenatal treatment of fenugreek seeds on the development of sensorimotor functions from birth to young adults. Pregnant mice were treated by gavage with 1 g/kg/day of lyophilized fenugreek seeds aqueous extract (FSAE or distilled water during the gestational period. Behavioral tests revealed in prenatally treated mice a significant delay in righting, cliff avoidance, negative geotaxis responses and the swimming development. In addition, extracellular recording of motor output in spinal cord isolated from neonatal mice showed that the frequency of spontaneous activity and fictive locomotion was reduced in FSAE-exposed mice. On the other hand, the cross-correlation coefficient in control mice was significantly more negative than in treated animals indicating that alternating patterns are deteriorated in FSAE-treated animals. At advanced age, prenatally treated mice displayed altered locomotor coordination in the rotarod test and also changes in static and dynamic parameters assessed by the CatWalk automated gait analysis system. We conclude that FSAE impairs sensorimotor and coordination functions not only in neonates but also in adult mice. Moreover, spinal neuronal networks are less excitable in prenatally FSAE-exposed mice suggesting that modifications within the central nervous system are responsible, at least in part, for the motor impairments.

Anatomical influences on internally coupled ears in reptiles.

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Young, Bruce A

2016-10-01

Many reptiles, and other vertebrates, have internally coupled ears in which a patent anatomical connection allows pressure waves generated by the displacement of one tympanic membrane to propagate (internally) through the head and, ultimately, influence the displacement of the contralateral tympanic membrane. The pattern of tympanic displacement caused by this internal coupling can give rise to novel sensory cues. The auditory mechanics of reptiles exhibit more anatomical variation than in any other vertebrate group. This variation includes structural features such as diverticula and septa, as well as coverings of the tympanic membrane. Many of these anatomical features would likely influence the functional significance of the internal coupling between the tympanic membranes. Several of the anatomical components of the reptilian internally coupled ear are under active motor control, suggesting that in some reptiles the auditory system may be more dynamic than previously recognized.

Aldosterone Inhibits the Fetal Program and Increases Hypertrophy in the Heart of Hypertensive Mice

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Azibani, Feriel; Devaux, Yvan; Coutance, Guillaume; Schlossarek, Saskia; Polidano, Evelyne; Fazal, Loubina; Merval, Regine; Carrier, Lucie; Solal, Alain Cohen; Chatziantoniou, Christos; Launay, Jean-Marie; Samuel, Jane-Lise; Delcayre, Claude

2012-01-01

Background Arterial hypertension (AH) induces cardiac hypertrophy and reactivation of “fetal” gene expression. In rodent heart, alpha-Myosin Heavy Chain (MyHC) and its micro-RNA miR-208a regulate the expression of beta-MyHC and of its intronic miR-208b. However, the role of aldosterone in these processes remains unclear. Methodology/Principal Findings RT-PCR and western-blot were used to investigate the genes modulated by arterial hypertension and cardiac hyperaldosteronism. We developed a model of double-transgenic mice (AS-Ren) with cardiac hyperaldosteronism (AS mice) and systemic hypertension (Ren). AS-Ren mice had increased (x2) angiotensin II in plasma and increased (x2) aldosterone in heart. Ren and AS-Ren mice had a robust and similar hypertension (+70%) versus their controls. Anatomical data and echocardiography showed a worsening of cardiac hypertrophy (+41%) in AS-Ren mice (P<0.05 vs Ren). The increase of ANP (x 2.5; P<0.01) mRNA observed in Ren mice was blunted in AS-Ren mice. This non-induction of antitrophic natriuretic peptides may be involved in the higher trophic cardiac response in AS-Ren mice, as indicated by the markedly reduced cardiac hypertrophy in ANP-infused AS-Ren mice for one month. Besides, the AH-induced increase of ßMyHC and its intronic miRNA-208b was prevented in AS-Ren. The inhibition of miR 208a (−75%, p<0.001) in AS-Ren mice compared to AS was associated with increased Sox 6 mRNA (x 1.34; p<0.05), an inhibitor of ßMyHC transcription. Eplerenone prevented all aldosterone-dependent effects. Conclusions/Significance Our results indicate that increased aldosterone in heart inhibits the induction of atrial natriuretic peptide expression, via the mineralocorticoid receptor. This worsens cardiac hypertrophy without changing blood pressure. Moreover, this work reveals an original aldosterone-dependent inhibition of miR-208a in hypertension, resulting in the inhibition of β-myosin heavy chain expression through the induction of

Aldosterone inhibits the fetal program and increases hypertrophy in the heart of hypertensive mice.

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Feriel Azibani

Full Text Available BACKGROUND: Arterial hypertension (AH induces cardiac hypertrophy and reactivation of "fetal" gene expression. In rodent heart, alpha-Myosin Heavy Chain (MyHC and its micro-RNA miR-208a regulate the expression of beta-MyHC and of its intronic miR-208b. However, the role of aldosterone in these processes remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: RT-PCR and western-blot were used to investigate the genes modulated by arterial hypertension and cardiac hyperaldosteronism. We developed a model of double-transgenic mice (AS-Ren with cardiac hyperaldosteronism (AS mice and systemic hypertension (Ren. AS-Ren mice had increased (x2 angiotensin II in plasma and increased (x2 aldosterone in heart. Ren and AS-Ren mice had a robust and similar hypertension (+70% versus their controls. Anatomical data and echocardiography showed a worsening of cardiac hypertrophy (+41% in AS-Ren mice (P<0.05 vs Ren. The increase of ANP (x 2.5; P<0.01 mRNA observed in Ren mice was blunted in AS-Ren mice. This non-induction of antitrophic natriuretic peptides may be involved in the higher trophic cardiac response in AS-Ren mice, as indicated by the markedly reduced cardiac hypertrophy in ANP-infused AS-Ren mice for one month. Besides, the AH-induced increase of ßMyHC and its intronic miRNA-208b was prevented in AS-Ren. The inhibition of miR 208a (-75%, p<0.001 in AS-Ren mice compared to AS was associated with increased Sox 6 mRNA (x 1.34; p<0.05, an inhibitor of ßMyHC transcription. Eplerenone prevented all aldosterone-dependent effects. CONCLUSIONS/SIGNIFICANCE: Our results indicate that increased aldosterone in heart inhibits the induction of atrial natriuretic peptide expression, via the mineralocorticoid receptor. This worsens cardiac hypertrophy without changing blood pressure. Moreover, this work reveals an original aldosterone-dependent inhibition of miR-208a in hypertension, resulting in the inhibition of β-myosin heavy chain expression through the induction

Perceptions of science. The anatomical mission to Burma.

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Sappol, Michael

2003-10-10

Until the 1830s, most Americans were unfamiliar with the images of anatomy. Then a small vanguard of reformers and missionaries began to preach, at home and around the world, that an identification with the images and concepts of anatomy was a crucial part of the civilizing process. In his essay, Sappol charts the changes in the perception of self that resulted from this anatomical evangelism. Today, as anatomical images abound in the arts and the media, we still believe that anatomical images show us our inner reality.

Evaluation of influences of the Viennese Anatomical School on the work of the Croatian Anatomist Jelena Krmpotic-Nemanic.

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Dinjar, Kristijan; Toth, Jurica; Atalic, Bruno; Radanovic, Danijela; Maric, Svjetlana

2012-01-01

This paper tries to evaluate the connections between the Viennese Anatomical School and the Croatian Anatomist Jelena Krmpotic-Nemanic. 17 papers written by Professor Jelena Krmpotic-Nemanic in the last decade of her life were chosen for analyses. According to their themes they could be divided into three groups: ones which evaluate the anatomical terminology, ones which research the development of anatomical structures, and ones which describe the anatomical variations. Mentioned papers were analysed through their topics, methods of research and cited references. Analyses of the mentioned papers revealed the indirect link between the Viennese Anatomical School and the Professor Jelena Krmpotic-Nemanic, through her mentor Professor Drago Perovic, regarding the themes and the methods of her anatomical researches. It has also showed her preference for Austrian and German anatomical textbooks and atlases, primarily ones published in Vienna and Jena, rather than English and American ones. Finally, her direct connections with the Viennese Institute for the History of Medicine and the Viennese Josephinum Wax Models Museum were emphasized. Mentioned indirect and direct influences of the Viennese Anatomical School on the work of Professor Jelena Krmpotic-Nemanic were critically appraised.

Zinc Prevents the Development of Diabetic Cardiomyopathy in db/db Mice

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Shudong Wang

2017-03-01

Full Text Available Diabetic cardiomyopathy (DCM is highly prevalent in type 2 diabetes (T2DM patients. Zinc is an important essential trace metal, whose deficiency is associated with various chronic ailments, including vascular diseases. We assessed T2DM B6.BKS(D-Leprdb/J (db/db mice fed for six months on a normal diet containing three zinc levels (deficient, adequate, and supplemented, to explore the role of zinc in DCM development and progression. Cardiac function, reflected by ejection fraction, was significantly decreased, along with increased left ventricle mass and heart weight to tibial length ratio, in db/db mice. As a molecular cardiac hypertrophy marker, atrial natriuretic peptide levels were also significantly increased. Cardiac dysfunction and hypertrophy were accompanied by significantly increased fibrotic (elevated collagen accumulation as well as transforming growth factor β and connective tissue growth factor levels and inflammatory (enhanced expression of tumor necrosis factor alpha, interleukin-1β, caspase recruitment domain family member 9, and B-cell lymphoma/leukemia 10, and activated p38 mitogen-activated protein kinase responses in the heart. All these diabetic effects were exacerbated by zinc deficiency, and not affected by zinc supplementation, respectively. Mechanistically, oxidative stress and damage, mirrored by the accumulation of 3-nitrotyrosine and 4-hydroxy-2-nonenal, was significantly increased along with significantly decreased expression of Nrf2 and its downstream antioxidants (NQO-1 and catalase. This was also exacerbated by zinc deficiency in the db/db mouse heart. These results suggested that zinc deficiency promotes the development and progression of DCM in T2DM db/db mice. The exacerbated effects by zinc deficiency on the heart of db/db mice may be related to further suppression of Nrf2 expression and function.

Development of infection with Streptococcus bovis and Aspergillus sp. in irradiated mice after glycopeptide therapy

International Nuclear Information System (INIS)

Brook, I.; Tom, S.P.; Ledney, G.D.

1993-01-01

The use of ofloxacin and glycopeptides was evaluated for the treatment of infections arising in C3H/HeN female mice irradiated with 8.3 Gy from a 60 Co source. The 21 day regimen began 72 h after irradiation when each of five sets of experimental animals received three antimicrobial therapy regimens and a saline-treated control group. With 40 mice in each group, 20 were used to monitor survival, 20 for the recovery of bacteria from the liver culture. Treatment groups were oral ofloxacin; oral or intramuscular vancomycin oral teicoplanin, ofloxacin and vancomycin; ofloxacin and teicoplanin; or saline. Bacteria recovered from saline treated mice were Enterobacteriaceae and Streptococcus spp. By comparison, fewer Enterobacteriaceae were isolated from ofloxacin treated mice and fewer Streptococcus spp. in both vancomycin and teicoplanin treated mice. However, glycopeptide-treated mice developed infection with Aspergillis fumigatus and glycopeptide resistant Streptococcus bovis. Mortality rates within 60 days of irradiation were 100% in all treatment and control groups with the exception of ofloxacin which was 25%-35%. These data suggest that glycopeptide therapy increases rates of systemic infection with fungi and antibiotic resistant bacteria in irradiated mice. (Author)

Development of infection with Streptococcus bovis and Aspergillus sp. in irradiated mice after glycopeptide therapy

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Brook, I.; Tom, S.P.; Ledney, G.D. (Armed Forces Radiobiology Research Inst., Bethesda, MD (United States))

1993-11-01

The use of ofloxacin and glycopeptides was evaluated for the treatment of infections arising in C3H/HeN female mice irradiated with 8.3 Gy from a [sup 60]Co source. The 21 day regimen began 72 h after irradiation when each of five sets of experimental animals received three antimicrobial therapy regimens and a saline-treated control group. With 40 mice in each group, 20 were used to monitor survival, 20 for the recovery of bacteria from the liver culture. Treatment groups were oral ofloxacin; oral or intramuscular vancomycin oral teicoplanin, ofloxacin and vancomycin; ofloxacin and teicoplanin; or saline. Bacteria recovered from saline treated mice were Enterobacteriaceae and Streptococcus spp. By comparison, fewer Enterobacteriaceae were isolated from ofloxacin treated mice and fewer Streptococcus spp. in both vancomycin and teicoplanin treated mice. However, glycopeptide-treated mice developed infection with Aspergillis fumigatus and glycopeptide resistant Streptococcus bovis. Mortality rates within 60 days of irradiation were 100% in all treatment and control groups with the exception of ofloxacin which was 25%-35%. These data suggest that glycopeptide therapy increases rates of systemic infection with fungi and antibiotic resistant bacteria in irradiated mice. (Author).

Effects of a 4.7 T static magnetic field on fetal development in ICR mice

International Nuclear Information System (INIS)

Okazaki, Ryuji; Ootsuyama, Akira; Uchida, Soshi; Norimura, Toshiyuki

2001-01-01

In order to determine the effects of a 4.7 T static magnetic field (SMF) on fetal development in mice, we evaluated fetal teratogenesis and endochondral ossification following exposure in utero. Pregnant ICR mice were exposed to a 4.7 T SMF from day 7.5 to 9.5 of gestation in a whole-body dose, and sacrificed on day 18.5 of gestation. We examined with incidence of prenatal death, external malformations and fetal skeletal malformations. There were no significant differences observed in the incidence of prenatal death and/or malformations between SMF-exposed mice and control mice. Further, we evaluated the immunoreactivity for the vascular endothelial growth factor (VEGF), which is implicated in angiogenesis and osteogenesis, in the sternum of fetal mice following magnetic exposure. Our studies also indicated that on day 16.5 of gestation following SMF exposure, the immunoreactivity for VEGF was increased compared to unexposed controls. However, it was decreased in the exposed group compared to the control group on day 18.5 of gestation. DNA and proteoglycan (PG) synthesis were also measured in rabbit costal growth plate chondrocytes in vitro. No significant differences were observed in DNA synthesis between the SMF exposed chondrocytes and the control chondrocytes; however, PG synthesis in SMF exposed chondrocytes increased compared to the controls. Based on these results, we suggest that while SMF exposure promoted the endochondral ossification of chondrocytes, it did not induce any harmful effects on fetal development in ICR mice. (author)

Effects of a 4.7 T static magnetic field on fetal development in ICR mice

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Okazaki, Ryuji; Ootsuyama, Akira; Uchida, Soshi; Norimura, Toshiyuki [Univ. of Occupational and Environmental Health, Kitakyushu, Fukuoka (Japan). School of Medicine

2001-09-01

In order to determine the effects of a 4.7 T static magnetic field (SMF) on fetal development in mice, we evaluated fetal teratogenesis and endochondral ossification following exposure in utero. Pregnant ICR mice were exposed to a 4.7 T SMF from day 7.5 to 9.5 of gestation in a whole-body dose, and sacrificed on day 18.5 of gestation. We examined with incidence of prenatal death, external malformations and fetal skeletal malformations. There were no significant differences observed in the incidence of prenatal death and/or malformations between SMF-exposed mice and control mice. Further, we evaluated the immunoreactivity for the vascular endothelial growth factor (VEGF), which is implicated in angiogenesis and osteogenesis, in the sternum of fetal mice following magnetic exposure. Our studies also indicated that on day 16.5 of gestation following SMF exposure, the immunoreactivity for VEGF was increased compared to unexposed controls. However, it was decreased in the exposed group compared to the control group on day 18.5 of gestation. DNA and proteoglycan (PG) synthesis were also measured in rabbit costal growth plate chondrocytes in vitro. No significant differences were observed in DNA synthesis between the SMF exposed chondrocytes and the control chondrocytes; however, PG synthesis in SMF exposed chondrocytes increased compared to the controls. Based on these results, we suggest that while SMF exposure promoted the endochondral ossification of chondrocytes, it did not induce any harmful effects on fetal development in ICR mice. (author)

Uniportal anatomic combined unusual segmentectomies.

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González-Rivas, Diego; Lirio, Francisco; Sesma, Julio

2017-01-01

Nowadays, sublobar anatomic resections are gaining momentum as a valid alternative for early stage lung cancer. Despite being technically demanding, anatomic segmentectomies can be performed by uniportal video-assisted thoracic surgery (VATS) approach to combine the benefits of minimally invasiveness with the maximum lung sparing. This procedure can be even more complex if a combined resection of multiple segments from different lobes has to be done. Here we report five cases of combined and unusual segmentectomies done by the same experienced surgeon in high volume institutions to show uniportal VATS is a feasible approach for these complex resections and to share an excellent educational resource.

Human reconstructed skin xenografts on mice to model skin physiology.

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Salgado, Giorgiana; Ng, Yi Zhen; Koh, Li Fang; Goh, Christabelle S M; Common, John E

Xenograft models to study skin physiology have been popular for scientific use since the 1970s, with various developments and improvements to the techniques over the decades. Xenograft models are particularly useful and sought after due to the lack of clinically relevant animal models in predicting drug effectiveness in humans. Such predictions could in turn boost the process of drug discovery, since novel drug compounds have an estimated 8% chance of FDA approval despite years of rigorous preclinical testing and evaluation, albeit mostly in non-human models. In the case of skin research, the mouse persists as the most popular animal model of choice, despite its well-known anatomical differences with human skin. Differences in skin biology are especially evident when trying to dissect more complex skin conditions, such as psoriasis and eczema, where interactions between the immune system, epidermis and the environment likely occur. While the use of animal models are still considered the gold standard for systemic toxicity studies under controlled environments, there are now alternative models that have been approved for certain applications. To overcome the biological limitations of the mouse model, research efforts have also focused on "humanizing" the mice model to better recapitulate human skin physiology. In this review, we outline the different approaches undertaken thus far to study skin biology using human tissue xenografts in mice and the technical challenges involved. We also describe more recent developments to generate humanized multi-tissue compartment mice that carry both a functioning human immune system and skin xenografts. Such composite animal models provide promising opportunities to study drugs, disease and differentiation with greater clinical relevance. Copyright © 2017 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Eμ/miR-125b transgenic mice develop lethal B-cell malignancies.

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Enomoto, Y; Kitaura, J; Hatakeyama, K; Watanuki, J; Akasaka, T; Kato, N; Shimanuki, M; Nishimura, K; Takahashi, M; Taniwaki, M; Haferlach, C; Siebert, R; Dyer, M J S; Asou, N; Aburatani, H; Nakakuma, H; Kitamura, T; Sonoki, T

2011-12-01

MicroRNA-125b-1 (miR-125b-1) is a target of a chromosomal translocation t(11;14)(q24;q32) recurrently found in human B-cell precursor acute lymphoblastic leukemia (BCP-ALL). This translocation results in overexpression of miR-125b controlled by immunoglobulin heavy chain gene (IGH) regulatory elements. In addition, we found that six out of twenty-one BCP-ALL patients without t(11;14)(q24;q32) showed overexpression of miR-125b. Interestingly, four out of nine patients with BCR/ABL-positive BCP-ALL and one patient with B-cell lymphoid crisis that had progressed from chronic myelogenous leukemia overexpressed miR-125b. To examine the role of the deregulated expression of miR-125b in the development of B-cell tumor in vivo, we generated transgenic mice mimicking the t(11;14)(q24;q32) (Eμ/miR-125b-TG mice). Eμ/miR-125b-TG mice overexpressed miR-125b driven by IGH enhancer and promoter and developed IgM-negative or IgM-positive lethal B-cell malignancies with clonal proliferation. B cells obtained from the Eμ/miR-125b-TG mice were resistant to apoptosis induced by serum starvation. We identified Trp53inp1, a pro-apoptotic gene induced by cell stress, as a novel target gene of miR-125b in hematopoietic cells in vitro and in vivo. Our results provide direct evidence that miR-125b has important roles in the tumorigenesis of precursor B cells.

Diet-induced obesity promotes colon tumor development in azoxymethane-treated mice.

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Iina Tuominen

Full Text Available Obesity is an important risk factor for colon cancer in humans, and numerous studies have shown that a high fat diet enhances colon cancer development. As both increased adiposity and high fat diet can promote tumorigenesis, we examined the effect of diet-induced obesity, without ongoing high fat diet, on colon tumor development. C57BL/6J male mice were fed regular chow or high fat diet for 8 weeks. Diets were either maintained or switched resulting in four experimental groups: regular chow (R, high fat diet (H, regular chow switched to high fat diet (RH, and high fat diet switched to regular chow (HR. Mice were then administered azoxymethane to induce colon tumors. Tumor incidence and multiplicity were dramatically smaller in the R group relative to all groups that received high fat diet at any point. The effect of obesity on colon tumors could not be explained by differences in aberrant crypt foci number. Moreover, diet did not alter colonic expression of pro-inflammatory cytokines tumor necrosis factor-α, interleukin-6, interleukin-1β, and interferon-γ, which were measured immediately after azoxymethane treatment. Crypt apoptosis and proliferation, which were measured at the same time, were increased in the HR relative to all other groups. Our results suggest that factors associated with obesity - independently of ongoing high fat diet and obesity - promote tumor development because HR group animals had significantly more tumors than R group, and these mice were fed the same regular chow throughout the entire carcinogenic period. Moreover, there was no difference in the number of aberrant crypt foci between these groups, and thus the effect of obesity appears to be on subsequent stages of tumor development when early preneoplastic lesions transition into adenomas.

New function for an old enzyme: NEP deficient mice develop late-onset obesity.

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Matthias Becker

Full Text Available BACKGROUND: According to the World Health Organization (WHO there is a pandemic of obesity with approximately 300 million people being obese. Typically, human obesity has a polygenetic causation. Neutral endopeptidase (NEP, also known as neprilysin, is considered to be one of the key enzymes in the metabolism of many active peptide hormones. METHODOLOGY/PRINCIPAL FINDINGS: An incidental observation in NEP-deficient mice was a late-onset excessive gain in body weight exclusively from a ubiquitous accumulation of fat tissue. In accord with polygenetic human obesity, mice were characterized by deregulation of lipid metabolism, higher blood glucose levels, with impaired glucose tolerance. The key role of NEP in determining body mass was confirmed by the use of the NEP inhibitor candoxatril in wild-type mice that increased body weight due to increased food intake. This is a peripheral and not a central NEP action on the switch for appetite control, since candoxatril cannot cross the blood-brain barrier. Furthermore, we demonstrated that inhibition of NEP in mice with cachexia delayed rapid body weight loss. Thus, lack in NEP activity, genetically or pharmacologically, leads to a gain in body fat. CONCLUSIONS/SIGNIFICANCE: In the present study, we have identified NEP to be a crucial player in the development of obesity. NEP-deficient mice start to become obese under a normocaloric diet in an age of 6-7 months and thus are an ideal model for the typical human late-onset obesity. Therefore, the described obesity model is an ideal tool for research on development, molecular mechanisms, diagnosis, and therapy of the pandemic obesity.

Network of anatomical texts (NAnaTex), an open-source project for visualizing the interaction between anatomical terms.

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Momota, Ryusuke; Ohtsuka, Aiji

2018-01-01

Anatomy is the science and art of understanding the structure of the body and its components in relation to the functions of the whole-body system. Medicine is based on a deep understanding of anatomy, but quite a few introductory-level learners are overwhelmed by the sheer amount of anatomical terminology that must be understood, so they regard anatomy as a dull and dense subject. To help them learn anatomical terms in a more contextual way, we started a new open-source project, the Network of Anatomical Texts (NAnaTex), which visualizes relationships of body components by integrating text-based anatomical information using Cytoscape, a network visualization software platform. Here, we present a network of bones and muscles produced from literature descriptions. As this network is primarily text-based and does not require any programming knowledge, it is easy to implement new functions or provide extra information by making changes to the original text files. To facilitate collaborations, we deposited the source code files for the network into the GitHub repository ( https://github.com/ryusukemomota/nanatex ) so that anybody can participate in the evolution of the network and use it for their own non-profit purposes. This project should help not only introductory-level learners but also professional medical practitioners, who could use it as a quick reference.

Anatomic features involved in technical complexity of partial nephrectomy.

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Hou, Weibin; Yan, Weigang; Ji, Zhigang

2015-01-01

Nephrometry score systems, including RENAL nephrometry, preoperative aspects and dimensions used for an anatomical classification system, C-index, diameter-axial-polar nephrometry, contact surface area score, calculating resected and ischemized volume, renal tumor invasion index, surgical approach renal ranking score, zonal NePhRO score, and renal pelvic score, have been reviewed. Moreover, salient anatomic features like the perinephric fat and vascular variants also have been discussed. We then extract 7 anatomic characteristics, namely tumor size, spatial location, adjacency, exophytic/endophytic extension, vascular variants, pelvic anatomy, and perinephric fat as important features for partial nephrectomy. For novice surgeons, comprehensive and adequate anatomic consideration may help them in their early clinical practice. Copyright © 2015 Elsevier Inc. All rights reserved.

The growth and development of Schistosoma mansoni in mice exposed to sublethal doses of radiation

International Nuclear Information System (INIS)

Aitken, R.; Wilson, R.A.

1989-01-01

The maturation of Schistosoma mansoni was studied in mice exposed to various sublethal doses of radiation. Although the treatment of mice with 500 rads of radiation prior to infection did not alter parasite maturation, doses in excess of 500 rads led to a reduction in worm burden. This could not be attributed to a delay in the arrival of parasites in the hepatic portal system. Worms developing in mice treated with 800 rads commenced egg-laying about 1 wk later than worms in intact mice, and the rate of egg deposition appeared to be lower in irradiated hosts. The data demonstrate that exposure of C57BL/6 mice to doses of radiation in excess of 500 rads impairs their ability to carry infections of S. mansoni. The findings do not support the hypothesis that primary worm burdens in the mouse are controlled by a host immune response

Anatomically-aided PET reconstruction using the kernel method.

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Hutchcroft, Will; Wang, Guobao; Chen, Kevin T; Catana, Ciprian; Qi, Jinyi

2016-09-21

This paper extends the kernel method that was proposed previously for dynamic PET reconstruction, to incorporate anatomical side information into the PET reconstruction model. In contrast to existing methods that incorporate anatomical information using a penalized likelihood framework, the proposed method incorporates this information in the simpler maximum likelihood (ML) formulation and is amenable to ordered subsets. The new method also does not require any segmentation of the anatomical image to obtain edge information. We compare the kernel method with the Bowsher method for anatomically-aided PET image reconstruction through a simulated data set. Computer simulations demonstrate that the kernel method offers advantages over the Bowsher method in region of interest quantification. Additionally the kernel method is applied to a 3D patient data set. The kernel method results in reduced noise at a matched contrast level compared with the conventional ML expectation maximization algorithm.

Elastin-derived peptides are new regulators of insulin resistance development in mice

DEFF Research Database (Denmark)

Blaise, Sébastien; Romier, Béatrice; Kawecki, Charlotte

2013-01-01

. In the current study, we show that elastin-derived peptides (EDPs) may be involved in the development of insulin resistance (IRES) in mice. In chow-fed mice, acute or chronic intravenous injections of EDPs induced hyperglycemic effects associated with glucose uptake reduction and IRES in skeletal muscle, liver......, and adipose tissue. Based on in vivo, in vitro, and in silico approaches, we propose that this IRES is due to interaction between the insulin receptor (IR) and the neuraminidase-1 subunit of the elastin receptor complex triggered by EDPs. This interplay was correlated with decreased sialic acid levels...

Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice.

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Zhang, Hongsheng; Kang, Eunchai; Wang, Yaqing; Yang, Chaojuan; Yu, Hui; Wang, Qin; Chen, Zheyu; Zhang, Chen; Christian, Kimberly M; Song, Hongjun; Ming, Guo-Li; Xu, Zhiheng

2016-06-01

Several genome- and proteome-wide studies have associated transcription and translation changes of CRMP2 (collapsing response mediator protein 2) with psychiatric disorders, yet little is known about its function in the developing or adult mammalian brain in vivo. Here we show that brain-specific Crmp2 knockout (cKO) mice display molecular, cellular, structural and behavioural deficits, many of which are reminiscent of neural features and symptoms associated with schizophrenia. cKO mice exhibit enlarged ventricles and impaired social behaviour, locomotor activity, and learning and memory. Loss of Crmp2 in the hippocampus leads to reduced long-term potentiation, abnormal NMDA receptor composition, aberrant dendrite development and defective synapse formation in CA1 neurons. Furthermore, knockdown of crmp2 specifically in newborn neurons results in stage-dependent defects in their development during adult hippocampal neurogenesis. Our findings reveal a critical role for CRMP2 in neuronal plasticity, neural function and behavioural modulation in mice.

Anatomic and functional leg-length inequality: A review and recommendation for clinical decision-making. Part I, anatomic leg-length inequality: prevalence, magnitude, effects and clinical significance

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Knutson Gary A

2005-07-01

Full Text Available Abstract Background Leg-length inequality is most often divided into two groups: anatomic and functional. Part I of this review analyses data collected on anatomic leg-length inequality relative to prevalence, magnitude, effects and clinical significance. Part II examines the functional "short leg" including anatomic-functional relationships, and provides an outline for clinical decision-making. Methods Online database – Medline, CINAHL and MANTIS – and library searches for the time frame of 1970–2005 were done using the term "leg-length inequality". Results and Discussion Using data on leg-length inequality obtained by accurate and reliable x-ray methods, the prevalence of anatomic inequality was found to be 90%, the mean magnitude of anatomic inequality was 5.2 mm (SD 4.1. The evidence suggests that, for most people, anatomic leg-length inequality does not appear to be clinically significant until the magnitude reaches ~ 20 mm (~3/4". Conclusion Anatomic leg-length inequality is near universal, but the average magnitude is small and not likely to be clinically significant.

3D map of theranostic nanoparticles distribution in mice brain and liver by means of X-ray Phase Contrast Tomography

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Longo, E.; Bravin, A.; Brun, F.; Bukreeva, I.; Cedola, A.; Fratini, M.; Le Guevel, X.; Massimi, L.; Sancey, L.; Tillement, O.; Zeitoun, P.; de La Rochefoucauld, O.

2018-01-01

The word "theranostic" derives from the fusion of two terms: therapeutic and diagnostic. It is a promising research field that aims to develop innovative therapies with high target specificity by exploiting the therapeutic and diagnostic properties, in particular for metal-based nanoparticles (NPs) developed to erase cancer. In the framework of a combined research program on low dose X-ray imaging and theranostic nanoparticles (NPs), high resolution Phase-Contrast Tomography images of mice organs injected with gadolinium and gold-NPs were acquired at the European Synchrotron Radiation Facility (ESRF). Both compounds are good X-ray contrast agents due to their high attenuation coefficient with respect to biological tissues, especially immediately above K-edge energy. X-ray tomography is a powerful non-invasive technique to image the 3D vasculature network in order to detect abnormalities. Phase contrast methods provide more detailed anatomical information with higher discrimination among soft tissues. We present the images of mice liver and brain injected with gold and gadolinium NPs, respectively. We discuss different image processing methods used aiming at enhancing the accuracy on localizing nanoparticles.

Early thymic T cell development in young transgenic mice overexpressing human Cu/Zn superoxide dismutase, a model of Down syndrome.

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Laurent, Julien; Paly, Evelyne; Marche, Patrice N; London, Jacqueline

2006-06-01

Previous studies have shown that transgenic mice overexpressing Cu/Zn superoxide dismutase, a model of Down syndrome, exhibit premature thymic involution. We have performed a flow cytometry analysis of the developing thymus in these homozygous transgenic mice (hSOD1/hSOD1: Tg-SOD). Longitudinal follow-up analysis from day 3 to day 280 showed an early thymic development in Tg-SOD mice compared with controls. This early thymic development was associated with an increased migration of mature T cells to peripheral lymphoid organs. BrdU labeling showed no difference between Tg-SOD and control mice, confirming that the greater number of peripheral T cells in Tg-SOD mice was not due to extensive proliferation of these cells but rather to a greater pool of emigrant T cells in Tg-SOD.

Characterization of a sensitive mouse Aβ40 PD biomarker assay for Alzheimer's disease drug development in wild-type mice.

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Lu, Yanmei; Hoyte, Kwame; Montgomery, William H; Luk, Wilman; He, Dongping; Meilandt, William J; Zuchero, Y Joy Yu; Atwal, Jasvinder K; Scearce-Levie, Kimberly; Watts, Ryan J; DeForge, Laura E

2016-05-01

Transgenic mice that overexpress human amyloid precursor protein with Swedish or London (APPswe or APPlon) mutations have been widely used for preclinical Alzheimer's disease (AD) drug development. AD patients, however, rarely possess these mutations or overexpress APP. We developed a sensitive ELISA that specifically and accurately measures low levels of endogenous Aβ40 in mouse plasma, brain and CSF. In wild-type mice treated with a bispecific anti-TfR/BACE1 antibody, significant Aβ reductions were observed in the periphery and the brain. APPlon transgenic mice showed a slightly less reduction, whereas APPswe mice did not have any decrease. This sensitive and well-characterized mouse Aβ40 assay enables the use of wild-type mice for preclinical PK/PD and efficacy studies of potential AD therapeutics.

Gender-specific impairments on cognitive and behavioral development in mice exposed to fenvalerate during puberty.

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Meng, Xiu-Hong; Liu, Ping; Wang, Hua; Zhao, Xian-Feng; Xu, Zhong-Mei; Chen, Gui-Hai; Xu, De-Xiang

2011-06-24

In human and rodent models, endocrine disrupting chemicals (EDCs) interfere with the development of cognition and behaviors. Fenvalerate is a potential EDC. The purpose of this study was to examine whether pubertal fenvalerate exposure altered behavioral development. Mice were orally administered with either vehicle or fenvalerate (7.5 or 30 mg/kg/day) from postnatal day (PND) 28 to PND56. Learning and memory were assessed by Morris Water Maze. Aggressive performance was evaluated by aggressive behavior test. Anxiety-related activities were detected by three tests: open-field, plus-maze and black-white alley. Sensorimotor function was analyzed using beam walking and tightrope. Results found that the impairment for spatial learning and memory was more severe in fenvalerate-exposed female mice than in male mice. In addition, pubertal fenvalerate exposure inhibited aggressive behavior in males. Moreover, pubertal fenvalerate exposure increased anxiety activities in females. Altogether, these results suggest that pubertal fenvalerate exposure impairs spatial cognition and behavioral development in a gender-dependent manner. These findings identify fenvalerate as candidate environmental risk factors for cognitive and behavioral development, especially in the critical period of development. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Deletion of Foxp3+ regulatory T cells in genetically targeted mice supports development of intestinal inflammation

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Boehm Franziska

2012-07-01

Full Text Available Abstract Background Mice lacking Foxp3+ regulatory T (Treg cells develop severe tissue inflammation in lung, skin, and liver with premature death, whereas the intestine remains uninflamed. This study aims to demonstrate the importance of Foxp3+ Treg for the activation of T cells and the development of intestinal inflammation. Methods Foxp3-GFP-DTR (human diphtheria toxin receptor C57BL/6 mice allow elimination of Foxp3+ Treg by treatment with Dx (diphtheria toxin. The influence of Foxp3+ Treg on intestinal inflammation was tested using the CD4+ T-cell transfer colitis model in Rag−/− C57BL/6 mice and the acute DSS-colitis model. Results Continuous depletion of Foxp3+ Treg in Foxp3-GFP-DTR mice led to dramatic weight loss and death of mice by day 28. After 10 days of depletion of Foxp3+ Treg, isolated CD4+ T-cells were activated and produced extensive amounts of IFN-γ, IL-13, and IL-17A. Transfer of total CD4+ T-cells isolated from Foxp3-GFP-DTR mice did not result in any changes of intestinal homeostasis in Rag−/− C57BL/6 mice. However, administration of DTx between days 14 and 18 after T-cell reconstitution, lead to elimination of Foxp3+ Treg and to immediate weight loss due to intestinal inflammation. This pro-inflammatory effect of Foxp3+ Treg depletion consecutively increased inflammatory cytokine production. Further, the depletion of Foxp3+ Treg from Foxp3-GFP-DTR mice increased the severity of acute dSS-colitis accompanied by 80% lethality of Treg-depleted mice. CD4+ effector T-cells from Foxp3+ Treg-depleted mice produced significantly more pro-inflammatory cytokines. Conclusion Intermittent depletion of Foxp3+ Treg aggravates intestinal inflammatory responses demonstrating the importance of Foxp3+ Treg for the balance at the mucosal surface of the intestine.

Anatomical terminology and nomenclature: past, present and highlights.

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Kachlik, David; Baca, Vaclav; Bozdechova, Ivana; Cech, Pavel; Musil, Vladimir

2008-08-01

The anatomical terminology is a base for medical communication. It is elaborated into a nomenclature in Latin. Its history goes back to 1895, when the first Latin anatomical nomenclature was published as Basiliensia Nomina Anatomica. It was followed by seven revisions (Jenaiensia Nomina Anatomica 1935, Parisiensia Nomina Anatomica 1955, Nomina Anatomica 2nd to 6th edition 1960-1989). The last revision, Terminologia Anatomica, (TA) created by the Federative Committee on Anatomical Terminology and approved by the International Federation of Associations of Anatomists, was published in 1998. Apart from the official Latin anatomical terminology, it includes a list of recommended English equivalents. In this article, major changes and pitfalls of the nomenclature are discussed, as well as the clinical anatomy terms. The last revision (TA) is highly recommended to the attention of not only teachers, students and researchers, but also to clinicians, doctors, translators, editors and publishers to be followed in their activities.

Extra-Anatomic Revascularization of Extensive Coral Reef Aorta.

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Gaggiano, Andrea; Kasemi, Holta; Monti, Andrea; Laurito, Antonella; Maselli, Mauro; Manzo, Paola; Quaglino, Simone; Tavolini, Valeria

2017-10-01

Coral reef aorta (CRA) is a rare, potential lethal disease of the visceral aorta as it can cause visceral and renal infarction. Various surgical approaches have been proposed for the CRA treatment. The purpose of this article is to report different extensive extra-anatomic CRA treatment modalities tailored on the patients' clinical and anatomic presentation. From April 2006 to October 2012, 4 symptomatic patients with extensive CRA were treated at our department. Extra-anatomic aortic revascularization with selective visceral vessels clamping was performed in all cases. Technical success was 100%. No perioperative death was registered. All patients remained asymptomatic during the follow-up period (62, 49, 25, and 94 months, respectively), with bypasses and target vessels patency. The extra-anatomic bypass with selective visceral vessels clamping reduces the aortic occlusion time and the risk of organ ischemia. All approaches available should be considered on a case-by-case basis and in high-volume centers. Copyright © 2017 Elsevier Inc. All rights reserved.

Knock-in mice harboring a Ca(2+) desensitizing mutation in cardiac troponin C develop early onset dilated cardiomyopathy.

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McConnell, Bradley K; Singh, Sonal; Fan, Qiying; Hernandez, Adriana; Portillo, Jesus P; Reiser, Peter J; Tikunova, Svetlana B

2015-01-01

The physiological consequences of aberrant Ca(2+) binding and exchange with cardiac myofilaments are not clearly understood. In order to examine the effect of decreasing Ca(2+) sensitivity of cTnC on cardiac function, we generated knock-in mice carrying a D73N mutation (not known to be associated with heart disease in human patients) in cTnC. The D73N mutation was engineered into the regulatory N-domain of cTnC in order to reduce Ca(2+) sensitivity of reconstituted thin filaments by increasing the rate of Ca(2+) dissociation. In addition, the D73N mutation drastically blunted the extent of Ca(2+) desensitization of reconstituted thin filaments induced by cTnI pseudo-phosphorylation. Compared to wild-type mice, heterozygous knock-in mice carrying the D73N mutation exhibited a substantially decreased Ca(2+) sensitivity of force development in skinned ventricular trabeculae. Kaplan-Meier survival analysis revealed that median survival time for knock-in mice was 12 weeks. Echocardiographic analysis revealed that knock-in mice exhibited increased left ventricular dimensions with thinner walls. Echocardiographic analysis also revealed that measures of systolic function, such as ejection fraction (EF) and fractional shortening (FS), were dramatically reduced in knock-in mice. In addition, knock-in mice displayed electrophysiological abnormalities, namely prolonged QRS and QT intervals. Furthermore, ventricular myocytes isolated from knock-in mice did not respond to β-adrenergic stimulation. Thus, knock-in mice developed pathological features similar to those observed in human patients with dilated cardiomyopathy (DCM). In conclusion, our results suggest that decreasing Ca(2+) sensitivity of the regulatory N-domain of cTnC is sufficient to trigger the development of DCM.

Reappraising the functional implications of the primate visual anatomical hierarchy.

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Hegdé, Jay; Felleman, Daniel J

2007-10-01

The primate visual system has been shown to be organized into an anatomical hierarchy by the application of a few principled criteria. It has been widely assumed that cortical visual processing is also hierarchical, with the anatomical hierarchy providing a defined substrate for clear levels of hierarchical function. A large body of empirical evidence seemed to support this assumption, including the general observations that functional properties of visual neurons grow progressively more complex at progressively higher levels of the anatomical hierarchy. However, a growing body of evidence, including recent direct experimental comparisons of functional properties at two or more levels of the anatomical hierarchy, indicates that visual processing neither is hierarchical nor parallels the anatomical hierarchy. Recent results also indicate that some of the pathways of visual information flow are not hierarchical, so that the anatomical hierarchy cannot be taken as a strict flowchart of visual information either. Thus, while the sustaining strength of the notion of hierarchical processing may be that it is rather simple, its fatal flaw is that it is overly simplistic.

Effects of Dim Light at Night on Food Intake and Body Mass in Developing Mice.

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Cissé, Yasmine M; Peng, Juan; Nelson, Randy J

2017-01-01

Appropriately timed light is critical for circadian organization; exposure to dim light at night (dLAN) disrupts temporal organization of endogenous biological timing. Exposure to dLAN in adult mice is associated with elevated body mass and changes in metabolism putatively driven by voluntary changes in the time of food intake. We predicted that exposure of young mice to LAN could affect adult metabolic function. At 3 weeks (Experiment 1) or 5 weeks (Experiment 2) of age, mice were either maintained in standard light-dark (DARK) cycles or exposed to nightly dLAN (5 lux). In the first two experiments, food intake and locomotor activity were assessed after 4 weeks and a glucose tolerance test was administered after 6 weeks in experimental lighting conditions. In Experiment 3, tissues were collected around the clock at 6 h intervals to investigate rhythmic hepatic clock gene expression in mice exposed to dLAN from 3 or 5 weeks of age. Male and female mice exposed to dLAN beginning at 3 weeks of age displayed similar growth rates and body mass to DARK-reared offspring, despite increasing day-time food intake. Exposure to dLAN beginning at 5 weeks of age increased body mass and daytime food intake in male, but not female, mice. Consistent with the body mass phenotype, clock gene expression was unaltered in the liver. In contrast to adults, dLAN exposure during the development of the peripheral circadian system has sex- and development-dependent effects on body mass gain.

