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|
||
<a href="/clipboard/"
|
||
class="search-input-link clipboard-link hidden"
|
||
data-ga-category="featured_link"
|
||
data-ga-action="clipboard">
|
||
Clipboard <span class="amount-in-clipboard"></span>
|
||
</a>
|
||
</div>
|
||
|
||
<span class="search-input-link user-guide-link" role="navigation" aria-label="User guide">
|
||
<a href="/help/"
|
||
data-ga-category="featured_link"
|
||
data-ga-action="user_guide">
|
||
User Guide
|
||
</a>
|
||
</span>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
|
||
</form>
|
||
|
||
|
||
<div id="article-page-header">
|
||
<div id="article-top-actions-bar" class="article-top-actions-bar">
|
||
<div class="inner-wrap">
|
||
<div class="actions-container">
|
||
<div class="return-to-search">
|
||
|
||
|
||
</div>
|
||
|
||
<div class="multiple-results-actions " role="region" aria-label="save, email, send to">
|
||
<button id="save-results-panel-trigger"
|
||
type="button"
|
||
class="save-results save-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="save-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="open">
|
||
Save
|
||
</button><button id="email-results-panel-trigger"
|
||
type="button"
|
||
class="email-results email-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="email-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="open">
|
||
Email
|
||
</button><div class="more-actions dropdown-block"><button id="more-actions-trigger"
|
||
type="button"
|
||
class="trigger more-actions-trigger"
|
||
ref="linksrc=show_moreactions_btn"
|
||
aria-label="Send to"
|
||
aria-controls="more-actions-dropdown">Send to</button><div id="more-actions-dropdown" class="dropdown dropdown-container" hidden><div class="content"><ul class="more-actions-links"><li><a class="clipboard-panel-trigger dropdown-block-link "
|
||
href="#"
|
||
role="button"
|
||
data-ga-category="save_share"
|
||
data-ga-action="clipboard"
|
||
data-ga-label="send">
|
||
Clipboard
|
||
</a></li><li><a role="button" class="dropdown-block-link bibliography-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F12077348%2F%23open-bibliography-panel">My Bibliography</a></li><li><a role="button" class="dropdown-block-link collections-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F12077348%2F%23open-collections-panel">Collections</a></li><li><a role="button" class="citation-manager-panel-trigger dropdown-block-link citation-manager-trigger-target" href="#">Citation manager</a></li></ul></div></div></div>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region">
|
||
<button
|
||
class="trigger usa-button"
|
||
title="Change format"
|
||
data-ga-category="display_options"
|
||
data-ga-action="display_options_dialog">
|
||
<span class="button-label">Display options</span>
|
||
</button>
|
||
|
||
<div class="dropdown" hidden>
|
||
<div class="title">
|
||
Display options
|
||
</div>
|
||
|
||
<div class="content">
|
||
|
||
<div class="format-container">
|
||
<span class="option-label">
|
||
Format
|
||
</span>
|
||
<select name="format" data-initial-value="abstract" aria-label="Display format" id="article-display-format">
|
||
<option value="abstract">Abstract</option>
|
||
|
||
<option value="pubmed">PubMed</option>
|
||
|
||
<option value="pmid">PMID</option>
|
||
|
||
</select>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
</div>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="0PgtJS11i67QIAVtPpJYTDFWoh9xjAoihC0ymIunSHUkC11jsIm0nLbAWlRJcbWC">
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="article-panels-container" class="article-panels-container">
|
||
<div id="save-action-panel" class="save-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Save citation to file
|
||
</h2>
|
||
<form id="save-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="0PgtJS11i67QIAVtPpJYTDFWoh9xjAoihC0ymIunSHUkC11jsIm0nLbAWlRJcbWC">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="save-action-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="save-action-format" name="results-format" class="action-panel-selector">
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="pubmed-text">PubMed</option>
|
||
<option value="pmid">PMID