Effects of Dim Light at Night on Food Intake and Body Mass in Developing Mice

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Yasmine M. Cissé

2017-05-01

Full Text Available Appropriately timed light is critical for circadian organization; exposure to dim light at night (dLAN disrupts temporal organization of endogenous biological timing. Exposure to dLAN in adult mice is associated with elevated body mass and changes in metabolism putatively driven by voluntary changes in the time of food intake. We predicted that exposure of young mice to LAN could affect adult metabolic function. At 3 weeks (Experiment 1 or 5 weeks (Experiment 2 of age, mice were either maintained in standard light-dark (DARK cycles or exposed to nightly dLAN (5 lux. In the first two experiments, food intake and locomotor activity were assessed after 4 weeks and a glucose tolerance test was administered after 6 weeks in experimental lighting conditions. In Experiment 3, tissues were collected around the clock at 6 h intervals to investigate rhythmic hepatic clock gene expression in mice exposed to dLAN from 3 or 5 weeks of age. Male and female mice exposed to dLAN beginning at 3 weeks of age displayed similar growth rates and body mass to DARK-reared offspring, despite increasing day-time food intake. Exposure to dLAN beginning at 5 weeks of age increased body mass and daytime food intake in male, but not female, mice. Consistent with the body mass phenotype, clock gene expression was unaltered in the liver. In contrast to adults, dLAN exposure during the development of the peripheral circadian system has sex- and development-dependent effects on body mass gain.

Tritium toxicity on postnatally developing mice testes: a qualitative and quantitative evaluation

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Bhatia, A.L.

1982-01-01

The present study is an attempt to evaluate the possible radiobiological effects of tritiated water (HTO) on the testes of Swiss albino mice during postnatal development. Mice were continuously irradiated with different doses providing 46, 93 and 185 kBq of HTO per ml drinking water (after a priming injection) from day 1 after brith up to 6 weeks of age. Qualitative and quantitative studies were made at 6 weeks old mice testes and were compared with the sham-irradiated controls. A dose-dependent damage is noticed in the testes in the form of various radiopathological lesions such as intertubular edema, necrotic and pycnotic cells at various stages, mild cytoplasmic vacuolation, fibrosis, sclerosis, cellular edema etc. The number of various germ cells at their different phases were greatly reduced. 185 kBq/ml affect severely the spermatogonia and spermatid populations. The primary spermatocyte level was maintained at the range 64 +- 3.5%

Tritium toxicity on postnatally developing mice testes: a qualitative and quantitative evaluation

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Bhatia, A.L. (Rajasthan Univ., Jaipur (India). Radiation Biology Lab.)

1982-11-01

The present study is an attempt to evaluate the possible radiobiological effects of tritiated water (HTO) on the testes of Swiss albino mice during postnatal development. Mice were continuously irradiated with different doses providing 46, 93 and 185 kBq of HTO per ml drinking water (after a priming injection) from day 1 after brith up to 6 weeks of age. Qualitative and quantitative studies were made at 6 weeks old mice testes and were compared with the sham-irradiated controls. A dose-dependent damage is noticed in the testes in the form of various radiopathological lesions such as intertubular edema, necrotic and pycnotic cells at various stages, mild cytoplasmic vacuolation, fibrosis, sclerosis, cellular edema etc. The number of various germ cells at their different phases were greatly reduced. 185 kBq/ml affect severely the spermatogonia and spermatid populations. The primary spermatocyte level was maintained at the range 64 +- 3.5%.

The development of medical museums in the antebellum American South: slave bodies in networks of anatomical exchange.

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Kenny, Stephen C

2013-01-01

Prior to the American Civil War, museums were enthusiastically promoted in the annual circulars of southern medical colleges as valuable aids to medical education. Using case history narratives, medical college circulars, and announcements, this article examines the social origins of the region's collections of anatomical and pathological specimens and explores the professional agents and organizations responsible for their maintenance and development. The article is also concerned with exploring the racial framework in which these bodies and specimens were sourced and displayed. The social relations embodied in natural history and medical museum collections, and the emerging specialism of "negro medicine," were all elements of a context that subordinated and objectified blackness, as well as permitting and legitimizing the exploitation of black bodies. Medical museums function as a key case study for examining power relations among physicians, slaves, and slave owners, as well as underscoring southern medicine's dependence on slavery for its development.

Three-Dimensional Anatomic Evaluation of the Anterior Cruciate Ligament for Planning Reconstruction

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Yuichi Hoshino

2012-01-01

Full Text Available Anatomic study related to the anterior cruciate ligament (ACL reconstruction surgery has been developed in accordance with the progress of imaging technology. Advances in imaging techniques, especially the move from two-dimensional (2D to three-dimensional (3D image analysis, substantially contribute to anatomic understanding and its application to advanced ACL reconstruction surgery. This paper introduces previous research about image analysis of the ACL anatomy and its application to ACL reconstruction surgery. Crucial bony landmarks for the accurate placement of the ACL graft can be identified by 3D imaging technique. Additionally, 3D-CT analysis of the ACL insertion site anatomy provides better and more consistent evaluation than conventional “clock-face” reference and roentgenologic quadrant method. Since the human anatomy has a complex three-dimensional structure, further anatomic research using three-dimensional imaging analysis and its clinical application by navigation system or other technologies is warranted for the improvement of the ACL reconstruction.

Inexpensive anatomical trainer for bronchoscopy.

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Di Domenico, Stefano; Simonassi, Claudio; Chessa, Leonardo

2007-08-01

Flexible fiberoptic bronchoscopy is an indispensable tool for optimal management of intensive care unit patients. However, the acquisition of sufficient training in bronchoscopy is not straightforward during residency, because of technical and ethical problems. Moreover, the use of commercial simulators is limited by their high cost. In order to overcome these limitations, we realized a low-cost anatomical simulator to acquire and maintain the basic skill to perform bronchoscopy in ventilated patients. We used 1.5 mm diameter iron wire to construct the bronchial tree scaffold; glazier-putty was applied to create the anatomical model. The model was covered by several layers of newspaper strips previously immersed in water and vinilic glue. When the model completely dried up, it was detached from the scaffold by cutting it into six pieces, it was reassembled, painted and fitted with an endotracheal tube. We used very cheap material and the final cost was euro16. The trainer resulted in real-scale and anatomically accurate, with appropriate correspondence on endoscopic view between model and patients. All bronchial segments can be explored and easily identified by endoscopic and external vision. This cheap simulator is a valuable tool for practicing, particularly in a hospital with limited resources for medical training.

Anatomical Modularity of Verbal Working Memory? Functional Anatomical Evidence from a Famous Patient with Short-Term Memory Deficits.

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Paulesu, Eraldo; Shallice, Tim; Danelli, Laura; Sberna, Maurizio; Frackowiak, Richard S J; Frith, Chris D

2017-01-01

Cognitive skills are the emergent property of distributed neural networks. The distributed nature of these networks does not necessarily imply a lack of specialization of the individual brain structures involved. However, it remains questionable whether discrete aspects of high-level behavior might be the result of localized brain activity of individual nodes within such networks. The phonological loop of working memory, with its simplicity, seems ideally suited for testing this possibility. Central to the development of the phonological loop model has been the description of patients with focal lesions and specific deficits. As much as the detailed description of their behavior has served to refine the phonological loop model, a classical anatomoclinical correlation approach with such cases falls short in telling whether the observed behavior is based on the functions of a neural system resembling that seen in normal subjects challenged with phonological loop tasks or whether different systems have taken over. This is a crucial issue for the cross correlation of normal cognition, normal physiology, and cognitive neuropsychology. Here we describe the functional anatomical patterns of JB, a historical patient originally described by Warrington et al. (1971), a patient with a left temporo-parietal lesion and selective short phonological store deficit. JB was studied with the H 2 15 O PET activation technique during a rhyming task, which primarily depends on the rehearsal system of the phonological loop. No residual function was observed in the left temporo-parietal junction, a region previously associated with the phonological buffer of working memory. However, Broca's area, the major counterpart of the rehearsal system, was the major site of activation during the rhyming task. Specific and autonomous activation of Broca's area in the absence of afferent inputs from the other major anatomical component of the phonological loop shows that a certain degree of

Anatomically contoured plates for fixation of rib fractures.

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Bottlang, Michael; Helzel, Inga; Long, William B; Madey, Steven

2010-03-01

: Intraoperative contouring of long bridging plates for stabilization of flail chest injuries is difficult and time consuming. This study implemented for the first time biometric parameters to derive anatomically contoured rib plates. These plates were tested on a range of cadaveric ribs to quantify plate fit and to extract a best-fit plating configuration. : Three left and three right rib plates were designed, which accounted for anatomic parameters required when conforming a plate to the rib surface. The length lP over which each plate could trace the rib surface was evaluated on 109 cadaveric ribs. For each rib level 3-9, the plate design with the highest lP value was extracted to determine a best-fit plating configuration. Furthermore, the characteristic twist of rib surfaces was measured on 49 ribs to determine the surface congruency of anatomic plates with a constant twist. : The tracing length lP of the best-fit plating configuration ranged from 12.5 cm to 14.7 cm for ribs 3-9. The corresponding range for standard plates was 7.1-13.7 cm. The average twist of ribs over 8-cm, 12-cm, and 16-cm segments was 8.3 degrees, 20.6 degrees, and 32.7 degrees, respectively. The constant twist of anatomic rib plates was not significantly different from the average rib twist. : A small set of anatomic rib plates can minimize the need for intraoperative plate contouring for fixation of ribs 3-9. Anatomic rib plates can therefore reduce the time and complexity of flail chest stabilization and facilitate spanning of flail segments with long plates.

Anatomic mapping of molecular subtypes in diffuse glioma.

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Tang, Qisheng; Lian, Yuxi; Yu, Jinhua; Wang, Yuanyuan; Shi, Zhifeng; Chen, Liang

2017-09-15

Tumor location served as an important prognostic factor in glioma patients was considered to postulate molecular features according to cell origin theory. However, anatomic distribution of unique molecular subtypes was not widely investigated. The relationship between molecular phenotype and histological subgroup were also vague based on tumor location. Our group focuses on the study of glioma anatomic location of distinctive molecular subgroups and histology subtypes, and explores the possibility of their consistency based on clinical background. We retrospectively reviewed 143 cases with both molecular information (IDH1/TERT/1p19q) and MRI images diagnosed as cerebral diffuse gliomas. The anatomic distribution was analyzed between distinctive molecular subgroups and its relationship with histological subtypes. The influence of tumor location, molecular stratification and histology diagnosis on survival outcome was investigated as well. Anatomic locations of cerebral diffuse glioma indicate varied clinical outcome. Based on that, it can be stratified into five principal molecular subgroups according to IDH1/TERT/1p19q status. Triple-positive (IDH1 and TERT mutation with 1p19q codeletion) glioma tended to be oligodendroglioma present with much better clinical outcome compared to TERT mutation only group who is glioblastoma inclined (median overall survival 39 months VS 18 months). Five molecular subgroups were demonstrated with distinctive locational distribution. This kind of anatomic feature is consistent with its corresponding histological subtypes. Each molecular subgroup in glioma has unique anatomic location which indicates distinctive clinical outcome. Molecular diagnosis can be served as perfect complementary tool for the precise diagnosis. Integration of histomolecular diagnosis will be much more helpful in routine clinical practice in the future.

Chronic Pelvic Pain Development and Prostate Inflammation in Strains of Mice With Different Susceptibility to Experimental Autoimmune Prostatitis.

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Breser, Maria L; Motrich, Ruben D; Sanchez, Leonardo R; Rivero, Virginia E

2017-01-01

Experimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of the prostate characterized by peripheral prostate-specific autoimmune responses associated with prostate inflammation. EAP is induced in rodents upon immunization with prostate antigens (PAg) plus adjuvants and shares important clinical and immunological features with the human disease chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). EAP was induced in young NOD, C57BL/6, and BALB/c male mice by immunization with PAg plus complete Freund́s adjuvant. Tactile allodynia was assessed using Von Frey fibers as a measure of pelvic pain at baseline and at different time points after immunization. Using conventional histology, immunohistochemistry, FACS analysis, and protein arrays, an interstrain comparative study of prostate cell infiltration and inflammation was performed. Chronic pelvic pain development was similar between immunized NOD and C57BL/6 mice, although the severity of leukocyte infiltration was greater in the first case. Coversely, minimal prostate cell infiltration was observed in immunized BALB/c mice, who showed no pelvic pain development. Increased numbers of mast cells, mostly degranulated, were detected in prostate samples from NOD and C57BL/6 mice, while lower total counts and resting were observed in BALB/c mice. Prostate tissue from NOD mice revealed markedly increased expression levels of inflammatory cytokines, chemokines, adhesion molecules, vascular endothelial growth factor, and metalloproteinases. Similar results, but to a lesser extent, were observed when analyzing prostate tissue from C57BL/6 mice. On the contrary, the expression of the above mediators was very low in prostate tissue from immunized BALB/c mice, showing significantly slight increments only for CXCL1 and IL4. Our results provide new evidence indicating that NOD, C57BL/6, and BALB/c mice develop different degrees of chronic pelvic pain, type, and amount of prostate cell infiltration

Anatomical and ethological changes in poultry affected by osteopetrosis

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Krassimira Uzunova

2014-05-01

Full Text Available An integral veterinary hygiene survey in a farm rearing stock layers, 4 months of age, has been performed to throw light on the unknown etiology of sporadic osteopetrosis outbreaks. Observations (ethological and anatomical were conducted to evidence the development of the disease. The welfare of affected birds was assessed as poor after detailed analysis of all elements of housing environment. This was the cause for the development of the severe illness regardless of the fact that birds were preliminary vaccinated.

CT following US for possible appendicitis: anatomic coverage

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O' Malley, Martin E. [University of Toronto, Princess Margaret Hospital, 3-920, Joint Department of Medical Imaging, Toronto, Ontario (Canada); Alharbi, Fawaz [University of Toronto, Toronto General Hospital, NCSB 1C572, Joint Department of Medical Imaging, Toronto, Ontario (Canada); Qassim University, Department of Medical Imaging, Buraydah, Qassim (Saudi Arabia); Chawla, Tanya P. [University of Toronto, Mount Sinai Hospital, Room 567, Joint Department of Medical Imaging, Toronto, Ontario (Canada); Moshonov, Hadas [University of Toronto, Joint Department of Medical Imaging, Toronto, Ontario (Canada)

2016-02-15

To determine superior-inferior anatomic borders for CT following inconclusive/nondiagnostic US for possible appendicitis. Ninety-nine patients with possible appendicitis and inconclusive/nondiagnostic US followed by CT were included in this retrospective study. Two radiologists reviewed CT images and determined superior-inferior anatomic borders required to diagnose or exclude appendicitis and diagnose alternative causes. This ''targeted'' coverage was used to estimate potential reduction in anatomic coverage compared to standard abdominal/pelvic CT. The study group included 83 women and 16 men; mean age 32 (median, 29; range 18-73) years. Final diagnoses were: nonspecific abdominal pain 50/99 (51 %), appendicitis 26/99 (26 %), gynaecological 12/99 (12 %), gastrointestinal 9/99 (10 %), and musculoskeletal 2/99 (2 %). Median dose-length product for standard CT was 890.0 (range, 306.3 - 2493.9) mGy.cm. To confidently diagnose/exclude appendicitis or identify alternative diagnoses, maximum superior-inferior anatomic CT coverage was the superior border of L2-superior border of pubic symphysis, for both reviewers. Targeted CT would reduce anatomic coverage by 30-55 % (mean 39 %, median 40 %) compared to standard CT. When CT is performed for appendicitis following inconclusive/nondiagnostic US, targeted CT from the superior border of L2-superior border of pubic symphysis can be used resulting in significant reduction in exposure to ionizing radiation compared to standard CT. (orig.)

CT following US for possible appendicitis: anatomic coverage

International Nuclear Information System (INIS)

O'Malley, Martin E.; Alharbi, Fawaz; Chawla, Tanya P.; Moshonov, Hadas

2016-01-01

To determine superior-inferior anatomic borders for CT following inconclusive/nondiagnostic US for possible appendicitis. Ninety-nine patients with possible appendicitis and inconclusive/nondiagnostic US followed by CT were included in this retrospective study. Two radiologists reviewed CT images and determined superior-inferior anatomic borders required to diagnose or exclude appendicitis and diagnose alternative causes. This ''targeted'' coverage was used to estimate potential reduction in anatomic coverage compared to standard abdominal/pelvic CT. The study group included 83 women and 16 men; mean age 32 (median, 29; range 18-73) years. Final diagnoses were: nonspecific abdominal pain 50/99 (51 %), appendicitis 26/99 (26 %), gynaecological 12/99 (12 %), gastrointestinal 9/99 (10 %), and musculoskeletal 2/99 (2 %). Median dose-length product for standard CT was 890.0 (range, 306.3 - 2493.9) mGy.cm. To confidently diagnose/exclude appendicitis or identify alternative diagnoses, maximum superior-inferior anatomic CT coverage was the superior border of L2-superior border of pubic symphysis, for both reviewers. Targeted CT would reduce anatomic coverage by 30-55 % (mean 39 %, median 40 %) compared to standard CT. When CT is performed for appendicitis following inconclusive/nondiagnostic US, targeted CT from the superior border of L2-superior border of pubic symphysis can be used resulting in significant reduction in exposure to ionizing radiation compared to standard CT. (orig.)

The functional and anatomical dissection of somatosensory subpopulations using mouse genetics

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Claire E Le Pichon

2014-04-01

Full Text Available The word somatosensation comes from joining the Greek word for body (soma with a word for perception (sensation. Somatosensory neurons comprise the largest sensory system in mammals and have nerve endings coursing throughout the skin, viscera, muscle, and bone. Their cell bodies reside in a chain of ganglia adjacent to the dorsal spinal cord (the dorsal root ganglia and at the base of the skull (the trigeminal ganglia. While the neuronal cell bodies are intermingled within the ganglia, the somatosensory system is in reality composed of numerous sub-systems, each specialized to detect distinct stimuli, such as temperature and touch. Historically, somatosensory neurons have been classified using a diverse host of anatomical and physiological parameters, such as the size of the cell body, degree of myelination, histological labeling with markers, specialization of the nerve endings, projection patterns in the spinal cord and brainstem, receptive tuning, and conduction velocity of their action potentials. While useful, the picture that emerged was one of heterogeneity, with many markers at least partially overlapping. More recently, by capitalizing on advances in molecular techniques, researchers have identified specific ion channels and sensory receptors expressed in subsets of sensory neurons. These studies have proved invaluable as they allow genetic access to small subsets of neurons for further molecular dissection. Data being generated from transgenic mice favor the model whereby an array of dedicated neurons is responsible for selectively encoding different modalities. Here we review the current knowledge of the different sensory neuron subtypes in the mouse, the markers used to study them, and the neurogenetic strategies used to define their anatomical projections and functional roles.

Overproduction of Upper-Layer Neurons in the Neocortex Leads to Autism-like Features in Mice

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Wei-Qun Fang

2014-12-01

Full Text Available Summary: The functional integrity of the neocortex depends upon proper numbers of excitatory and inhibitory neurons; however, the consequences of dysregulated neuronal production during the development of the neocortex are unclear. As excess cortical neurons are linked to the neurodevelopmental disorder autism, we investigated whether the overproduction of neurons leads to neocortical malformation and malfunction in mice. We experimentally increased the number of pyramidal neurons in the upper neocortical layers by using the small molecule XAV939 to expand the intermediate progenitor population. The resultant overpopulation of neurons perturbs development of dendrites and spines of excitatory neurons and alters the laminar distribution of interneurons. Furthermore, these phenotypic changes are accompanied by dysregulated excitatory and inhibitory synaptic connection and balance. Importantly, these mice exhibit behavioral abnormalities resembling those of human autism. Thus, our findings collectively suggest a causal relationship between neuronal overproduction and autism-like features, providing developmental insights into the etiology of autism. : Fang et al. generated a mouse model with excessive excitatory neurons in the neocortex by manipulating embryonic neurogenesis. Overproduction of neurons results in autism-like anatomical and behavioral features. These findings suggest a causal relationship between overproduction of neurons and cortical malfunction and provide developmental insights into the etiology of autism.

Development of ghrelin transgenic mice for elucidation of clinical implication of ghrelin.

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Aotani, Daisuke; Ariyasu, Hiroyuki; Shimazu-Kuwahara, Satoko; Shimizu, Yoshiyuki; Nomura, Hidenari; Murofushi, Yoshiteru; Kaneko, Kentaro; Izumi, Ryota; Matsubara, Masaki; Kanda, Hajime; Noguchi, Michio; Tanaka, Tomohiro; Kusakabe, Toru; Miyazawa, Takashi; Nakao, Kazuwa

2017-01-01

To elucidate the clinical implication of ghrelin, we have been trying to generate variable models of transgenic (Tg) mice overexpressing ghrelin. We generated Tg mice overexpressing des-acyl ghrelin in a wide variety of tissues under the control of β-actin promoter. While plasma des-acyl ghrelin level in the Tg mice was 44-fold greater than that of control mice, there was no differences in the plasma ghrelin level between des-acyl ghrelin Tg and the control mice. The des-acyl ghrelin Tg mice exhibited the lower body weight and the shorter body length due to modulation of GH-IGF-1 axis. We tried to generate Tg mice expressing a ghrelin analog, which possessed ghrelin-like activity (Trp 3 -ghrelin Tg mice). The plasma Trp 3 -ghrelin concentration in Trp 3 -ghrelin Tg mice was approximately 85-fold higher than plasma ghrelin (acylated ghrelin) concentration seen in the control mice. Because Trp 3 -ghrelin is approximately 24-fold less potent than ghrelin, the plasma Trp 3 -ghrelin concentration in Trp 3 -ghrelin Tg mice was calculated to have approximately 3.5-fold biological activity greater than that of ghrelin (acylated ghrelin) in the control mice. Trp 3 -ghrelin Tg mice did not show any phenotypes except for reduced insulin sensitivity in 1-year old. After the identification of ghrelin O-acyltransferase (GOAT), we generated doubly Tg mice overexpressing both mouse des-acyl ghrelin and mouse GOAT in the liver by cross-mating the two kinds of Tg mice. The plasma ghrelin concentration of doubly Tg mice was approximately 2-fold higher than that of the control mice. No apparent phenotypic changes in body weight and food intake were observed in doubly Tg mice. Further studies are ongoing in our laboratory to generate Tg mice with the increased plasma ghrelin level to a greater extent. The better understanding of physiological and pathophysiological significance of ghrelin from experiments using an excellent animal model may provide a new therapeutic approach for human

Exploring brain function from anatomical connectivity

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Gorka eZamora-López

2011-06-01

Full Text Available The intrinsic relationship between the architecture of the brain and the range of sensory and behavioral phenomena it produces is a relevant question in neuroscience. Here, we review recent knowledge gained on the architecture of the anatomical connectivity by means of complex network analysis. It has been found that corticocortical networks display a few prominent characteristics: (i modular organization, (ii abundant alternative processing paths and (iii the presence of highly connected hubs. Additionally, we present a novel classification of cortical areas of the cat according to the role they play in multisensory connectivity. All these properties represent an ideal anatomical substrate supporting rich dynamical behaviors, as-well-as facilitating the capacity of the brain to process sensory information of different modalities segregated and to integrate them towards a comprehensive perception of the real world. The result here exposed are mainly based in anatomical data of cats’ brain, but we show how further observations suggest that, from worms to humans, the nervous system of all animals might share fundamental principles of organization.

Anatomic variability of the vascularized composite osteomyocutaneous flap from the medial femoral condyle: an anatomical study

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Trung-Hau Le Thua

2014-12-01

Full Text Available Aim: The anatomical study and clinical application for the vascularized corticoperiosteal flap from the medial femoral condyle have been performed and described previously. Although prior studies have described the composite osteomyocutaneous flap from the medial femoral condyle, a detailed analysis of the vascularity of this region has not yet been fully evaluated. Methods: This anatomical study described the variability of the arteries from the medial femoral condyle in 40 cadaveric specimens. Results: The descending genicular artery (DGA was found in 33 of 40 cases (82.5%. The  superomedial genicular artery (SGA was present in 10 cases (25%. All 33 cases (100% of the DGA had articular branches to the periosteum of the medial femoral condyle. Muscular branches and saphenous branches of the DGA were present in 25 cases (62.5% and 26 cases (70.3%, respectively. Conclusion: The current study demonstrates that the size and length of the vessels to the medial femoral condyle are sufficient for a vascularized bone flap. A careful preoperative vascular assessment is essential prior to use of the vascularized composite osteomyocutaneous flap from the medial femoral condyle, because of the considerable anatomical variations in different branches of the DGA.

Anatomical entity recognition with a hierarchical framework augmented by external resources.

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Yan Xu

Full Text Available References to anatomical entities in medical records consist not only of explicit references to anatomical locations, but also other diverse types of expressions, such as specific diseases, clinical tests, clinical treatments, which constitute implicit references to anatomical entities. In order to identify these implicit anatomical entities, we propose a hierarchical framework, in which two layers of named entity recognizers (NERs work in a cooperative manner. Each of the NERs is implemented using the Conditional Random Fields (CRF model, which use a range of external resources to generate features. We constructed a dictionary of anatomical entity expressions by exploiting four existing resources, i.e., UMLS, MeSH, RadLex and BodyPart3D, and supplemented information from two external knowledge bases, i.e., Wikipedia and WordNet, to improve inference of anatomical entities from implicit expressions. Experiments conducted on 300 discharge summaries showed a micro-averaged performance of 0.8509 Precision, 0.7796 Recall and 0.8137 F1 for explicit anatomical entity recognition, and 0.8695 Precision, 0.6893 Recall and 0.7690 F1 for implicit anatomical entity recognition. The use of the hierarchical framework, which combines the recognition of named entities of various types (diseases, clinical tests, treatments with information embedded in external knowledge bases, resulted in a 5.08% increment in F1. The resources constructed for this research will be made publicly available.

Aging has small effects on initial ischemic acute kidney injury development despite changing intrarenal immunologic micromilieu in mice.

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Jang, Hye Ryoun; Park, Ji Hyeon; Kwon, Ghee Young; Park, Jae Berm; Lee, Jung Eun; Kim, Dae Joong; Kim, Yoon-Goo; Kim, Sung Joo; Oh, Ha Young; Huh, Wooseong

2016-02-15

Inflammatory process mediated by innate and adaptive immune systems is a major pathogenic mechanism of renal ischemia-reperfusion injury (IRI). There are concerns that organ recipients may be at increased risk of developing IRI after receiving kidneys from elder donors. To reveal the effects of aging on the development of renal IRI, we compared the immunologic micromilieu of normal and postischemic kidneys from mice of three different ages (9 wk, 6 mo, and 12 mo). There was a higher number of total T cells, especially effector memory CD4/CD8 T cells, and regulatory T cells in the normal kidneys of old mice. On day 2 after IRI, the proportion of necrotic tubules and renal functional changes were comparable between groups although old mice had a higher proportion of damaged tubule compared with young mice. More T cells, but less B cells, trafficked into the postischemic kidneys of old mice. The infiltration of NK T cells was similar across the groups. Macrophages and neutrophils were comparable between groups in both normal kidneys and postischemic kidneys. The intrarenal expressions of TNF-α and VEGF were decreased in normal and postischemic kidneys of aged mice. These mixed effects of aging on lymphocytes and cytokines/chemokines were not different between the two groups of old mice. Our study demonstrates that aging alters the intrarenal micromilieu but has small effects on the development of initial renal injury after IRI. Further study investigating aging-dependent differences in the repair process of renal IRI may be required. Copyright © 2016 the American Physiological Society.

Suppressive effects of cacao polyphenols on the development of atherosclerosis in apolipoprotein E-deficient mice.

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Natsume, Midori; Baba, Seigo

2014-01-01

Previous studies in humans have shown that the cacao polyphenols, (-)-epicatechin and its oligomers, prevent in vitro and ex vivo low-density lipoprotein oxidation mediated by free radical generators and metal ions and also reduce plasma LDL-cholesterol levels. The aim of this study was to examine the effects of cacao polyphenols on the development of atherosclerosis in apolipoprotein E-deficient (-/-) mice. Mice aged 8 weeks (n = 90) were randomized into three groups, and fed either normal mouse chow (controls) or chow supplemented with 0.25 or 0.40 % cacao polyphenols for 16 weeks. The mean plaque area in cross-sections of the brachiocephalic trunk was measured and found to be lower in the 0.25 % cacao polyphenol group than in the control group (p cacao polyphenol group (p cacao polyphenols inhibit the development of atherosclerosis in apolipoprotein E-deficient (-/-) mice by reducing oxidative stress and inflammatory responses.

Excess TSH causes abnormal skeletal development in young mice with hypothyroidism via suppressive effects on the growth plate.

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Endo, Toyoshi; Kobayashi, Tetsuro

2013-09-01

Hypothyroidism in the young leads to irreversible growth failure. hyt/hyt Mice have a nonfunctional TSH receptor (TSHR) and are severely hypothyroid, but growth retardation was not observed in adult mice. We found that epiphysial cartilage as well as cultured chondrocytes expressed functional TSHR at levels comparable to that seen in the thyroid, and that addition of TSH to cultured chondrocytes suppressed expression of chondrocyte differentiation marker genes such as Sox-9 and type IIa collagen. Next, we compared the long bone phenotypes of two distinct mouse models of hypothyroidism: thyroidectomized (THYx) mice and hyt/hyt mice. Although both THYx and hyt/hyt mice were severely hypothyroid and had similar serum Ca(2+) and growth hormone levels, the tibia was shorter and the proliferating and hypertrophic zones in the growth plate was significantly narrower in THYx mice than in hyt/hyt mice. Supplementation of hyt/hyt mice thyroid hormone resulted in a wider growth plate compared with that of wild-type mice. Expressions of chondrocyte differentiation marker genes Sox-9 and type IIa collagen in growth plate from THYx mice were 52 and 60% lower than those of hyt/hyt mice, respectively. High serum TSH causes abnormal skeletal development in young mice with hypothyroidism via suppressive effects on the growth plate.

Haploinsufficiency of myostatin protects against aging-related declines in muscle function and enhances the longevity of mice.

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Mendias, Christopher L; Bakhurin, Konstantin I; Gumucio, Jonathan P; Shallal-Ayzin, Mark V; Davis, Carol S; Faulkner, John A

2015-08-01

The molecular mechanisms behind aging-related declines in muscle function are not well understood, but the growth factor myostatin (MSTN) appears to play an important role in this process. Additionally, epidemiological studies have identified a positive correlation between skeletal muscle mass and longevity. Given the role of myostatin in regulating muscle size, and the correlation between muscle mass and longevity, we tested the hypotheses that the deficiency of myostatin would protect oldest-old mice (28-30 months old) from an aging-related loss in muscle size and contractility, and would extend the maximum lifespan of mice. We found that MSTN(+/-) and MSTN(-/-) mice were protected from aging-related declines in muscle mass and contractility. While no differences were detected between MSTN(+/+) and MSTN(-/-) mice, MSTN(+/-) mice had an approximately 15% increase in maximal lifespan. These results suggest that targeting myostatin may protect against aging-related changes in skeletal muscle and contribute to enhanced longevity. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Gross and morphometric anatomical changes of the thyroid gland in ...

African Journals Online (AJOL)

Gross and morphometric anatomical changes of the thyroid gland in the West African Dwarf Goat ( Capra hircus ) during the foetal and post-natal periods of development. ... The right lobe was more cranially located on the larynx and trachea than the left lobe in all age groups. Thyroid isthmus was absent in few foetal thyroid ...

Morpho-anatomical investigations on Momordica charantia L. (Cucurbitaceae

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İlham Eröz Poyraz

2016-05-01

Full Text Available Momordica charantia L. (Cucurbitaceae used for some medicinal purposes like antidiabetic, anticancer, antiviral and treat to gastritis was investigated. Morphological studies were supported by morphometric measurements and drawings of male and female flowers, fruit and seeds of the species. In anatomical studies, cross sections of stem and leaf, upper and lower surface sections of leaves were evaluated. It was detected that the stem with typical anatomical properties of a climbing dicotyl plant. The leaves were amphistotamic and with lots of cyctoliths on the lower surface of leaves. Stomata are anomocytic and situated much more at the lower surface of leaves. Morpho-anatomical investigations on Momordica charantia L. (Cucurbitaceae*

Familial intracranial aneurysms: is anatomic vulnerability heritable?

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Mackey, Jason; Brown, Robert D; Moomaw, Charles J; Hornung, Richard; Sauerbeck, Laura; Woo, Daniel; Foroud, Tatiana; Gandhi, Dheeraj; Kleindorfer, Dawn; Flaherty, Matthew L; Meissner, Irene; Anderson, Craig; Rouleau, Guy; Connolly, E Sander; Deka, Ranjan; Koller, Daniel L; Abruzzo, Todd; Huston, John; Broderick, Joseph P

2013-01-01

Previous studies have suggested that family members with intracranial aneurysms (IAs) often harbor IAs in similar anatomic locations. IA location is important because of its association with rupture. We tested the hypothesis that anatomic susceptibility to IA location exists using a family-based IA study. We identified all affected probands and first-degree relatives (FDRs) with a definite or probable phenotype in each family. We stratified each IA of the probands by major arterial territory and calculated each family's proband-FDR territory concordance and overall contribution to the concordance analysis. We then matched each family unit to an unrelated family unit selected randomly with replacement and performed 1001 simulations. The median concordance proportions, odds ratios (ORs), and P values from the 1001 logistic regression analyses were used to represent the final results of the analysis. There were 323 family units available for analysis, including 323 probands and 448 FDRs, with a total of 1176 IAs. IA territorial concordance was higher in the internal carotid artery (55.4% versus 45.6%; OR, 1.54 [1.04-2.27]; P=0.032), middle cerebral artery (45.8% versus 30.5%; OR, 1.99 [1.22-3.22]; P=0.006), and vertebrobasilar system (26.6% versus 11.3%; OR, 2.90 [1.05-8.24], P=0.04) distributions in the true family compared with the comparison family. Concordance was also higher when any location was considered (53.0% versus 40.7%; OR, 1.82 [1.34-2.46]; PIA development, we found that IA territorial concordance was higher when probands were compared with their own affected FDRs than with comparison FDRs, which suggests that anatomic vulnerability to IA formation exists. Future studies of IA genetics should consider stratifying cases by IA location.

Glucocorticoid treatment of MCMV infected newborn mice attenuates CNS inflammation and limits deficits in cerebellar development.

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Kate Kosmac

2013-03-01

Full Text Available Infection of the developing fetus with human cytomegalovirus (HCMV is a major cause of central nervous system disease in infants and children; however, mechanism(s of disease associated with this intrauterine infection remain poorly understood. Utilizing a mouse model of HCMV infection of the developing CNS, we have shown that peripheral inoculation of newborn mice with murine CMV (MCMV results in CNS infection and developmental abnormalities that recapitulate key features of the human infection. In this model, animals exhibit decreased granule neuron precursor cell (GNPC proliferation and altered morphogenesis of the cerebellar cortex. Deficits in cerebellar cortical development are symmetric and global even though infection of the CNS results in a non-necrotizing encephalitis characterized by widely scattered foci of virus-infected cells with mononuclear cell infiltrates. These findings suggested that inflammation induced by MCMV infection could underlie deficits in CNS development. We investigated the contribution of host inflammatory responses to abnormal cerebellar development by modulating inflammatory responses in infected mice with glucocorticoids. Treatment of infected animals with glucocorticoids decreased activation of CNS mononuclear cells and expression of inflammatory cytokines (TNF-α, IFN-β and IFNγ in the CNS while minimally impacting CNS virus replication. Glucocorticoid treatment also limited morphogenic abnormalities and normalized the expression of developmentally regulated genes within the cerebellum. Importantly, GNPC proliferation deficits were normalized in MCMV infected mice following glucocorticoid treatment. Our findings argue that host inflammatory responses to MCMV infection contribute to deficits in CNS development in MCMV infected mice and suggest that similar mechanisms of disease could be responsible for the abnormal CNS development in human infants infected in-utero with HCMV.

Cerebral blood flow reduction in Alzheimer's disease: impact of capillary occlusions on mice and humans

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Berg, Maxime; Merlo, Adlan; Peyrounette, Myriam; Doyeux, Vincent; Smith, Amy; Cruz-Hernandez, Jean; Bracko, Oliver; Haft-Javaherian, Mohammad; Nishimura, Nozomi; Schaffer, Chris B.; Davit, Yohan; Quintard, Michel; Lorthois, Sylvie

2017-11-01

Alzheimer's disease may be the most common form of dementia, yet a satisfactory diagnosis procedure has still to be found. Recent studies suggest that a significant decrease of cerebral blood flow, probably caused by white blood cells stalling small vessels, may be among the earliest biological markers. To assess this hypothesis we derive a blood flow model, validate it against in vitro controlled experiments and in vivo measurements made on mice. We then investigate the influence of capillary occlusions on regional perfusion (sum of all arteriole flowrates feeding the network) of large mice and humans anatomical networks. Consistent with experiments, we observe no threshold effect, so that even a small percentage of occlusions (2-4%) leads to significant blood flow decrease (5-12%). We show that both species share the same linear dependance, suggesting possible translation from mice to human. ERC BrainMicroFlow GA61510, CALMIP HPC (Grant 2017-1541).

Mice deleted for cell division cycle 73 gene develop parathyroid and uterine tumours: model for the hyperparathyroidism-jaw tumour syndrome.

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Walls, G V; Stevenson, M; Lines, K E; Newey, P J; Reed, A A C; Bowl, M R; Jeyabalan, J; Harding, B; Bradley, K J; Manek, S; Chen, J; Wang, P; Williams, B O; Teh, B T; Thakker, R V

2017-07-13

The hyperparathyroidism-jaw tumour (HPT-JT) syndrome is an autosomal dominant disorder characterized by occurrence of parathyroid tumours, often atypical adenomas and carcinomas, ossifying jaw fibromas, renal tumours and uterine benign and malignant neoplasms. HPT-JT is caused by mutations of the cell division cycle 73 (CDC73) gene, located on chromosome 1q31.2 and encodes a 531 amino acid protein, parafibromin. To facilitate in vivo studies of Cdc73 in tumourigenesis we generated conventional (Cdc73 +/- ) and conditional parathyroid-specific (Cdc73 +/L /PTH-Cre and Cdc73 L/L /PTH-Cre) mouse models. Mice were aged to 18-21 months and studied for survival, tumour development and proliferation, and serum biochemistry, and compared to age-matched wild-type (Cdc73 +/+ and Cdc73 +/+ /PTH-Cre) littermates. Survival of Cdc73 +/- mice, when compared to Cdc73 +/+ mice was reduced (Cdc73 +/- =80%; Cdc73 +/+ =90% at 18 months of age, Pfourfold higher than that in parathyroid glands of wild-type littermates (P<0.0001). Cdc73 +/- , Cdc73 +/L /PTH-Cre and Cdc73 L/L /PTH-Cre mice had higher mean serum calcium concentrations than wild-type littermates, and Cdc73 +/- mice also had increased mean serum parathyroid hormone (PTH) concentrations. Parathyroid tumour development, and elevations in serum calcium and PTH, were similar in males and females. Cdc73 +/- mice did not develop bone or renal tumours but female Cdc73 +/- mice, at 18 months of age, had uterine neoplasms comprising squamous metaplasia, adenofibroma and adenomyoma. Uterine neoplasms, myometria and jaw bones of Cdc73 +/- mice had increased proliferation rates that were 2-fold higher than in Cdc73 +/+ mice (P<0.05). Thus, our studies, which have established mouse models for parathyroid tumours and uterine neoplasms that develop in the HPT-JT syndrome, provide in vivo models for future studies of these tumours.

[Cellular subcutaneous tissue. Anatomic observations].

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Marquart-Elbaz, C; Varnaison, E; Sick, H; Grosshans, E; Cribier, B

2001-11-01

We showed in a companion paper that the definition of the French "subcutaneous cellular tissue" considerably varied from the 18th to the end of the 20th centuries and has not yet reached a consensus. To address the anatomic reality of this "subcutaneous cellular tissue", we investigated the anatomic structures underlying the fat tissue in normal human skin. Sixty specimens were excised from the surface to the deep structures (bone, muscle, cartilage) on different body sites of 3 cadavers from the Institut d'Anatomie Normale de Strasbourg. Samples were paraffin-embedded, stained and analysed with a binocular microscope taking x 1 photographs. Specimens were also excised and fixed after subcutaneous injection of Indian ink, after mechanic tissue splitting and after performing artificial skin folds. The aspects of the deep parts of the skin greatly varied according to their anatomic localisation. Below the adipose tissue, we often found a lamellar fibrous layer which extended from the interlobular septa and contained horizontally distributed fat cells. No specific tissue below the hypodermis was observed. Artificial skin folds concerned either exclusively the dermis, when they were superficial or included the hypodermis, but no specific structure was apparent in the center of the fold. India ink diffused to the adipose tissue, mainly along the septa, but did not localise in a specific subcutaneous compartment. This study shows that the histologic aspects of the deep part of the skin depend mainly on the anatomic localisation. Skin is composed of epidermis, dermis and hypodermis and thus the hypodermis can not be considered as being "subcutaneous". A difficult to individualise, fibrous lamellar structure in continuity with the interlobular septa is often found under the fat lobules. This structure is a cleavage line, as is always the case with loose connective tissues, but belongs to the hypodermis (i.e. fat tissue). No specific tissue nor any virtual space was

Anatomical structure of virginal plants of Ikonnikovia kaufmanniana (Regel Lincz.

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Aygul Аkhmetova

2014-04-01

Full Text Available In the paper is represented anatomical characteristic of vegetative organs of the rare, endangered and endemic species – Ikonnikovia kaufmanniana, which has been studied in conditions of three different coenopopulations. As a result, it was established that vegetative organs of these plants are characterized by different stage of development of its tissues dependently from the habitat.

Automatic, anatomically selective, artifact-free enhancement of digital chest radiographs

International Nuclear Information System (INIS)

Sezan, M.I.; Tekalp, A.M.; Schaetzing, R.

1988-01-01

The authors propose a technique for automatic, anatomically selective, artifact-free enhancement of digital chest radiographs. Anatomically selective enhancement is motivated by the different enhancement requirements of the lung field and the mediastinum. A recent peak detection algorithm is applied to the image histogram to automatically determine a gray-level threshold between the lung and mediastinum fields. The gray-level threshold facilitates anatomically selective gray-scale modification and unsharp masking. Further, in an attempt to suppress possible white-band artifacts due to unsharp masking at sharp edges, local-contrast adaptivity is incorporated into anatomically selective unsharp masking by designing an anatomy-sensitive emphasis parameter that varied asymmetrically with positive and negative values of the local image contrast

A high-fat diet activates oncogenic Kras and COX2 to induce development of pancreatic ductal adenocarcinoma in mice.

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Philip, Bincy; Roland, Christina L; Daniluk, Jaroslaw; Liu, Yan; Chatterjee, Deyali; Gomez, Sobeyda B; Ji, Baoan; Huang, Haojie; Wang, Huamin; Fleming, Jason B; Logsdon, Craig D; Cruz-Monserrate, Zobeida

2013-12-01

Obesity is a risk factor for pancreatic ductal adenocarcinoma (PDAC), but it is not clear how obesity contributes to pancreatic carcinogenesis. The oncogenic form of KRAS is expressed during early stages of PDAC development and is detected in almost all of these tumors. However, there is evidence that mutant KRAS requires an additional stimulus to activate its full oncogenic activity and that this stimulus involves the inflammatory response. We investigated whether the inflammation induced by a high-fat diet, and the accompanying up-regulation of cyclooxygenase-2 (COX2), increases Kras activity during pancreatic carcinogenesis in mice. We studied mice with acinar cell-specific expression of KrasG12D (LSL-Kras/Ela-CreERT mice) alone or crossed with COX2 conditional knockout mice (COXKO/LSL-Kras/Ela-CreERT). We also studied LSL-Kras/PDX1-Cre mice. All mice were fed isocaloric diets with different amounts of fat, and a COX2 inhibitor was administered to some LSL-Kras/Ela-CreERT mice. Pancreata were collected from mice and analyzed for Kras activity, levels of phosphorylated extracellular-regulated kinase, inflammation, fibrosis, pancreatic intraepithelial neoplasia (PanIN), and PDACs. Pancreatic tissues from LSL-Kras/Ela-CreERT mice fed high-fat diets (HFDs) had increased Kras activity, fibrotic stroma, and numbers of PanINs and PDACs than LSL-Kras/Ela-CreERT mice fed control diets; the mice fed the HFDs also had shorter survival times than mice fed control diets. Administration of a COX2 inhibitor to LSL-Kras/Ela-CreERT mice prevented these effects of HFDs. We also observed a significant reduction in survival times of mice fed HFDs. COXKO/LSL-Kras/Ela-CreERT mice fed HFDs had no evidence for increased numbers of PanIN lesions, inflammation, or fibrosis, as opposed to the increases observed in LSL-Kras/Ela-CreERT mice fed HFDs. In mice, an HFD can activate oncogenic Kras via COX2, leading to pancreatic inflammation and fibrosis and development of PanINs and PDAC. This

Ghrelin treatment prevents development of activity based anorexia in mice.

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Legrand, Romain; Lucas, Nicolas; Breton, Jonathan; Azhar, Saïda; do Rego, Jean-Claude; Déchelotte, Pierre; Coëffier, Moïse; Fetissov, Sergueï O

2016-06-01

Stimulation of feeding is necessary for treatment of pathological conditions of chronic malnutrition due to anorexia. Ghrelin, a hunger hormone, is one of the candidate for pharmacological treatments of anorexia, but because of its instability in plasma has limited efficacy. We previously showed that plasmatic IgG protect ghrelin from degradation and that IgG from obese subjects and mice may increase ghrelin׳s orexigenic effect. In this study we tested if ghrelin alone or combined with IgG may improve feeding in chronically food-restricted mice with or without physical activity-based anorexia (ABA) induced by free access to a running wheel. Mice received a single daily intraperitoneal injection of ghrelin (1nM) together or not with total IgG (1nM) from obese ob/ob or lean mice before access to food during 8 days of 3h/day feeding time. We found that both ghrelin and ghrelin combined with IgG from obese, but not lean mice, prevented ABA, however, they were not able to diminish body weight loss. Physical activity was lower during the feeding period and was increased shortly after feeding in mice receiving ghrelin together with IgG from obese mice. In food-restricted mice without ABA, ghrelin treatments did not have significant effects on food intake. Thus, this study supports pharmacological use of ghrelin or ghrelin combined with IgG from obese animals for treatment of anorexia accompanied by elevated physical activity. The utility of combining ghrelin with protective IgG should be further determined in animal models of anorexia with unrestricted access to food. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Mice lacking hippocampal left-right asymmetry show non-spatial learning deficits.

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Shimbo, Akihiro; Kosaki, Yutaka; Ito, Isao; Watanabe, Shigeru

2018-01-15

Left-right asymmetry is known to exist at several anatomical levels in the brain and recent studies have provided further evidence to show that it also exists at a molecular level in the hippocampal CA3-CA1 circuit. The distribution of N-methyl-d-aspartate (NMDA) receptor NR2B subunits in the apical and basal synapses of CA1 pyramidal neurons is asymmetrical if the input arrives from the left or right CA3 pyramidal neurons. In the present study, we examined the role of hippocampal asymmetry in cognitive function using β2-microglobulin knock-out (β2m KO) mice, which lack hippocampal asymmetry. We tested β2m KO mice in a series of spatial and non-spatial learning tasks and compared the performances of β2m KO and C57BL6/J wild-type (WT) mice. The β2m KO mice appeared normal in both spatial reference memory and spatial working memory tasks but they took more time than WT mice in learning the two non-spatial learning tasks (i.e., a differential reinforcement of lower rates of behavior (DRL) task and a straight runway task). The β2m KO mice also showed less precision in their response timing in the DRL task and showed weaker spontaneous recovery during extinction in the straight runway task. These results indicate that hippocampal asymmetry is important for certain characteristics of non-spatial learning. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of catechins and caffeine on the development of atherosclerosis in mice.

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Liu, Litong; Nagai, Izumi; Gao, Ying; Matsushima, Yoshibumi; Kawai, Yoshichika; Sayama, Kazutoshi

2017-10-01

Atherosclerosis is one of the diseases related to metabolic syndrome which is caused by obesity. Previous reports have shown that green tea and its components have anti-obesity effect. We examined whether catechins and caffeine can prevent the development of atherosclerosis by oral administration, singly or in combination to the atherosclerosis model mice. Results demonstrated that the number of atherosclerotic regions in the aorta was significantly reduced by the combined treatment, and the atherosclerotic area was also improved. Serum HDL-C increased by caffeine single treatment, but no effect on the TG and TC by any treatments. Moreover, ECG illuviated to atheromatous lesions in aorta and the illuviation was enhanced by caffeine. The mRNA expression levels of LOX-1 and TNF-α showed a tendency to suppress by the combined treatment. These results indicated that the combined administration of catechins and caffeine has the inhibitory effect on the development of atherosclerosis in mice.

Histologic and biochemical alterations predict pulmonary mechanical dysfunction in aging mice with chronic lung inflammation.

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Christopher B Massa

2017-08-01

Full Text Available Both aging and chronic inflammation produce complex structural and biochemical alterations to the lung known to impact work of breathing. Mice deficient in surfactant protein D (Sftpd develop progressive age-related lung pathology characterized by tissue destruction/remodeling, accumulation of foamy macrophages and alteration in surfactant composition. This study proposes to relate changes in tissue structure seen in normal aging and in chronic inflammation to altered lung mechanics using a computational model. Alterations in lung function in aging and Sftpd -/- mice have been inferred from fitting simple mechanical models to respiratory impedance data (Zrs, however interpretation has been confounded by the simultaneous presence of multiple coexisting pathophysiologic processes. In contrast to the inverse modeling approach, this study uses simulation from experimental measurements to recapitulate how aging and inflammation alter Zrs. Histologic and mechanical measurements were made in C57BL6/J mice and congenic Sftpd-/- mice at 8, 27 and 80 weeks of age (n = 8/group. An anatomic computational model based on published airway morphometry was developed and Zrs was simulated between 0.5 and 20 Hz. End expiratory pressure dependent changes in airway caliber and recruitment were estimated from mechanical measurements. Tissue elements were simulated using the constant phase model of viscoelasticity. Baseline elastance distribution was estimated in 8-week-old wild type mice, and stochastically varied for each condition based on experimentally measured alteration in elastic fiber composition, alveolar geometry and surfactant composition. Weighing reduction in model error against increasing model complexity allowed for identification of essential features underlying mechanical pathology and their contribution to Zrs. Using a maximum likelihood approach, alteration in lung recruitment and diminished elastic fiber density were shown predictive of mechanical

Histologic and biochemical alterations predict pulmonary mechanical dysfunction in aging mice with chronic lung inflammation.

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Massa, Christopher B; Groves, Angela M; Jaggernauth, Smita U; Laskin, Debra L; Gow, Andrew J

2017-08-01

Both aging and chronic inflammation produce complex structural and biochemical alterations to the lung known to impact work of breathing. Mice deficient in surfactant protein D (Sftpd) develop progressive age-related lung pathology characterized by tissue destruction/remodeling, accumulation of foamy macrophages and alteration in surfactant composition. This study proposes to relate changes in tissue structure seen in normal aging and in chronic inflammation to altered lung mechanics using a computational model. Alterations in lung function in aging and Sftpd -/- mice have been inferred from fitting simple mechanical models to respiratory impedance data (Zrs), however interpretation has been confounded by the simultaneous presence of multiple coexisting pathophysiologic processes. In contrast to the inverse modeling approach, this study uses simulation from experimental measurements to recapitulate how aging and inflammation alter Zrs. Histologic and mechanical measurements were made in C57BL6/J mice and congenic Sftpd-/- mice at 8, 27 and 80 weeks of age (n = 8/group). An anatomic computational model based on published airway morphometry was developed and Zrs was simulated between 0.5 and 20 Hz. End expiratory pressure dependent changes in airway caliber and recruitment were estimated from mechanical measurements. Tissue elements were simulated using the constant phase model of viscoelasticity. Baseline elastance distribution was estimated in 8-week-old wild type mice, and stochastically varied for each condition based on experimentally measured alteration in elastic fiber composition, alveolar geometry and surfactant composition. Weighing reduction in model error against increasing model complexity allowed for identification of essential features underlying mechanical pathology and their contribution to Zrs. Using a maximum likelihood approach, alteration in lung recruitment and diminished elastic fiber density were shown predictive of mechanical alteration at

DNA mismatch repair deficiency accelerates lung neoplasm development in K-rasLA1/+ mice: a brief report

International Nuclear Information System (INIS)

Downey, Charlene M; Jirik, Frank R

2015-01-01

Inherited as well as acquired deficiencies in specific DNA mismatch repair (MMR) components are associated with the development of a wide range of benign and malignant neoplasms. Loss of key members such as MSH2 and MLH1 severely cripples the ability of the cell to recognize and correct such lesions as base:base mismatches and replicative DNA polymerase errors such as slippages at repetitive sequences. Genomic instability resulting from MMR deficiency not only predisposes cells to malignant transformation but may also promote tumor progression. To test the latter, we interbred Msh2 −/− mice with the K-ras LA1/+ transgenic line that spontaneously develops a range of premalignant and malignant lung lesions. Compared to K-ras LA1/+ mice, K-ras LA1/+ ; Msh2 −/− mice developed lung adenomas and adenocarcinomas at an increased frequency and also demonstrated evidence of accelerated adenocarcinoma growth. Since MMR defects have been identified in some human lung cancers, the mutant mice may not only be of preclinical utility but they will also be useful in identifying gene alterations able to act in concert with Kras mutants to promote tumor progression

Radio-guided sentinel lymph node identification by lymphoscintigraphy fused with an anatomical vector profile: clinical applications.

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Niccoli Asabella, A; Antonica, F; Renna, M A; Rubini, D; Notaristefano, A; Nicoletti, A; Rubini, G

2013-12-01

To develop a method to fuse lymphoscintigraphic images with an adaptable anatomical vector profile and to evaluate its role in the clinical practice. We used Adobe Illustrator CS6 to create different vector profiles, we fused those profiles, using Adobe Photoshop CS6, with lymphoscintigraphic images of the patient. We processed 197 lymphoscintigraphies performed in patients with cutaneous melanomas, breast cancer or delayed lymph drainage. Our models can be adapted to every patient attitude or position and contain different levels of anatomical details ranging from external body profiles to the internal anatomical structures like bones, muscles, vessels, and lymph nodes. If needed, more new anatomical details can be added and embedded in the profile without redrawing them, saving a lot of time. Details can also be easily hidden, allowing the physician to view only relevant information and structures. Fusion times are about 85 s. The diagnostic confidence of the observers increased significantly. The validation process showed a slight shift (mean 4.9 mm). We have created a new, practical, inexpensive digital technique based on commercial software for fusing lymphoscintigraphic images with built-in anatomical reference profiles. It is easily reproducible and does not alter the original scintigraphic image. Our method allows a more meaningful interpretation of lymphoscintigraphies, an easier recognition of the anatomical site and better lymph node dissection planning.

Potential contribution of progesterone receptors to the development of sexual behavior in male and female mice.

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Desroziers, Elodie; Brock, Olivier; Bakker, Julie

2017-04-01

We previously showed that estradiol can have both defeminizing and feminizing effects on the developing mouse brain. Pre- and early postnatal estradiol defeminized the ability to show lordosis in adulthood, whereas prepubertal estradiol feminized this ability. Furthermore, we found that estradiol upregulates progesterone receptors (PR) during development, inducing both a male-and female-typical pattern of PR expression in the mouse hypothalamus. In the present study, we took advantage of a newly developed PR antagonist (ZK 137316) to determine whether PR contributes to either male- or female-typical sexual differentiation. Thus groups of male and female C57Bl/6j mice were treated with ZK 137316 or OIL as control: males were treated neonatally (P0-P10), during the critical period for male sexual differentiation, and females were treated prepubertally (P15-P25), during the critical period for female sexual differentiation. In adulthood, mice were tested for sexual behavior. In males, some minor effects of neonatal ZK treatment on sexual behavior were observed: latencies to the first mount, intromission and ejaculation were decreased in neonatally ZK treated males; however, this effect disappeared by the second mating test. By contrast, female mice treated with ZK during the prepubertal period showed significantly less lordosis than OIL-treated females. Mate preferences were not affected in either males or females treated with ZK during development. Taken together, these results suggest a role for PR and thus perhaps progesterone in the development of lordosis behavior in female mice. By contrast, no obvious role for PR can be discerned in the development of male sexual behavior. Copyright © 2016 Elsevier Inc. All rights reserved.

An interactive three-dimensional virtual body structures system for anatomical training over the internet.

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Temkin, Bharti; Acosta, Eric; Malvankar, Ameya; Vaidyanath, Sreeram

2006-04-01

The Visible Human digital datasets make it possible to develop computer-based anatomical training systems that use virtual anatomical models (virtual body structures-VBS). Medical schools are combining these virtual training systems and classical anatomy teaching methods that use labeled images and cadaver dissection. In this paper we present a customizable web-based three-dimensional anatomy training system, W3D-VBS. W3D-VBS uses National Library of Medicine's (NLM) Visible Human Male datasets to interactively locate, explore, select, extract, highlight, label, and visualize, realistic 2D (using axial, coronal, and sagittal views) and 3D virtual structures. A real-time self-guided virtual tour of the entire body is designed to provide detailed anatomical information about structures, substructures, and proximal structures. The system thus facilitates learning of visuospatial relationships at a level of detail that may not be possible by any other means. The use of volumetric structures allows for repeated real-time virtual dissections, from any angle, at the convenience of the user. Volumetric (3D) virtual dissections are performed by adding, removing, highlighting, and labeling individual structures (and/or entire anatomical systems). The resultant virtual explorations (consisting of anatomical 2D/3D illustrations and animations), with user selected highlighting colors and label positions, can be saved and used for generating lesson plans and evaluation systems. Tracking users' progress using the evaluation system helps customize the curriculum, making W3D-VBS a powerful learning tool. Our plan is to incorporate other Visible Human segmented datasets, especially datasets with higher resolutions, that make it possible to include finer anatomical structures such as nerves and small vessels. (c) 2006 Wiley-Liss, Inc.

A Proposed Set of Metrics to Reduce Patient Safety Risk From Within the Anatomic Pathology Laboratory.

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Banks, Peter; Brown, Richard; Laslowski, Alex; Daniels, Yvonne; Branton, Phil; Carpenter, John; Zarbo, Richard; Forsyth, Ramses; Liu, Yan-Hui; Kohl, Shane; Diebold, Joachim; Masuda, Shinobu; Plummer, Tim; Dennis, Eslie

2017-05-01

Anatomic pathology laboratory workflow consists of 3 major specimen handling processes. Among the workflow are preanalytic, analytic, and postanalytic phases that contain multistep subprocesses with great impact on patient care. A worldwide representation of experts came together to create a system of metrics, as a basis for laboratories worldwide, to help them evaluate and improve specimen handling to reduce patient safety risk. Members of the Initiative for Anatomic Pathology Laboratory Patient Safety (IAPLPS) pooled their extensive expertise to generate a list of metrics highlighting processes with high and low risk for adverse patient outcomes. : Our group developed a universal, comprehensive list of 47 metrics for patient specimen handling in the anatomic pathology laboratory. Steps within the specimen workflow sequence are categorized as high or low risk. In general, steps associated with the potential for specimen misidentification correspond to the high-risk grouping and merit greater focus within quality management systems. Primarily workflow measures related to operational efficiency can be considered low risk. Our group intends to advance the widespread use of these metrics in anatomic pathology laboratories to reduce patient safety risk and improve patient care with development of best practices and interlaboratory error reporting programs. © American Society for Clinical Pathology 2017.

Early Results of Anatomic Double Bundle Anterior Cruciate Ligament Reconstruction

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Demet Pepele

2014-01-01

Aim: The goal in anterior cruciate ligament reconstruction (ACLR) is to restore the normal anatomic structure and function of the knee. In the significant proportion of patients after the traditional single-bundle ACLR, complaints of instability still continue. Anatomic double bundle ACLR may provide normal kinematics in knees, much closer to the natural anatomy. The aim of this study is to clinically assess the early outcomes of our anatomical double bundle ACLR. Material and Method: In our ...

Phenotypic characterization of miR-92a-/- mice reveals an important function of miR-92a in skeletal development.

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Daniela Penzkofer

Full Text Available MicroRNAs (miRNAs, miRs emerged as key regulators of gene expression. Germline hemizygous deletion of the gene that encodes the miR-17∼92 miRNA cluster was associated with microcephaly, short stature and digital abnormalities in humans. Mice deficient for the miR-17∼92 cluster phenocopy several features such as growth and skeletal development defects and exhibit impaired B cell development. However, the individual contribution of miR-17∼92 cluster members to this phenotype is unknown. Here we show that germline deletion of miR-92a in mice is not affecting heart development and does not reduce circulating or bone marrow-derived hematopoietic cells, but induces skeletal defects. MiR-92a-/- mice are born at a reduced Mendelian ratio, but surviving mice are viable and fertile. However, body weight of miR-92a-/- mice was reduced during embryonic and postnatal development and adulthood. A significantly reduced body and skull length was observed in miR-92a-/- mice compared to wild type littermates. µCT analysis revealed that the length of the 5th mesophalanx to 5th metacarpal bone of the forelimbs was significantly reduced, but bones of the hindlimbs were not altered. Bone density was not affected. These findings demonstrate that deletion of miR-92a is sufficient to induce a developmental skeletal defect.

Control of Both Myeloid Cell Infiltration and Angiogenesis by CCR1 Promotes Liver Cancer Metastasis Development in Mice

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Mathieu Paul Rodero

2013-06-01

Full Text Available Expression of the CC chemokine receptor 1 (CCR1 by tumor cells has been associated with protumoral activity; however, its role in nontumoral cells during tumor development remains elusive. Here, we investigated the role of CCR1 deletion on stromal and hematopoietic cells in a liver metastasis tumor model. Metastasis development was strongly impaired in CCR1-deficient mice compared to control mice and was associated with reduced liver monocyte infiltration. To decipher the role of myeloid cells, sublethally irradiated mice were reconstituted with CCR1-deficient bone marrow (BM and showed better survival rates than the control reconstituted mice. These results point toward the involvement of CCR1 myeloid cell infiltration in the promotion of tumor burden. In addition, survival rates were extended in CCR1-deficient mice receiving either control or CCR1-deficient BM, indicating that host CCR1 expression on nonhematopoietic cells also supports tumor growth. Finally, we found defective tumor-induced neoangiogenesis (in vitro and in vivo in CCR1-deficient mice. Overall, our results indicate that CCR1 expression by both hematopoietic and nonhematopoietic cells favors tumor aggressiveness. We propose CCR1 as a potential therapeutical target for liver metastasis therapy.

Modulation of Specific Sensory Cortical Areas by Segregated Basal Forebrain Cholinergic Neurons Demonstrated by Neuronal Tracing and Optogenetic Stimulation in Mice.

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Chaves-Coira, Irene; Barros-Zulaica, Natali; Rodrigo-Angulo, Margarita; Núñez, Ángel

2016-01-01

Neocortical cholinergic activity plays a fundamental role in sensory processing and cognitive functions. Previous results have suggested a refined anatomical and functional topographical organization of basal forebrain (BF) projections that may control cortical sensory processing in a specific manner. We have used retrograde anatomical procedures to demonstrate the existence of specific neuronal groups in the BF involved in the control of specific sensory cortices. Fluoro-Gold (FlGo) and Fast Blue (FB) fluorescent retrograde tracers were deposited into the primary somatosensory (S1) and primary auditory (A1) cortices in mice. Our results revealed that the BF is a heterogeneous area in which neurons projecting to different cortical areas are segregated into different neuronal groups. Most of the neurons located in the horizontal limb of the diagonal band of Broca (HDB) projected to the S1 cortex, indicating that this area is specialized in the sensory processing of tactile stimuli. However, the nucleus basalis magnocellularis (B) nucleus shows a similar number of cells projecting to the S1 as to the A1 cortices. In addition, we analyzed the cholinergic effects on the S1 and A1 cortical sensory responses by optogenetic stimulation of the BF neurons in urethane-anesthetized transgenic mice. We used transgenic mice expressing the light-activated cation channel, channelrhodopsin-2, tagged with a fluorescent protein (ChR2-YFP) under the control of the choline-acetyl transferase promoter (ChAT). Cortical evoked potentials were induced by whisker deflections or by auditory clicks. According to the anatomical results, optogenetic HDB stimulation induced more extensive facilitation of tactile evoked potentials in S1 than auditory evoked potentials in A1, while optogenetic stimulation of the B nucleus facilitated either tactile or auditory evoked potentials equally. Consequently, our results suggest that cholinergic projections to the cortex are organized into segregated

Anatomical planes: are we teaching accurate surface anatomy?

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Mirjalili, S Ali; McFadden, Sarah L; Buckenham, Tim; Wilson, Ben; Stringer, Mark D

2012-10-01

Anatomical planes used in clinical practice and teaching anatomy are largely derived from cadaver studies. Numerous inconsistencies in clinically important surface markings exist between and within anatomical reference texts. The aim of this study was to reassess the accuracy of common anatomical planes in vivo using computed tomographic (CT) imaging. CT scans of the trunk in supine adults at end tidal inspiration were analyzed by dual consensus reporting to determine the anatomy of five anatomical planes: sternal angle, transpyloric, subcostal, supracristal, and the plane of the pubic crest. Patients with kyphosis, scoliosis, or abnormal lordosis, distorting space-occupying lesions, or visceromegaly were excluded. Among 153 thoracic CT scans (mean age 63 years, 53% female), the sternal angle was most common at T4 (females) or T4/5 (males) vertebral level, and the tracheal bifurcation, aortic arch, and pulmonary trunk were most often below this plane. In 108 abdominal CT scans (mean age 60 years, 59% female), the subcostal and supracristal planes were most often at L2 (58%) and L4 (69%), respectively. In 52 thoracoabdominal CT scans (mean age 61 years, 56% female), the transpyloric plane was between lower L1 and upper L2 (75%); in this plane were the superior mesenteric artery (56%), formation of the portal vein (53%), tip of the ninth rib (60%), and the left renal hilum (54%), but the right renal hilum and gallbladder fundus were more often below. The surface anatomy of anatomical planes needs revising in the light of results from living subjects using modern imaging techniques. Copyright © 2012 Wiley Periodicals, Inc.

Defects in the CAPN1 Gene Result in Alterations in Cerebellar Development and Cerebellar Ataxia in Mice and Humans

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Yubin Wang

2016-06-01

Full Text Available A CAPN1 missense mutation in Parson Russell Terrier dogs is associated with spinocerebellar ataxia. We now report that homozygous or heterozygous CAPN1-null mutations in humans result in cerebellar ataxia and limb spasticity in four independent pedigrees. Calpain-1 knockout (KO mice also exhibit a mild form of ataxia due to abnormal cerebellar development, including enhanced neuronal apoptosis, decreased number of cerebellar granule cells, and altered synaptic transmission. Enhanced apoptosis is due to absence of calpain-1-mediated cleavage of PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1, which results in inhibition of the Akt pro-survival pathway in developing granule cells. Injection of neonatal mice with the indirect Akt activator, bisperoxovanadium, or crossing calpain-1 KO mice with PHLPP1 KO mice prevented increased postnatal cerebellar granule cell apoptosis and restored granule cell density and motor coordination in adult mice. Thus, mutations in CAPN1 are an additional cause of ataxia in mammals, including humans.

Nos2 inactivation promotes the development of medulloblastoma in Ptch1(+/- mice by deregulation of Gap43-dependent granule cell precursor migration.

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Daniel Haag

Full Text Available Medulloblastoma is the most common malignant brain tumor in children. A subset of medulloblastoma originates from granule cell precursors (GCPs of the developing cerebellum and demonstrates aberrant hedgehog signaling, typically due to inactivating mutations in the receptor PTCH1, a pathomechanism recapitulated in Ptch1(+/- mice. As nitric oxide may regulate GCP proliferation and differentiation, we crossed Ptch1(+/- mice with mice lacking inducible nitric oxide synthase (Nos2 to investigate a possible influence on tumorigenesis. We observed a two-fold higher medulloblastoma rate in Ptch1(+/- Nos2(-/- mice compared to Ptch1(+/- Nos2(+/+ mice. To identify the molecular mechanisms underlying this finding, we performed gene expression profiling of medulloblastomas from both genotypes, as well as normal cerebellar tissue samples of different developmental stages and genotypes. Downregulation of hedgehog target genes was observed in postnatal cerebellum from Ptch1(+/+ Nos2(-/- mice but not from Ptch1(+/- Nos2(-/- mice. The most consistent effect of Nos2 deficiency was downregulation of growth-associated protein 43 (Gap43. Functional studies in neuronal progenitor cells demonstrated nitric oxide dependence of Gap43 expression and impaired migration upon Gap43 knock-down. Both effects were confirmed in situ by immunofluorescence analyses on tissue sections of the developing cerebellum. Finally, the number of proliferating GCPs at the cerebellar periphery was decreased in Ptch1(+/+ Nos2(-/- mice but increased in Ptch1(+/- Nos2(-/ (- mice relative to Ptch1(+/- Nos2(+/+ mice. Taken together, these results indicate that Nos2 deficiency promotes medulloblastoma development in Ptch1(+/- mice through retention of proliferating GCPs in the external granular layer due to reduced Gap43 expression. This study illustrates a new role of nitric oxide signaling in cerebellar development and demonstrates that the localization of pre-neoplastic cells during

Optimization of a Clinically Relevant Model of White Matter Stroke in Mice: Histological and Functional Evidences

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Ahmad, Abdullah S.; Satriotomo, Irawan; Fazal, Jawad A.; Nadeau, Stephen E.; Doré, Sylvain

2015-01-01

Background and Purpose White matter (WM) injury during stroke increases the risk of disability and gloomy prognosis of post-stroke rehabilitation. However, modeling of WM loss in rodents has proven to be challenging. Methods We report improved WM injury models in male C57BL/6 mice. Mice were given either endothelin-1 (ET-1) or L-N5-(1-iminoethyl)ornitine (L-NIO) into the periventricular white matter (PVWM), in the corpus callosum (CC), or in the posterior limb of internal capsule (PLIC). Anatomical and functional outcomes were quantified on day 7 post injection. Results Injection of ET-1 or L-NIO caused a small focal lesion in the injection site in the PVWM. No significant motor function deficits were observed in the PVWM lesion model. We next targeted the PLIC by using single or double injections of L-NIO and found that this strategy induced small focal infarction. Interestingly, injection of L-NIO in the PLIC also resulted in gliosis, and significant motor function deficits. Conclusions By employing different agents, doses, and locations, this study shows the feasibility of inducing brain WM injury accompanied with functional deficits in mice. Selective targeting of the injury location, behavioral testing, and the agents chosen to induce WM injury are all keys to successfully develop a mouse model and subsequent testing of therapeutic interventions against WM injury. PMID:27512724

Genetic pharmacotherapy as an early CNS drug development strategy: testing glutaminase inhibition for schizophrenia treatment in adult mice

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Susana eMingote

2016-01-01

Full Text Available Genetic pharmacotherapy is an early drug development strategy for the identification of novel CNS targets in mouse models prior to the development of specific ligands. Here for the first time, we have implemented this strategy to address the potential therapeutic value of a glutamate-based pharmacotherapy for schizophrenia involving inhibition of the glutamate recycling enzyme phosphate-activated glutaminase. Mice constitutively heterozygous for GLS1, the gene encoding glutaminase, manifest a schizophrenia resilience phenotype, a key dimension of which is an attenuated locomotor response to propsychotic amphetamine challenge. If resilience is due to glutaminase deficiency in adulthood, then glutaminase inhibitors should have therapeutic potential. However, this has been difficult to test given the dearth of neuroactive glutaminase inhibitors. So, we used genetic pharmacotherapy to test the therapeutic potential of glutaminase inhibition. We specifically asked whether adult induction of GLS1 heterozygosity would attenuate amphetamine responsiveness. We generated conditional floxGLS1 mice and crossed them with global CAG ERT2 cre/+ mice to produce GLS1 iHET mice, susceptible to tamoxifen induction of GLS1 heterozygosity. One month after tamoxifen treatment of adult GLS1 iHET mice, we found a 50% reduction in GLS1 allelic abundance and glutaminase mRNA levels in the brain. While GLS1 iHET mice showed some recombination prior to tamoxifen, there was no impact on mRNA levels. We then asked whether induction of GLS heterozygosity would attenuate the locomotor response to propsychotic amphetamine challenge. Before tamoxifen, control and GLS1 iHET mice did not differ in their response to amphetamine. One month after tamoxifen treatment, amphetamine-induced hyperlocomotion was blocked in GLS1 iHET mice. The block was largely maintained after 5 months. Thus, a genetically induced glutaminase reduction — mimicking pharmacological inhibition — strongly

Placental growth factor deficiency is associated with impaired cerebral vascular development in mice.

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Luna, Rayana Leal; Kay, Vanessa R; Rätsep, Matthew T; Khalaj, Kasra; Bidarimath, Mallikarjun; Peterson, Nichole; Carmeliet, Peter; Jin, Albert; Croy, B Anne

2016-02-01

Placental growth factor (PGF) is expressed in the developing mouse brain and contributes to vascularization and vessel patterning. PGF is dynamically expressed in fetal mouse brain, particularly forebrain, and is essential for normal cerebrovascular development. PGF rises in maternal plasma over normal human and mouse pregnancy but is low in many women with the acute onset hypertensive syndrome, pre-eclampsia (PE). Little is known about the expression of PGF in the fetus during PE. Pgf  (-/-) mice appear normal but recently cerebral vascular defects were documented in adult Pgf  (-/-) mice. Here, temporal-spatial expression of PGF is mapped in normal fetal mouse brains and cerebral vasculature development is compared between normal and congenic Pgf  (-/-) fetuses to assess the actions of PGF during cerebrovascular development. Pgf/PGF, Vegfa/VEGF, Vegf receptor (Vegfr)1 and Vegfr2 expression were examined in the brains of embryonic day (E)12.5, 14.5, 16.5 and 18.5 C57BL/6 (B6) mice using quantitative PCR and immunohistochemistry. The cerebral vasculature was compared between Pgf  (-/-) and B6 embryonic and adult brains using whole mount techniques. Vulnerability to cerebral ischemia was investigated using a left common carotid ligation assay. Pgf/PGF and Vegfr1 are highly expressed in E12.5-14.5 forebrain relative to VEGF and Vegfr2. Vegfa/VEGF is relatively more abundant in hindbrain (HB). PGF and VEGF expression were similar in midbrain. Delayed HB vascularization was seen at E10.5 and 11.5 in Pgf  (-/-) brains. At E14.5, Pgf  (-/-) circle of Willis showed unilateral hypoplasia and fewer collateral vessels, defects that persisted post-natally. Functionally, adult Pgf  (-/-) mice experienced cerebral ischemia after left common carotid arterial occlusion while B6 mice did not. Since Pgf  (-/-) mice were used, consequences of complete absence of maternal and fetal PGF were defined. Therefore, the effects of maternal versus fetal PGF

PDK1 Deficit Impairs the Development of the Dentate Gyrus in Mice.

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Xu, Min; Han, Xiaoning; Liu, Rui; Li, Yanjun; Qi, Cui; Yang, Zhongzhou; Zhao, Chunjie; Gao, Jun

2018-02-06

3-Phosphoinositide-dependent protein kinase-1 (PDK1) is crucial for the development of the dentate gyrus (DG), the first gateway receiving afferent inputs from the entorhinal cortex. However, the role of PDK1 in DG development is unclear. In the present study, by crossing Pdk1fl/fl mice with the Emx1-cre line, we identified that the ablation of PDK1 disrupted the development of DG via decreasing the proliferation, and increasing the differentiation of dentate neural progenitor cells, downregulating AKT activity and upregulating GSK3β signaling. Moreover, PDK1 deletion disrupted the distribution of Reelin+ cells and decreased the level of Reelin mRNA which may contribute to the defective migration of progenitor cells and the disrupted radial glial scaffolds. Furthermore, the inhibition of GSK3β activity partially restored the decreased proliferation of primary neural stem cells in vitro. Taken together, our data indicated that the ablation of PDK1 affected the proliferation and differentiation of dentate neural progenitor cells in mice. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

CDKL5 knockout leads to altered inhibitory transmission in the cerebellum of adult mice.

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Sivilia, S; Mangano, C; Beggiato, S; Giuliani, A; Torricella, R; Baldassarro, V A; Fernandez, M; Lorenzini, L; Giardino, L; Borelli, A C; Ferraro, L; Calzà, L

2016-06-01

Mutations in the X-linked cyclin-dependent kinase-like 5 gene (CDKL5) are associated to severe neurodevelopmental alterations including motor symptoms. In order to elucidate the neurobiological substrate of motor symptoms in CDKL5 syndrome, we investigated the motor function, GABA and glutamate pathways in the cerebellum of CDKL5 knockout female mice. Behavioural data indicate that CDKL5-KO mice displayed impaired motor coordination on the Rotarod test, and altered steps, as measured by the gait analysis using the CatWalk test. A higher reduction in spontaneous GABA efflux, than that in glutamate, was observed in CDKL5-KO mouse cerebellar synaptosomes, leading to a significant increase of spontaneous glutamate/GABA efflux ratio in these animals. On the contrary, there were no differences between groups in K(+) -evoked GABA and glutamate efflux. The anatomical analysis of cerebellar excitatory and inhibitory pathways showed a selective defect of the GABA-related marker GAD67 in the molecular layer in CDKL5-KO mice, while the glutamatergic marker VGLUT1 was unchanged in the same area. Fine cerebellar structural abnormalities such as a reduction of the inhibitory basket 'net' estimated volume and an increase of the pinceau estimated volume were also observed in CDKL5-KO mice. Finally, the BDNF mRNA expression level in the cerebellum, but not in the hippocampus, was reduced compared with WT animals. These data suggest that CDKL5 deletion during development more markedly impairs the establishment of a correct GABAergic cerebellar network than that of glutamatergic one, leading to the behavioural symptoms associated with CDKL5 mutation. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Finite-element modeling of the human neurocranium under functional anatomical aspects.

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Mall, G; Hubig, M; Koebke, J; Steinbuch, R

1997-08-01

Due to its functional significance the human skull plays an important role in biomechanical research. The present work describes a new Finite-Element model of the human neurocranium. The dry skull of a middle-aged woman served as a pattern. The model was developed using only the preprocessor (Mentat) of a commercial FE-system (Marc). Unlike that of other FE models of the human skull mentioned in the literature, the geometry in this model was designed according to functional anatomical findings. Functionally important morphological structures representing loci minoris resistentiae, especially the foramina and fissures of the skull base, were included in the model. The results of two linear static loadcase analyses in the region of the skull base underline the importance of modeling from the functional anatomical point of view.

Patterns of Glycoconjugate Distribution during Molar Tooth Germ Development in Mice

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AR. Varasteh

2007-09-01

Full Text Available Objective: The aim of the present study was to evaluate the structure and distribution of Glycoconjugates during molar tooth germ development in mice.Materials and Methods: Sixteen tooth germs were obtained from BALB/c mice embryos 15 to 18 days post-gestation and fixed in 10% formalin. After routine tissue processing, 5μm sections were cut and stained with BSA1-B4 and PNA using the lectin histochemical method. All slides were evaluated by light microscopy.Results: Both lectins showed positive reaction in the tooth germ but with spatiotemporal differences. During bell stage, the reaction was strong with BSA1-B4 but moderate with PNA. Strong PNA uptake was observed in the odontoblastic and ameloblastic nuclei alongwith the apical cytoplasm of the ameloblasts.Conclusion: Although the lectins that were used in the present study recognize the same terminal sugar residue, they reacted with different disaccharide sequences with various penaltomer sugars. Therefore it may be assumed that the pattern of affinity for different parts of the developing tooth germ such as ameloblasts and odontoblasts is different in various lectins.

The Anatomical Institute at the University of Greifswald during National Socialism: The procurement of bodies and their use for anatomical purposes.

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Alvermann, Dirk; Mittenzwei, Jan

2016-05-01

This is the first comprehensive account of body procurement at the Anatomical Institute at Greifswald University during National Socialism (NS). As in all other German anatomical departments, the bodies received during this period included increasing numbers of victims of the NS regime. Prior to 1939, 90% of all bodies came from hospitals, state nursing homes and mental institutions (Heil- und Pflegeanstalten), but dropped to less than 30% after 1941. While the total catchment area for body procurement decreased, the number of suppliers increased and included prisons, POW camps, Gestapo offices and military jurisdiction authorities. Among the 432 documented bodies delivered to the institute, 132 came from state nursing homes and mental institutions, mainly from Ueckermünde. These were bodies of persons, who probably were victims of "euthanasia" crimes. The Anatomical Institute also procured 46 bodies of forced laborers, of whom at least twelve had been executed. Other groups of victims included 21 bodies of executed Wehrmacht soldiers and 16 Russian prisoners of war from the camp Stalag II C in Greifswald, who had died of starvation and exhaustion. From 1941 onwards, the number of bodies delivered from prisons and penitentiaries greatly increased. In total, 60 bodies of prisoners, mainly from the penitentiary in Gollnow, were delivered to the Anatomical Institute. Greifswald Anatomical Institute was not just a passive recipient of bodies from all of these sources, but the anatomists actively lobbied with the authorities for an increased body supply for teaching and research purposes. Copyright © 2016 Elsevier GmbH. All rights reserved.

Anatomical Modularity of Verbal Working Memory? Functional Anatomical Evidence from a Famous Patient with Short-Term Memory Deficits

Directory of Open Access Journals (Sweden)

Eraldo Paulesu

2017-05-01

Full Text Available Cognitive skills are the emergent property of distributed neural networks. The distributed nature of these networks does not necessarily imply a lack of specialization of the individual brain structures involved. However, it remains questionable whether discrete aspects of high-level behavior might be the result of localized brain activity of individual nodes within such networks. The phonological loop of working memory, with its simplicity, seems ideally suited for testing this possibility. Central to the development of the phonological loop model has been the description of patients with focal lesions and specific deficits. As much as the detailed description of their behavior has served to refine the phonological loop model, a classical anatomoclinical correlation approach with such cases falls short in telling whether the observed behavior is based on the functions of a neural system resembling that seen in normal subjects challenged with phonological loop tasks or whether different systems have taken over. This is a crucial issue for the cross correlation of normal cognition, normal physiology, and cognitive neuropsychology. Here we describe the functional anatomical patterns of JB, a historical patient originally described by Warrington et al. (1971, a patient with a left temporo-parietal lesion and selective short phonological store deficit. JB was studied with the H215O PET activation technique during a rhyming task, which primarily depends on the rehearsal system of the phonological loop. No residual function was observed in the left temporo-parietal junction, a region previously associated with the phonological buffer of working memory. However, Broca's area, the major counterpart of the rehearsal system, was the major site of activation during the rhyming task. Specific and autonomous activation of Broca's area in the absence of afferent inputs from the other major anatomical component of the phonological loop shows that a certain

Fusion of the midplane with the left intersectional plane: a liver anatomical variation revisited with multidetector-row CT

International Nuclear Information System (INIS)

Lucidarme, Olivier; Taboury, Jacques; Savier, Eric; Hannoun, Laurent; Cadi, Mehdi; Grenier, Philippe A.

2006-01-01

This article updates the description of an anatomical variation of the liver, in which the gallbladder is adjacent to the ligamentum teres, that was described until now as ''right-sided ligamentum teres and right umbilical portion of the portal vein''. A study of eight patients showing this anatomical variation has led to a new archetypal anatomical description of the hepatic and portal veins, using multidetector-row computed tomography (MDCT) with three-dimensional (3D) volume-rendering (VR) reconstructions. While 2D axial imaging gave the same information, MDCT imaging with VR reconstructions provided a clear 3D visualization of this anatomical variation. Typical features can be described as follows: (1) juxtaposition of the ligamentum teres and the gallbladder; (2) typical portal vein branching with a right posterior branch, a left posterior branch and a main medial branch that terminates in the ligamentum teres; (3) two main hepatic veins and a hypotrophied medial hepatic vein. We think, based on the direct comparison of anatomical findings and knowledge of chronological embryological development, that this abnormality results from the defective development of the central part of the liver and not from the persistence of the right rather than the left umbilical vein. Because of the presence of only one medial plane, containing both the gallbladder and the ligamentum teres, we propose renaming it ''fusion of hepatic planes''. (orig.)

The endogenous preproglucagon system is not essential for gut growth homeostasis in mice.

Science.gov (United States)

Wismann, Pernille; Barkholt, Pernille; Secher, Thomas; Vrang, Niels; Hansen, Henrik B; Jeppesen, Palle Bekker; Baggio, Laurie L; Koehler, Jacqueline A; Drucker, Daniel J; Sandoval, Darleen A; Jelsing, Jacob

2017-07-01

The prevalence of obesity and related co-morbidities is reaching pandemic proportions. Today, the most effective obesity treatments are glucagon-like peptide 1 (GLP-1) analogs and bariatric surgery. Interestingly, both intervention paradigms have been associated with adaptive growth responses in the gut; however, intestinotrophic mechanisms associated with or secondary to medical or surgical obesity therapies are poorly understood. Therefore, the objective of this study was to assess the local basal endogenous and pharmacological intestinotrophic effects of glucagon-like peptides and bariatric surgery in mice. We used in situ hybridization to provide a detailed and comparative anatomical map of the local distribution of GLP-1 receptor ( Glp1r ), GLP-2 receptor ( Glp2r ), and preproglucagon ( Gcg ) mRNA expression throughout the mouse gastrointestinal tract. Gut development in GLP-1R-, GLP-2R-, or GCG-deficient mice was compared to their corresponding wild-type controls, and intestinotrophic effects of GLP-1 and GLP-2 analogs were assessed in wild-type mice. Lastly, gut volume was determined in a mouse model of vertical sleeve gastrectomy (VSG). Comparison of Glp1r , Glp2r , and Gcg mRNA expression indicated a widespread, but distinct, distribution of these three transcripts throughout all compartments of the mouse gastrointestinal tract. While mice null for Glp1r or Gcg showed normal intestinal morphology, Glp2r -/- mice exhibited a slight reduction in small intestinal mucosa volume. Pharmacological treatment with GLP-1 and GLP-2 analogs significantly increased gut volume. In contrast, VSG surgery had no effect on intestinal morphology. The present study indicates that the endogenous preproglucagon system, exemplified by the entire GCG gene and the receptors for GLP-1 and GLP-2, does not play a major role in normal gut development in the mouse. Furthermore, elevation in local intestinal and circulating levels of GLP-1 and GLP-2 achieved after VSG has limited impact

Analysis of Pathogenesis of Autoimmune Insulitis in NOD Mice: Adoptive Transfer Experiments of Insulitis in ILI and NOD Nude Mice

OpenAIRE

Nakamura, Moritaka; Nishimura, Masahiko; Koide, Yukio; Takato, O.Yoshida

2003-01-01

In an effort to study the pathophysiological events in the development of insulitis in NOD mice, we have developed ILI- and NOD-nu/nu mice. ILI mice are a nondiabetic inbred strain but are derived from the same Jcl:ICR mouse as NOD mice and share the same H-2 allotype with NOD mice. Splenocytes and CD4+ cells from diabetic NOD mice appeared to transfer insulitis to ILI-nu/nu mice, suggesting that ILI mice already express autoantigen(s) responsible for insulitis. But reciprocal thymic grafts f...

Lacrimal Gland Pathologies from an Anatomical Perspective

Directory of Open Access Journals (Sweden)

Mahmut Sinan Abit

2015-06-01

Full Text Available Most of the patients in our daily practice have one or more ocular surface disorders including conjucntivitis, keratitis, dry eye disease, meibomian gland dysfunction, contact lens related symptoms, refractive errors,computer vision syndrome. Lacrimal gland has an important role in all above mentioned pathologies due to its major secretory product. An anatomical and physiological knowledge about lacrimal gland is a must in understanding basic and common ophthalmological cases. İn this paper it is aimed to explain the lacrimal gland diseases from an anatomical perspective.

Human CD4 restores normal T cell development and function in mice deficient in murine CD4

OpenAIRE

1994-01-01

The ability of a human coreceptor to function in mice was investigated by generating human CD4 (hCD4)-expressing transgenic mice on a mouse CD4-deficient (mCD4-/-) background. From developing thymocyte to matured T lymphocyte functions, hCD4 was shown to be physiologically active. By examining the expansion and deletion of specific V beta T cell families in mutated mice with and without hCD4, it was found that hCD4 can participate in positive and negative selection. Mature hCD4 single positiv...

The Science and Politics of Naming: Reforming Anatomical Nomenclature, ca. 1886-1955.

Science.gov (United States)

Buklijas, Tatjana

2017-04-01

Anatomical nomenclature is medicine's official language. Early in their medical studies, students are expected to memorize not only the bodily geography but also the names for all the structures that, by consensus, constitute the anatomical body. The making and uses of visual maps of the body have received considerable historiographical attention, yet the history of production, communication, and reception of anatomical names-a history as long as the history of anatomy itself-has been studied far less. My essay examines the reforms of anatomical naming between the first modern nomenclature, the 1895 Basel Nomina Anatomica (BNA), and the 1955 Nomina Anatomica Parisiensia (NAP, also known as PNA), which is the basis for current anatomical terminology. I focus on the controversial and ultimately failed attempt to reform anatomical nomenclature, known as Jena Nomina Anatomica (INA), of 1935. Discussions around nomenclature reveal not only how anatomical names are made and communicated, but also the relationship of anatomy with the clinic; disciplinary controversies within anatomy; national traditions in science; and the interplay between international and scientific disciplinary politics. I show how the current anatomical nomenclature, a successor to the NAP, is an outcome of both political and disciplinary tensions that reached their peak before 1945. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Adam8 Limits the Development of Allergic Airway Inflammation in Mice

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Knolle, Martin D.; Nakajima, Takahiro; Hergrueter, Anja; Gupta, Kushagra; Polverino, Francesca; Craig, Vanessa J.; Fyfe, Susanne E.; Zahid, Muhammad; Permaul, Perdita; Cernadas, Manuela; Montano, Gilbert; Tesfaigzi, Yohannes; Sholl, Lynette; Kobzik, Lester; Israel, Elliot; Owen, Caroline A.

2013-01-01

To determine whether a disintegrin and a metalloproteinase-8 (Adam8) regulates allergic airway inflammation (AAI) and airway hyper-responsiveness (AHR), we compared AAI and AHR in wild type (WT) versus Adam8−/− mice in different genetic backgrounds sensitized and challenged with ovalbumin (OVA) or house dust mite protein extract (HDM). OVA- and HDM-treated Adam8−/− mice had higher lung leukocyte counts, more airway mucus metaplasia, greater lung levels of some TH2 cytokines, and higher methacholine-induced increases in central airway resistance than allergen-treated WT mice. Studies of OVA-treated Adam8 bone marrow chimeric mice confirmed that leukocyte-derived Adam8 predominantly mediated Adam8’s anti-inflammatory activities in murine airways. Airway eosinophils and macrophages both expressed Adam8 in WT mice with AAI. Adam8 limited AAI and AHR in mice by reducing leukocyte survival because: 1) Adam8−/− mice with AAI had fewer apoptotic eosinophils and macrophages in their airways than WT mice with AAI; and 2) Adam8−/− macrophages and eosinophils had reduced rates of apoptosis compared with WT leukocytes when the intrinsic (but not the extrinsic) apoptosis pathway was triggered in the cells in vitro. ADAM8 was robustly expressed by airway granulocytes in lung sections from human asthma patients but, surprisingly, airway macrophages had less ADAM8 staining than airway eosinophils. Thus, ADAM8 has anti-inflammatory activities during AAI in mice by activating the intrinsic apoptosis pathway in myeloid leukocytes. Strategies that increase ADAM8 levels in myeloid leukocytes may have therapeutic efficacy in asthma. PMID:23670189

Deformable meshes for medical image segmentation accurate automatic segmentation of anatomical structures

CERN Document Server

Kainmueller, Dagmar

2014-01-01

? Segmentation of anatomical structures in medical image data is an essential task in clinical practice. Dagmar Kainmueller introduces methods for accurate fully automatic segmentation of anatomical structures in 3D medical image data. The author's core methodological contribution is a novel deformation model that overcomes limitations of state-of-the-art Deformable Surface approaches, hence allowing for accurate segmentation of tip- and ridge-shaped features of anatomical structures. As for practical contributions, she proposes application-specific segmentation pipelines for a range of anatom

A general XML schema and SPM toolbox for storage of neuro-imaging results and anatomical labels.

Science.gov (United States)

Keator, David Bryant; Gadde, Syam; Grethe, Jeffrey S; Taylor, Derek V; Potkin, Steven G

2006-01-01

With the increased frequency of multisite, large-scale collaborative neuro-imaging studies, the need for a general, self-documenting framework for the storage and retrieval of activation maps and anatomical labels becomes evident. To address this need, we have developed and extensible markup language (XML) schema and associated tools for the storage of neuro-imaging activation maps and anatomical labels. This schema, as part of the XML-based Clinical Experiment Data Exchange (XCEDE) schema, provides storage capabilities for analysis annotations, activation threshold parameters, and cluster and voxel-level statistics. Activation parameters contain information describing the threshold, degrees of freedom, FWHM smoothness, search volumes, voxel sizes, expected voxels per cluster, and expected number of clusters in the statistical map. Cluster and voxel statistics can be stored along with the coordinates, threshold, and anatomical label information. Multiple threshold types can be documented for a given cluster or voxel along with the uncorrected and corrected probability values. Multiple atlases can be used to generate anatomical labels and stored for each significant voxel or cluter. Additionally, a toolbox for Statistical Parametric Mapping software (http://www. fil. ion.ucl.ac.uk/spm/) was created to capture the results from activation maps using the XML schema that supports both SPM99 and SPM2 versions (http://nbirn.net/Resources/Users/ Applications/xcede/SPM_XMLTools.htm). Support for anatomical labeling is available via the Talairach Daemon (http://ric.uthscsa. edu/projects/talairachdaemon.html) and Automated Anatomical Labeling (http://www. cyceron.fr/freeware/).

16 CFR Figure 1 to Part 1203 - Anatomical Planes

Science.gov (United States)

2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Anatomical Planes 1 Figure 1 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 1 Figure 1 to Part 1203—Anatomical Planes ER10MR98.001 ...

Feature-based morphometry: discovering group-related anatomical patterns.

Science.gov (United States)

Toews, Matthew; Wells, William; Collins, D Louis; Arbel, Tal

2010-02-01

This paper presents feature-based morphometry (FBM), a new fully data-driven technique for discovering patterns of group-related anatomical structure in volumetric imagery. In contrast to most morphometry methods which assume one-to-one correspondence between subjects, FBM explicitly aims to identify distinctive anatomical patterns that may only be present in subsets of subjects, due to disease or anatomical variability. The image is modeled as a collage of generic, localized image features that need not be present in all subjects. Scale-space theory is applied to analyze image features at the characteristic scale of underlying anatomical structures, instead of at arbitrary scales such as global or voxel-level. A probabilistic model describes features in terms of their appearance, geometry, and relationship to subject groups, and is automatically learned from a set of subject images and group labels. Features resulting from learning correspond to group-related anatomical structures that can potentially be used as image biomarkers of disease or as a basis for computer-aided diagnosis. The relationship between features and groups is quantified by the likelihood of feature occurrence within a specific group vs. the rest of the population, and feature significance is quantified in terms of the false discovery rate. Experiments validate FBM clinically in the analysis of normal (NC) and Alzheimer's (AD) brain images using the freely available OASIS database. FBM automatically identifies known structural differences between NC and AD subjects in a fully data-driven fashion, and an equal error classification rate of 0.80 is achieved for subjects aged 60-80 years exhibiting mild AD (CDR=1). Copyright (c) 2009 Elsevier Inc. All rights reserved.

Maternal exposure to nanosized titanium dioxide suppresses embryonic development in mice

Directory of Open Access Journals (Sweden)

Hong F

2017-08-01

Full Text Available Fashui Hong,1–4 Yingjun Zhou,1–4 Xiaoyang Zhao,5 Lei Sheng,5 Ling Wang6 1Jiangsu Collaborative Innovation Center of Regional Modern Agriculture and Environmental Protection, 2Jiangsu Key Laboratory for Food Safety and Nutritional Function, 3Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, 4School of Life Sciences, Huaiyin Normal University, Huaian, 5Medical College of Soochow University, Suzhou, 6Library of Soochow University, Suzhou, Jiangsu, China Abstract: Although nanoscale titanium dioxide (nano-TiO2 has been extensively used in industrial food applications and daily products for pregnant women, infants, and children, its potential toxicity on fetal development has been rarely studied. The main objective of this investigation was to establish the effects of maternal exposure of nano-TiO2 on developing embryos. Female imprinting control region mice were orally administered nano-TiO2 from gestational day 0 to 17. Our findings showed that Ti concentrations in maternal serum, placenta, and fetus were increased in nano-TiO2-exposed mice when compared to controls, which resulted in reductions in the contents of calcium and zinc in maternal serum, placenta, and fetus, maternal weight gain, placental weight, fetal weight, number of live fetuses, and fetal crown–rump length as well as cauda length, and caused an increase in the number of both dead fetuses and resorptions. Furthermore, maternal nano-TiO2 exposure inhibited development of the fetal skeleton, suggesting a significant absence of cartilage, reduced or absent ossification, and an increase in the number of fetuses with dysplasia, including exencephaly, spina bifida, coiled tail, scoliosis, rib absence, and sternum absence. These findings indicated that nano-TiO2 can cross the blood–fetal barrier and placental barrier, thereby delaying the development of fetal mice and inducing skeletal malformation. These factors may be associated with reductions in

The Fate of Anatomical Collections

NARCIS (Netherlands)

Knoeff, Rina; Zwijnenberg, Robert

Almost every medical faculty possesses anatomical and/or pathological collections: human and animal preparations, wax- and other models, as well as drawings, photographs, documents and archives relating to them. In many institutions these collections are well-preserved, but in others they are poorly

Interfractional Variations in Patient Setup and Anatomic Change Assessed by Daily Computed Tomography

International Nuclear Information System (INIS)

Li, X. Allen; Qi, X. Sharon; Pitterle, Marissa; Kalakota, Kapila; Mueller, Kevin; Erickson, Beth A.; Wang Dian; Schultz, Christopher J.; Firat, Selim Y.; Wilson, J. Frank

2007-01-01

Purpose: To analyze the interfractional variations in patient setup and anatomic changes at seven anatomic sites observed in image-guided radiotherapy. Methods and Materials: A total of 152 patients treated at seven anatomic sites using a Hi-Art helical tomotherapy system were analyzed. Daily tomotherapy megavoltage computed tomography images acquired before each treatment were fused to the planning kilovoltage computed tomography images to determine the daily setup errors and organ motions and deformations. The setup errors were corrected before treatment and were used, along with the organ motions, to determine the clinical target volume/planning target volume margins. The organ motions and deformations for 3 representative patient cases (pancreas, uterus, and soft-tissue sarcoma) and for 14 kidneys of 7 patients are presented. Results: Interfractional setup errors in the skull, brain, and head and neck are significantly smaller than those in the chest, abdomen, pelvis, and extremities. These site-specific relationships are statistically significant. The margins required to account for these setup errors range from 3 to 8 mm for the seven sites. The margin to account for both setup errors and organ motions for kidney is 16 mm. Substantial interfractional anatomic changes were observed. For example, the pancreas moved up to ±20 mm and volumes of the uterus and sarcoma varied ≤30% and 100%, respectively. Conclusion: The interfractional variations in patient setup and in shapes, sizes, and positions of both targets and normal structures are site specific and may be used to determine the site-specific margins. The data presented in this work dealing with seven anatomic sites may be useful in developing adaptive radiotherapy

Notes from the field: Investigation of infectious disease risks associated with a nontransplant anatomical donation center--Arizona, 2014.

Science.gov (United States)

de Perio, Marie A; Bernard, Bruce P; Delaney, Lisa J; Pesik, Nicki; Cohen, Nicole J

2014-05-02

CDC is investigating reports of potential occupational exposure to human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and Mycobacterium tuberculosis among workers performing preparation and dissection procedures on human nontransplant anatomical materials at a nontransplant anatomical donation center in Arizona. CDC is working with Arizona public health officials to inform persons exposed to these potentially infected materials. Nontransplant anatomical centers around the United States process thousands of donated cadavers annually. These materials (which might be fresh, frozen, or chemically preserved) are used by universities and surgical instrument and pharmaceutical companies for medical education and research. The American Association of Tissue Banks has developed accreditation policies for nontransplant anatomical donation organizations. It also has written standards that specify exclusion criteria for donor material, as well as use of proper environmental controls and safe work practices to prevent transmission of infectious agents during receipt and handling of nontransplant anatomical materials. At the center under investigation, which is now closed, these standards might not have been consistently implemented.

Anatomical success in patients after retinectomy for complex retinal detachment

International Nuclear Information System (INIS)

Mukhtar, A.; Ishaq, M.; Islam, Q.U.

2015-01-01

To evaluate the efficacy of primary and redo retinectomy in eyes with complex retinal detachment. Study Design: Quasi-experimental study. Place and Duration of Study: Armed Forces Institute of Ophthalmology Rawalpindi from Jan 2012 to June 2013. Patients and Methods: Fifty eight eyes (patients) underwent relaxing retinectomies for complex retinal detachment with proliferative vitreoretinopathy or intrinsic retinal shortening. Operative technique included pars plana vitrectomy, proliferative vitreoretinopathy management, use of intraoperative perfluorocarbon liquid, retinectomy, endolaser and intraocular temponade. The main outcome was anatomic success, defined as complete retinal reattachment at four months follow up. Eighteen eyes out of the same primary group underwent second retinectomy because of anatomical failure. Results: Mean age of study population was 53.78 ± 15.11 years, 56.9% of patients were male(s). Anatomic success rate after 1st retinectomy was achieved in 68.96% (40 eyes out of 58). In eighteen eyes that underwent 2nd retinectomy, anatomic success rate was 72.22% (13 eyes out of 18). Overall success rate was 91.3% (53 eyes out of 58) in our study. Conclusions: Relaxing retinectomies for retinal shortening can improve the anatomical success rate in patients with complex RD. (author)

Effects of neonatal oxytocin manipulation on development of social behaviors in mice.

Science.gov (United States)

Mogi, Kazutaka; Ooyama, Rumi; Nagasawa, Miho; Kikusui, Takefumi

2014-06-22

The oxytocin (OT) neural system is thought to be involved in the underlying mechanisms that guide the development of social behaviors. In the present study, we examined the effects of neonatal oxytocin manipulation in mice. Within 24 hours after birth, pups in the treatment group randomly received an intraperitoneal injection of OT or OT antagonist (OTA), and those in the control group received a saline injection or handling only. Some of these mice underwent a test that counted the number of isolation-induced ultrasound vocalizations they made on postnatal day 6, and they were further tested for sociability at 8-9 weeks of age and for neuroendocrine stress response to novel environments at 19-20 weeks of age. Another group of mice was tested for alloparental responsiveness at 13-15 weeks of age. The OT injection affected sociability and alloparental responsiveness. In an approach/avoidance test, most of the mice made a social approach to an unfamiliar conspecific of the same sex, but females that had received a neonatal injection of 3 μg of OTA did not show this response. The neonatal OTA treatment appeared to inhibit females' sociability in a dose-dependent fashion. In a retrieving test, females that had received a neonatal injection of 3 μg of OT retrieved significantly more pups than did those that had received 3 μg of OTA, although neither of the treatments caused the females to behave significantly differently from control group females. Meanwhile, a neonatal injection of 3 μg of OTA increased the latency to retrieve pups in males. These results suggested that neonatal OT action may positively regulate alloparental responsiveness in adulthood. Considering that the organizational effects of OT have also been shown in voles and rats, the mechanism by which neonatal OT modifies the development of social behaviors appears to be common to all rodents. Copyright © 2014 Elsevier Inc. All rights reserved.

Population of anatomically variable 4D XCAT adult phantoms for imaging research and optimization

Energy Technology Data Exchange (ETDEWEB)

Segars, W. P.; Bond, Jason; Frush, Jack; Hon, Sylvia; Eckersley, Chris; Samei, E. [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 (United States); Williams, Cameron H.; Frush, D. [Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 (United States); Feng Jianqiao; Tward, Daniel J.; Ratnanather, J. T.; Miller, M. I. [Center for Imaging Science, Johns Hopkins University, Baltimore, Maryland 21218 (United States)

2013-04-15

Purpose: The authors previously developed the 4D extended cardiac-torso (XCAT) phantom for multimodality imaging research. The XCAT consisted of highly detailed whole-body models for the standard male and female adult, including the cardiac and respiratory motions. In this work, the authors extend the XCAT beyond these reference anatomies by developing a series of anatomically variable 4D XCAT adult phantoms for imaging research, the first library of 4D computational phantoms. Methods: The initial anatomy of each phantom was based on chest-abdomen-pelvis computed tomography data from normal patients obtained from the Duke University database. The major organs and structures for each phantom were segmented from the corresponding data and defined using nonuniform rational B-spline surfaces. To complete the body, the authors manually added on the head, arms, and legs using the original XCAT adult male and female anatomies. The structures were scaled to best match the age and anatomy of the patient. A multichannel large deformation diffeomorphic metric mapping algorithm was then used to calculate the transform from the template XCAT phantom (male or female) to the target patient model. The transform was applied to the template XCAT to fill in any unsegmented structures within the target phantom and to implement the 4D cardiac and respiratory models in the new anatomy. Each new phantom was refined by checking for anatomical accuracy via inspection of the models. Results: Using these methods, the authors created a series of computerized phantoms with thousands of anatomical structures and modeling cardiac and respiratory motions. The database consists of 58 (35 male and 23 female) anatomically variable phantoms in total. Like the original XCAT, these phantoms can be combined with existing simulation packages to simulate realistic imaging data. Each new phantom contains parameterized models for the anatomy and the cardiac and respiratory motions and can, therefore, serve

Population of anatomically variable 4D XCAT adult phantoms for imaging research and optimization

International Nuclear Information System (INIS)

Segars, W. P.; Bond, Jason; Frush, Jack; Hon, Sylvia; Eckersley, Chris; Samei, E.; Williams, Cameron H.; Frush, D.; Feng Jianqiao; Tward, Daniel J.; Ratnanather, J. T.; Miller, M. I.

2013-01-01

Purpose: The authors previously developed the 4D extended cardiac-torso (XCAT) phantom for multimodality imaging research. The XCAT consisted of highly detailed whole-body models for the standard male and female adult, including the cardiac and respiratory motions. In this work, the authors extend the XCAT beyond these reference anatomies by developing a series of anatomically variable 4D XCAT adult phantoms for imaging research, the first library of 4D computational phantoms. Methods: The initial anatomy of each phantom was based on chest–abdomen–pelvis computed tomography data from normal patients obtained from the Duke University database. The major organs and structures for each phantom were segmented from the corresponding data and defined using nonuniform rational B-spline surfaces. To complete the body, the authors manually added on the head, arms, and legs using the original XCAT adult male and female anatomies. The structures were scaled to best match the age and anatomy of the patient. A multichannel large deformation diffeomorphic metric mapping algorithm was then used to calculate the transform from the template XCAT phantom (male or female) to the target patient model. The transform was applied to the template XCAT to fill in any unsegmented structures within the target phantom and to implement the 4D cardiac and respiratory models in the new anatomy. Each new phantom was refined by checking for anatomical accuracy via inspection of the models. Results: Using these methods, the authors created a series of computerized phantoms with thousands of anatomical structures and modeling cardiac and respiratory motions. The database consists of 58 (35 male and 23 female) anatomically variable phantoms in total. Like the original XCAT, these phantoms can be combined with existing simulation packages to simulate realistic imaging data. Each new phantom contains parameterized models for the anatomy and the cardiac and respiratory motions and can, therefore

Evaluation of anatomical and physical properties of Khaya nthotheca

African Journals Online (AJOL)

The anatomical and physical properties of Khaya anthotheca (Welw.) C. DC wood from the transition forest of middle altitude (zone 1) and the humid dense forest of low altitude (zone 2) in the East of the Democratic Republic of Congo were evaluated to ascertain the effect of growth area on the anatomical and physical ...

Laryngeal spaces and lymphatics: current anatomic concepts

International Nuclear Information System (INIS)

Welsh, L.W.; Welsh, J.J.; Rizzo, T.A. Jr.

1983-01-01

This investigation evaluates the anatomic concepts of individual spaces or compartments within the larynx by isotope and dye diffusion. The authors identified continuity of spaces particularly within the submucosal planes and a relative isolation within the fixed structures resulting from the longitudinal pattern of fibroelastic tissues, muscle bands, and perichondrium. The historical data of anatomic resistance are refuted by the radioisotope patterns of dispersion and the histologic evidence of tissue permeability to the carbon particles. There is little clinical application of the compartment concept to the perimeter of growth and the configuration of extensive endolaryngeal cancers. The internal and extralaryngeal lymphatic network is presented and the regional associations are identified. The normal ipsilateral relationship is distorted by dispersion within the endolarynx supervening the anatomic midline. The effects of lymphatic obstruction caused by regional lymphadenectomy, tumor fixation, and irradiation-infection sequelae are illustrated; these result in widespread bilateral lymphatic nodal terminals. Finally, the evidence suggests that the internal network is modified by external interruption to accommodate an outflow system in continuity with the residual patent lymphatic channels

[Lymphoscintigrams with anatomical landmarks obtained with vector graphics].

Science.gov (United States)

Rubini, Giuseppe; Antonica, Filippo; Renna, Maria Antonia; Ferrari, Cristina; Iuele, Francesca; Stabile Ianora, Antonio Amato; Losco, Matteo; Niccoli Asabella, Artor

2012-11-01

Nuclear medicine images are difficult to interpret because they do not include anatomical details. The aim of this study was to obtain lymphoscintigrams with anatomical landmarks that could be easily interpreted by General Physicians. Traditional lymphoscintigrams were processed with Adobe© Photoshop® CS6 and converted into vector images created by Illustrator®. The combination with a silhouette vector improved image interpretation, without resulting in longer radiation exposure or acquisition times.

SU-C-207B-02: Maximal Noise Reduction Filter with Anatomical Structures Preservation

Energy Technology Data Exchange (ETDEWEB)

Maitree, R; Guzman, G; Chundury, A; Roach, M; Yang, D [Washington University School of Medicine, St Louis, MO (United States)

2016-06-15

Purpose: All medical images contain noise, which can result in an undesirable appearance and can reduce the visibility of anatomical details. There are varieties of techniques utilized to reduce noise such as increasing the image acquisition time and using post-processing noise reduction algorithms. However, these techniques are increasing the imaging time and cost or reducing tissue contrast and effective spatial resolution which are useful diagnosis information. The three main focuses in this study are: 1) to develop a novel approach that can adaptively and maximally reduce noise while preserving valuable details of anatomical structures, 2) to evaluate the effectiveness of available noise reduction algorithms in comparison to the proposed algorithm, and 3) to demonstrate that the proposed noise reduction approach can be used clinically. Methods: To achieve a maximal noise reduction without destroying the anatomical details, the proposed approach automatically estimated the local image noise strength levels and detected the anatomical structures, i.e. tissue boundaries. Such information was used to adaptively adjust strength of the noise reduction filter. The proposed algorithm was tested on 34 repeating swine head datasets and 54 patients MRI and CT images. The performance was quantitatively evaluated by image quality metrics and manually validated for clinical usages by two radiation oncologists and one radiologist. Results: Qualitative measurements on repeated swine head images demonstrated that the proposed algorithm efficiently removed noise while preserving the structures and tissues boundaries. In comparisons, the proposed algorithm obtained competitive noise reduction performance and outperformed other filters in preserving anatomical structures. Assessments from the manual validation indicate that the proposed noise reduction algorithm is quite adequate for some clinical usages. Conclusion: According to both clinical evaluation (human expert ranking) and

SU-C-207B-02: Maximal Noise Reduction Filter with Anatomical Structures Preservation

International Nuclear Information System (INIS)

Maitree, R; Guzman, G; Chundury, A; Roach, M; Yang, D

2016-01-01

Purpose: All medical images contain noise, which can result in an undesirable appearance and can reduce the visibility of anatomical details. There are varieties of techniques utilized to reduce noise such as increasing the image acquisition time and using post-processing noise reduction algorithms. However, these techniques are increasing the imaging time and cost or reducing tissue contrast and effective spatial resolution which are useful diagnosis information. The three main focuses in this study are: 1) to develop a novel approach that can adaptively and maximally reduce noise while preserving valuable details of anatomical structures, 2) to evaluate the effectiveness of available noise reduction algorithms in comparison to the proposed algorithm, and 3) to demonstrate that the proposed noise reduction approach can be used clinically. Methods: To achieve a maximal noise reduction without destroying the anatomical details, the proposed approach automatically estimated the local image noise strength levels and detected the anatomical structures, i.e. tissue boundaries. Such information was used to adaptively adjust strength of the noise reduction filter. The proposed algorithm was tested on 34 repeating swine head datasets and 54 patients MRI and CT images. The performance was quantitatively evaluated by image quality metrics and manually validated for clinical usages by two radiation oncologists and one radiologist. Results: Qualitative measurements on repeated swine head images demonstrated that the proposed algorithm efficiently removed noise while preserving the structures and tissues boundaries. In comparisons, the proposed algorithm obtained competitive noise reduction performance and outperformed other filters in preserving anatomical structures. Assessments from the manual validation indicate that the proposed noise reduction algorithm is quite adequate for some clinical usages. Conclusion: According to both clinical evaluation (human expert ranking) and

Sildenafil citrate (Viagra) impairs fertilization and early embryo development in mice.

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Glenn, David R J; McClure, Neil; Cosby, S Louise; Stevenson, Michael; Lewis, Sheena E M

2009-03-01

To determine the effects of sildenafil citrate, a cyclic monophosphate-specific type 5 phosphodiesterase inhibitor known to affect sperm function, on fertilization and early embryo cleavage. This acute mammal study included male and female mice assigned randomly, the females sacrificed after mating and their oocytes/embryos evaluated at four time periods after treatment. Academic research environment. Male and female CBAB(6) mice. Female mice were injected intraperitoneally with 5 IU gonadotropin (hCG) to stimulate follicular growth and induce ovulation. They were each caged with a male that had been gavaged with sildenafil citrate (0.06 mg/0.05 mL) and allowed to mate. After 12, 36, 60, and 84 h, females were killed, their oviducts were dissected out, and retrieved embryos were assessed for blastomere number and quality. Fertilization rates and numbers of embryos were evaluated after treatment. Fertilization rates (day 1) were markedly reduced (-33%) in matings where the male had taken sildenafil citrate. Over days 2-4, the numbers of embryos developing in the treated group were significantly fewer than in the control group. There was also a trend for impaired cleavage rates within those embryos, although this did not reach significance. The impairments to fertility caused by sildenafil citrate have important implications for infertility centers and for couples who are using this drug precoitally while attempting to conceive.

Development of a reactive stroma associated with prostatic intraepithelial neoplasia in EAF2 deficient mice.

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Laura E Pascal

Full Text Available ELL-associated factor 2 (EAF2 is an androgen-responsive tumor suppressor frequently deleted in advanced prostate cancer that functions as a transcription elongation factor of RNA Pol II through interaction with the ELL family proteins. EAF2 knockout mice on a 129P2/OLA-C57BL/6J background developed late-onset lung adenocarcinoma, hepatocellular carcinoma, B-cell lymphoma and high-grade prostatic intraepithelial neoplasia. In order to further characterize the role of EAF2 in the development of prostatic defects, the effects of EAF2 loss were compared in different murine strains. In the current study, aged EAF2(-/- mice on both the C57BL/6J and FVB/NJ backgrounds exhibited mPIN lesions as previously reported on a 129P2/OLA-C57BL/6J background. In contrast to the 129P2/OLA-C57BL/6J mixed genetic background, the mPIN lesions in C57BL/6J and FVB/NJ EAF2(-/- mice were associated with stromal defects characteristic of a reactive stroma and a statistically significant increase in prostate microvessel density. Stromal inflammation and increased microvessel density was evident in EAF2-deficient mice on a pure C57BL/6J background at an early age and preceded the development of the histologic epithelial hyperplasia and neoplasia found in the prostates of older EAF2(-/- animals. Mice deficient in EAF2 had an increased recovery rate and a decreased overall response to the effects of androgen deprivation. EAF2 expression in human cancer was significantly down-regulated and microvessel density was significantly increased compared to matched normal prostate tissue; furthermore EAF2 expression was negatively correlated with microvessel density. These results suggest that the EAF2 knockout mouse on the C57BL/6J and FVB/NJ genetic backgrounds provides a model of PIN lesions associated with an altered prostate microvasculature and reactive stromal compartment corresponding to that reported in human prostate tumors.

Embryonic Lethality Due to Arrested Cardiac Development in Psip1/Hdgfrp2 Double-Deficient Mice.

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Hao Wang

Full Text Available Hepatoma-derived growth factor (HDGF related protein 2 (HRP2 and lens epithelium-derived growth factor (LEDGF/p75 are closely related members of the HRP2 protein family. LEDGF/p75 has been implicated in numerous human pathologies including cancer, autoimmunity, and infectious disease. Knockout of the Psip1 gene, which encodes for LEDGF/p75 and the shorter LEDGF/p52 isoform, was previously shown to cause perinatal lethality in mice. The function of HRP2 was by contrast largely unknown. To learn about the role of HRP2 in development, we knocked out the Hdgfrp2 gene, which encodes for HRP2, in both normal and Psip1 knockout mice. Hdgfrp2 knockout mice developed normally and were fertile. By contrast, the double deficient mice died at approximate embryonic day (E 13.5. Histological examination revealed ventricular septal defect (VSD associated with E14.5 double knockout embryos. To investigate the underlying molecular mechanism(s, RNA recovered from ventricular tissue was subjected to RNA-sequencing on the Illumina platform. Bioinformatic analysis revealed several genes and biological pathways that were significantly deregulated by the Psip1 knockout and/or Psip1/Hdgfrp2 double knockout. Among the dozen genes known to encode for LEDGF/p75 binding factors, only the expression of Nova1, which encodes an RNA splicing factor, was significantly deregulated by the knockouts. However the expression of other RNA splicing factors, including the LEDGF/p52-interacting protein ASF/SF2, was not significantly altered, indicating that deregulation of global RNA splicing was not a driving factor in the pathology of the VSD. Tumor growth factor (Tgf β-signaling, which plays a key role in cardiac morphogenesis during development, was the only pathway significantly deregulated by the double knockout as compared to control and Psip1 knockout samples. We accordingly speculate that deregulated Tgf-β signaling was a contributing factor to the VSD and prenatal lethality

Anatomical knowledge retention in third-year medical students prior to obstetrics and gynecology and surgery rotations.

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Jurjus, Rosalyn A; Lee, Juliet; Ahle, Samantha; Brown, Kirsten M; Butera, Gisela; Goldman, Ellen F; Krapf, Jill M

2014-01-01

Surgical anatomy is taught early in medical school training. The literature shows that many physicians, especially surgical specialists, think that anatomical knowledge of medical students is inadequate and nesting of anatomical sciences later in the clinical curriculum may be necessary. Quantitative data concerning this perception of an anatomical knowledge deficit are lacking, as are specifics as to what content should be reinforced. This study identifies baseline areas of strength and weakness in the surgical anatomy knowledge of medical students entering surgical rotations. Third-year medical students completed a 20-25-question test at the beginning of the General Surgery and Obstetrics and Gynecology rotations. Knowledge of inguinal anatomy (45.3%), orientation in abdominal cavity (38.8%), colon (27.7%), and esophageal varices (12.8%) was poor. The numbers in parentheses are the percentage of questions answered correctly per topic. In comparing those scores to matched test items from this cohort as first-year students in the anatomy course, the drop in retention overall was very significant (P = 0.009) from 86.9 to 51.5%. Students also scored lower in questions relating to pelvic organs (46.7%), urogenital development (54.0%), pulmonary development (17.8%), and pregnancy (17.8%). These data showed that indeed, knowledge of surgical anatomy is poor for medical students entering surgical clerkships. These data collected will be utilized to create interactive learning modules, aimed at improving clinically relevant anatomical knowledge retention. These modules, which will be available to students during their inpatient surgical rotations, connect basic anatomy principles to clinical cases, with the ultimate goal of closing the anatomical knowledge gap. © 2014 American Association of Anatomists.

Development of a physiologically based pharmacokinetic model for bisphenol A in pregnant mice

International Nuclear Information System (INIS)

Kawamoto, Yuko; Matsuyama, Wakoto; Wada, Masahiro; Hishikawa, Junko; Chan, Melissa Pui Ling; Nakayama, Aki; Morisawa, Shinsuke

2007-01-01

Bisphenol A (BPA) is a weakly estrogenic monomer used to produce polymers for food contact and other applications, so there is potential for oral exposure of humans to trace amounts via ingestion. To date, no physiologically based pharmacokinetic (PBPK) model has been located for BPA in pregnant mice with or without fetuses. An estimate by a mathematical model is essential since information on humans is difficult to obtain experimentally. The PBPK model was constructed based on the pharmacokinetic data of our experiment following single oral administration of BPA to pregnant mice. The risk assessment of bisphenol A (BPA) on the development of human offspring is an important issue. There have been limited data on the exposure level of human fetuses to BPA (e.g. BPA concentration in cord blood) and no information is available on the pharmacokinetics of BPA in humans with or without fetuses. In the present study, we developed a physiologically based pharmacokinetic (PBPK) model describing the pharmacokinetics of BPA in a pregnant mouse with the prospect of future extrapolation to humans. The PBPK model was constructed based on the pharmacokinetic data of an experiment we executed on pregnant mice following single oral administration of BPA. The model could describe the rapid transfer of BPA through the placenta to the fetus and the slow disappearance from fetuses. The simulated time courses after three-time repeated oral administrations of BPA by the constructed model fitted well with the experimental data, and the simulation for the 10 times lower dose was also consistent with the experiment. This suggested that the PBPK model for BPA in pregnant mice was successfully verified and is highly promising for extrapolation to humans who are expected to be exposed more chronically to lower doses

The Intermingled History of Occupational Therapy and Anatomical Education: A Retrospective Exploration

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Carroll, Melissa A.; Lawson, Katherine

2014-01-01

Few research articles have addressed the anatomical needs of entry-level occupational therapy students. Given this paucity of empirical evidence, there is a lack of knowledge regarding anatomical education in occupational therapy. This article will primarily serve as a retrospective look at the inclusion of anatomical education in the occupational…

Targeting surface nucleolin with a multivalent pseudopeptide delays development of spontaneous melanoma in RET transgenic mice

International Nuclear Information System (INIS)

El Khoury, Diala; Courty, José; Hovanessian, Ara G; Prévost-Blondel, Armelle; Destouches, Damien; Lengagne, Renée; Krust, Bernard; Hamma-Kourbali, Yamina; Garcette, Marylène; Niro, Sandra; Kato, Masashi; Briand, Jean-Paul

2010-01-01

The importance of cell-surface nucleolin in cancer biology was recently highlighted by studies showing that ligands of nucleolin play critical role in tumorigenesis and angiogenesis. By using a specific antagonist that binds the C-terminal tail of nucleolin, the HB-19 pseudopeptide, we recently reported that HB-19 treatment markedly suppressed the progression of established human breast tumor cell xenografts in the athymic nude mice without apparent toxicity. The in vivo antitumoral action of HB-19 treatment was assessed on the spontaneous development of melanoma in the RET transgenic mouse model. Ten days old RET mice were treated with HB-19 in a prophylactic setting that extended 300 days. In parallel, the molecular basis for the action of HB-19 was investigated on a melanoma cell line (called TIII) derived from a cutaneous nodule of a RET mouse. HB-19 treatment of RET mice caused a significant delay in the onset of cutaneous tumors, several-months delay in the incidence of large tumors, a lower frequency of cutaneous nodules, and a reduction of visceral metastatic nodules while displaying no toxicity to normal tissue. Moreover, microvessel density was significantly reduced in tumors recovered from HB-19 treated mice compared to corresponding controls. Studies on the melanoma-derived tumor cells demonstrated that HB-19 treatment of TIII cells could restore contact inhibition, impair anchorage-independent growth, and reduce their tumorigenic potential in mice. Moreover, HB-19 treatment caused selective down regulation of transcripts coding matrix metalloproteinase 2 and 9, and tumor necrosis factor-α in the TIII cells and in melanoma tumors of RET mice. Although HB-19 treatment failed to prevent the development of spontaneous melanoma in the RET mice, it delayed for several months the onset and frequency of cutaneous tumors, and exerted a significant inhibitory effect on visceral metastasis. Consequently, HB-19 could provide a novel therapeutic agent by itself or

Trichostatin A suppresses lung adenocarcinoma development in Grg1 overexpressing transgenic mice

International Nuclear Information System (INIS)

Liu, Ju; Li, Yan; Dong, Fengyun; Li, Liqun; Masuda, Takahiro; Allen, Thaddeus D.; Lobe, Corrinne G.

2015-01-01

Trichostatin A (TSA) is a histone deacetylase inhibitor and a potential therapeutic for various malignancies. The in vivo effect of TSA, however, has not been investigated in a transgenic lung cancer model. Previously, we generated transgenic mice with overexpression of Groucho-related-gene 1 (Grg1) and these mice all developed mucinous lung adenocarcinoma. Grg1 is a transcriptional co-repressor protein, the function of which is thought to depend on HDAC activity. However, functions outside the nucleus have also been proposed. We tested the supposition that Grg1-induced tumorigenesis is HDAC-dependent by assaying the therapeutic effect of TSA in the Grg1 transgenic mouse model. We found that TSA significantly inhibited lung tumorigenesis in Grg1 transgenic mice (p < 0.01). TSA did not affect overall Grg1 protein levels, but instead reduced ErbB1 and ErbB2 expression, which are upregulated by Grg1 in the absence of TSA. We confirmed this effect in A549 cells. Furthermore, lapatinib, an inhibitor of both ErbB1 and ErbB2, effectively masked the effect of TSA on the inhibition of A549 cell proliferation and migration, suggesting TSA does work, at least in part, by downregulating ErbB receptors. We additionally found that TSA reduced the expression of VEGF and VEGFR2, but not basic FGF and FGFR1. Our findings indicate that TSA effectively inhibits Grg1-induced lung tumorigenesis through the down-regulation of ErbB1 and ErbB2, as well as reduced VEGF signaling. This suggests TSA and other HDAC inhibitors could have therapeutic value in the treatment of lung cancers with Grg1 overexpression. - Highlights: • TSA suppresses lung tumorigenesis in Grg1 overexpressing transgenic mice. • TSA does not affect overall Grg1 protein levels in the mice and in A549 cells. • TSA reduces ErbB1 and ErbB2 expression in the mice and in A549 cells. • Lapatinib masks TSA-induced inhibition of A549 cell proliferation and migration. • TSA inhibits VEGF signaling, but not basic FGF

Trichostatin A suppresses lung adenocarcinoma development in Grg1 overexpressing transgenic mice

Energy Technology Data Exchange (ETDEWEB)

Liu, Ju, E-mail: ju.liu@sdu.edu.cn [Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan (China); Molecular and Cellular Biology Division, Sunnybrook Health Science Centre, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5 (Canada); Li, Yan [Children' s Health Care Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014 (China); Dong, Fengyun; Li, Liqun [Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan (China); Masuda, Takahiro; Allen, Thaddeus D. [Molecular and Cellular Biology Division, Sunnybrook Health Science Centre, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5 (Canada); Lobe, Corrinne G. [Molecular and Cellular Biology Division, Sunnybrook Health Science Centre, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5 (Canada); Miami Mice Research Corp., MaRS Centre, Heritage Bldg., 101 College Street, Toronto, Ontario M5G 1L7 (Canada)

2015-08-07

Trichostatin A (TSA) is a histone deacetylase inhibitor and a potential therapeutic for various malignancies. The in vivo effect of TSA, however, has not been investigated in a transgenic lung cancer model. Previously, we generated transgenic mice with overexpression of Groucho-related-gene 1 (Grg1) and these mice all developed mucinous lung adenocarcinoma. Grg1 is a transcriptional co-repressor protein, the function of which is thought to depend on HDAC activity. However, functions outside the nucleus have also been proposed. We tested the supposition that Grg1-induced tumorigenesis is HDAC-dependent by assaying the therapeutic effect of TSA in the Grg1 transgenic mouse model. We found that TSA significantly inhibited lung tumorigenesis in Grg1 transgenic mice (p < 0.01). TSA did not affect overall Grg1 protein levels, but instead reduced ErbB1 and ErbB2 expression, which are upregulated by Grg1 in the absence of TSA. We confirmed this effect in A549 cells. Furthermore, lapatinib, an inhibitor of both ErbB1 and ErbB2, effectively masked the effect of TSA on the inhibition of A549 cell proliferation and migration, suggesting TSA does work, at least in part, by downregulating ErbB receptors. We additionally found that TSA reduced the expression of VEGF and VEGFR2, but not basic FGF and FGFR1. Our findings indicate that TSA effectively inhibits Grg1-induced lung tumorigenesis through the down-regulation of ErbB1 and ErbB2, as well as reduced VEGF signaling. This suggests TSA and other HDAC inhibitors could have therapeutic value in the treatment of lung cancers with Grg1 overexpression. - Highlights: • TSA suppresses lung tumorigenesis in Grg1 overexpressing transgenic mice. • TSA does not affect overall Grg1 protein levels in the mice and in A549 cells. • TSA reduces ErbB1 and ErbB2 expression in the mice and in A549 cells. • Lapatinib masks TSA-induced inhibition of A549 cell proliferation and migration. • TSA inhibits VEGF signaling, but not basic FGF

Haloperidol inhibits the development of atherosclerotic lesions in LDL receptor knockout mice.

Science.gov (United States)

van der Sluis, Ronald J; Nahon, Joya E; Reuwer, Anne Q; Van Eck, Miranda; Hoekstra, Menno

2015-05-01

Antipsychotic drugs have been shown to modulate the expression of ATP-binding cassette transporter A1 (ABCA1), a key factor in the anti-atherogenic reverse cholesterol transport process, in vitro. Here we evaluated the potential of the typical antipsychotic drug haloperidol to modulate the cholesterol efflux function of macrophages in vitro and their susceptibility to atherosclerosis in vivo. Thioglycollate-elicited peritoneal macrophages were used for in vitro studies. Hyperlipidaemic low-density lipoprotein (LDL) receptor knockout mice were implanted with a haloperidol-containing pellet and subsequently fed a Western-type diet for 5 weeks to induce the development of atherosclerotic lesions in vivo. Haloperidol induced a 54% decrease in the mRNA expression of ABCA1 in peritoneal macrophages. This coincided with a 30% decrease in the capacity of macrophages to efflux cholesterol to apolipoprotein A1. Haloperidol treatment stimulated the expression of ABCA1 (+51%) and other genes involved in reverse cholesterol transport, that is, CYP7A1 (+98%) in livers of LDL receptor knockout mice. No change in splenic ABCA1 expression was noted. However, the average size of the atherosclerotic size was significantly smaller (-31%) in the context of a mildly more atherogenic metabolic phenotype upon haloperidol treatment. More importantly, haloperidol markedly lowered MCP-1 expression (-70%) and secretion (-28%) by peritoneal macrophages. Haloperidol treatment lowered the susceptibility of hyperlipidaemic LDL receptor knockout mice to develop atherosclerotic lesions. Our findings suggest that the beneficial effect of haloperidol on atherosclerosis susceptibility can be attributed to its ability to inhibit macrophage chemotaxis. © 2015 The British Pharmacological Society.

Long-term cannabidiol treatment prevents the development of social recognition memory deficits in Alzheimer's disease transgenic mice.

Science.gov (United States)

Cheng, David; Spiro, Adena S; Jenner, Andrew M; Garner, Brett; Karl, Tim

2014-01-01

Impairments in cognitive ability and widespread pathophysiological changes caused by neurotoxicity, neuroinflammation, oxidative damage, and altered cholesterol homeostasis are associated with Alzheimer's disease (AD). Cannabidiol (CBD) has been shown to reverse cognitive deficits of AD transgenic mice and to exert neuroprotective, anti-oxidative, and anti-inflammatory properties in vitro and in vivo. Here we evaluate the preventative properties of long-term CBD treatment in male AβPPSwe/PS1ΔE9 (AβPP × PS1) mice, a transgenic model of AD. Control and AD transgenic mice were treated orally from 2.5 months of age with CBD (20 mg/kg) daily for 8 months. Mice were then assessed in the social preference test, elevated plus maze, and fear conditioning paradigms, before cortical and hippocampal tissues were analyzed for amyloid load, oxidative damage, cholesterol, phytosterols, and inflammation. We found that AβPP × PS1 mice developed a social recognition deficit, which was prevented by CBD treatment. CBD had no impact on anxiety or associative learning. The prevention of the social recognition deficit was not associated with any changes in amyloid load or oxidative damage. However, the study revealed a subtle impact of CBD on neuroinflammation, cholesterol, and dietary phytosterol retention, which deserves further investigation. This study is the first to demonstrate CBD's ability to prevent the development of a social recognition deficit in AD transgenic mice. Our findings provide the first evidence that CBD may have potential as a preventative treatment for AD with a particular relevance for symptoms of social withdrawal and facial recognition.

Deregulation of mTOR signaling is involved in thymic lymphoma development in Atm-/- mice

International Nuclear Information System (INIS)

Kuang, Xianghong; Shen, Jianjun; Wong, Paul K.Y.; Yan, Mingshan

2009-01-01

Abnormal thymocyte development with thymic lymphomagenesis inevitably occurs in Atm-/- mice, indicating that ATM plays a pivotal role in regulating postnatal thymocyte development and preventing thymic lymphomagenesis. The mechanism for ATM controls these processes is unclear. We have shown previously that c-Myc, an oncoprotein regulated by the mammalian target of rapamycin (mTOR), is overexpressed in Atm-/- thymocytes. Here, we show that inhibition of mTOR signaling with its specific inhibitor, rapamycin, suppresses normal thymocyte DNA synthesis by downregulating 4EBP1, but not S6K, and that 4EBP1 phosphorylation and cyclin D1 expression are coordinately increased in Atm-/- thymocytes. Administration of rapamycin to Atm-/- mice attenuates elevated phospho-4EBP1, c-Myc and cyclin D1 in their thymocytes, and delays thymic lymphoma development. These results indicate that mTOR downstream effector 4EBP1 is essential for normal thymocyte proliferation, but deregulation of 4EBP1 in Atm deficiency is a major factor driving thymic lymphomagenesis in the animals.

Mice lacking major brain gangliosides develop parkinsonism.

Science.gov (United States)

Wu, Gusheng; Lu, Zi-Hua; Kulkarni, Neil; Amin, Ruchi; Ledeen, Robert W

2011-09-01

Parkinson's disease (PD) is the second most prevalent late-onset neurodegenerative disorder that affects nearly 1% of the global population aged 65 and older. Whereas palliative treatments are in use, the goal of blocking progression of motor and cognitive disability remains unfulfilled. A better understanding of the basic pathophysiological mechanisms underlying PD would help to advance that goal. The present study provides evidence that brain ganglioside abnormality, in particular GM1, may be involved. This is based on use of the genetically altered mice with disrupted gene Galgt1 for GM2/GD2 synthase which depletes GM2/GD2 and all the gangliotetraose gangliosides that constitute the major molecular species of brain. These knockout mice show overt motor disability on aging and clear indications of motor impairment with appropriate testing at an earlier age. This disability was rectified by L-dopa administration. These mice show other characteristic symptoms of PD, including depletion of striatal dopamine (DA), loss of DA neurons of the substantia nigra pars compacta, and aggregation of alpha synuclein. These manifestations of parkinsonism were largely attenuated by administration of LIGA-20, a membrane permeable analog of GM1 that penetrates the blood brain barrier and enters living neurons. These results suggest that perturbation of intracellular mechanisms mediated by intracellular GM1 may be a contributing factor to PD.

The Composition of Colonic Commensal Bacteria According to Anatomical Localization in Colorectal Cancer

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Liuyang Zhao

2017-02-01

Full Text Available Colorectal cancer (CRC is a multistage disease resulting from complex factors, including genetic mutations, epigenetic changes, chronic inflammation, diet, and lifestyle. Recent accumulating evidence suggests that the gut microbiota is a new and important player in the development of CRC. Imbalance of the gut microbiota, especially dysregulated gut bacteria, contributes to colon cancer through mechanisms of inflammation, host defense modulations, oxidative stress, and alterations in bacterial-derived metabolism. Gut commensal bacteria are anatomically defined as four populations: luminal commensal bacteria, mucus-resident bacteria, epithelium-resident bacteria, and lymphoid tissue-resident commensal bacteria. The bacterial flora that are harbored in the gastrointestinal (GI tract vary both longitudinally and cross-sectionally by different anatomical localization. It is notable that the translocation of colonic commensal bacteria is closely related to CRC progression. CRC-associated bacteria can serve as a non-invasive and accurate biomarker for CRC diagnosis. In this review, we summarize recent findings on the oncogenic roles of gut bacteria with different anatomical localization in CRC progression.

Mice deficient in CD38 develop an attenuated form of collagen type II-induced arthritis.

Science.gov (United States)

Postigo, Jorge; Iglesias, Marcos; Cerezo-Wallis, Daniela; Rosal-Vela, Antonio; García-Rodríguez, Sonia; Zubiaur, Mercedes; Sancho, Jaime; Merino, Ramón; Merino, Jesús

2012-01-01

CD38, a type II transmembrane glycoprotein expressed in many cells of the immune system, is involved in cell signaling, migration and differentiation. Studies in CD38 deficient mice (CD38 KO mice) indicate that this molecule controls inflammatory immune responses, although its involvement in these responses depends on the disease model analyzed. Here, we explored the role of CD38 in the control of autoimmune responses using chicken collagen type II (col II) immunized C57BL/6-CD38 KO mice as a model of collagen-induced arthritis (CIA). We demonstrate that CD38 KO mice develop an attenuated CIA that is accompanied by a limited joint induction of IL-1β and IL-6 expression, by the lack of induction of IFNγ expression in the joints and by a reduction in the percentages of invariant NKT (iNKT) cells in the spleen. Immunized CD38 KO mice produce high levels of circulating IgG1 and low of IgG2a anti-col II antibodies in association with reduced percentages of Th1 cells in the draining lymph nodes. Altogether, our results show that CD38 participates in the pathogenesis of CIA controlling the number of iNKT cells and promoting Th1 inflammatory responses.

Mice deficient in CD38 develop an attenuated form of collagen type II-induced arthritis.

Directory of Open Access Journals (Sweden)

Jorge Postigo

Full Text Available CD38, a type II transmembrane glycoprotein expressed in many cells of the immune system, is involved in cell signaling, migration and differentiation. Studies in CD38 deficient mice (CD38 KO mice indicate that this molecule controls inflammatory immune responses, although its involvement in these responses depends on the disease model analyzed. Here, we explored the role of CD38 in the control of autoimmune responses using chicken collagen type II (col II immunized C57BL/6-CD38 KO mice as a model of collagen-induced arthritis (CIA. We demonstrate that CD38 KO mice develop an attenuated CIA that is accompanied by a limited joint induction of IL-1β and IL-6 expression, by the lack of induction of IFNγ expression in the joints and by a reduction in the percentages of invariant NKT (iNKT cells in the spleen. Immunized CD38 KO mice produce high levels of circulating IgG1 and low of IgG2a anti-col II antibodies in association with reduced percentages of Th1 cells in the draining lymph nodes. Altogether, our results show that CD38 participates in the pathogenesis of CIA controlling the number of iNKT cells and promoting Th1 inflammatory responses.

Pituitary mammosomatotroph adenomas develop in old mice transgenic for growth hormone-releasing hormone

DEFF Research Database (Denmark)

Asa, S L; Kovacs, K; Stefaneanu, L

1990-01-01

It has been shown that mice transgenic for human growth hormone-releasing hormone (GRH) develop hyperplasia of pituitary somatotrophs and mammosomatotrophs, cells capable of producing both growth hormone and prolactin, by 8 months of age. We now report for the first time that old GRH-transgenic...

SMOC1 is essential for ocular and limb development in humans and mice.

Science.gov (United States)

Okada, Ippei; Hamanoue, Haruka; Terada, Koji; Tohma, Takaya; Megarbane, Andre; Chouery, Eliane; Abou-Ghoch, Joelle; Jalkh, Nadine; Cogulu, Ozgur; Ozkinay, Ferda; Horie, Kyoji; Takeda, Junji; Furuichi, Tatsuya; Ikegawa, Shiro; Nishiyama, Kiyomi; Miyatake, Satoko; Nishimura, Akira; Mizuguchi, Takeshi; Niikawa, Norio; Hirahara, Fumiki; Kaname, Tadashi; Yoshiura, Koh-Ichiro; Tsurusaki, Yoshinori; Doi, Hiroshi; Miyake, Noriko; Furukawa, Takahisa; Matsumoto, Naomichi; Saitsu, Hirotomo

2011-01-07

Microphthalmia with limb anomalies (MLA) is a rare autosomal-recessive disorder, presenting with anophthalmia or microphthalmia and hand and/or foot malformation. We mapped the MLA locus to 14q24 and successfully identified three homozygous (one nonsense and two splice site) mutations in the SPARC (secreted protein acidic and rich in cysteine)-related modular calcium binding 1 (SMOC1) in three families. Smoc1 is expressed in the developing optic stalk, ventral optic cup, and limbs of mouse embryos. Smoc1 null mice recapitulated MLA phenotypes, including aplasia or hypoplasia of optic nerves, hypoplastic fibula and bowed tibia, and syndactyly in limbs. A thinned and irregular ganglion cell layer and atrophy of the anteroventral part of the retina were also observed. Soft tissue syndactyly, resulting from inhibited apoptosis, was related to disturbed expression of genes involved in BMP signaling in the interdigital mesenchyme. Our findings indicate that SMOC1/Smoc1 is essential for ocular and limb development in both humans and mice.

Anatomically ordered tapping interferes more with one-digit addition than two-digit addition: a dual-task fMRI study.

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Soylu, Firat; Newman, Sharlene D

2016-02-01

Fingers are used as canonical representations for numbers across cultures. In previous imaging studies, it was shown that arithmetic processing activates neural resources that are known to participate in finger movements. Additionally, in one dual-task study, it was shown that anatomically ordered finger tapping disrupts addition and subtraction more than multiplication, possibly due to a long-lasting effect of early finger counting experiences on the neural correlates and organization of addition and subtraction processes. How arithmetic task difficulty and tapping complexity affect the concurrent performance is still unclear. If early finger counting experiences have bearing on the neural correlates of arithmetic in adults, then one would expect anatomically and non-anatomically ordered tapping to have different interference effects, given that finger counting is usually anatomically ordered. To unravel these issues, we studied how (1) arithmetic task difficulty and (2) the complexity of the finger tapping sequence (anatomical vs. non-anatomical ordering) affect concurrent performance and use of key neural circuits using a mixed block/event-related dual-task fMRI design with adult participants. The results suggest that complexity of the tapping sequence modulates interference on addition, and that one-digit addition (fact retrieval), compared to two-digit addition (calculation), is more affected from anatomically ordered tapping. The region-of-interest analysis showed higher left angular gyrus BOLD response for one-digit compared to two-digit addition, and in no-tapping conditions than dual tapping conditions. The results support a specific association between addition fact retrieval and anatomically ordered finger movements in adults, possibly due to finger counting strategies that deploy anatomically ordered finger movements early in the development.

Interferon-γ Promotes Inflammation and Development of T-Cell Lymphoma in HTLV-1 bZIP Factor Transgenic Mice.

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Yu Mitagami

2015-08-01

Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 is an etiological agent of several inflammatory diseases and a T-cell malignancy, adult T-cell leukemia (ATL. HTLV-1 bZIP factor (HBZ is the only viral gene that is constitutively expressed in HTLV-1-infected cells, and it has multiple functions on T-cell signaling pathways. HBZ has important roles in HTLV-1-mediated pathogenesis, since HBZ transgenic (HBZ-Tg mice develop systemic inflammation and T-cell lymphomas, which are similar phenotypes to HTLV-1-associated diseases. We showed previously that in HBZ-Tg mice, HBZ causes unstable Foxp3 expression, leading to an increase in regulatory T cells (Tregs and the consequent induction of IFN-γ-producing cells, which in turn leads to the development of inflammation in the mice. In this study, we show that the severity of inflammation is correlated with the development of lymphomas in HBZ-Tg mice, suggesting that HBZ-mediated inflammation is closely linked to oncogenesis in CD4+ T cells. In addition, we found that IFN-γ-producing cells enhance HBZ-mediated inflammation, since knocking out IFN-γ significantly reduced the incidence of dermatitis as well as lymphoma. Recent studies show the critical roles of the intestinal microbiota in the development of Tregs in vivo. We found that even germ-free HBZ-Tg mice still had an increased number of Tregs and IFN-γ-producing cells, and developed dermatitis, indicating that an intrinsic activity of HBZ evokes aberrant T-cell differentiation and consequently causes inflammation. These results show that immunomodulation by HBZ is implicated in both inflammation and oncogenesis, and suggest a causal connection between HTLV-1-associated inflammation and ATL.

Anatomical database generation for radiation transport modeling from computed tomography (CT) scan data

International Nuclear Information System (INIS)

Margle, S.M.; Tinnel, E.P.; Till, L.E.; Eckerman, K.F.; Durfee, R.C.

1989-01-01

Geometric models of the anatomy are used routinely in calculations of the radiation dose in organs and tissues of the body. Development of such models has been hampered by lack of detailed anatomical information on children, and models themselves have been limited to quadratic conic sections. This summary reviews the development of an image processing workstation used to extract anatomical information from routine diagnostic CT procedure. A standard IBM PC/AT microcomputer has been augmented with an automatically loading 9-track magnetic tape drive, an 8-bit 1024 x 1024 pixel graphics adapter/monitor/film recording package, a mouse/trackball assembly, dual 20 MB removable cartridge media, a 72 MB disk drive, and a printer. Software utilized by the workstation includes a Geographic Information System (modified for manipulation of CT images), CAD software, imaging software, and various modules to ease data transfer among the software packages. 5 refs., 3 figs

Gender-specific effects of endogenous testosterone: female alpha-estrogen receptor-deficient C57Bl/6J mice develop glomerulosclerosis.

Science.gov (United States)

Elliot, S J; Berho, M; Korach, K; Doublier, S; Lupia, E; Striker, G E; Karl, M

2007-08-01

Young female mice on a C57Bl/6J (B6) background are considered glomerulosclerosis (GS)-resistant but aging B6 mice develop mild GS. Estrogen deficiency accelerates while estrogen replacement retards GS in young sclerosis-prone oligosyndactyly mutant mice on an ROP background. To explore the effects of sex hormones on glomerular structure and function in the context of gender and genetic background, we studied mice in which the estrogen-receptor (ER) genes alpha- or -beta were deleted (alpha- or betaER knockout (KO)) and crossed into the B6 background. We also studied ovariectomized (Ovx) B6 mice given testosterone. Male and female betaERKO and male alphaERKO mice had no glomerular dysfunction at 9 months of age; however, alphaERKO female mice displayed albuminuria and GS. Ovx prevented glomerular dysfunction in alphaERKO female mice by eliminating endogenous testosterone production while exogenous testosterone induced GS in Ovx B6 mice. Androgen receptor (AR) expression and function was found in microdissected glomeruli and cultured mesangial cells. Testosterone compared to placebo increased both AR expression and TGF-beta1 mRNA levels in glomeruli isolated from female B6 mice. Estrogen deficiency had no deleterious effects on the glomeruli in B6 mice. Our study shows that genetic traits strongly influence the GS-promoting effects of estrogen deficiency while testosterone induces GS in a gender-specific manner.

Evaluation of 3D printed anatomically scalable transfemoral prosthetic knee.

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Ramakrishnan, Tyagi; Schlafly, Millicent; Reed, Kyle B

2017-07-01

This case study compares a transfemoral amputee's gait while using the existing Ossur Total Knee 2000 and our novel 3D printed anatomically scalable transfemoral prosthetic knee. The anatomically scalable transfemoral prosthetic knee is 3D printed out of a carbon-fiber and nylon composite that has a gear-mesh coupling with a hard-stop weight-actuated locking mechanism aided by a cross-linked four-bar spring mechanism. This design can be scaled using anatomical dimensions of a human femur and tibia to have a unique fit for each user. The transfemoral amputee who was tested is high functioning and walked on the Computer Assisted Rehabilitation Environment (CAREN) at a self-selected pace. The motion capture and force data that was collected showed that there were distinct differences in the gait dynamics. The data was used to perform the Combined Gait Asymmetry Metric (CGAM), where the scores revealed that the overall asymmetry of the gait on the Ossur Total Knee was more asymmetric than the anatomically scalable transfemoral prosthetic knee. The anatomically scalable transfemoral prosthetic knee had higher peak knee flexion that caused a large step time asymmetry. This made walking on the anatomically scalable transfemoral prosthetic knee more strenuous due to the compensatory movements in adapting to the different dynamics. This can be overcome by tuning the cross-linked spring mechanism to emulate the dynamics of the subject better. The subject stated that the knee would be good for daily use and has the potential to be adapted as a running knee.

Anatomical studies on the development of Metasequoia glyptostroboides Hu et Cheng wood

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Alina Hejnowicz

2015-01-01

Full Text Available Variability of anatomical characters within a 15 year old stem is presented by the method of contour lines, where against a schematic longitudinal section of a stem points corresponding to the same values for a character are joined by lines, similarly as altitudes in cartography. The method permits prediction of future trends in character changes. It was thus established that tracheid dimensions and diameter of bordered pits in early wood tracheids increase with age of tree and do not reach maximal values before the 15th year. The annual ring width and the height of the rays attain maximal values before the 15th year while the dimensions of ray cells and the percentage of late wood reach almost constant values during the first year or two.

Development of intraepithelial T lymphocytes in the intestine of irradiated SCID mice by adult liver hematopoietic stem cells from normal mice

International Nuclear Information System (INIS)

Yamagiwa, Satoshi; Seki, Shuhji; Shirai, Katsuaki; Yoshida, Yuhei; Miyaji, Chikako; Watanabe, Hisami; Abo, Toru

1999-01-01

Background/Aims: We recently reported the adult mouse liver to contain c-kit + stem cells that can give rise to multilineage leukocytes. This study was designed to determine whether or not adult mouse liver stem cells can generate intraepithelial T cells in the intestine as well as to examine the possibility that adult liver c-kit + stem cells originate from the fetal liver. Methods: Adult liver mononuclear cells, bone marrow (BM) cells, liver c-kit + cells or bone BM c-kit + cells of BALB/c mice were i.v. transferred into 4 Gy irradiated CB17/-SCID mice. In other experiments, fetal liver cells from Ly5.1 C57BL/6 mice and T cell depleted adult BM cells from Ly5.2 C57BL/6 mice were simultaneously transferred into irradiated C57BL/6 SCID mice (Ly5.2). At 1 to 8 weeks after cell transfer, the SCID mice were examined. Results: Not only BM cells and BM c-kit + cells but also liver mononuclear cells and liver c-kit + cells reconstituted γδT cells, CD4 + CD8 + double-positive T cells and CDiα + β - T cells of intestinal intraepithelial lymphocytes of SCID mice. Injection of a mixture of fetal liver cells from Ly5.1 C57BL/6 mice and adult BM cells from Ly5.2 C57BL/6 mice into Ly5.2 C57BL/6 SCID mice induced both Ly5.1 and Ly5.2 T cells, while also generating c-kit + cells of both Ly5.1 and Ly5.2 origins in the liver. Conclusions: Adult mouse liver stem cells were able to generate intestinal intraepithelial T cells of the SCID mice, and it is thus suggested that some adult liver stem cells may indeed be derived from the fetal liver. (au)

Purified blueberry anthocyanins and blueberry juice alter development of obesity in mice fed an obesogenic high-fat diet.

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Prior, Ronald L; E Wilkes, Samuel; R Rogers, Theodore; Khanal, Ramesh C; Wu, Xianli; Howard, Luke R

2010-04-14

Male C57BL/6J mice (25 days of age) were fed either a low-fat diet (10% kcal from fat) (LF) or a high-fat diet (45% kcal from fat) (HF45) for a period of 72 days. Blueberry juice or purified blueberry anthocyanins (0.2 or 1.0 mg/mL) in the drinking water were included in LF or HF45 treatments. Sucrose was added to the drinking water of one treatment to test if the sugars in blueberry juice would affect development of obesity. Total body weights (g) and body fat (%) were higher and body lean tissue (%) was lower in the HF45 fed mice compared to the LF fed mice after 72 days, but in mice fed HF45 diet plus blueberry juice or blueberry anthocyanins (0.2 mg/mL), body fat (%) was not different from those mice fed the LF diet. Anthocyanins (ACNs) decreased retroperitoneal and epididymal adipose tissue weights. Fasting serum glucose concentrations were higher in mice fed the HF45 diet. However, it was reduced to LF levels in mice fed the HF45 diet plus 0.2 mg of ACNs/mL in the drinking water, but not with blueberry juice. beta cell function (HOMA-BCF) score was lowered with HF45 feeding but returned to normal levels in mice fed the HF45 diet plus purified ACNs (0.2 mg/mL). Serum leptin was elevated in mice fed HF45 diet, and feeding either blueberry juice or purified ACNs (0.2 mg/mL) decreased serum leptin levels relative to HF45 control. Sucrose in drinking water, when consumption was restricted to the volume of juice consumed, produced lower serum leptin and insulin levels, leptin/fat, and retroperitoneal and total fat (% BW). Blueberry juice was not as effective as the low dose of anthocyanins in the drinking water in preventing obesity. Additional studies are needed to determine factors responsible for the differing responses of blueberry juice and whole blueberry in preventing the development of obesity.

Hypertension is a conditional factor for the development of cardiac hypertrophy in type 2 diabetic mice.

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Marc van Bilsen

Full Text Available BACKGROUND: Type 2 diabetes is frequently associated with co-morbidities, including hypertension. Here we investigated if hypertension is a critical factor in myocardial remodeling and the development of cardiac dysfunction in type 2 diabetic db/db mice. METHODS: Thereto, 14-wks-old male db/db mice and non-diabetic db/+ mice received vehicle or angiotensin II (AngII for 4 wks to induce mild hypertension (n = 9-10 per group. Left ventricular (LV function was assessed by serial echocardiography and during a dobutamine stress test. LV tissue was subjected to molecular and (immunohistochemical analysis to assess effects on hypertrophy, fibrosis and inflammation. RESULTS: Vehicle-treated diabetic mice neither displayed marked myocardial structural remodeling nor cardiac dysfunction. AngII-treatment did not affect body weight and fasting glucose levels, and induced a comparable increase in blood pressure in diabetic and control mice. Nonetheless, AngII-induced LV hypertrophy was significantly more pronounced in diabetic than in control mice as assessed by LV mass (increase +51% and +34%, respectively, p<0.01 and cardiomyocyte size (+53% and +31%, p<0.001. This was associated with enhanced LV mRNA expression of markers of hypertrophy and fibrosis and reduced activation of AMP-activated protein kinase (AMPK, while accumulation of Advanced Glycation End products (AGEs and the expression levels of markers of inflammation were not altered. Moreover, AngII-treatment reduced LV fractional shortening and contractility in diabetic mice, but not in control mice. CONCLUSIONS: Collectively, the present findings indicate that type 2 diabetes in its early stage is not yet associated with adverse cardiac structural changes, but already renders the heart more susceptible to hypertension-induced hypertrophic remodeling.

Anatomical image-guided fluorescence molecular tomography reconstruction using kernel method

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Baikejiang, Reheman; Zhao, Yue; Fite, Brett Z.; Ferrara, Katherine W.; Li, Changqing

2017-01-01

Abstract. Fluorescence molecular tomography (FMT) is an important in vivo imaging modality to visualize physiological and pathological processes in small animals. However, FMT reconstruction is ill-posed and ill-conditioned due to strong optical scattering in deep tissues, which results in poor spatial resolution. It is well known that FMT image quality can be improved substantially by applying the structural guidance in the FMT reconstruction. An approach to introducing anatomical information into the FMT reconstruction is presented using the kernel method. In contrast to conventional methods that incorporate anatomical information with a Laplacian-type regularization matrix, the proposed method introduces the anatomical guidance into the projection model of FMT. The primary advantage of the proposed method is that it does not require segmentation of targets in the anatomical images. Numerical simulations and phantom experiments have been performed to demonstrate the proposed approach’s feasibility. Numerical simulation results indicate that the proposed kernel method can separate two FMT targets with an edge-to-edge distance of 1 mm and is robust to false-positive guidance and inhomogeneity in the anatomical image. For the phantom experiments with two FMT targets, the kernel method has reconstructed both targets successfully, which further validates the proposed kernel method. PMID:28464120

Changes in hippocampal synaptic functions and protein expression in monosodium glutamate-treated obese mice during development of glucose intolerance.

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Sasaki-Hamada, Sachie; Hojo, Yuki; Koyama, Hajime; Otsuka, Hayuma; Oka, Jun-Ichiro

2015-05-01

Glucose is the sole neural fuel for the brain and is essential for cognitive function. Abnormalities in glucose tolerance may be associated with impairments in cognitive function. Experimental obese model mice can be generated by an intraperitoneal injection of monosodium glutamate (MSG; 2 mg/g) once a day for 5 days from 1 day after birth. MSG-treated mice have been shown to develop glucose intolerance and exhibit chronic neuroendocrine dysfunction associated with marked cognitive malfunctions at 28-29  weeks old. Although hippocampal synaptic plasticity is impaired in MSG-treated mice, changes in synaptic transmission remain unknown. Here, we investigated whether glucose intolerance influenced cognitive function, synaptic properties and protein expression in the hippocampus. We demonstrated that MSG-treated mice developed glucose intolerance due to an impairment in the effectiveness of insulin actions, and showed cognitive impairments in the Y-maze test. Moreover, long-term potentiation (LTP) at Schaffer collateral-CA1 pyramidal synapses in hippocampal slices was impaired, and the relationship between the slope of extracellular field excitatory postsynaptic potential and stimulus intensity of synaptic transmission was weaker in MSG-treated mice. The protein levels of vesicular glutamate transporter 1 and GluA1 glutamate receptor subunits decreased in the CA1 region of MSG-treated mice. These results suggest that deficits in glutamatergic presynapses as well as postsynapses lead to impaired synaptic plasticity in MSG-treated mice during the development of glucose intolerance, though it remains unknown whether impaired LTP is due to altered inhibitory transmission. It may be important to examine changes in glucose tolerance in order to prevent cognitive malfunctions associated with diabetes. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Medical students call for national standards in anatomical education.

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Farey, John E; Sandeford, Jonathan C; Evans-McKendry, Greg D

2014-11-01

The diminishing number of hours dedicated to formal instruction in anatomy has led to a debate within medical education as to the level required for safe clinical practice. We provide a review of the current state of anatomical education in Australian medical schools and state the case for national standards. In light of the review presented, council members of the Australian Medical Students' Association voted to affirm that consideration should be given to developing undergraduate learning goals for anatomy, providing a codified medical student position on the teaching of anatomy in Australian medical schools. Crucially, the position states that time-intensive methods of instruction such as dissection should be a rite of passage for medical students in the absence of evidence demonstrating the superiority of modern teaching methods. We believe the bodies with a vested interest in the quality of medical graduates, namely the Australian Medical Council, Medical Deans Australia & New Zealand, and the postgraduate colleges should collaborate and develop clear guidelines that make explicit the core knowledge of anatomy expected of medical graduates at each stage of their career with a view to safe clinical practice. In addition, Australian universities have a role to play in conducting further research into contemporary learning styles and the most efficacious methods of delivering anatomical education. © 2014 Royal Australasian College of Surgeons.

Development of quantitative analysis method for stereotactic brain image. Assessment of reduced accumulation in extent and severity using anatomical segmentation

International Nuclear Information System (INIS)

Mizumura, Sunao; Kumita, Shin-ichiro; Cho, Keiichi; Ishihara, Makiko; Nakajo, Hidenobu; Toba, Masahiro; Kumazaki, Tatsuo

2003-01-01

Through visual assessment by three-dimensional (3D) brain image analysis methods using stereotactic brain coordinates system, such as three-dimensional stereotactic surface projections and statistical parametric mapping, it is difficult to quantitatively assess anatomical information and the range of extent of an abnormal region. In this study, we devised a method to quantitatively assess local abnormal findings by segmenting a brain map according to anatomical structure. Through quantitative local abnormality assessment using this method, we studied the characteristics of distribution of reduced blood flow in cases with dementia of the Alzheimer type (DAT). Using twenty-five cases with DAT (mean age, 68.9 years old), all of whom were diagnosed as probable Alzheimer's disease based on National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA), we collected I-123 iodoamphetamine SPECT data. A 3D brain map using the 3D-stereotactic surface projections (SSP) program was compared with the data of 20 cases in the control group, who age-matched the subject cases. To study local abnormalities on the 3D images, we divided the whole brain into 24 segments based on anatomical classification. We assessed the extent of an abnormal region in each segment (rate of the coordinates with a Z-value that exceeds the threshold value, in all coordinates within a segment), and severity (average Z-value of the coordinates with a Z-value that exceeds the threshold value). This method clarified orientation and expansion of reduced accumulation, through classifying stereotactic brain coordinates according to the anatomical structure. This method was considered useful for quantitatively grasping distribution abnormalities in the brain and changes in abnormality distribution. (author)

Long-lived hypopituitary Ames dwarf mice are resistant to the detrimental effects of high-fat diet on metabolic function and energy expenditure.

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Hill, Cristal M; Fang, Yimin; Miquet, Johanna G; Sun, Liou Y; Masternak, Michal M; Bartke, Andrzej

2016-06-01

Growth hormone (GH) signaling stimulates the production of IGF-1; however, increased GH signaling may induce insulin resistance and can reduce life expectancy in both mice and humans. Interestingly, disruption of GH signaling by reducing plasma GH levels significantly improves health span and extends lifespan in mice, as observed in Ames dwarf mice. In addition, these mice have increased adiposity, yet are more insulin sensitive compared to control mice. Metabolic stressors such as high-fat diet (HFD) promote obesity and may alter longevity through the GH signaling pathway. Therefore, our objective was to investigate the effects of a HFD (metabolic stressor) on genetic mechanisms that regulate metabolism during aging. We show that Ames dwarf mice fed HFD for 12 weeks had an increase in subcutaneous and visceral adiposity as a result of diet-induced obesity, yet are more insulin sensitive and have higher levels of adiponectin compared to control mice fed HFD. Furthermore, energy expenditure was higher in Ames dwarf mice fed HFD than in control mice fed HFD. Additionally, we show that transplant of epididymal white adipose tissue (eWAT) from Ames dwarf mice fed HFD into control mice fed HFD improves their insulin sensitivity. We conclude that Ames dwarf mice are resistant to the detrimental metabolic effects of HFD and that visceral adipose tissue of Ames dwarf mice improves insulin sensitivity in control mice fed HFD. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

PC Assisted Anatomical Measurements in 3D Using CT Data

DEFF Research Database (Denmark)

Hvidtfeldt, Mogens; Pedersen, Steen

1999-01-01

To assess facilities and applications of a programme for a PC based CT measurements in 3D of anatomical angelse in the skeleton.......To assess facilities and applications of a programme for a PC based CT measurements in 3D of anatomical angelse in the skeleton....

Anatomical variations of the circle of Willis and cerebrovascular accidents in transitional Albania

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Edlira Harizi (Shemsi

2015-12-01

Full Text Available Aim: The purpose of this study was twofold: i in a case-control design, to determine the relationship between anatomical variations of the circle of Willis and cerebrovascular accidents; ii to assess the association between anatomical variations of the circle of Willis and aneurisms among patients with subarachnoid hemorrhage. Methods: A case-control study was conducted in Albania in 2013-2014, including 100 patients with subarachnoid hemorrhage and 100 controls (individuals without cerebrovascular accidents. Patients with subarachnoid hemorrhage underwent a CT angiography procedure, whereas individuals in the control group underwent a magnetic resonance angiography procedure. Binary logistic regression was used to assess the association between cerebrovascular accidents and the anatomical variations of the circle of Willis. Conversely, Fisher’s exact test was used to compare the prevalence of aneurisms between subarachnoid hemorrhage patients with and without anatomical variations of the circle of Willis. Results: Among patients, there were 22 (22% cases with anatomical variations of the circle of Willis compared with 10 (10% individuals in the control group (P=0.033. There was no evidence of a statistically significant difference in the types of the anatomical variations of the circle of Willis between patients and controls (P=0.402. In age- and-sex adjusted logistic regression models, there was evidence of a significant positive association between cerebrovascular accidents and the anatomical variations of the circle of Willis (OR=1.87, 95%CI=1.03-4.68, P=0.048. Within the patients’ group, of the 52 cases with aneurisms, there were 22 (42.3% individuals with anatomical variations of the circle of Willis compared with no individuals with anatomical variations among the 48 patients without aneurisms (P<0.001. Conclusion: This study provides useful evidence on the association between anatomical variations of the circle of Willis and

Effects of Breeding Configuration on Maternal and Weanling Behavior in Laboratory Mice.

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Braden, Gillian C; Rasmussen, Skye; Monette, Sebastien; Tolwani, Ravi J

2017-07-01

Although numerous studies have evaluated the effect of housing density on the wellbeing of laboratory mice, little is known about the effect of breeding configuration on mouse behavior. The 8th edition of the Guide for the Care and Use of Laboratory Animals lists the recommended minimal floor area per animal for a female mouse and her litter as 51 in.2 We sought to determine the effects of pair, trio, and harem breeding configurations on the maternal and weanling behavior of C57BL/6J (B6) and 129S6/SvEvTac (129) mice on the basis of nest scores and performance in pup retrieval tests, open-field test (OFT), elevated plus maze, and tail suspension test; we concurrently evaluated cage microenvironment, reproductive indices, and anatomic and clinical pathology. Harem breeding configurations enhanced B6 maternal behaviors as evidenced by significantly shorter pup retrieval times. Trio- and harem-raised B6 weanlings showed increased exploratory behaviors, as evidenced by greater time spent in the center of the OFT, when compared with pair-raised B6 mice. Conversely, breeding configuration did not alter pup retrieval times for 129 mice, and on the day of weaning trio- and harem-raised 129 mice demonstrated increased anxiety-like behavior, as evidenced by greater time spent in the periphery of the OFT, when compared with pair-raised counterparts. Behavioral differences were not noted on subsequent days for either strain. Trio- and harem-raised B6 and 129 weanling mice had significantly higher weaning weights than weanlings raised in a pair breeding configuration. Trio and harem breeding in a standard 67-in.2 shoebox cage did not detrimentally affect the evaluated welfare parameters in either C57BL/6J or 129S6/SvEvTac mice.

Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice

DEFF Research Database (Denmark)

Kiilerich, Pia; Myrmel, Lene Secher; Fjære, Even

2016-01-01

Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low protein....../sucrose ratio precipitated obesity and reduced survival relative to mice fed a low-fat diet. By contrast, intake of a high-fat diet with a high protein/sucrose ratio attenuated lifelong weight gain and adipose tissue expansion, and survival was not significantly altered relative to low-fat-fed mice. Our...... findings support the notion that reduced survival in response to high-fat/high-sucrose feeding is linked to obesity development. Digital gene expression analyses, further validated by qPCR, demonstrated that the protein/sucrose ratio modulated global gene expression over time in liver and adipose tissue...

Inducible knockdown of pregnancy-associated plasma protein-A gene expression in adult female mice extends life span.

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Bale, Laurie K; West, Sally A; Conover, Cheryl A

2017-08-01

Pregnancy-associated plasma protein-A (PAPP-A) knockout (KO) mice, generated through homologous recombination in embryonic stem cells, have a significantly increased lifespan compared to wild-type littermates. However, it is unknown whether this longevity advantage would pertain to PAPP-A gene deletion in adult animals. In the present study, we used tamoxifen (Tam)-inducible Cre recombinase-mediated excision of the floxed PAPP-A (fPAPP-A) gene in mice at 5 months of age. fPAPP-A mice, which were either positive (pos) or negative (neg) for Tam-Cre, received Tam treatment with quarterly boosters. Only female mice could be used with this experimental design. fPAPP-A/neg and fPAPP-A/pos mice had similar weights at the start of the experiment and showed equivalent weight gain. We found that fPAPP-A/pos mice had a significant extension of life span (P = 0.005). The median life span was increased by 21% for fPAPP-A/pos compared to fPAPP-A/neg mice. Analysis of mortality in life span quartiles indicated that the proportion of deaths of fPAPP-A/pos mice were lower than fPAPP-A/neg mice at young adult ages (P = 0.002 for 601-800 days) and higher than fPAPP-A/neg mice at older ages (P = 0.004 for >1000 days). Thus, survival curves and age-specific mortality indicate that female mice with knockdown of PAPP-A gene expression as adults have an extended healthy life span. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Cell-cycle arrest in mature adipocytes impairs BAT development but not WAT browning, and reduces adaptive thermogenesis in mice.

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Okamatsu-Ogura, Yuko; Fukano, Keigo; Tsubota, Ayumi; Nio-Kobayashi, Junko; Nakamura, Kyoko; Morimatsu, Masami; Sakaue, Hiroshi; Saito, Masayuki; Kimura, Kazuhiro

2017-07-27

We previously reported brown adipocytes can proliferate even after differentiation. To test the involvement of mature adipocyte proliferation in cell number control in fat tissue, we generated transgenic (Tg) mice over-expressing cell-cycle inhibitory protein p27 specifically in adipocytes, using the aP2 promoter. While there was no apparent difference in white adipose tissue (WAT) between wild-type (WT) and Tg mice, the amount of brown adipose tissue (BAT) was much smaller in Tg mice. Although BAT showed a normal cellular morphology, Tg mice had lower content of uncoupling protein 1 (UCP1) as a whole, and attenuated cold exposure- or β3-adrenergic receptor (AR) agonist-induced thermogenesis, with a decrease in the number of mature brown adipocytes expressing proliferation markers. An agonist for the β3-AR failed to increase the number of proliferating brown adipocytes, UCP1 content in BAT, and oxygen consumption in Tg mice, although the induction and the function of beige adipocytes in inguinal WAT from Tg mice were similar to WT mice. These results show that brown adipocyte proliferation significantly contributes to BAT development and adaptive thermogenesis in mice, but not to induction of beige adipocytes.

Ageing Fxr deficient mice develop increased energy expenditure, improved glucose control and liver damage resembling NASH.

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Mikael Bjursell

Full Text Available Nuclear receptor subfamily 1, group H, member 4 (Nr1h4, FXR is a bile acid activated nuclear receptor mainly expressed in the liver, intestine, kidney and adrenal glands. Upon activation, the primary function is to suppress cholesterol 7 alpha-hydroxylase (Cyp7a1, the rate-limiting enzyme in the classic or neutral bile acid synthesis pathway. In the present study, a novel Fxr deficient mouse line was created and studied with respect to metabolism and liver function in ageing mice fed chow diet. The Fxr deficient mice were similar to wild type mice in terms of body weight, body composition, energy intake and expenditure as well as behaviours at a young age. However, from 15 weeks of age and onwards, the Fxr deficient mice had almost no body weight increase up to 39 weeks of age mainly because of lower body fat mass. The lower body weight gain was associated with increased energy expenditure that was not compensated by increased food intake. Fasting levels of glucose and insulin were lower and glucose tolerance was improved in old and lean Fxr deficient mice. However, the Fxr deficient mice displayed significantly increased liver weight, steatosis, hepatocyte ballooning degeneration and lobular inflammation together with elevated plasma levels of ALT, bilirubin and bile acids, findings compatible with non-alcoholic steatohepatitis (NASH and cholestasis. In conclusion, ageing Fxr deficient mice display late onset leanness associated with elevated energy expenditure and improved glucose control but develop severe NASH-like liver pathology.

Ageing Fxr deficient mice develop increased energy expenditure, improved glucose control and liver damage resembling NASH.

Science.gov (United States)

Bjursell, Mikael; Wedin, Marianne; Admyre, Therése; Hermansson, Majlis; Böttcher, Gerhard; Göransson, Melker; Lindén, Daniel; Bamberg, Krister; Oscarsson, Jan; Bohlooly-Y, Mohammad

2013-01-01

Nuclear receptor subfamily 1, group H, member 4 (Nr1h4, FXR) is a bile acid activated nuclear receptor mainly expressed in the liver, intestine, kidney and adrenal glands. Upon activation, the primary function is to suppress cholesterol 7 alpha-hydroxylase (Cyp7a1), the rate-limiting enzyme in the classic or neutral bile acid synthesis pathway. In the present study, a novel Fxr deficient mouse line was created and studied with respect to metabolism and liver function in ageing mice fed chow diet. The Fxr deficient mice were similar to wild type mice in terms of body weight, body composition, energy intake and expenditure as well as behaviours at a young age. However, from 15 weeks of age and onwards, the Fxr deficient mice had almost no body weight increase up to 39 weeks of age mainly because of lower body fat mass. The lower body weight gain was associated with increased energy expenditure that was not compensated by increased food intake. Fasting levels of glucose and insulin were lower and glucose tolerance was improved in old and lean Fxr deficient mice. However, the Fxr deficient mice displayed significantly increased liver weight, steatosis, hepatocyte ballooning degeneration and lobular inflammation together with elevated plasma levels of ALT, bilirubin and bile acids, findings compatible with non-alcoholic steatohepatitis (NASH) and cholestasis. In conclusion, ageing Fxr deficient mice display late onset leanness associated with elevated energy expenditure and improved glucose control but develop severe NASH-like liver pathology.

Clinical and anatomical observations of a two-headed lamb.

Science.gov (United States)

Fisher, K R; Partlow, G D; Walker, A F

1986-04-01

The clinical and anatomical features of a live-born diprosopic lamb are described. There are no complete anatomical analyses of two-faced lambs in the literature despite the frequency of conjoined twinning in sheep. The lamb had two heads fused in the occipital region. Each head had two eyes. The pinnae of the medial ears were fused. Caudal to the neck the lamb appeared grossly normal. The lamb was unable to raise its heads or stand. Both heads showed synchronous sucking motions and cranial reflexes were present. Nystagmus, strabismus, and limb incoordination were present. The respiratory and heart rates were elevated. There was a grade IV murmur over the left heart base and a palpable thrill on the left side. Each head possessed a normal nasopharynx, oropharynx, and tongue. There was a singular laryngopharnyx and esophagus although the hyoid apparatus was partially duplicated. The cranial and cervical musculature reflected the head duplications. The aortic trunk emerged from the right ventricle just to the right of the conus arteriosus. A ventricular septal defect, patent foramen ovale, and ductus arteriosus were present along with malformed atrioventricular valves. Brainstem fusion began at the cranial medulla oblongata between cranial nerves IX and XII. The cerebella were separate but small. The ventromedial structures from each medulla oblongata were compressed into an extraneous midline remnant of tissue which extended caudally to the level of T2. The clinical signs therefore reflected the anatomical anomalies. A possible etiology for this diprosopus might be the presence early in development of an excessively large block of chordamesoderm. This would allow for the formation of two head folds and hence two "heads."

Congenital blindness is associated with large-scale reorganization of anatomical networks.

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Hasson, Uri; Andric, Michael; Atilgan, Hicret; Collignon, Olivier

2016-03-01

Blindness is a unique model for understanding the role of experience in the development of the brain's functional and anatomical architecture. Documenting changes in the structure of anatomical networks for this population would substantiate the notion that the brain's core network-level organization may undergo neuroplasticity as a result of life-long experience. To examine this issue, we compared whole-brain networks of regional cortical-thickness covariance in early blind and matched sighted individuals. This covariance is thought to reflect signatures of integration between systems involved in similar perceptual/cognitive functions. Using graph-theoretic metrics, we identified a unique mode of anatomical reorganization in the blind that differed from that found for sighted. This was seen in that network partition structures derived from subgroups of blind were more similar to each other than they were to partitions derived from sighted. Notably, after deriving network partitions, we found that language and visual regions tended to reside within separate modules in sighted but showed a pattern of merging into shared modules in the blind. Our study demonstrates that early visual deprivation triggers a systematic large-scale reorganization of whole-brain cortical-thickness networks, suggesting changes in how occipital regions interface with other functional networks in the congenitally blind. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Prefrontal-Thalamic Anatomical Connectivity and Executive Cognitive Function in Schizophrenia.

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Giraldo-Chica, Monica; Rogers, Baxter P; Damon, Stephen M; Landman, Bennett A; Woodward, Neil D

2018-03-15

Executive cognitive functions, including working memory, cognitive flexibility, and inhibition, are impaired in schizophrenia. Executive functions rely on coordinated information processing between the prefrontal cortex (PFC) and thalamus, particularly the mediodorsal nucleus. This raises the possibility that anatomical connectivity between the PFC and mediodorsal thalamus may be 1) reduced in schizophrenia and 2) related to deficits in executive function. The current investigation tested these hypotheses. Forty-five healthy subjects and 62 patients with a schizophrenia spectrum disorder completed a battery of tests of executive function and underwent diffusion-weighted imaging. Probabilistic tractography was used to quantify anatomical connectivity between six cortical regions, including PFC, and the thalamus. Thalamocortical anatomical connectivity was compared between healthy subjects and patients with schizophrenia using region-of-interest and voxelwise approaches, and the association between PFC-thalamic anatomical connectivity and severity of executive function impairment was examined in patients. Anatomical connectivity between the thalamus and PFC was reduced in schizophrenia. Voxelwise analysis localized the reduction to areas of the mediodorsal thalamus connected to lateral PFC. Reduced PFC-thalamic connectivity in schizophrenia correlated with impaired working memory but not cognitive flexibility and inhibition. In contrast to reduced PFC-thalamic connectivity, thalamic connectivity with somatosensory and occipital cortices was increased in schizophrenia. The results are consistent with models implicating disrupted PFC-thalamic connectivity in the pathophysiology of schizophrenia and mechanisms of cognitive impairment. PFC-thalamic anatomical connectivity may be an important target for procognitive interventions. Further work is needed to determine the implications of increased thalamic connectivity with sensory cortex. Copyright © 2017 Society of

Development of donor-derived thymic lymphomas after allogeneic bone marrow transplantation in AKR/J mice

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Yasumizu, R.; Hiai, H.; Sugiura, K.

1988-01-01

The transplantation of bone marrow cells from BALB/c (but not C57BL/6 and C3H/HeN) mice was observed to lead to the development of thymic lymphomas (leukemias) in AKR/J mice. Two leukemic cell lines, CAK1.3 and CAK4.4, were established from the primary culture of two thymic lymphoma, and surface phenotypes of these cell lines found to be H-2d and Thy-1.2+, indicating that these lymphoma cells are derived from BALB/c donor bone marrow cells. Further analyses of surface markers revealed that CAK1.3 is L3T4+ Lyt2+ IL2R-, whereas CAK4.4 is L3T4- Lyt2- IL2R+. Both CAK1.3 and CAK4.4 were transplantable into BALB/c but not AKR/J mice, further indicating that these cells are of BALB/c bone marrow donor origin. The cells were found to produce XC+-ecotropic viruses, but xenotropic and mink cell focus-forming viruses were undetectable. Inasmuch as thymic lymphomas are derived from bone marrow cells of leukemia-resistant BALB/c strain of mice under the allogeneic environment of leukemia-prone AKR/J mice, this animal model may serve as a useful tool not only for the analysis of leukemic relapse after bone marrow transplantation but also for elucidation of the mechanism of leukemogenesis

A different role of angiotensin II type 1a receptor in the development and hypertrophy of plantaris muscle in mice.

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Zempo, Hirofumi; Suzuki, Jun-Ichi; Ogawa, Masahito; Watanabe, Ryo; Isobe, Mitsuaki

2016-02-01

The role of angiotensin II type 1 (AT1) receptors in muscle development and hypertrophy remains unclear. This study was designed to reveal the effects that a loss of AT1 receptors has on skeletal muscle development and hypertrophy in mice. Eight-week-old male AT1a receptor knockout (AT1a(-/-)) mice were used for this experiment. The plantaris muscle to body weight ratio, muscle fiber cross-sectional area, and number of muscle fibers of AT1a(-/-) mice was significantly greater than wild type (WT) mice in the non-intervention condition. Next, the functional overload (OL) model was used to induce plantaris muscle hypertrophy by surgically removing the two triceps muscles consisting of the calf, soleus, and gastrocnemius muscles in mice. After 14 days of OL intervention, the plantaris muscle weight, the amount of fiber, and the fiber area increased. However, the magnitude of the increment of plantaris weight was not different between the two strains. Agtr1a mRNA expression did not change after OL in WT muscle. Actually, the Agt mRNA expression level of WT-OL was lower than WT-Control (C) muscle. An atrophy-related gene, atrogin-1 mRNA expression levels of AT1a(-/-)-C, WT-OL, and AT1a(-/-)-OL muscle were lower than that of WT-C muscle. Our findings suggest that AT1 receptor contributes to plantaris muscle development via atrogin-1 in mice.

A Methodology for Anatomic Ultrasound Image Diagnostic Quality Assessment

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Hemmsen, Martin Christian; Lange, Theis; Brandt, Andreas Hjelm

2017-01-01

are presented. Earlier uses of the methodology has shown that it ensures validity of the assessment, as it separates the influences between developer, investigator, and assessor once a research protocol has been established. This separation reduces confounding influences on the result from the developer......This paper discusses methods for assessment of ultrasound image quality based on our experiences with evaluating new methods for anatomic imaging. It presents a methodology to ensure a fair assessment between competing imaging methods using clinically relevant evaluations. The methodology...... to properly reveal the clinical value. The paper exemplifies the methodology using recent studies of Synthetic Aperture Sequential Beamforming tissue harmonic imaging....

Tetranectin Knockout Mice Develop Features of Parkinson Disease

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Er-song Wang

2014-07-01

Full Text Available Background/Aims: Aggregation of insoluble α-synuclein to form Lewy bodies (LBs may contribute to the selective loss of midbrain dopaminergic neurons in Parkinson disease (PD. Lack of robust animal models has impeded elucidation of the molecular mechanisms of LB formation and other critical aspects of PD pathogenesis. Methods: We established a mouse model with targeted deletion of the plasminogen-binding protein tetranectin (TN gene (TN-/- and measured the behavioral and histopathological features of PD. Results: Aged (15-to 20-month-old TN-/- mice displayed motor deficits resembling PD symptoms, including limb rigidity and both slower ambulation (bradykinesia and reduced rearing activity in the open field. In addition, these mice exhibited more numerous α-synuclein-positive LB-like inclusions within the substantia nigra pars compacta (SNc and reduced numbers of SNc dopaminergic neurons than age-matched wild type (WT mice. These pathological changes were also accompanied by loss of dopamine terminals in the dorsal striatum. Conclusion: The TN-/- mouse exhibits several key features of PD and so may be a valuable model for studying LB formation and testing candidate neuroprotective therapies for PD and other synucleinopathies.

Effects of perinatal coexposure to methylmercury and polychlorinated biphenyls on neurobehavioral development in mice

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Sugawara, Norio [Tohoku University School of Medicine, Environmental Health Sciences, Aoba-ku, Sendai (Japan); Hirosaki University Graduate School of Medicine, Department of Neuropsychiatry, Hirosaki (Japan); Ohba, Takashi; Nakai, Kunihiko; Nakamura, Tomoyuki; Suzuki, Keita; Kameo, Satomi; Shimada, Miyuki; Kurokawa, Naoyuki; Satoh, Chieko; Satoh, Hiroshi [Tohoku University School of Medicine, Environmental Health Sciences, Aoba-ku, Sendai (Japan); Kakita, Akiyoshi [Niigata University, Department of Pathological Neuroscience, Resource Branch for Brain Disease Research, Brain Research Institute, Niigata (Japan)

2008-06-15

Methylmercury (MeHg) and polychlorinated biphenyls (PCBs) are environmental pollutants that cause neurobehavioral deficits in humans. Because exposures to MeHg and PCBs occur through fish consumption, it is necessary to clarify the effects of the interaction of the two pollutants. Therefore, we investigated the effects of perinatal exposure to MeHg and PCBs on the neurobehavioral development in mice. Female mice (C57BL/6Cr) were divided into four groups according to the type of exposure: (1) vehicle control, (2) MeHg alone, (3) PCBs alone, and (4) MeHg + PCBs. The MeHg-exposed groups were fed with a diet containing 5 ppm MeHg (as Hg), from 4 weeks before mating, throughout pregnancy, and lactation. The PCB-exposed groups were given a commercial mixture of PCBs, Aroclor 1254, at 18 mg/kg body weight in corn oil by gavage every 3 days from day 5 after breeding and continued until postnatal day (PND) 20. Before weaning, an assessment of eye opening showed the interactive effects between MeHg and PCBs on PND 12: The coexposure group showed a similar response to the control group, whereas the MeHg- and PCB-exposed groups showed a high response than the former two groups. We also observed delay in development of grasp reflex by MeHg exposure on PNDs 12 and 14. When the offspring mice were 8 weeks old, the group exposed to PCBs alone showed increases in the frequencies of excrement defecation and urine traces in an open-field test. Analysis of the latency revealed the antagonistic interaction between the MeHg and PCBs: The latency increased by either MeHg or PCB exposure was decreased by coexposure. Treatment with MeHg decreased the distance walked by the mice, and MeHg interacted with PCBs. Moris' water maze test showed that the MeHg-treated mice took a long time to reach the submerged platform; however, this MeHg exposure showed no interaction with PCB exposure. The spontaneous locomotion activity of the mice was not affected by the chemical exposure at 9 weeks of

Preventive effects of andrographolide on the development of diabetes in autoimmune diabetic NOD mice by inducing immune tolerance.

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Zhang, Chengliang; Gui, Ling; Xu, Yanjiao; Wu, Tao; Liu, Dong

2013-08-01

Andrographolide, an active component in traditional anti-diabetic herbal plants, is a diterpenoid lactone isolated from Andrographis paniculata because of its potent anti-inflammatory and hypoglycemic effects. However, the effect of andrographolide on the development of diabetes in autoimmune non-obese diabetic (NOD) mice remains unknown. This study aimed to investigate the protective effects of andrographolide on the development of autoimmune diabetes and clarify the underlying mechanism. NOD mice were randomly divided into four groups and administered with water and andrographolide at 50, 100, and 150mg/kg body weight for four weeks. ICR mice were also selected as the control group. Oral glucose tolerance and histopathological insulitis were examined. Th1/Th2/Th17 cytokine secretion was determined by ELISA. The transcriptional profiles of T-bet, GATA3, and RORγt in the pancreatic lymphatic node samples derived from the NOD mice were detected by RT-PCR. After four weeks of oral supplementation, andrographolide significantly inhibited insulitis, delayed the onset, and suppressed the development of diabetes in 30-week-old NOD mice in a dose dependent manner. This protective status was correlated with a substantially decreased production of interferon (IFN)-γ and interleukin (IL)-2, increased IL-10 and transforming growth factor (TGF)-β, and a reduced IL-17. Andrographolide also increased GATA3 mRNA expression but decreased T-bet and RORγt mRNA expressions. Our results suggested that andrographolide prevented type 1 diabetes by maintaining Th1/Th2/Th17 homeostasis. Copyright © 2013 Elsevier B.V. All rights reserved.

Electrocautery device does not provide adequate pulmonary vessel sealing in transumbilical anatomic pulmonary lobectomy.

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Liu, Hung-Ping; Chu, Yen; Wu, Yi-Cheng; Hsieh, Ming-Ju; Liu, Chieng-Ying; Chen, Tzu-Ping; Chao, Yin-Kai; Wu, Ching-Yang; Yeh, Chi-Ju; Ko, Po-Jen; Liu, Yun-Hen

2016-05-01

Safe pulmonary vessel sealing device plays a crucial role in anatomic lung resection. In 2014, we reported high rates of massive bleeding complications during transumbilical lobectomy in a canine model due to difficulty in managing the pulmonary vessel with an endostapler. In this animal survival series, we aimed to evaluate the outcome of pulmonary vessel sealing with an electrocautery device to simplify the transumbilical thoracic surgery. Under general anesthesia, a 3-cm longitudinal incision was made over the umbilicus. Under video guidance, a bronchoscope was inserted through the incision for exploration. The diaphragmatic wound was created with an electrocautery knife and used as the entrance into the thoracic cavity. Using the transumbilical technique, anatomic lobectomy was performed with electrosurgical devices and endoscopic vascular staplers in 15 canines. Transumbilical endoscopic anatomic lobectomy was successfully completed in 12 of the 15 animals. Intraoperative bleeding developed in three animals during pulmonary hilum dissection, where one animal was killed due to hemodynamic instability and the other two animals required thoracotomy to complete the operation. There were five delayed bleeding and surgical mortality cases caused by inadequate vessel sealing by electrosurgical devices. Postmortem examination confirmed correct transumbilical lobectomy in the twelve animals that survived the operations. Transumbilical anatomic lobectomy is technically feasible in a canine model; however, the electrosurgical devices were not effective in sealing the pulmonary vessel in the current canine model.

mPeriod2 Brdm1 and other single Period mutant mice have normal food anticipatory activity.

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Pendergast, Julie S; Wendroth, Robert H; Stenner, Rio C; Keil, Charles D; Yamazaki, Shin

2017-11-14

Animals anticipate the timing of food availability via the food-entrainable oscillator (FEO). The anatomical location and timekeeping mechanism of the FEO are unknown. Several studies showed the circadian gene, Period 2, is critical for FEO timekeeping. However, other studies concluded that canonical circadian genes are not essential for FEO timekeeping. In this study, we re-examined the effects of the Per2 Brdm1 mutation on food entrainment using methods that have revealed robust food anticipatory activity in other mutant lines. We examined food anticipatory activity, which is the output of the FEO, in single Period mutant mice. Single Per1, Per2, and Per3 mutant mice had robust food anticipatory activity during restricted feeding. In addition, we found that two different lines of Per2 mutant mice (ldc and Brdm1) anticipated restricted food availability. To determine if FEO timekeeping persisted in the absence of the food cue, we assessed activity during fasting. Food anticipatory (wheel-running) activity in all Period mutant mice was also robust during food deprivation. Together, our studies demonstrate that the Period genes are not necessary for the expression of food anticipatory activity.

Thyroid Hormone Economy in the Perinatal Mouse Brain: Implications for Cerebral Cortex Development.

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Bárez-López, Soledad; Obregon, Maria Jesus; Bernal, Juan; Guadaño-Ferraz, Ana

2018-05-01

Thyroid hormones (THs, T4 and the transcriptionally active hormone T3) play an essential role in neurodevelopment; however, the mechanisms underlying T3 brain delivery during mice fetal development are not well known. This work has explored the sources of brain T3 during mice fetal development using biochemical, anatomical, and molecular approaches. The findings revealed that during late gestation, a large amount of fetal brain T4 is of maternal origin. Also, in the developing mouse brain, fetal T3 content is regulated through the conversion of T4 into T3 by type-2 deiodinase (D2) activity, which is present from earlier prenatal stages. Additionally, D2 activity was found to be essential to mediate expression of T3-dependent genes in the cerebral cortex, and also necessary to generate the transient cerebral cortex hyperthyroidism present in mice lacking the TH transporter Monocarboxylate transporter 8. Notably, the gene encoding for D2 (Dio2) was mainly expressed at the blood-cerebrospinal fluid barrier (BCSFB). Overall, these data signify that T4 deiodinated by D2 may be the only source of T3 during neocortical development. We therefore propose that D2 activity at the BCSFB converts the T4 transported across the choroid plexus into T3, thus supplying the brain with active hormone to maintain TH homeostasis.

Macrophage inhibitory cytokine-1 (MIC-1/GDF15 slows cancer development but increases metastases in TRAMP prostate cancer prone mice.

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Yasmin Husaini

Full Text Available Macrophage inhibitory cytokine-1 (MIC-1/GDF15, a divergent member of the TGF-β superfamily, is over-expressed by many common cancers including those of the prostate (PCa and its expression is linked to cancer outcome. We have evaluated the effect of MIC-1/GDF15 overexpression on PCa development and spread in the TRAMP transgenic model of spontaneous prostate cancer. TRAMP mice were crossed with MIC-1/GDF15 overexpressing mice (MIC-1(fms to produce syngeneic TRAMP(fmsmic-1 mice. Survival rate, prostate tumor size, histopathological grades and extent of distant organ metastases were compared. Metastasis of TC1-T5, an androgen independent TRAMP cell line that lacks MIC-1/GDF15 expression, was compared by injecting intravenously into MIC-1(fms and syngeneic C57BL/6 mice. Whilst TRAMP(fmsmic-1 survived on average 7.4 weeks longer, had significantly smaller genitourinary (GU tumors and lower PCa histopathological grades than TRAMP mice, more of these mice developed distant organ metastases. Additionally, a higher number of TC1-T5 lung tumor colonies were observed in MIC-1(fms mice than syngeneic WT C57BL/6 mice. Our studies strongly suggest that MIC-1/GDF15 has complex actions on tumor behavior: it limits local tumor growth but may with advancing disease, promote metastases. As MIC-1/GDF15 is induced by all cancer treatments and metastasis is the major cause of cancer treatment failure and cancer deaths, these results, if applicable to humans, may have a direct impact on patient care.

High incidence of HPV-associated head and neck cancers in FA deficient mice is associated with E7's induction of DNA damage through its inactivation of pocket proteins.

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Park, Jung Wook; Shin, Myeong-Kyun; Pitot, Henry C; Lambert, Paul F

2013-01-01

Fanconi anemia (FA) patients are highly susceptible to solid tumors at multiple anatomical sites including head and neck region. A subset of head and neck cancers (HNCs) is associated with 'high-risk' HPVs, particularly HPV16. However, the correlation between HPV oncogenes and cancers in FA patients is still unclear. We previously learned that FA deficiency in mice predisposes HPV16 E7 transgenic mice to HNCs. To address HPV16 E6's oncogenic potential under FA deficiency in HNCs, we utilized HPV16 E6-transgenic mice (K14E6) and HPV16 E6/E7-bi-transgenic mice (K14E6E7) on genetic backgrounds sufficient or deficient for one of the fanc genes, fancD2 and monitored their susceptibility to HNCs. K14E6 mice failed to develop tumor. However, E6 and fancD2-deficiency accelerated E7-driven tumor development in K14E6E7 mice. The increased tumor incidence was more correlated with E7-driven DNA damage than proliferation. We also found that deficiency of pocket proteins, pRb, p107, and p130 that are well-established targets of E7, could recapitulate E7's induction of DNA damage. Our findings support the hypothesis that E7 induces HPV-associated HNCs by promoting DNA damage through the inactivation of pocket proteins, which explains why a deficiency in DNA damage repair would increase susceptibility to E7-driven cancer. Our results further demonstrate the unexpected finding that FA deficiency does not predispose E6 transgenic mice to HNCs, indicating a specificity in the synergy between FA deficiency and HPV oncogenes in causing HNCs.

High incidence of HPV-associated head and neck cancers in FA deficient mice is associated with E7's induction of DNA damage through its inactivation of pocket proteins.

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Jung Wook Park

Full Text Available Fanconi anemia (FA patients are highly susceptible to solid tumors at multiple anatomical sites including head and neck region. A subset of head and neck cancers (HNCs is associated with 'high-risk' HPVs, particularly HPV16. However, the correlation between HPV oncogenes and cancers in FA patients is still unclear. We previously learned that FA deficiency in mice predisposes HPV16 E7 transgenic mice to HNCs. To address HPV16 E6's oncogenic potential under FA deficiency in HNCs, we utilized HPV16 E6-transgenic mice (K14E6 and HPV16 E6/E7-bi-transgenic mice (K14E6E7 on genetic backgrounds sufficient or deficient for one of the fanc genes, fancD2 and monitored their susceptibility to HNCs. K14E6 mice failed to develop tumor. However, E6 and fancD2-deficiency accelerated E7-driven tumor development in K14E6E7 mice. The increased tumor incidence was more correlated with E7-driven DNA damage than proliferation. We also found that deficiency of pocket proteins, pRb, p107, and p130 that are well-established targets of E7, could recapitulate E7's induction of DNA damage. Our findings support the hypothesis that E7 induces HPV-associated HNCs by promoting DNA damage through the inactivation of pocket proteins, which explains why a deficiency in DNA damage repair would increase susceptibility to E7-driven cancer. Our results further demonstrate the unexpected finding that FA deficiency does not predispose E6 transgenic mice to HNCs, indicating a specificity in the synergy between FA deficiency and HPV oncogenes in causing HNCs.

Toll-like receptor 2 signaling protects mice from tumor development in a mouse model of colitis-induced cancer.

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Emily L Lowe

2010-09-01

Full Text Available Inflammatory bowel disease (IBD is a disorder of chronic inflammation with increased susceptibility to colorectal cancer. The etiology of IBD is unclear but thought to result from a dysregulated adaptive and innate immune response to microbial products in a genetically susceptible host. Toll-like receptor (TLR signaling induced by intestinal commensal bacteria plays a crucial role in maintaining intestinal homeostasis, innate immunity and the enhancement of intestinal epithelial cell (IEC integrity. However, the role of TLR2 in the development of colorectal cancer has not been studied. We utilized the AOM-DSS model for colitis-associated colorectal cancer (CAC in wild type (WT and TLR2(-/- mice. Colons harvested from WT and TLR2(-/- mice were used for histopathology, immunohistochemistry, immunofluorescence and cytokine analysis. Mice deficient in TLR2 developed significantly more and larger colorectal tumors than their WT controls. We provide evidence that colonic epithelium of TLR2(-/- mice have altered immune responses and dysregulated proliferation under steady-state conditions and during colitis, which lead to inflammatory growth signals and predisposition to accelerated neoplastic growth. At the earliest time-points assessed, TLR2(-/- colons exhibited a significant increase in aberrant crypt foci (ACF, resulting in tumors that developed earlier and grew larger. In addition, the intestinal microenvironment revealed significantly higher levels of IL-6 and IL-17A concomitant with increased phospho-STAT3 within ACF. These observations indicate that in colitis, TLR2 plays a protective role against the development of CAC.

ROOT ANATOMICAL PLASTICITY IN RESPONSE TO SALT STRESS UNDER REAL AND FULL-SEASON FIELD CONDITIONS AND DETERMINATION OF NEW ANATOMIC SELECTION CHARACTERS FOR BREEDING SALT-RESISTANT RICE (Oryza sativa L.

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Mehmet AYBEKE

2016-12-01

Full Text Available Specific understanding of root anatomy plasticity under salt stress is lacking and requires creation of efficient screening techniques for stress condition s. To fill this gap, this study aimed to determine the anatomical plasticity in root chracteristics of 31 different rice cultivars (from ‘Best’ to ‘Low’ yielding grown under real field conditions (saline and non-saline from planting to harvesting and to reveal detailed root anatomical parameters that can be used to select and breed salt-tolerant rice. Anatomical and histochemical features of all cultivars and thin structures of the apoplastic barriers were investigated. The amount of silica (Si, 35 different anatomical characteristics, anatomical plasticity characteristics, plasticity rates, plasticity trends and changes and strategies of each group under saline and non-saline conditions were compared. The results showed that protective anatomical characters improved/remained equal to, and worsened/remained equal to those of the controls, in the ‘Best’ and other groups, respectively, from non-saline to saline conditions. Anatomical plasticity is essentially directly related to apoplastic barrier features. High genotypic variation was observed in root anatomy in all cultivars, but foremost traits were as follows: (1 cell size, (2 Si presence, (3 Si accumulation shape, (4 Si distribution towards root stele, (5 xylem arch features, (6 lignification-suberization properties in apoplastic barriers and their degrees, (7 presence/absence of idioblast cells filled with gummic and phenolic substances and (8 moderate anatomical plasticity. Cultivars with the most stabile anatomy under saline and non-saline conditions should be used to select and breed salt-resistant rice.

Anatomic variation of cranial parasympathetic ganglia

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Selma Siéssere

2008-06-01

Full Text Available Having broad knowledge of anatomy is essential for practicing dentistry. Certain anatomical structures call for detailed studies due to their anatomical and functional importance. Nevertheless, some structures are difficult to visualize and identify due to their small volume and complicated access. Such is the case of the parasympathetic ganglia located in the cranial part of the autonomic nervous system, which include: the ciliary ganglion (located deeply in the orbit, laterally to the optic nerve, the pterygopalatine ganglion (located in the pterygopalatine fossa, the submandibular ganglion (located laterally to the hyoglossus muscle, below the lingual nerve, and the otic ganglion (located medially to the mandibular nerve, right beneath the oval foramen. The aim of this study was to present these structures in dissected anatomic specimens and perform a comparative analysis regarding location and morphology. The proximity of the ganglia and associated nerves were also analyzed, as well as the number and volume of fibers connected to them. Human heads were dissected by planes, partially removing the adjacent structures to the point we could reach the parasympathetic ganglia. With this study, we concluded that there was no significant variation regarding the location of the studied ganglia. Morphologically, our observations concur with previous classical descriptions of the parasympathetic ganglia, but we observed variations regarding the proximity of the otic ganglion to the mandibular nerve. We also observed that there were variations regarding the number and volume of fiber bundles connected to the submandibular, otic, and pterygopalatine ganglia.

Motor hypertonia and lack of locomotor coordination in mutant mice lacking DSCAM.

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Lemieux, Maxime; Laflamme, Olivier D; Thiry, Louise; Boulanger-Piette, Antoine; Frenette, Jérôme; Bretzner, Frédéric

2016-03-01

Down syndrome cell adherence molecule (DSCAM) contributes to the normal establishment and maintenance of neural circuits. Whereas there is abundant literature regarding the role of DSCAM in the neural patterning of the mammalian retina, less is known about motor circuits. Recently, DSCAM mutation has been shown to impair bilateral motor coordination during respiration, thus causing death at birth. DSCAM mutants that survive through adulthood display a lack of locomotor endurance and coordination in the rotarod test, thus suggesting that the DSCAM mutation impairs motor control. We investigated the motor and locomotor functions of DSCAM(2J) mutant mice through a combination of anatomical, kinematic, force, and electromyographic recordings. With respect to wild-type mice, DSCAM(2J) mice displayed a longer swing phase with a limb hyperflexion at the expense of a shorter stance phase during locomotion. Furthermore, electromyographic activity in the flexor and extensor muscles was increased and coactivated over 20% of the step cycle over a wide range of walking speeds. In contrast to wild-type mice, which used lateral walk and trot at walking speed, DSCAM(2J) mice used preferentially less coordinated gaits, such as out-of-phase walk and pace. The neuromuscular junction and the contractile properties of muscles, as well as their muscle spindles, were normal, and no signs of motor rigidity or spasticity were observed during passive limb movements. Our study demonstrates that the DSCAM mutation induces dystonic hypertonia and a disruption of locomotor gaits. Copyright © 2016 the American Physiological Society.

Generating Facial Expressions Using an Anatomically Accurate Biomechanical Model.

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Wu, Tim; Hung, Alice; Mithraratne, Kumar

2014-11-01

This paper presents a computational framework for modelling the biomechanics of human facial expressions. A detailed high-order (Cubic-Hermite) finite element model of the human head was constructed using anatomical data segmented from magnetic resonance images. The model includes a superficial soft-tissue continuum consisting of skin, the subcutaneous layer and the superficial Musculo-Aponeurotic system. Embedded within this continuum mesh, are 20 pairs of facial muscles which drive facial expressions. These muscles were treated as transversely-isotropic and their anatomical geometries and fibre orientations were accurately depicted. In order to capture the relative composition of muscles and fat, material heterogeneity was also introduced into the model. Complex contact interactions between the lips, eyelids, and between superficial soft tissue continuum and deep rigid skeletal bones were also computed. In addition, this paper investigates the impact of incorporating material heterogeneity and contact interactions, which are often neglected in similar studies. Four facial expressions were simulated using the developed model and the results were compared with surface data obtained from a 3D structured-light scanner. Predicted expressions showed good agreement with the experimental data.

Computational investigation of nonlinear microwave tomography on anatomically realistic breast phantoms

DEFF Research Database (Denmark)

Jensen, P. D.; Rubæk, Tonny; Mohr, J. J.

2013-01-01

The performance of a nonlinear microwave tomography algorithm is tested using simulated data from anatomically realistic breast phantoms. These tests include several different anatomically correct breast models from the University of Wisconsin-Madison repository with and without tumors inserted....

The Endocannabinoid System across Postnatal Development in Transmembrane Domain Neuregulin 1 Mutant Mice

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Rose Chesworth

2018-02-01

Full Text Available The use of cannabis is a well-established component risk factor for schizophrenia, particularly in adolescent individuals with genetic predisposition for the disorder. Alterations to the endocannabinoid system have been found in the prefrontal cortex of patients with schizophrenia. Thus, we assessed whether molecular alterations exist in the endocannabinoid signalling pathway during brain development in a mouse model for the schizophrenia risk gene neuregulin 1 (Nrg1. We analysed transcripts encoding key molecules of the endocannabinoid system in heterozygous transmembrane domain Nrg1 mutant mice (Nrg1 TM HET, which is known to have increased sensitivity to cannabis exposure. Tissue from the prelimbic cortex and hippocampus of male and female Nrg1 TM HET mice and wild type-like littermates was collected at postnatal days (PNDs 7, 10, 14, 21, 28, 35, 49, and 161. Quantitative polymerase chain reaction was conducted to assess mRNA levels of cannabinoid receptor 1 (CB1R and enzymes for the synthesis and breakdown of the endocannabinoid 2-arachidonoylglycerol [i.e., diacylglycerol lipase alpha (DAGLα, monoglyceride lipase (MGLL, and α/β-hydrolase domain-containing 6 (ABHD6]. No sex differences were found for any transcripts in either brain region; thus, male and female data were pooled. Hippocampal and cortical mRNA expression of DAGLα, MGLL, and ABHD6 increased until PND 21–35 and then decreased and stabilised for the rest of postnatal development. Hippocampal CB1R mRNA expression increased until PND 21 and decreased after this age. Expression levels of these endocannabinoid markers did not differ in Nrg1 TM HET compared to control mice at any time point. Here, we demonstrate dynamic changes in the developmental trajectory of several key endocannabinoid system transcripts in the mouse brain, which may correspond with periods of endocannabinoid system maturation. Nrg1 TM HET mutation did not alter the developmental trajectory of the

Anatomical Mercury: Changing Understandings of Quicksilver, Blood, and the Lymphatic System, 1650-1800.

Science.gov (United States)

Hendriksen, Marieke M A

2015-10-01

The use of mercury as an injection mass in anatomical experiments and preparations was common throughout Europe in the long eighteenth century, and refined mercury-injected preparations as well as plates of anatomical mercury remain today. The use and meaning of mercury in related disciplines such as medicine and chemistry in the same period have been studied, but our knowledge of anatomical mercury is sparse and tends to focus on technicalities. This article argues that mercury had a distinct meaning in anatomy, which was initially influenced by alchemical and classical understandings of mercury. Moreover, it demonstrates that the choice of mercury as an anatomical injection mass was deliberate and informed by an intricate cultural understanding of its materiality, and that its use in anatomical preparations and its perception as an anatomical material evolved with the understanding of the circulatory and lymphatic systems. By using the material culture of anatomical mercury as a starting point, I seek to provide a new, object-driven interpretation of complex and strongly interrelated historiographical categories such as mechanism, vitalism, chemistry, anatomy, and physiology, which are difficult to understand through a historiography that focuses exclusively on ideas. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Anatomical variability of the trunk wood and root tissues of ...

African Journals Online (AJOL)

The aim of this study was to investigate the anatomical structure of the trunk wood and the roots of A. nitida and R. racemosa, two mangrove trees from Gabon. The anatomical differences between the trunks and the roots were used to understand their bio-remediating differences through heavy metals. It was found that the ...

Quantitative evaluation of anatomical noise in chest digital tomosynthesis, digital radiography, and computed tomography

International Nuclear Information System (INIS)

Lee, D.; Kim, D.; Choi, S.; Kim, H.-J.; Choi, S.; Lee, H.

2017-01-01

Lung cancer is currently the worldwide leading cause of death from cancer. Thus, detection of lung cancer at its early stages is critical for improving the survival rate of patients. Chest digital tomosynthesis (CDT) is a recently developed imaging modality, combining many advantages of digital radiography (DR) and computed tomography (CT). This method has the potential to be widely used in the clinical setting. In this study, we introduce a developed CDT R/F system and compare its image quality with those of DR and CT, especially with respect to anatomical noise and lung nodule conspicuity, for LUNGMAN phantoms. The developed CDT R/F system consists of a CsI scintillator flat panel detector, X-ray tube, and tomosynthesis data acquisition geometry. For CDT R/F imaging, 41 projections were acquired at different angles, over the ± 20° angular range, in a linear translation geometry. To evaluate the clinical effectiveness of the CDT R/F system, the acquired images were compared with CT (Philips brilliance CT 64, Philips healthcare, U.S.) and DR (ADR-M, LISTEM, Korea) phantom images in terms of the anatomical noise power spectrum (aNPS). DR images exhibited low conspicuity for a small-size lung nodule, while CDT R/F and CT exhibited relatively high sensitivity for all lung nodule sizes. The aNPS of the CDT R/F system was better than that of DR, by resolving anatomical overlapping problems. In conclusion, the developed CDT R/F system is likely to contribute to early diagnosis of lung cancer, while requiring a relatively low patient dose, compared with CT.

Quantitative evaluation of anatomical noise in chest digital tomosynthesis, digital radiography, and computed tomography

Science.gov (United States)

Lee, D.; Choi, S.; Lee, H.; Kim, D.; Choi, S.; Kim, H.-J.

2017-04-01

Lung cancer is currently the worldwide leading cause of death from cancer. Thus, detection of lung cancer at its early stages is critical for improving the survival rate of patients. Chest digital tomosynthesis (CDT) is a recently developed imaging modality, combining many advantages of digital radiography (DR) and computed tomography (CT). This method has the potential to be widely used in the clinical setting. In this study, we introduce a developed CDT R/F system and compare its image quality with those of DR and CT, especially with respect to anatomical noise and lung nodule conspicuity, for LUNGMAN phantoms. The developed CDT R/F system consists of a CsI scintillator flat panel detector, X-ray tube, and tomosynthesis data acquisition geometry. For CDT R/F imaging, 41 projections were acquired at different angles, over the ± 20° angular range, in a linear translation geometry. To evaluate the clinical effectiveness of the CDT R/F system, the acquired images were compared with CT (Philips brilliance CT 64, Philips healthcare, U.S.) and DR (ADR-M, LISTEM, Korea) phantom images in terms of the anatomical noise power spectrum (aNPS). DR images exhibited low conspicuity for a small-size lung nodule, while CDT R/F and CT exhibited relatively high sensitivity for all lung nodule sizes. The aNPS of the CDT R/F system was better than that of DR, by resolving anatomical overlapping problems. In conclusion, the developed CDT R/F system is likely to contribute to early diagnosis of lung cancer, while requiring a relatively low patient dose, compared with CT.

Vitamin K2 biosynthetic enzyme, UBIAD1 is essential for embryonic development of mice.

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Nakagawa, Kimie; Sawada, Natsumi; Hirota, Yoshihisa; Uchino, Yuri; Suhara, Yoshitomo; Hasegawa, Tomoka; Amizuka, Norio; Okamoto, Tadashi; Tsugawa, Naoko; Kamao, Maya; Funahashi, Nobuaki; Okano, Toshio

2014-01-01

UbiA prenyltransferase domain containing 1 (UBIAD1) is a novel vitamin K2 biosynthetic enzyme screened and identified from the human genome database. UBIAD1 has recently been shown to catalyse the biosynthesis of Coenzyme Q10 (CoQ10) in zebrafish and human cells. To investigate the function of UBIAD1 in vivo, we attempted to generate mice lacking Ubiad1, a homolog of human UBIAD1, by gene targeting. Ubiad1-deficient (Ubiad1(-/-)) mouse embryos failed to survive beyond embryonic day 7.5, exhibiting small-sized body and gastrulation arrest. Ubiad1(-/-) embryonic stem (ES) cells failed to synthesize vitamin K2 but were able to synthesize CoQ9, similar to wild-type ES cells. Ubiad1(+/-) mice developed normally, exhibiting normal growth and fertility. Vitamin K2 tissue levels and synthesis activity were approximately half of those in the wild-type, whereas CoQ9 tissue levels and synthesis activity were similar to those in the wild-type. Similarly, UBIAD1 expression and vitamin K2 synthesis activity of mouse embryonic fibroblasts prepared from Ubiad1(+/-) E15.5 embryos were approximately half of those in the wild-type, whereas CoQ9 levels and synthesis activity were similar to those in the wild-type. Ubiad1(-/-) mouse embryos failed to be rescued, but their embryonic lifespans were extended to term by oral administration of MK-4 or CoQ10 to pregnant Ubiad1(+/-) mice. These results suggest that UBIAD1 is responsible for vitamin K2 synthesis but may not be responsible for CoQ9 synthesis in mice. We propose that UBIAD1 plays a pivotal role in embryonic development by synthesizing vitamin K2, but may have additional functions beyond the biosynthesis of vitamin K2.

Characterisation of connective tissue from the hypertrophic skeletal muscle of myostatin null mice.

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Elashry, Mohamed I; Collins-Hooper, Henry; Vaiyapuri, Sakthivel; Patel, Ketan

2012-06-01

Myostatin is a potent inhibitor of muscle development. Genetic deletion of myostatin in mice results in muscle mass increase, with muscles often weighing three times their normal values. Contracting muscle transfers tension to skeletal elements through an elaborate connective tissue network. Therefore, the connective tissue of skeletal muscle is an integral component of the contractile apparatus. Here we examine the connective tissue architecture in myostatin null muscle. We show that the hypertrophic muscle has decreased connective tissue content compared with wild-type muscle. Secondly, we show that the hypertrophic muscle fails to show the normal increase in muscle connective tissue content during ageing. Therefore, genetic deletion of myostatin results in an increase in contractile elements but a decrease in connective tissue content. We propose a model based on the contractile profile of muscle fibres that reconciles this apparent incompatible tissue composition phenotype. © 2012 The Authors. Journal of Anatomy © 2012 Anatomical Society.

Development of myenteric cholinergic neurons in ChAT-Cre;R26R-YFP mice.

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Hao, Marlene M; Bornstein, Joel C; Young, Heather M

2013-10-01

Cholinergic neurons are the major excitatory neurons of the enteric nervous system (ENS), and include intrinsic sensory neurons, interneurons, and excitatory motor neurons. Cholinergic neurons have been detected in the embryonic ENS; however, the development of these neurons has been difficult to study as they are difficult to detect prior to birth using conventional immunohistochemistry. In this study we used ChAT-Cre;R26R-YFP mice to examine the development of cholinergic neurons in the gut of embryonic and postnatal mice. Cholinergic (YFP+) neurons were first detected at embryonic day (E)11.5, and the proportion of cholinergic neurons gradually increased during pre- and postnatal development. At birth, myenteric cholinergic neurons comprised less than half of their adult proportions in the small intestine (25% of myenteric neurons were YFP+ at P0 compared to 62% in adults). The earliest cholinergic neurons appear to mainly project anally. Projections into the presumptive circular muscle were first observed at E14.5. A subpopulation of cholinergic neurons coexpress calbindin through embryonic and postnatal development, but only a small proportion coexpressed neuronal nitric oxide synthase. Our study shows that cholinergic neurons in the ENS develop over a protracted period of time. © 2013 Wiley Periodicals, Inc.

Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development

NARCIS (Netherlands)

T. Baardman (Taco); M.V. Zwier (Mathijs V.); L.J. Wisse (Lambertus); A.C. Gittenberger-De Groot (Adriana); W.S. Kerstjens-Frederikse (Wilhelmina); R.M.W. Hofstra (Robert); A. Jurdzinski (Angelika); B.P. Hierck (Beerend); M.R.M. Jongbloed (Monique); R.M.F. Berger (Rolf); T. Plösch (Torsten); M.C. DeRuiter (Marco)

2016-01-01

textabstractLipoprotein-related receptor protein 2 (LRP2) is important for development of the embryonic neural crest and brain in both mice and humans. Although a role in cardiovascular development can be expected, the hearts of Lrp2 knockout (KO) mice have not yet been investigated. We studied the

Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development

NARCIS (Netherlands)

Baardman, Maria E.; Zwier, Mathijs V.; Wisse, Lambertus J.; Gittenberger-de Groot, Adriana C.; Kerstjens-Frederikse, Wilhelmina S.; Hofstra, Robert M. W.; Jurdzinski, Angelika; Hierck, Beerend P.; Jongbloed, Monique R. M.; Berger, Rolf M. F.; Plosch, Torsten; DeRuiter, Marco C.

2016-01-01

Lipoprotein-related receptor protein 2 (LRP2) is important for development of the embryonic neural crest and brain in both mice and humans. Although a role in cardiovascular development can be expected, the hearts of Lrp2 knockout (KO) mice have not yet been investigated. We studied the

Skeletal development of mice lacking bone sialoprotein (BSP--impairment of long bone growth and progressive establishment of high trabecular bone mass.

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Wafa Bouleftour

Full Text Available Adult Ibsp-knockout mice (BSP-/- display shorter stature, lower bone turnover and higher trabecular bone mass than wild type, the latter resulting from impaired bone resorption. Unexpectedly, BSP knockout also affects reproductive behavior, as female mice do not construct a proper "nest" for their offsprings. Multiple crossing experiments nonetheless indicated that the shorter stature and lower weight of BSP-/- mice, since birth and throughout life, as well as their shorter femur and tibia bones are independent of the genotype of the mothers, and thus reflect genetic inheritance. In BSP-/- newborns, µCT analysis revealed a delay in membranous primary ossification, with wider cranial sutures, as well as thinner femoral cortical bone and lower tissue mineral density, reflected in lower expression of bone formation markers. However, trabecular bone volume and osteoclast parameters of long bones do not differ between genotypes. Three weeks after birth, osteoclast number and surface drop in the mutants, concomitant with trabecular bone accumulation. The growth plates present a thinner hypertrophic zone in newborns with lower whole bone expression of IGF-1 and higher IHH in 6 days old BSP-/- mice. At 3 weeks the proliferating zone is thinner and the hypertrophic zone thicker in BSP-/- than in BSP+/+ mice of either sex, maybe reflecting a combination of lower chondrocyte proliferation and impaired cartilage resorption. Six days old BSP-/- mice display lower osteoblast marker expression but higher MEPE and higher osteopontin(Opn/Runx2 ratio. Serum Opn is higher in mutants at day 6 and in adults. Thus, lack of BSP alters long bone growth and membranous/cortical primary bone formation and mineralization. Endochondral development is however normal in mutant mice and the accumulation of trabecular bone observed in adults develops progressively in the weeks following birth. Compensatory high Opn may allow normal endochondral development in BSP-/- mice

Comparative epidermal anatomical studies in six taxa of genus Nephrolepis Swart in Nigeria

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A. A. Fajuke

2018-04-01

Full Text Available Anatomical studies in six taxa of genus Nephrolepis; N. biserrata, N. cordifolia, N. exaltata (i & (ii, N. biserrata var. furcans and N. undulata were carried out with a view to identify anatomic characters of taxonomic values. Both qualitative and quantitative anatomical studies were carried out. Quantitative data were subjected to descriptive statistical analysis. Anatomical characters studied include venation patterns, trichome types, presence and absence of stomata and values of the stomatal index which are valuable in delimiting the species. The overall results showed overlaps in the quantitative anatomical attributes of the Nephrolepis taxa studied suggesting that they belong to the same genus. Qualitative anatomical attributes that separated the genus into distinct taxa are the presence of simple multicellular glandular trichomes in N. biserrata and simple multicellular non-glandular trichomes in N. exaltata (i and N. exalta (ii while N. biserrata var. furcans and N. undulata have simple unicellular non-glandular trichomes and absence of trichome in N. cordifolia. Presence of anisocytic, diacytic or anomocytic stomata were of diagnostic important in the six taxa.

[Study on the effect of promoting intelligence development and preventing hypoxia/reoxygenation injury of selenium-banqiao-Codonopsis pilosula-overground part in mice].

Science.gov (United States)

Xiao, Benjian; Chen, Guodong; Lan, Zongping

2005-08-01

To study on the effect of promoting intelligence development and preventing Hypoxia/Reoxygenation injury of Selenium-Banqiao-Codonopsis pilosula-overground part in mice. Promoting Intelligence Development experiment was induced by PIA; Hypoxia/reoxygenation ingury model was established to observe the activity of ROS, SOD, MOD and CAT in blood. Selenium-Banqiao-Codonopsis pilosula-overground part could enhance the learning and memory ability of old mice and obviously extend the swimming time of mice. It could also decrease the quality of ROS and MDA, increase the activity of SOD, but no significant effect on CAT. Selenium-Banqiao-Codonopsis pilosula-overground part has effect on promoting intelligence development and preventing hypoxia/reoxygenation injury.

High Incidence of HPV-Associated Head and Neck Cancers in FA Deficient Mice Is Associated with E7’s Induction of DNA Damage through Its Inactivation of Pocket Proteins

Science.gov (United States)

Park, Jung Wook; Shin, Myeong-Kyun; Pitot, Henry C.; Lambert, Paul F.

2013-01-01

Fanconi anemia (FA) patients are highly susceptible to solid tumors at multiple anatomical sites including head and neck region. A subset of head and neck cancers (HNCs) is associated with ‘high-risk’ HPVs, particularly HPV16. However, the correlation between HPV oncogenes and cancers in FA patients is still unclear. We previously learned that FA deficiency in mice predisposes HPV16 E7 transgenic mice to HNCs. To address HPV16 E6’s oncogenic potential under FA deficiency in HNCs, we utilized HPV16 E6-transgenic mice (K14E6) and HPV16 E6/E7-bi-transgenic mice (K14E6E7) on genetic backgrounds sufficient or deficient for one of the fanc genes, fancD2 and monitored their susceptibility to HNCs. K14E6 mice failed to develop tumor. However, E6 and fancD2-deficiency accelerated E7-driven tumor development in K14E6E7 mice. The increased tumor incidence was more correlated with E7-driven DNA damage than proliferation. We also found that deficiency of pocket proteins, pRb, p107, and p130 that are well-established targets of E7, could recapitulate E7’s induction of DNA damage. Our findings support the hypothesis that E7 induces HPV-associated HNCs by promoting DNA damage through the inactivation of pocket proteins, which explains why a deficiency in DNA damage repair would increase susceptibility to E7-driven cancer. Our results further demonstrate the unexpected finding that FA deficiency does not predispose E6 transgenic mice to HNCs, indicating a specificity in the synergy between FA deficiency and HPV oncogenes in causing HNCs. PMID:24086435

Sulforaphane ameliorates the development of experimental autoimmune encephalomyelitis by antagonizing oxidative stress and Th17-related inflammation in mice.

Science.gov (United States)

Li, Bin; Cui, Wei; Liu, Jia; Li, Ru; Liu, Qian; Xie, Xiao-Hua; Ge, Xiao-Li; Zhang, Jing; Song, Xiu-Juan; Wang, Ying; Guo, Li

2013-12-01

Sulforaphane (SFN) is an organosulfur compound present in vegetables and has potent anti-oxidant and anti-inflammatory activities. This study was aimed at investigating the effect of treatment with SFN on inflammation and oxidative stress, and the potential mechanisms underlying the action of SFN in experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. Treatment with SFN significantly inhibited the development and severity of EAE in mice, accompanied by mitigating inflammatory infiltration and demyelination in the spinal cord of mice. The protective effect of SFN was associated with significantly improved distribution of claudin-5 and occludin, and decreased levels of MMP-9 expression, preserving the blood-brain barrier. Furthermore, the protection of SFN was also related to decreased levels of oxidative stress in the brains of mice by enhanced activation of the Nrf2/ARE pathway and increased levels of anti-oxidant HO-1 and NQO1 expression. In addition, treatment with SFN inhibited antigen-specific Th17 responses and enhanced IL-10 responses. Our data indicated that treatment with SFN inhibited EAE development and severity in mice by its anti-oxidant activity and antagonizing autoimmune inflammation. Our findings suggest that SFN and its analogues may be promising reagents for intervention of multiple sclerosis and other autoimmune diseases. © 2013.

Role of protein kinase C family in the cerebellum-dependent adaptive learning of horizontal optokinetic response eye movements in mice.

Science.gov (United States)

Shutoh, Fumihiro; Katoh, Akira; Ohki, Masafumi; Itohara, Shigeyoshi; Tonegawa, Susumu; Nagao, Soichi

2003-07-01

Among the subtypes of the Ca2+-dependent protein kinase C (PKC), which play a crucial role in long-term depression (LTD), both alpha and gamma are expressed in the cerebellar floccular Purkinje cells. To reveal the functional differences of PKC subtypes, we examined the adaptability of ocular reflexes of PKCgamma mutant mice, which show mild ataxia and normal LTD. In mutant mice, gains of the horizontal optokinetic eye response (HOKR) were reduced. Adaptation of the HOKR was not affected but its retinal slip dependency was altered in mutant mice. Sustained 1-h sinusoidal screen oscillation, which induced a relatively large amount of retinal slips in both mutant and wild-type mice, increased the HOKR gain in wild-type mice but not in mutant mice. In contrast, exposure to 1 h of sustained slower screen oscillations, which induced relatively small retinal slips in mutant and wild-type mice, increased the HOKR gain in both mutant and wild-type mice. Adaptation of the HOKR of the mutant mice to slow screen oscillation and those of wild-type mice to fast and slow screen oscillations were all abolished by local applications of a PKC inhibitor (chelerythrine) within the flocculi. Electrophysiological and anatomical studies showed no appreciable changes in the sources and magnitudes of climbing fibre inputs, which mediate retinal slip signals to the flocculus in the mutant mice. These results suggest that PKCgamma has a modulatory role in determining retinal slip dependency, and other PKC subtypes, e.g. PKCalpha, may play a crucial role in the adaptation of the HOKR.

The clinical importance of the anatomic variations in the paranasal sinuses

International Nuclear Information System (INIS)

Teixeira Junior, Francisco Ribeiro; Bretas, Elisa Almeida Sathler; Madeira, Ivana Andrade; Diniz, Renata Furletti; Ribeiro, Marcelo Almeida; Motta, Emilia Guerra Pinto Coelho; Moreira, Wanderval

2008-01-01

The anatomic variations of the paranasal sinuses are common findings. The importance of such variations predisposing disease through the obstruction of the drainage pathway has been discussed by several authors, although it is not yet a matter of agreement. The literature was reviewed and a iconographic assay was prepared aiming the discussion of the importance of the main anatomic variations of the paranasal sinuses. The prevalence of anatomic variations of the paranasal sinuses varies largely amongst studies and its role in sinus disease is controversial. In this article, it is described the different variations associated to paranasal disease and how they relate to pathologic conditions. Most studies confirm the concept that anatomic variations of the paranasal sinuses are related to disease when they obstruct the drainage pathways. The knowledge of such alterations and its relations to pathologic conditions is expected from the general radiologist. (author)

Adiponectin haploinsufficiency promotes mammary tumor development in MMTV-PyVT mice by modulation of phosphatase and tensin homolog activities.

Directory of Open Access Journals (Sweden)

Janice B B Lam

Full Text Available Adiponectin is an adipokine possessing beneficial effects on obesity-related medical complications. A negative association of adiponectin levels with breast cancer development has been demonstrated. However, the precise role of adiponectin deficiency in mammary carcinogenesis remains elusive.In the present study, MMTV-polyomavirus middle T antigen (MMTV-PyVT transgenic mice with reduced adiponectin expressions were established and the stromal effects of adiponectin haploinsufficiency on mammary tumor development evaluated. In mice from both FVB/N and C57BL/6J backgrounds, insufficient adiponectin production promoted mammary tumor onset and development. A distinctive basal-like subtype of tumors, with a more aggressive phenotype, was derived from adiponectin haplodeficient MMTV-PyVT mice. Comparing with those from control MMTV-PyVT mice, the isolated mammary tumor cells showed enhanced tumor progression in re-implanted nude mice, accelerated proliferation in primary cultures, and hyperactivated phosphatidylinositol-3-kinase (PI3K/Akt/beta-catenin signaling, which at least partly attributed to the decreased phosphatase and tensin homolog (PTEN activities. Further analysis revealed that PTEN was inactivated by a redox-regulated mechanism. Increased association of PTEN-thioredoxin complexes was detected in tumors derived from mice with reduced adiponectin levels. The activities of thioredoxin (Trx1 and thioredoxin reductase (TrxR1 were significantly elevated, whereas treatment with either curcumin, an irreversible inhibitor of TrxR1, or adiponectin largely attenuated their activities and resulted in the re-activation of PTEN in these tumor cells. Moreover, adiponectin could inhibit TrxR1 promoter-mediated transcription and restore the mRNA expressions of TrxR1.Adiponectin haploinsufficiency facilitated mammary tumorigenesis by down-regulation of PTEN activity and activation of PI3K/Akt signalling pathway through a mechanism involving Trx1/TrxR1

Anatomical models and wax Venuses: art masterpieces or scientific craft works?

Science.gov (United States)

Ballestriero, R

2010-02-01

The art of wax modelling has an ancient origin but rose to prominence in 14th century Italy with the cult of votive artefacts. With the advent of Neoclassicism this art, now deemed repulsive, continued to survive in a scientific environment, where it flourished in the study of normal and pathological anatomy, obstetrics, zoology and botany. The achievement of having originated the creation of anatomical models in coloured wax must be ascribed to a joint effort undertaken by the Sicilian wax modeller Gaetano Giulio Zumbo and the French surgeon Guillaume Desnoues in the late 17th century. Interest in anatomical wax models spread throughout Europe during the 18th century, first in Bologna with Ercole Lelli, Giovanni Manzolini and Anna Morandi, and then in Florence with Felice Fontana and Clemente Susini. In England, the art of anatomical ceroplastics was brought to London from Florence by the sculptor Joseph Towne. Throughout the centuries many anatomical artists preferred this material due to the remarkable mimetic likeness obtained, far surpassing any other material. Independent of the material used, whether wood, wax or clay, anatomical models were always considered merely craft works confined to hospitals or faculties of medicine and have survived to this day only because of their scientific interest. Italian and English waxes are stylistically different but the remarkable results obtained by Susini and Towne, and the fact that some contemporary artists are again representing anatomical wax bodies in their works, makes the border that formerly separated art and craft indistinguishable.

How accurate is anatomic limb alignment in predicting mechanical limb alignment after total knee arthroplasty?

Science.gov (United States)

Lee, Seung Ah; Choi, Sang-Hee; Chang, Moon Jong

2015-10-27

Anatomic limb alignment often differs from mechanical limb alignment after total knee arthroplasty (TKA). We sought to assess the accuracy, specificity, and sensitivity for each of three commonly used ranges for anatomic limb alignment (3-9°, 5-10° and 2-10°) in predicting an acceptable range (neutral ± 3°) for mechanical limb alignment after TKA. We also assessed whether the accuracy of anatomic limb alignment was affected by anatomic variation. This retrospective study included 314 primary TKAs. The alignment of the limb was measured with both anatomic and mechanical methods of measurement. We also measured anatomic variation, including the femoral bowing angle, tibial bowing angle, and neck-shaft angle of the femur. All angles were measured on the same full-length standing anteroposterior radiographs. The accuracy, specificity, and sensitivity for each range of anatomic limb alignment were calculated and compared using mechanical limb alignment as the reference standard. The associations between the accuracy of anatomic limb alignment and anatomic variation were also determined. The range of 2-10° for anatomic limb alignment showed the highest accuracy, but it was only 73 % (3-9°, 65 %; 5-10°, 67 %). The specificity of the 2-10° range was 81 %, which was higher than that of the other ranges (3-9°, 69 %; 5-10°, 67 %). However, the sensitivity of the 2-10° range to predict varus malalignment was only 16 % (3-9°, 35 %; 5-10°, 68 %). In addition, the sensitivity of the 2-10° range to predict valgus malalignment was only 43 % (3-9°, 71 %; 5-10°, 43 %). The accuracy of anatomical limb alignment was lower for knees with greater femoral (odds ratio = 1.2) and tibial (odds ratio = 1.2) bowing. Anatomic limb alignment did not accurately predict mechanical limb alignment after TKA, and its accuracy was affected by anatomic variation. Thus, alignment after TKA should be assessed by measuring mechanical alignment rather than anatomic

Prenatal stress challenge impairs fetal lung development and asthma severity sex-specifically in mice.

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Zazara, Dimitra E; Perani, Clara V; Solano, María E; Arck, Petra C

2018-02-01

Allergic asthma is an increasing health problem worldwide. Interestingly, prenatal challenges such as stress have been associated with an increased risk for asthma during childhood. The underlying pathogenesis of how prenatal stress increases the risk for asthma still remains unclear. Potential targets could be that the fetal immune ontogeny or fetal lung development are compromised by prenatal challenges. Here, we aimed to identify whether prenatal stress challenge affects fetal lung development in mice. C57BL/6 pregnant mice were challenged with sound stress and fetal lung development was assessed histologically. Whilst prenatal stress challenge did not profoundly affect lung development in male fetuses, it resulted in less extensive terminal sacs, surrounded by thicker mesenchymal tissue in female fetuses. Thus, prenatal stress disrupted fetal lung development sex-specifically. Interestingly, upon prenatal stress challenge, the airway hyperresponsiveness and eosinophilic inflammation- two hallmarks of asthma - were significantly increased in adult female offspring, whilst regulatory CD4+ T cells were reduced. These findings strongly underpin the sex-specific association between s challenged fetal development and a sex-specific altered severity of asthma in adult offspring. Our model now allows to identify maternal markers through which the risk for asthma and possible other diseases is vertically transferred before birth in response to challenges. Such identification then opens avenues for primary disease prevention. Copyright © 2017 Elsevier B.V. All rights reserved.

Framework for radiation pneumonitis risk stratification based on anatomic and perfused lung dosimetry

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Dhami, Gurleen; Zeng, Jing; Patel, Shilpen A.; Rengan, Ramesh [University of Washington School of Medicine, Department of Radiation Oncology, Seattle, WA (United States); Vesselle, Hubert J.; Kinahan, Paul E.; Miyaoka, Robert S. [University of Washington School of Medicine, Department of Radiology, Seattle, WA (United States); Bowen, Stephen R. [University of Washington School of Medicine, Department of Radiation Oncology, Seattle, WA (United States); University of Washington School of Medicine, Department of Radiology, Seattle, WA (United States)

2017-05-15

To design and apply a framework for predicting symptomatic radiation pneumonitis in patients undergoing thoracic radiation, using both pretreatment anatomic and perfused lung dose-volume parameters. Radiation treatment planning CT scans were coregistered with pretreatment [{sup 99m}Tc]MAA perfusion SPECT/CT scans of 20 patients who underwent definitive thoracic radiation. Clinical radiation pneumonitis was defined as grade ≥ 2 (CTCAE v4 grading system). Anatomic lung dose-volume parameters were collected from the treatment planning scans. Perfusion dose-volume parameters were calculated from pretreatment SPECT/CT scans. Equivalent doses in 2 Gy per fraction were calculated in the lung to account for differences in treatment regimens and spatial variations in lung dose (EQD2{sub lung}). Anatomic lung dosimetric parameters (MLD) and functional lung dosimetric parameters (pMLD{sub 70%}) were identified as candidate predictors of grade ≥ 2 radiation pneumonitis (AUC > 0.93, p < 0.01). Pairing of an anatomic and functional dosimetric parameter (e.g., MLD and pMLD{sub 70%}) may further improve prediction accuracy. Not all individuals with high anatomic lung dose (MLD > 13.6 GyEQD2{sub lung}, 19.3 Gy for patients receiving 60 Gy in 30 fractions) developed radiation pneumonitis, but all individuals who also had high mean dose to perfused lung (pMLD{sub 70%} > 13.3 GyEQD2) developed radiation pneumonitis. The preliminary application of this framework revealed differences between anatomic and perfused lung dosimetry in this limited patient cohort. The addition of perfused lung parameters may help risk stratify patients for radiation pneumonitis, especially in treatment plans with high anatomic mean lung dose. Further investigations are warranted. (orig.) [German] Erstellung und Anwendung eines Rahmenwerks zur Vorhersage symptomatischer Strahlenpneumonitis bei Patienten mit einer Thorax-Bestrahlung anhand anatomischer und perfundierter Lungendosis-Volumen-Parameter in der

Heterozygous Lmna(delK32) mice develop dilated cardiomyopathy through a combined pathomechanism of haploinsufficiency and peptide toxicity

DEFF Research Database (Denmark)

Cattin, M. E.; Bertrand, A. T.; Schlossarek, S.

2013-01-01

itself has a clear deleterious effect on engineered heart tissues force of contraction, it also leads to the nuclear aggregation of viral-mediated expression of K32-lamin. In conclusion, Het mice are the first knock-in Lmna model with cardiac-specific phenotype at the heterozygous state. Altogether, our....... The pathomechanisms linking mutations to DCM remain to be elucidated. We investigated the phenotype and associated pathomechanisms of heterozygous Lmna(K32/) (Het) knock-in mice, which carry a human mutation. Het mice developed a cardiac-specific phenotype. Two phases, with two different pathomechanisms, could...... be observed that lead to the development of cardiac dysfunction, DCM and death between 35 and 70 weeks of age. In young Het hearts, there was a clear reduction in lamin A/C level, mainly due to the degradation of toxic K32-lamin. As a side effect, lamin A/C haploinsufficiency probably triggers the cardiac...

Arterio-venous anastomoses in mice affect perfusion measurements with dynamic contrast enhanced CT

International Nuclear Information System (INIS)

Gabra, Peter; Lee, Ting-Yim; Shen, Gang; Xuan, Jim

2010-01-01

Accurate measurement of perfusion with dynamic contrast enhanced CT requires an arterial input curve (AIC) uncontaminated by venous sources. Arterio-venous anastomoses (AVAs) are sources of contamination if contrast is injected intravenously. We seek to identify AVAs in mice and associated errors in perfusion measurements. Six transgenic mice with spontaneous prostate tumor were scanned with a micro-CT scanner (GE Healthcare (GE)) using a high resolution anatomical and a lower resolution perfusion protocol. For the anatomical protocol, a CT scan was performed during injection of an iodinated contrast agent (Hypaque) into a tail vein. Images covering the thoracic, abdominal and pelvic regions at an isotropic resolution of 175 µm were reconstructed and rendered in 3D to show the arterial and venous tree (Advantage Window, GE). For the perfusion protocol, each mouse was continuously scanned for 40 s and the contrast agent (Hypaque) was injected via a tail vein 5 s into scanning. Tumor images were reconstructed every second. Tumor blood flow (BF) and volume (BV) maps were calculated with CT perfusion software (GE) using AIC measured either from abdominal aorta (AA) or tail (caudal) artery (TA). In all mice, there was an AVA from the bifurcation of the inferior vena cava to the tail artery shunting venous blood and portion of the contrast agent injected into the tail vein into the TA. Contrast arrival time at the TA preceded that at the AA by 3.3 ± 0.5 s (P < 0.05). Mean tumor BV and BF values calculated with AA versus TA were 10.0 ± 1.8 versus 4.8 ± 2.1 ml (100 g) −1 (P < 0.05) and 108.8 ± 26.5 versus 33.0 ± 8.5 ml min −1 100 g −1 (P < 0.05), respectively. AVA in the murine pelvic region can result in inaccurate and more variable measurements of pelvic organ/tissue perfusion when the tail artery is used as the AIC

Increasing Hematopoietic Stem Cell Yield to Develop Mice with Human Immune Systems

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Juan-Carlos Biancotti

2013-01-01

Full Text Available Hematopoietic stem cells (HSCs are unique in their capacity to give rise to all mature cells of the immune system. For years, HSC transplantation has been used for treatment of genetic and neoplastic diseases of the hematopoietic and immune systems. The sourcing of HSCs from human umbilical cord blood has salient advantages over isolation from mobilized peripheral blood. However, poor sample yield has prompted development of methodologies to expand HSCs ex vivo. Cytokines, trophic factors, and small molecules have been variously used to promote survival and proliferation of HSCs in culture, whilst strategies to lower the concentration of inhibitors in the culture media have recently been applied to promote HSC expansion. In this paper, we outline strategies to expand HSCs in vitro, and to improve engraftment and reconstitution of human immune systems in immunocompromised mice. To the extent that these “humanized” mice are representative of the endogenous human immune system, they will be invaluable tools for both basic science and translational medicine.

Deficiency in monocarboxylate transporter 1 (MCT1) in mice delays regeneration of peripheral nerves following sciatic nerve crush

KAUST Repository

Morrison, Brett M.; Tsingalia, Akivaga; Vidensky, Svetlana; Lee, Youngjin; Jin, Lin; Farah, Mohamed H.; Lengacher, Sylvain; Magistretti, Pierre J.; Pellerin, Luc; Rothsteinb, Jeffrey D.

2015-01-01

Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons. In the current study, MCT1 is shown to localize within the peripheral nervous system to perineurial cells, dorsal root ganglion neurons, and Schwann cells by MCT1 immunofluorescence in wild-type mice and tdTomato fluorescence in MCT1 BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves of MCT1 heterozygous mice are crushed and peripheral nerve regeneration was quantified electrophysiologically and anatomically. Compound muscle action potential (CMAP) recovery is delayed from a median of 21. days in wild-type mice to greater than 38. days in MCT1 heterozygote mice. In fact, half of the MCT1 heterozygote mice have no recovery of CMAP at 42. days, while all of the wild-type mice recovered. In addition, muscle fibers remain 40% more atrophic and neuromuscular junctions 40% more denervated at 42. days post-crush in the MCT1 heterozygote mice than wild-type mice. The delay in nerve regeneration is not only in motor axons, as the number of regenerated axons in the sural sensory nerve of MCT1 heterozygote mice at 4. weeks and tibial mixed sensory and motor nerve at 3. weeks is also significantly reduced compared to wild-type mice. This delay in regeneration may be partly due to failed Schwann cell function, as there is reduced early phagocytosis of myelin debris and remyelination of axon segments. These data for the first time demonstrate that MCT1 is critical for regeneration of both sensory and motor axons in mice following sciatic nerve crush.

Anatomically based lower limb nerve model for electrical stimulation

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Soboleva Tanya K

2007-12-01

Full Text Available Abstract Background Functional Electrical Stimulation (FES is a technique that aims to rehabilitate or restore functionality of skeletal muscles using external electrical stimulation. Despite the success achieved within the field of FES, there are still a number of questions that remain unanswered. One way of providing input to the answers is through the use of computational models. Methods This paper describes the development of an anatomically based computer model of the motor neurons in the lower limb of the human leg and shows how it can be used to simulate electrical signal propagation from the beginning of the sciatic nerve to a skeletal muscle. One-dimensional cubic Hermite finite elements were used to represent the major portions of the lower limb nerves. These elements were fit to data that had been digitised using images from the Visible Man project. Nerves smaller than approximately 1 mm could not be seen in the images, and thus a tree-branching algorithm was used to connect the ends of the fitted nerve model to the respective skeletal muscle. To simulate electrical propagation, a previously published mammalian nerve model was implemented and solved on the anatomically based nerve mesh using a finite difference method. The grid points for the finite difference method were derived from the fitted finite element mesh. By adjusting the tree-branching algorithm, it is possible to represent different levels of motor-unit recruitment. Results To illustrate the process of a propagating nerve stimulus to a muscle in detail, the above method was applied to the nerve tree that connects to the human semitendinosus muscle. A conduction velocity of 89.8 m/s was obtained for a 15 μm diameter nerve fibre. This signal was successfully propagated down the motor neurons to a selected group of motor units in the muscle. Conclusion An anatomically and physiologically based model of the posterior motor neurons in the human lower limb was developed. This

Anatomía y desarrollo del fruto en Piriqueta y Turnera (Turneraceae Anatomy and development of fruits in Piriqueta and Turnera (Turneraceae

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Ana Maria Gonzalez

2010-12-01

Full Text Available En este estudio se analiza la anatomía, estructura y desarrollo de los frutos en 12 especies de Piriqueta y 30 especies de Turnera; con el objetivo de identificar la estructura involucrada en la dehiscencia y verificar la existencia de patrones en la organización del fruto entre las especies analizadas. El ovario es sincárpico, tricarpelar, unilocular con placentación parietal, presentando la misma estructura en todas las especies. Ambas epidermis carpelares son uniestratificadas y tienen estomas, el mesófilo es parenquimático con 3 haces dorsales y 3 marginales. Durante el desarrollo del fruto, la epidermis externa forma un epicarpo papiloso en las especies de Piriqueta. El mesocarpio deriva de los estratos medios del ovario, formando un estrato mecánico de braquiesclereidas. Estas esclereidas pueden organizarse como un cilindro continuo determinando frutos de superficie lisa o agruparse en nidos, unidos o no, determinando así frutos granulares, verrugosos, o tuberculados. Las cápsulas son loculicidas, con línea de dehiscencia formada por macroesclereidas dispuestas longitudinalmente en el fruto, paralelas al haz carpelar dorsal. Se concluye que los diferentes tipos de pericarpio son un rasgo post-fecundación, dado que la estructura del ovario es exactamente la misma en todas las especies analizadas. Se analiza la anatomía del fruto en relación al esquema taxonómico actualizado.The aims of this work were to describe the morphology, anatomy and development of the fruits of 12 species of Piriqueta and 30 species of Turnera; to identify the structures related to the process of dehiscence of the capsule; and to verify the occurrence of standards carpological structure between the studied species. The ovary is 3-carpellar, syncarpous, unilocular with parietal placentation and has the same anatomical structure in all studied species. The outer and inner epidermises are single-layered with stomata; the ovarian mesophyll is composed by

Computerized Tomographic Study on the Anatomic Variation of the Paranasal Sinus

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Choi, Sun Kyung; Lim, Sug Young; Koh, Kwang Joon [Dept. of Oral and Maxillofacial Radiology and Institute of Oral Bio Science, College of Dentistry, Chonbuk National University, Chonju (Korea, Republic of); Park, Mi Ju [Dept. of Prosthodontics, School of Denstistry, Chonbuk National Universty, Chonju (Korea, Republic of)

1999-08-15

To evaluate the anatomic variations of the paranasal sinuses on computed tomographs. The author examined the CT images of the paranasal sinuses retrospectively in 500 patients who visited Chonbuk National University Hospital between January 1996 and December 1997. The highest incidence of anatomic variation of the paranasal sinuses in bilateral structures was agger nasi cell (73.2%), followed by concha bullosa (31.1%), Onodi cell (24.0%), Haller cell (19.8%), maxillary sinus septum (13.0%), paradoxical middle turbinate (2.5%), pneumatized uncinate process (2.0%), and bent uncinate process. The highest incidence of anatomic variation in midline structures was nasal septum deviation(53.2%), followed by nasal septumaerated (29.4%), bulla galli (24.7%) asymmetric intersphenoid septum (22.3%), and nasal septum spur (13.8%). The correlation between anatomic variation and paranasal sinusitis was not found. The results of this study will aid in the diagnosis and treatment of paranasal sinus diseases, especially in the treatment planning before functional endoscopic surgery.

Computerized Tomographic Study on the Anatomic Variation of the Paranasal Sinus

International Nuclear Information System (INIS)

Choi, Sun Kyung; Lim, Sug Young; Koh, Kwang Joon; Park, Mi Ju

1999-01-01

To evaluate the anatomic variations of the paranasal sinuses on computed tomographs. The author examined the CT images of the paranasal sinuses retrospectively in 500 patients who visited Chonbuk National University Hospital between January 1996 and December 1997. The highest incidence of anatomic variation of the paranasal sinuses in bilateral structures was agger nasi cell (73.2%), followed by concha bullosa (31.1%), Onodi cell (24.0%), Haller cell (19.8%), maxillary sinus septum (13.0%), paradoxical middle turbinate (2.5%), pneumatized uncinate process (2.0%), and bent uncinate process. The highest incidence of anatomic variation in midline structures was nasal septum deviation(53.2%), followed by nasal septumaerated (29.4%), bulla galli (24.7%) asymmetric intersphenoid septum (22.3%), and nasal septum spur (13.8%). The correlation between anatomic variation and paranasal sinusitis was not found. The results of this study will aid in the diagnosis and treatment of paranasal sinus diseases, especially in the treatment planning before functional endoscopic surgery.

Anatomical location differences between mutated and wild-type isocitrate dehydrogenase 1 in low-grade gliomas.

Science.gov (United States)

Yu, Jinhua; Shi, Zhifeng; Ji, Chunhong; Lian, Yuxi; Wang, Yuanyuan; Chen, Liang; Mao, Ying

2017-10-01

Anatomical location of gliomas has been considered as a factor implicating the contributions of a specific precursor cells during the tumor growth. Isocitrate dehydrogenase 1 (IDH1) is a pathognomonic biomarker with a significant impact on the development of gliomas and remarkable prognostic effect. The correlation between anatomical location of tumor and IDH1 states for low-grade gliomas was analyzed quantitatively in this study. Ninety-two patients diagnosed of low-grade glioma pathologically were recruited in this study, including 65 patients with IDH1-mutated glioma and 27 patients with wide-type IDH1. A convolutional neural network was designed to segment the tumor from three-dimensional magnetic resonance imaging images. Voxel-based lesion symptom mapping was then employed to study the tumor location distribution differences between gliomas with mutated and wild-type IDH1. In order to characterize the location differences quantitatively, the Automated Anatomical Labeling Atlas was used to partition the standard brain atlas into 116 anatomical volumes of interests (AVOIs). The percentages of tumors with different IDH1 states in 116 AVOIs were calculated and compared. Support vector machine and AdaBoost algorithms were used to estimate the IDH1 status based on the 116 location features of each patient. Experimental results proved that the quantitative tumor location measurement could be a very important group of imaging features in biomarker estimation based on radiomics analysis of glioma.

An Update on the Status of Anatomical Sciences Education in United States Medical Schools

Science.gov (United States)

Drake, Richard L.; McBride, Jennifer M.; Pawlina, Wojciech

2014-01-01

Curricular changes continue at United States medical schools and directors of gross anatomy, microscopic anatomy, neuroscience/neuroanatomy, and embryology courses continue to adjust and modify their offerings. Developing and supplying data related to current trends in anatomical sciences education is important if informed decisions are going to…

Clonidine treatment delays postnatal motor development and blocks short-term memory in young mice.

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Cristina Calvino-Núñez

Full Text Available During the development of the nervous system, the perinatal period is particularly sensitive as neuronal connections are still forming in the brain of the neonate. Alpha2-adrenergic receptors are overexpressed temporarily in proliferative zones in the developing brain, reaching a peak during the first postnatal week of life. Both stimulation and blocking of these receptors during this period alter the development of neural circuits, affecting synaptic connectivity and neuronal responses. They even affect motor and cognitive skills later on in the adult. It's especially important to look for the early neurological consequences resulting from such modifications, because they may go unnoticed. The main objective of the present study has been to reaffirm the importance of the maturation of alpha-adrenergic system in mice, by carrying out a comprehensive examination of motor, behavioral and cognitive effects in neonates, during early postnatal development, following chronic administration of the drug Clonidine, an alpha2 adrenergic system agonist. Our study shows that mice treated postnatally with clonidine present a temporal delay in the appearance of developmental markers, a slow execution of vestibular reflexes during first postnatal week of life and a blockade of the short term memory in the novel object recognition task. Shortly after the treatment the startle response is hyperreactive.

Impaired intervertebral disc development and premature disc degeneration in mice with notochord-specific deletion of CCN2.

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Bedore, Jake; Sha, Wei; McCann, Matthew R; Liu, Shangxi; Leask, Andrew; Séguin, Cheryle A

2013-10-01

Currently, our ability to treat intervertebral disc (IVD) degeneration is hampered by an incomplete understanding of disc development and aging. The specific function of matricellular proteins, including CCN2, during these processes remains an enigma. The aim of this study was to determine the tissue-specific localization of CCN proteins and to characterize their role in IVD tissues during embryonic development and age-related degeneration by using a mouse model of notochord-specific CCN2 deletion. Expression of CCN proteins was assessed in IVD tissues from wild-type mice beginning on embryonic day 15.5 to 17 months of age. Given the enrichment of CCN2 in notochord-derived tissues, we generated notochord-specific CCN2-null mice to assess the impact on the IVD structure and extracellular matrix composition. Using a combination of histologic evaluation and magnetic resonance imaging (MRI), IVD health was assessed. Loss of the CCN2 gene in notochord-derived cells disrupted the formation of IVDs in embryonic and newborn mice, resulting in decreased levels of aggrecan and type II collagen and concomitantly increased levels of type I collagen within the nucleus pulposus. CCN2-knockout mice also had altered expression of CCN1 (Cyr61) and CCN3 (Nov). Mirroring its role during early development, notochord-specific CCN2 deletion accelerated age-associated degeneration of IVDs. Using a notochord-specific gene targeting strategy, this study demonstrates that CCN2 expression by nucleus pulposus cells is essential to the regulation of IVD development and age-associated tissue maintenance. The ability of CCN2 to regulate the composition of the intervertebral disc suggests that it may represent an intriguing clinical target for the treatment of disc degeneration. Copyright © 2013 by the American College of Rheumatology.

The suitability of 129SvEv mice for studying depressive-like behaviour: both males and females develop learned helplessness.

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Chourbaji, Sabine; Pfeiffer, Natascha; Dormann, Christof; Brandwein, Christiane; Fradley, Rosa; Sheardown, Malcolm; Gass, P

2010-07-29

Behavioural studies using transgenic techniques in mice usually require extensive backcrossing to a defined background strain, e.g. to C57BL/6. In this study we investigated whether backcrossing can be replaced by using the 129SvEv strain from which the embryonic stem cells are generally obtained for gene targeting strategies to analyze e.g. depression-like behaviour. For that purpose we subjected male and female 129SvEv mice to two frequently used depression tests and compared them with commonly used C57BL/6 mice. 129SvEv and C57BL/6 mice exhibited differing profiles with regard to locomotion and pain sensitivity. However, in the learned helplessness paradigm, a procedure, which represents a valid method to detect depressive-like behaviour, 129SvEv animals develop a similar level of helplessness as C57BL/6 mice. One great advantage of the 129SvEv animals though, is the fact that in this strain even females develop helplessness, which could not be produced in C57BL/6 mice. In the tail suspension test, both genders of 129SvEv exhibited more despair behaviour than C57BL/6 animals. We therefore suggest that this strain may be utilized in the establishment of new test procedures for affective diseases, since costly and time-consuming backcrossing can be prevented, depressive-like behaviour may be analyzed effectively, and gender-specific topics could be addressed in an adequate way. Copyright 2010 Elsevier B.V. All rights reserved.

Touching Anatomy. : On the Handling of Anatomical Preparations in the Anatomical Cabinets of Frederik Ruysch (1638-1731)

NARCIS (Netherlands)

Knoeff, Rina

2015-01-01

This paper argues that the anatomical Cabinets of Dutch anatomist Frederik Ruysch must be understood as an early modern workshop in which preparations were continuously handled. It is claimed that preparations actively appealed to anatomists and visitors to handle, re-dissect, touch, and even kiss

Neurobehavioral development of CD-1 mice after combined gestational and postnatal exposure to ozone

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Dell` Omo, G [Section of Behavioral Pathophysiology, Lab. di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Rome (Italy); Fiore, M [Section of Behavioral Pathophysiology, Lab. di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Rome (Italy); Petruzzi, S [Section of Behavioral Pathophysiology, Lab. di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Rome (Italy); Alleva, E [Section of Behavioral Pathophysiology, Lab. di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Rome (Italy); Bignami, G [Section of Behavioral Pathophysiology, Lab. di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Rome (Italy)

1995-09-01

Outbred CD-1 mice were exposed continuously to ozone (O{sub 3}, 0.6 ppm) from 6 days prior to the formation of breeding pairs to the time of weaning of the offspring on postnatal day 22 (PND 22) or to PND 26. One half of the mice in each of eight O{sub 3} and eight control litters were subjected on PND 24 to a 20-min open-field test after IP treatment by either saline or scopolamine (2 mg/kg). The remaining mice (those exposed until PND 26) were subjected on PNDs 28-31 to a conditioned place preference (CPP) test, using a short schedule with a single IP injection on PND 29 of either d-amphetamine (3.3 mg/kg) or saline. Subsequently, the saline mice of the open-field experiment were used on PND 59 for an activity test in one of the CPP apparatus compartments after IP treatment by either d-amphetamine (same dose) or saline. In addition, the saline mice of the CPP experiment underwent a multitrial, step-through passive avoidance (PA) acquisition test on PND 59 or 60, followed 24 h later by a single-trial retention test. In the absence of effects on reproductive performance (proportion of successful pregnancies, litter size, offspring viability, and sex ratio), O{sub 3} offspring showed a long-lasting reduction in body weight without modification of sec differences. Ozone effects on neurobehavioral development were not large and quite selective, including: attenuation of the sex differences in several responses (rearing and sniffing in the open-field, activity in the final CPP test session); a change in response choices in the final CPP test, in the absence of a main effect on conditioning; a reduction of grooming in the activity test on PND 29; and impairment of PA acquisition limited to the initial period of training. (orig.)

Neurobehavioral development of CD-1 mice after combined gestational and postnatal exposure to ozone.

Science.gov (United States)

Dell'Omo, G; Fiore, M; Petruzzi, S; Alleva, E; Bignami, G

1995-01-01

Outbred CD-1 mice were exposed continuously to ozone (O3, 0.6 ppm) from 6 days prior to the formation of breeding pairs to the time of weaning of the offspring on postnatal day 22 (PND 22) or to PND 26. One half of the mice in each of eight O3 and eight control litters were subjected on PND 24 to a 20-min open-field test after IP treatment by either saline or scopolamine (2 mg/kg). The remaining mice (those exposed until PND 26) were subjected on PNDs 28-31 to a conditioned place preference (CPP) test, using a short schedule with a single IP injection on PND 29 of either d-amphetamine (3.3 mg/kg) or saline. Subsequently, the saline mice of the open-field experiment were used on PND 59 for an activity test in one of the CPP apparatus compartments after IP treatment by either d-amphetamine (same dose) or saline. In addition, the saline mice of the CPP experiment underwent a multi-trial, step-through passive avoidance (PA) acquisition test on PND 59 or 60, followed 24 h later by a single-trial retention test. In the absence of effects on reproductive performance (proportion of successful pregnancies, litter size, offspring viability, and sex ratio), O3 offspring showed a long-lasting reduction in body weight without modification of sex differences. Ozone effects on neurobehavioral development were not large and quite selective, including: attenuation of the sex differences in several responses (rearing and sniffing in the open-field, activity in the final CPP test session); a change in response choices in the final CPP test, in the absence of a main effect on conditioning; a reduction of grooming in the activity test on PND 29; and impairment of PA acquisition limited to the initial period of training.

Anatomically Plausible Surface Alignment and Reconstruction

DEFF Research Database (Denmark)

Paulsen, Rasmus R.; Larsen, Rasmus

2010-01-01

With the increasing clinical use of 3D surface scanners, there is a need for accurate and reliable algorithms that can produce anatomically plausible surfaces. In this paper, a combined method for surface alignment and reconstruction is proposed. It is based on an implicit surface representation...

Development of a multi-scale and multi-modality imaging system to characterize tumours and their microenvironment in vivo

Science.gov (United States)

Rouffiac, Valérie; Ser-Leroux, Karine; Dugon, Emilie; Leguerney, Ingrid; Polrot, Mélanie; Robin, Sandra; Salomé-Desnoulez, Sophie; Ginefri, Jean-Christophe; Sebrié, Catherine; Laplace-Builhé, Corinne

2015-03-01

In vivo high-resolution imaging of tumor development is possible through dorsal skinfold chamber implantable on mice model. However, current intravital imaging systems are weakly tolerated along time by mice and do not allow multimodality imaging. Our project aims to develop a new chamber for: 1- long-term micro/macroscopic visualization of tumor (vascular and cellular compartments) and tissue microenvironment; and 2- multimodality imaging (photonic, MRI and sonography). Our new experimental device was patented in March 2014 and was primarily assessed on 75 mouse engrafted with 4T1-Luc tumor cell line, and validated in confocal and multiphoton imaging after staining the mice vasculature using Dextran 155KDa-TRITC or Dextran 2000kDa-FITC. Simultaneously, a universal stage was designed for optimal removal of respiratory and cardiac artifacts during microscopy assays. Experimental results from optical, ultrasound (Bmode and pulse subtraction mode) and MRI imaging (anatomic sequences) showed that our patented design, unlike commercial devices, improves longitudinal monitoring over several weeks (35 days on average against 12 for the commercial chamber) and allows for a better characterization of the early and late tissue alterations due to tumour development. We also demonstrated the compatibility for multimodality imaging and the increase of mice survival was by a factor of 2.9, with our new skinfold chamber. Current developments include: 1- defining new procedures for multi-labelling of cells and tissue (screening of fluorescent molecules and imaging protocols); 2- developing ultrasound and MRI imaging procedures with specific probes; 3- correlating optical/ultrasound/MRI data for a complete mapping of tumour development and microenvironment.

The comparative study of anatomical structure of stem and ovule development of four cultivars of Glycine max L. merr in water deficit stress

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Parissa Jonoubi

2014-08-01

Full Text Available Drought stress is one of the most important limiting factors that affect different aspects of plants vegetative and reproductive growth. It is one of the most important limiting factors of crop productivity. Regarding to the importance of soybean as an oilseed plant, and in order to identify the drought tolerant cultivars as well as evaluating of the effects of drought stress on anatomical structureof four soybean cultivars (Clin, Clark, M9 and L17, two series of experiments were carried out as randomized complete design. In the first experiment, at optimum conditions, plants were irrigated after 50 mm evaporation from germination to the end of growing period, whereas the second experiment was irrigated after 150 mm (sever stress evaporation from evaporation pan. The results showed that the effect of water deficit stress on cortex thickness and number of layers, Phloem and xylem thickness, diameter of vessel elements, number of vessel element rows, number of vessel elements in stem, pith and stele thickness, stem diameter and number of trichomes were significant. Relative acceleration of embryo sac development was observed in all plants under water deficit stress except for Clark cultivar. Evaluation of anatomical factors on these cultivars showed that Clin cultivar was more tolerant to water deficit stress compared to other cultivars.

An Lck-cre transgene accelerates autoantibody production and lupus development in (NZB × NZW)F1 mice

Science.gov (United States)

Nelson, Richard K.; Gould, Karen A.

2015-01-01

Lupus is an autoimmune disease characterized by the development of antinuclear autoantibodies and immune complex-mediated tissue damage. T cells in lupus patients appear to undergo apoptosis at an increased rate, and this enhanced T cell apoptosis has been postulated to contribute to lupus pathogenesis by increasing autoantigen load. However, there is no direct evidence to support this hypothesis. In this study, we show that an Lck-cre transgene, which increases T cell apoptosis as a result of T cell specific expression of cre recombinase, accelerates the development of autoantibodies and nephritis in lupus-prone (NZB×NZW)F1 mice. Although the enhanced T cell apoptosis in Lck-cre transgenic mice resulted in an overall decrease in the relative abundance of splenic CD4+ and CD8+ T cells, the proportion of activated CD4+ T cells was increased and no significant change was observed in the relative abundance of suppressive T cells. We postulate that the Lck-cre transgene promoted lupus by enhancing T cells apoptosis, which, in conjunction with the impaired clearance of apoptotic cells in lupus-prone mice, increased the nuclear antigen load and accelerated the development of anti-nuclear autoantibodies. Furthermore, our results also underscore the importance of including cre-only controls in studies using the cre-lox system. PMID:26385218

PAVA: Physiological and Anatomical Visual Analytics for Mapping of Tissue-Specific Concentration and Time-Course Data

Science.gov (United States)

We describe the development and implementation of a Physiological and Anatomical Visual Analytics tool (PAVA), a web browser-based application, used to visualize experimental/simulated chemical time-course data (dosimetry), epidemiological data and Physiologically-Annotated Data ...

Defining the spatial relationships between eight anatomic planes in the 11+6 to 13+6 weeks fetus: a pilot study.

Science.gov (United States)

Abu-Rustum, Reem S; Ziade, M Fouad; Abu-Rustum, Sameer E

2012-09-01

Our study aims at investigating the spatial relationships between eight anatomic planes in the 11+6 to 13+6 weeks fetus. This is a retrospective pilot study where three-dimensional and four-dimensional stored data sets were manipulated to retrieve eight anatomic planes starting from the midsagittal plane of the fetus. Standardization of volumes was performed at the level of the transverse abdominal circumference plane. Parallel shift was utilized and the spatial relationships between eight anatomic planes were established. The median and the range were calculated for each of the planes, and they were evaluated as a function of the fetal crown-rump length. P planes were found to adhere to normal distribution curves, and most of the planes were in a definable relationship to each other with statistically significant correlations. To our knowledge, this is the first study to describe the possible spatial relationships between eight two-dimensional anatomic planes in the 11+6 to 13+6 weeks fetus, utilizing a standardized approach. Defining these spatial relationships may serve as the first step for the potential future development of automation software for fetal anatomic assessment at 11+6 to 13+6 weeks. © 2012 John Wiley & Sons, Ltd.

Sonographic and Anatomic Description of the Subtalar Joint

DEFF Research Database (Denmark)

Mandl, Peter; Bong, David; Balint, Peter V

2018-01-01

Our study provides a detailed anatomic and sonographic description of the subtalar joint, a single joint that, anatomically, is divided into the anterior subtalar joint (ASTJ) and the posterior subtalar joint (PSTJ). Cadaver specimens of the ankle and foot were examined in detail by ultrasound (US......), and the subtalar joints of all the specimens were injected with colored latex of a contrasting color under US guidance. Compatible with other studies, examination of the sections revealed lack of communication between the ASTJ and the PSTJ and communication between the PSTJ and the posterior recess...... of agreement between images acquired in cadaver specimens and images acquired in four centers using healthy patients....

Cell surface fucosylation does not affect development of colon tumors in mice with germline Smad3 mutation

Science.gov (United States)

Domino, Steven E.; Karnak, David M.; Hurd, Elizabeth A.

2006-01-01

Background/Aims: Neoplasia-related alterations in cell surface α(1,2)fucosylated glycans have been reported in multiple tumors including colon, pancreas, endometrium, cervix, bladder, lung, and choriocarcinoma. Spontaneous colorectal tumors from mice with a germline null mutation of transforming growth factor-β signaling gene Smad3 (Madh3) were tested for α(1,2)fucosylated glycan expression. Methods: Ulex Europaeus Agglutinin-I lectin staining, fucosyltransferase gene northern blot analysis, and a cross of mutant mice with Fut2 and Smad3 germline mutations were performed. Results: Spontaneous colorectal tumors from Smad3 (-/-) homozygous null mice were found to express α(1,2)fucosylated glycans in an abnormal pattern compared to adjacent nonneoplastic colon. Northern blot analysis of α(1,2)fucosyltransferase genes Fut1 and Fut2 revealed that Fut2, but not Fut1, steady-state mRNA levels were significantly increased in tumors relative to adjacent normal colonic mucosa. Mutant mice with a Fut2-inactivating germline mutation were crossed with Smad3 targeted mice. In Smad3 (-/-)/Fut2 (-/-) double knock-out mice, UEA-I lectin staining was eliminated from colon and colon tumors, however, the number and size of tumors present by 24 weeks of age did not vary regardless of the Fut2 genotype. Conclusions: In this model of colorectal cancer, cell surface α(1,2)fucosylation does not affect development of colon tumors. PMID:17264540

A role for the epidermal growth factor receptor signaling in development of intestinal serrated polyps in mice and humans.

Science.gov (United States)

Bongers, Gerold; Muniz, Luciana R; Pacer, Michelle E; Iuga, Alina C; Thirunarayanan, Nanthakumar; Slinger, Erik; Smit, Martine J; Reddy, E Premkumar; Mayer, Lloyd; Furtado, Glaucia C; Harpaz, Noam; Lira, Sergio A

2012-09-01

Epithelial cancers can be initiated by activating mutations in components of the mitogen-activated protein kinase signaling pathway such as v-raf murine sarcoma viral oncogene homolog B1 (BRAF), v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), or epidermal growth factor receptor (EGFR). Human intestinal serrated polyps are a heterogeneous group of benign lesions, but some progress to colorectal cancer. Tumors that arise from these polyps frequently contain activating mutations in BRAF or KRAS, but little is known about the role of EGFR activation in their development. Polyp samples were obtained from adults during screening colonoscopies at Mount Sinai Hospital in New York. We measured levels of EGFR protein and phosphorylation in human serrated polyps by immunohistochemical and immunoblot analyses. We generated transgenic mice that express the ligand for EGFR, Heparin-binding EGF-like growth factor (HB-EGF), in the intestine. EGFR and the extracellular-regulated kinases (ERK)1/2 were phosphorylated in serrated areas of human hyperplastic polyps (HPPs), sessile serrated adenomas, and traditional serrated adenomas. EGFR and ERK1/2 were phosphorylated in the absence of KRAS or BRAF activating mutations in a subset of HPP. Transgenic expression of the EGFR ligand HB-EGF in the intestines of mice promoted development of small cecal serrated polyps. Mice that expressed a combination of HB-EGF and US28 (a constitutively active, G-protein-coupled receptor that increases processing of HB-EGF from the membrane) rapidly developed large cecal serrated polyps. These polyps were similar to HPPs and had increased phosphorylation of EGFR and ERK1/2 within the serrated epithelium. Administration of pharmacologic inhibitors of EGFR or MAPK to these transgenic mice significantly reduced polyp development. Activation of EGFR signaling in the intestine of mice promotes development of serrated polyps. EGFR signaling also is activated in human HPPs, sessile serrated adenomas

Flt3 Ligand Regulates the Development of Innate Lymphoid Cells in Fetal and Adult Mice.

Science.gov (United States)

Baerenwaldt, Anne; von Burg, Nicole; Kreuzaler, Matthias; Sitte, Selina; Horvath, Edit; Peter, Annick; Voehringer, David; Rolink, Antonius G; Finke, Daniela

2016-03-15

Flt3 ligand (Flt3L) promotes survival of lymphoid progenitors in the bone marrow and differentiation of dendritic cells (DCs), but its role in regulating innate lymphoid cells (ILCs) during fetal and adult life is not understood. By using Flt3L knockout and transgenic mice, we demonstrate that Flt3L controls ILC numbers by regulating the pool of α4β7(-) and α4β7(+) lymphoid tissue inducer cell progenitors in the fetal liver and common lymphoid progenitors in the bone marrow. Deletion of flt3l severely reduced the number of fetal liver progenitors and lymphoid tissue inducer cells in the neonatal intestine, resulting in impaired development of Peyer's patches. In the adult intestine, NK cells and group 2 and 3 ILCs were severely reduced. This effect occurred independently of DCs as ILC numbers were normal in mice in which DCs were constitutively deleted. Finally, we could show that administration of Flt3L increased the number of NKp46(-) group 3 ILCs in wild-type and even in Il7(-/-) mice, which generally have reduced numbers of ILCs. Taken together, Flt3L significantly contributes to ILC and Peyer's patches development by targeting lymphoid progenitor cells during fetal and adult life. Copyright © 2016 by The American Association of Immunologists, Inc.

Exposure to bisphenol A, but not phthalates, increases spontaneous diabetes type 1 development in NOD mice.

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Bodin, Johanna; Kocbach Bølling, Anette; Wendt, Anna; Eliasson, Lena; Becher, Rune; Kuper, Frieke; Løvik, Martinus; Nygaard, Unni Cecilie

2015-01-01

Type 1 diabetes mellitus (T1DM) is an autoimmune destruction of insulin producing pancreatic beta-cells due to a genetic predisposition and can be triggered by environmental factors. We have previously shown that bisphenol A (BPA) accelerates the spontaneous development of diabetes in non-obese diabetic (NOD) mice. Here, we hypothesized that oral exposure to a mixture of the endocrine disruptors BPA and phthalates, relevant for human exposure, would accelerate diabetes development compared to BPA alone. NOD mice were exposed to BPA (1 mg/l), a mixture of phthalates (DEHP 1 mg/l, DBP 0.2 mg/l, BBP 10 mg/l and DiBP 20 mg/l) or a combination of BPA and the phthalate mixture through drinking water from conception and throughout life. Previous observations that BPA exposure increased the prevalence of diabetes and insulitis and decreased the number of tissue resident macrophages in pancreas were confirmed, and extended by demonstrating that BPA exposure also impaired the phagocytic activity of peritoneal macrophages. None of these effects were observed after phthalate exposure alone. The phthalate exposure in combination with BPA seemed to dampen the BPA effects on macrophage number and function as well as diabetes development, but not insulitis development. Exposure to BPA alone or in combination with phthalates decreased cytokine release (TNFα, IL-6, IL-10, IFNγ, IL-4) from in vitro stimulated splenocytes and lymph node cells, indicating systemic changes in immune function. In conclusion, exposure to BPA, but not to phthalates or mixed exposure to BPA and phthalates, accelerated diabetes development in NOD mice, apparently in part via systemic immune alterations including decreased macrophage function.

Exposure to bisphenol A, but not phthalates, increases spontaneous diabetes type 1 development in NOD mice

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Johanna Bodin

2015-01-01

Full Text Available Type 1 diabetes mellitus (T1DM is an autoimmune destruction of insulin producing pancreatic beta-cells due to a genetic predisposition and can be triggered by environmental factors. We have previously shown that bisphenol A (BPA accelerates the spontaneous development of diabetes in non-obese diabetic (NOD mice. Here, we hypothesized that oral exposure to a mixture of the endocrine disruptors BPA and phthalates, relevant for human exposure, would accelerate diabetes development compared to BPA alone. NOD mice were exposed to BPA (1 mg/l, a mixture of phthalates (DEHP 1 mg/l, DBP 0.2 mg/l, BBP 10 mg/l and DiBP 20 mg/l or a combination of BPA and the phthalate mixture through drinking water from conception and throughout life. Previous observations that BPA exposure increased the prevalence of diabetes and insulitis and decreased the number of tissue resident macrophages in pancreas were confirmed, and extended by demonstrating that BPA exposure also impaired the phagocytic activity of peritoneal macrophages. None of these effects were observed after phthalate exposure alone. The phthalate exposure in combination with BPA seemed to dampen the BPA effects on macrophage number and function as well as diabetes development, but not insulitis development. Exposure to BPA alone or in combination with phthalates decreased cytokine release (TNFα, IL-6, IL-10, IFNγ, IL-4 from in vitro stimulated splenocytes and lymph node cells, indicating systemic changes in immune function. In conclusion, exposure to BPA, but not to phthalates or mixed exposure to BPA and phthalates, accelerated diabetes development in NOD mice, apparently in part via systemic immune alterations including decreased macrophage function.

Incomplete development of the spleen and the deformity in the chimeras between asplenic mutant (Dominant hemimelia) and normal mice.

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Suto, J; Wakayama, T; Imamura, K; Goto, S; Fukuta, K

1995-08-01

The semidominant gene Dh (Dominant hemimelia) induces skeletal and visceral abnormalities of various degrees and failure of the spleen in mice. The homozygous individual (Dh/Dh) seems to be lethal. The present experiment was designed to investigate the ability Dh cells to form a spleen and the genesis of the hind limb malformations by Dh/Dh and Dh/+ cells in chimeric mice. The Dh/Dh and Dh/+ embryos were produced in the F2 progeny of a cross between inbred strains of Dh/+ and DDD mice. They were aggregated with C3H/He or C57BL/6 embryos to make chimeras. Identification of Dh/Dh or Dh/+ embryos was carried out by Pep-3, and chimerism was analyzed by Gpi-1. Of 25 chimeras carrying the Dh gene, four mice formed a small spleen, two mice had a vestigial spleen, and the others no spleen. The tissues of the incompletely developed spleens were normal histologically and Dh cells were involved in the tissues of the spleen. In the chimeric mice, hindlimb malformation by the Dh gene was reduced in severity and the lethality of the homozygote (Dh/Dh) was rescued.

C57BL/6 mice need MHC class II Aq to develop collagen-induced arthritis dependent on autoreactive T cells.

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Bäcklund, Johan; Li, Cuiqin; Jansson, Erik; Carlsen, Stefan; Merky, Patrick; Nandakumar, Kutty-Selva; Haag, Sabrina; Ytterberg, Jimmy; Zubarev, Roman A; Holmdahl, Rikard

2013-07-01

Collagen-induced arthritis (CIA) has traditionally been performed in MHC class II A(q)-expressing mice, whereas most genetically modified mice are on the C57BL/6 background (expressing the b haplotype of the major histocompatibility complex (MHC) class II region). However, C57BL/6 mice develop arthritis after immunisation with chicken-derived collagen type II (CII), but arthritis susceptibility has been variable, and the immune specificity has not been clarified. To establish a CIA model on the C57BL/6 background with a more predictable and defined immune response to CII. Both chicken and rat CII were arthritogenic in C57BL/6 mice provided they were introduced with high doses of Mycobacterium tuberculosis adjuvant. However, contaminating pepsin was strongly immunogenic and was essential for arthritis development. H-2(b)-restricted T cell epitopes on chicken or rat CII could not be identified, but expression of A(q) on the C57BL/6 background induced T cell response to the CII260-270 epitope, and also prolonged the arthritis to be more chronic. The putative (auto)antigen and its arthritogenic determinants in C57BL/6 mice remains undisclosed, questioning the value of the model for addressing T cell-driven pathological pathways in arthritis. To circumvent this impediment, we recommend MHC class II congenic C57BL/6N.Q mice, expressing A(q), with which T cell determinants have been thoroughly characterised.

Chronic ankle instability: Arthroscopic anatomical repair.

Science.gov (United States)

Arroyo-Hernández, M; Mellado-Romero, M; Páramo-Díaz, P; García-Lamas, L; Vilà-Rico, J

Ankle sprains are one of the most common injuries. Despite appropriate conservative treatment, approximately 20-40% of patients continue to have chronic ankle instability and pain. In 75-80% of cases there is an isolated rupture of the anterior talofibular ligament. A retrospective observational study was conducted on 21 patients surgically treated for chronic ankle instability by means of an arthroscopic anatomical repair, between May 2012 and January 2013. There were 15 men and 6 women, with a mean age of 30.43 years (range 18-48). The mean follow-up was 29 months (range 25-33). All patients were treated by arthroscopic anatomical repair of anterior talofibular ligament. Four (19%) patients were found to have varus hindfoot deformity. Associated injuries were present in 13 (62%) patients. There were 6 cases of osteochondral lesions, 3 cases of posterior ankle impingement syndrome, and 6 cases of peroneal pathology. All these injuries were surgically treated in the same surgical time. A clinical-functional study was performed using the American Orthopaedic Foot and Ankle Society (AOFAS) score. The mean score before surgery was 66.12 (range 60-71), and after surgery it increased up to a mean of 96.95 (range 90-100). All patients were able to return to their previous sport activity within a mean of 21.5 weeks (range 17-28). Complications were found in 3 (14%) patients. Arthroscopic anatomical ligament repair technique has excellent clinical-functional results with a low percentage of complications, and enables patients to return to their previous sport activity within a short period of time. Copyright © 2016 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

Study of Sperm Parameters and Sperm Fertility in Mice were Exposed to Tamoxifen during Embryonic Development

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J Soleimanirad

2017-05-01

Full Text Available Introduction: Tamoxifen is steroidal drug, which mainly treats breast cancer and also used to stimulate ovulation. The purpose of the present study was the evaluation of sperm parameters and fertility of mice whose mothers had received tamoxifen during pregnancy. Methods: In this study, 30 female and 15 male mice of NMRI were selected for mating. After mating female mice were randomly divided into two groups, the first group (control and second group (experimental. All of which contained 15 mice. From the day 13th day of pregnancy, experimental group has received tamoxifen with the dosage of 5 mg/kg for 7 days. After childbirth of the mated mice, male infants were selected. After reaching the age of puberty (6-8Weeks, adult mice were sacrificed by the cervical dislocation. After take sperm, sperm parameters (count, normality and motility, and sperm fertility was performed. In this study SPSS software and statistical t-test was used (p <0.001. Results: Studies showed that sperm parameters and sperm fertilization were significantly different. The number of sperm in the control group was 83.50±28.20 million, and in the experimental group was 60±14.14 million. There was a decrease in average sperm count in the experimental group compared with the control group (p <0.001. Our findings from in vitro fertilization culture media showed that embryos formation and oocyte disruption between control and experimental groups significantly different (p <0.001. Conclusion: The results showed that tamoxifen exposure during development can cause histological changes in the seminiferous tubules, which can lead to infertility.

Generation of a new bioluminescent model for visualisation of mammary tumour development in transgenic mice

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Zagozdzon Agnieszka M

2012-05-01

Full Text Available Abstract Background Numerous transgenic models have been generated to study breast cancer. However, despite many advantages, traditional transgenic models for breast cancer are also burdened with difficulties in early detection and longitudinal observation of transgene-induced tumours, which in most cases are randomly located and occur at various time points. Methods such as palpation followed by mechanical measurement of the tumours are of limited value in transgenic models. There is a crucial need for making these previously generated models suitable for modern methods of tumour visualisation and monitoring, e.g. by bioluminescence-based techniques. This approach was successfully used in the current study. Results A new mouse strain (MMTV-Luc2 mice expressing Luc2 luciferase primarily in mammary tissue in females, with low-level background expression in internal organs, was generated and bred to homozygosity. After these mice were intercrossed with MMTV-PyVT mice, all double transgenic females developed mammary tumours by the age of 10 weeks, the localisation and progression of which could be effectively monitored using the luminescence-based in vivo imaging. Luminescence-based readout allowed for early visualisation of the locally overgrown mammary tissue and for longitudinal evaluation of local progression of the tumours. When sampled ex vivo at the age of 10 weeks, all tumours derived from MMTV-Luc2PyVT females displayed robust bioluminescent signal. Conclusions We have created a novel transgenic strain for visualisation and longitudinal monitoring of mammary tumour development in transgenic mice as an addition and/or a new and more advanced alternative to manual methods. Generation of this mouse strain is vital for making many of the existing mammary tumour transgenic models applicable for in vivo imaging techniques.

Generation of a new bioluminescent model for visualisation of mammary tumour development in transgenic mice

LENUS (Irish Health Repository)

Zagozdzon, Agnieszka M

2012-05-30

AbstractBackgroundNumerous transgenic models have been generated to study breast cancer. However, despite many advantages, traditional transgenic models for breast cancer are also burdened with difficulties in early detection and longitudinal observation of transgene-induced tumours, which in most cases are randomly located and occur at various time points. Methods such as palpation followed by mechanical measurement of the tumours are of limited value in transgenic models. There is a crucial need for making these previously generated models suitable for modern methods of tumour visualisation and monitoring, e.g. by bioluminescence-based techniques. This approach was successfully used in the current study.ResultsA new mouse strain (MMTV-Luc2 mice) expressing Luc2 luciferase primarily in mammary tissue in females, with low-level background expression in internal organs, was generated and bred to homozygosity. After these mice were intercrossed with MMTV-PyVT mice, all double transgenic females developed mammary tumours by the age of 10 weeks, the localisation and progression of which could be effectively monitored using the luminescence-based in vivo imaging. Luminescence-based readout allowed for early visualisation of the locally overgrown mammary tissue and for longitudinal evaluation of local progression of the tumours. When sampled ex vivo at the age of 10 weeks, all tumours derived from MMTV-Luc2PyVT females displayed robust bioluminescent signal.ConclusionsWe have created a novel transgenic strain for visualisation and longitudinal monitoring of mammary tumour development in transgenic mice as an addition and\\/or a new and more advanced alternative to manual methods. Generation of this mouse strain is vital for making many of the existing mammary tumour transgenic models applicable for in vivo imaging techniques.

Anatomical approach for surgery of the male posterior urethra.

Science.gov (United States)

Dalpiaz, Orietta; Mitterberger, Michael; Kerschbaumer, Andrea; Pinggera, Germar M; Bartsch, Georg; Strasser, Hannes

2008-11-01

To investigate, in a morphological study, the anatomy of the male rhabdosphincter and the relation between the membranous urethra, the rhabdosphincter and the neurovascular bundles (NVBs) to provide the anatomical basis for surgical approach of the posterior urethra as successful outcomes in urethral reconstructive surgery still remain a challenging issue. In all, 11 complete pelves and four tissue blocks of prostate, rectum, membranous urethra and the rhabdosphincter were studied. Besides anatomical preparations, the posterior urethra and their relationship were studied by means of serial histological sections. In the histological cross-sections, the rhabdosphincter forms an omega-shaped loop around the anterior and lateral aspects of the membranous urethra. Ventrally and laterally, it is separated from the membranous urethra by a delicate sheath of connective tissue. Through a midline approach displacing the nerves and vessels laterally, injuries to the NVBs can be avoided. With meticulous dissection of the delicate ventral connective tissue sheath between the ventral wall of the membranous urethra and the rhabdosphincter, the two structures can be separated without damage to either of them. This anatomical approach can be used for dissection of the anterior urethral wall in urethral surgery. Based on precise anatomical knowledge, the ventral wall of the posterior urethra can be dissected and exposed without injuring the rhabdosphincter and the NVBs. This approach provides the basis for sparing of the rhabdosphincter and for successful outcomes in urethral surgery for the treatment of bulbo-membranous urethral strictures.

Entire litters developed from transferred eggs in whole body x-irradiated female mice

International Nuclear Information System (INIS)

Lin, T.P.

1980-01-01

The sensitivity of mouse eggs to sublethal x-irradiation was determined in vitro and in vivo with regard to the development of donor litters in foster mothers. One thousand seven hundred fifty-eight unfertilized eggs of agouti dark-eyed donor mice were transferred into 293 unirradiated or x-irradiated, mated female pink-eyed mice. Two hundred thirty-nine recipients became pregnant; of these 35 produced litters containing solely dark-eyed fetuses. Sublethal doses of x-radiation administered to donor eggs in vitro before transferring into unirradiated recipients did not influence significantly the number of litters of exclusively dark-eyed fetuses produced. However, recipients irradiated by 250 roentgens (r) produced more solely dark-eyed litters than did those irradiated with 100 r. In 21 pregnant females irradiated by 100 r, only 3 (14%) developed solely dark-eyed fetuses as compared to 22 pregnant females irradiated by 250 r, of which 13 (59%) developed solely dark-eyed fetuses, all from unirradiated, transferred eggs. Of another group of 22 pregnant females which received 250 r body irradiation and subsequently received eggs also irradiated by 250 r, only 7 (32%) produced litters of dark-eyed fetuses. No one female of these three groups carried native fetuses. Such radiation-induced infertility resulting from damage of native eggs rather than loss of mother's ability to carry a pregnancy, is frequently remedied by egg transfer

Laparoscopic sacrocolpopexy with bone anchor fixation: short-term anatomic and functional results.

NARCIS (Netherlands)

Withagen, M.I.J.; Vierhout, M.E.; Mannaerts, G.H.; Weiden, R.M.F. van der

2012-01-01

INTRODUCTION AND HYPOTHESIS: The aim of this study was to evaluate short-term anatomic and functional outcomes and safety of laparoscopic sacrocolpopexy with bone anchor fixation. METHODS: A prospective cohort study of women undergoing laparoscopic sacrocolpopexy between 2004 and 2009. Anatomic

Genetic Mapping in Mice Reveals the Involvement of Pcdh9 in Long-Term Social and Object Recognition and Sensorimotor Development.

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Bruining, Hilgo; Matsui, Asuka; Oguro-Ando, Asami; Kahn, René S; Van't Spijker, Heleen M; Akkermans, Guus; Stiedl, Oliver; van Engeland, Herman; Koopmans, Bastijn; van Lith, Hein A; Oppelaar, Hugo; Tieland, Liselotte; Nonkes, Lourens J; Yagi, Takeshi; Kaneko, Ryosuke; Burbach, J Peter H; Yamamoto, Nobuhiko; Kas, Martien J

2015-10-01

Quantitative genetic analysis of basic mouse behaviors is a powerful tool to identify novel genetic phenotypes contributing to neurobehavioral disorders. Here, we analyzed genetic contributions to single-trial, long-term social and nonsocial recognition and subsequently studied the functional impact of an identified candidate gene on behavioral development. Genetic mapping of single-trial social recognition was performed in chromosome substitution strains, a sophisticated tool for detecting quantitative trait loci (QTL) of complex traits. Follow-up occurred by generating and testing knockout (KO) mice of a selected QTL candidate gene. Functional characterization of these mice was performed through behavioral and neurological assessments across developmental stages and analyses of gene expression and brain morphology. Chromosome substitution strain 14 mapping studies revealed an overlapping QTL related to long-term social and object recognition harboring Pcdh9, a cell-adhesion gene previously associated with autism spectrum disorder. Specific long-term social and object recognition deficits were confirmed in homozygous (KO) Pcdh9-deficient mice, while heterozygous mice only showed long-term social recognition impairment. The recognition deficits in KO mice were not associated with alterations in perception, multi-trial discrimination learning, sociability, behavioral flexibility, or fear memory. Rather, KO mice showed additional impairments in sensorimotor development reflected by early touch-evoked biting, rotarod performance, and sensory gating deficits. This profile emerged with structural changes in deep layers of sensory cortices, where Pcdh9 is selectively expressed. This behavior-to-gene study implicates Pcdh9 in cognitive functions required for long-term social and nonsocial recognition. This role is supported by the involvement of Pcdh9 in sensory cortex development and sensorimotor phenotypes. Copyright © 2015 Society of Biological Psychiatry. Published

Anatomical relationship between the optic nerve and posterior paranasal sinuses on ostiomeatal unit CT

International Nuclear Information System (INIS)

Cho, June Il; Kim, Hong In; Seol, Hae Young; Lee, Nam Joon; Kim, Jung Hyuk; Cha, In Ho

1997-01-01

To determine the anatomic variations that can lead to optic nerve damage during the sugical treatment of posterior paranasal sinus lesions two hundred optic nerves of 100 persons were examined using ostiomeatal unit CT(OMU CT). The anatomical features of this nerve and posterior paranasal sinuses were classified into four types:the optic nerve adjacent to the sphenoid sinus without indentation of the sinus wall (type 1);the optic nerve adjacent to the sphenoid sinus, causing indentation of the sinus wall (type 2);the optic nerve passing through the sphenoid sinus (type 3);and the optic nerve adjacent to the sphenoid sinus and posterior ethmoid sinus (type 4). Bony dehiscence around the optic nerve and pneumatization of the anterior clinoid process were also evaluated. The anatomical classification of the optic nerve and posterior paranasal sinuses was as follows:type 1, 1326(66%); type 2, 60(30%); type 3, 6(3%), and type 4, 2(1%). Bony dehiscence around the optic nerve had developed in 58 cases (29%) and pneumatization of the anterior clinoid process in 13(6.5%). These conditions were most common in type 3 optic nerve, and second most common in type 2. The 2 and 3 optic nerves, bony dehiscence around the optic nerve and pneumatization of the anterior clinoid process are the anatomic variations that can lead to optic nerve damage during the surgical treatment of posterior paranasal sinus lesions. To prevent optic nerve damage, these factors should be carefully evaluated by OMU CT

Anatomical variations of paranasal sinuses at multislice computed tomography: what to look for

International Nuclear Information System (INIS)

Miranda, Christiana Maia Nobre Rocha de; Maranhao, Carol Pontes de Miranda; Padilha, Igor Gomes; Farias, Lucas de Padua Gomes de; Jatoba, Mayara Stephanie de Araujo; Andrade, Anna Carolina Mendonca de; Padilha, Bruno Gomes

2011-01-01

Multislice computed tomography is currently the imaging modality of choice for evaluating paranasal sinuses and adjacent structures. Such a method has been increasingly utilized in the assessment of anatomical variations, allowing their accurate identification with high anatomical details. Some anatomical variations may predispose to sinusal diseases, constituting areas of high risk for injuries and complications during surgical procedures. Therefore, the recognition of such variations is critical in the preoperative evaluation for endoscopic surgery. (author)

Anatomical variations of paranasal sinuses at multislice computed tomography: what to look for

Energy Technology Data Exchange (ETDEWEB)

Miranda, Christiana Maia Nobre Rocha de; Maranhao, Carol Pontes de Miranda [Clinica de Medicina Nuclear e Radiologia de Maceio (Medradius), Maceio, AL (Brazil). Setor de Tomografia Computadorizada; Arraes, Fabiana Maia Nobre Rocha [Clinica Sinus, Maceio, AL (Brazil); Padilha, Igor Gomes; Farias, Lucas de Padua Gomes de; Jatoba, Mayara Stephanie de Araujo; Andrade, Anna Carolina Mendonca de; Padilha, Bruno Gomes [Universidade Federal de Alagoas (UFAL), Maceio, AL (Brazil)

2011-07-15

Multislice computed tomography is currently the imaging modality of choice for evaluating paranasal sinuses and adjacent structures. Such a method has been increasingly utilized in the assessment of anatomical variations, allowing their accurate identification with high anatomical details. Some anatomical variations may predispose to sinusal diseases, constituting areas of high risk for injuries and complications during surgical procedures. Therefore, the recognition of such variations is critical in the preoperative evaluation for endoscopic surgery. (author)

Abnormal megakaryocyte development and platelet function in Nbeal2(-/-) mice.

Science.gov (United States)

Kahr, Walter H A; Lo, Richard W; Li, Ling; Pluthero, Fred G; Christensen, Hilary; Ni, Ran; Vaezzadeh, Nima; Hawkins, Cynthia E; Weyrich, Andrew S; Di Paola, Jorge; Landolt-Marticorena, Carolina; Gross, Peter L

2013-11-07

Gray platelet syndrome (GPS) is an inherited bleeding disorder associated with macrothrombocytopenia and α-granule-deficient platelets. GPS has been linked to loss of function mutations in NEABL2 (neurobeachin-like 2), and we describe here a murine GPS model, the Nbeal2(-/-) mouse. As in GPS, Nbeal2(-/-) mice exhibit splenomegaly, macrothrombocytopenia, and a deficiency of platelet α-granules and their cargo, including von Willebrand factor (VWF), thrombospondin-1, and platelet factor 4. The platelet α-granule membrane protein P-selectin is expressed at 48% of wild-type levels and externalized upon platelet activation. The presence of P-selectin and normal levels of VPS33B and VPS16B in Nbeal2(-/-) platelets suggests that NBEAL2 acts independently of VPS33B/VPS16B at a later stage of α-granule biogenesis. Impaired Nbeal2(-/-) platelet function was shown by flow cytometry, platelet aggregometry, bleeding assays, and intravital imaging of laser-induced arterial thrombus formation. Microscopic analysis detected marked abnormalities in Nbeal2(-/-) bone marrow megakaryocytes, which when cultured showed delayed maturation, decreased survival, decreased ploidy, and developmental abnormalities, including abnormal extracellular distribution of VWF. Our results confirm that α-granule secretion plays a significant role in platelet function, and they also indicate that abnormal α-granule formation in Nbeal2(-/-) mice has deleterious effects on megakaryocyte survival, development, and platelet production.

An anatomical and functional topography of human auditory cortical areas

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Michelle eMoerel

2014-07-01

Full Text Available While advances in magnetic resonance imaging (MRI throughout the last decades have enabled the detailed anatomical and functional inspection of the human brain non-invasively, to date there is no consensus regarding the precise subdivision and topography of the areas forming the human auditory cortex. Here, we propose a topography of the human auditory areas based on insights on the anatomical and functional properties of human auditory areas as revealed by studies of cyto- and myelo-architecture and fMRI investigations at ultra-high magnetic field (7 Tesla. Importantly, we illustrate that - whereas a group-based approach to analyze functional (tonotopic maps is appropriate to highlight the main tonotopic axis - the examination of tonotopic maps at single subject level is required to detail the topography of primary and non-primary areas that may be more variable across subjects. Furthermore, we show that considering multiple maps indicative of anatomical (i.e. myelination as well as of functional properties (e.g. broadness of frequency tuning is helpful in identifying auditory cortical areas in individual human brains. We propose and discuss a topography of areas that is consistent with old and recent anatomical post mortem characterizations of the human auditory cortex and that may serve as a working model for neuroscience studies of auditory functions.

Assessment of Anatomical Knowledge and Core Trauma Competency Vascular Skills.

Science.gov (United States)

Granite, Guinevere; Pugh, Kristy; Chen, Hegang; Longinaker, Nyaradzo; Garofalo, Evan; Shackelford, Stacy; Shalin, Valerie; Puche, Adam; Pasley, Jason; Sarani, Babak; Henry, Sharon; Bowyer, Mark; Mackenzie, Colin

2018-03-01

Surgical residents express confidence in performing specific vascular exposures before training, but such self-reported confidence did not correlate with co-located evaluator ratings. This study reports residents' self-confidence evaluated before and after Advanced Surgical Skills for Exposure in Trauma (ASSET) cadaver-based training, and 12-18 mo later. We hypothesize that residents will better judge their own skill after ASSET than before when compared with evaluator ratings. Forty PGY2-7 surgical residents performed four procedures: axillary artery (AA), brachial artery (BA), femoral artery exposure and control (FA), and lower extremity fasciotomy (FAS) at the three evaluations. Using 5-point Likert scales, surgeons self-assessed their confidence in anatomical understanding and procedure performance after each procedure and evaluators rated each surgeon accordingly. For all the three evaluations, residents consistently rated their anatomical understanding (p < 0.04) and surgical performance (p < 0.03) higher than evaluators for both FA and FAS. Residents rated their anatomical understanding and surgical performance higher (p < 0.005) than evaluators for BA after training and up to 18 mo later. Only for third AA evaluation were there no rating differences. Residents overrate their anatomical understanding and performance abilities for BA, FA, and FAS even after performing the procedures and being debriefed three times in 18 mo.

Effect of anatomical variability in brain on transcranial magnetic stimulation treatment

Science.gov (United States)

Syeda, F.; Magsood, H.; Lee, E. G.; El-Gendy, A. A.; Jiles, D. C.; Hadimani, R. L.

2017-05-01

Transcranial Magnetic Stimulation is a non-invasive clinical therapy used to treat depression and migraine, and shows further promise as treatment for Parkinson's disease, Alzheimer's disease, and other neurological disorders. However, it is yet unclear as to how anatomical differences may affect stimulation from this treatment. We use finite element analysis to model and analyze the results of Transcranial Magnetic Stimulation in various head models. A number of heterogeneous head models have been developed using MRI data of real patients, including healthy individuals as well as patients of Parkinson's disease. Simulations of Transcranial Magnetic Stimulation performed on 22 anatomically different models highlight the differences in induced stimulation. A standard Figure of 8 coil is used with frequency 2.5 kHz, placed 5 mm above the head. We compare cortical stimulation, volume of brain tissue stimulated, specificity, and maximum E-field induced in the brain for models ranging from ages 20 to 60. Results show that stimulation varies drastically between patients of the same age and health status depending upon brain-scalp distance, which is not necessarily a linear progression with age.

Agonistic anti-TIGIT treatment inhibits T cell responses in LDLr deficient mice without affecting atherosclerotic lesion development.

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Amanda C Foks

Full Text Available OBJECTIVE: Co-stimulatory and co-inhibitory molecules are mainly expressed on T cells and antigen presenting cells and strongly orchestrate adaptive immune responses. Whereas co-stimulatory molecules enhance immune responses, signaling via co-inhibitory molecules dampens the immune system, thereby showing great therapeutic potential to prevent cardiovascular diseases. Signaling via co-inhibitory T cell immunoglobulin and ITIM domain (TIGIT directly inhibits T cell activation and proliferation, and therefore represents a novel therapeutic candidate to specifically dampen pro-atherogenic T cell reactivity. In the present study, we used an agonistic anti-TIGIT antibody to determine the effect of excessive TIGIT-signaling on atherosclerosis. METHODS AND RESULTS: TIGIT was upregulated on CD4(+ T cells isolated from mice fed a Western-type diet in comparison with mice fed a chow diet. Agonistic anti-TIGIT suppressed T cell activation and proliferation both in vitro and in vivo. However, agonistic anti-TIGIT treatment of LDLr(-/- mice fed a Western-type diet for 4 or 8 weeks did not affect atherosclerotic lesion development in comparison with PBS and Armenian Hamster IgG treatment. Furthermore, elevated percentages of dendritic cells were observed in the blood and spleen of agonistic anti-TIGIT-treated mice. Additionally, these cells showed an increased activation status but decreased IL-10 production. CONCLUSIONS: Despite the inhibition of splenic T cell responses, agonistic anti-TIGIT treatment does not affect initial atherosclerosis development, possibly due to increased activity of dendritic cells.

Pathophysiological and behavioral deficits in developing mice following rotational acceleration-deceleration traumatic brain injury

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Guoxiang Wang

2018-01-01

Full Text Available Abusive head trauma (AHT is the leading cause of death from trauma in infants and young children. An AHT animal model was developed on 12-day-old mice subjected to 90° head extension-flexion sagittal shaking repeated 30, 60, 80 and 100 times. The mortality and time until return of consciousness were dependent on the number of repeats and severity of the injury. Following 60 episodes of repeated head shakings, the pups demonstrated apnea and/or bradycardia immediately after injury. Acute oxygen desaturation was observed by pulse oximetry during respiratory and cardiac suppression. The cerebral blood perfusion was assessed by laser speckle contrast analysis (LASCA using a PeriCam PSI system. There was a severe reduction in cerebral blood perfusion immediately after the trauma that did not significantly improve within 24 h. The injured mice began to experience reversible sensorimotor function at 9 days postinjury (dpi, which had completely recovered at 28 dpi. However, cognitive deficits and anxiety-like behavior remained. Subdural/subarachnoid hemorrhage, damage to the brain-blood barrier and parenchymal edema were found in all pups subjected to 60 insults. Proinflammatory response and reactive gliosis were upregulated at 3 dpi. Degenerated neurons were found in the cerebral cortex and olfactory tubercles at 30 dpi. This mouse model of repetitive brain injury by rotational head acceleration-deceleration partially mimics the major pathophysiological and behavioral events that occur in children with AHT. The resultant hypoxia/ischemia suggests a potential mechanism underlying the secondary rotational acceleration-deceleration-induced brain injury in developing mice.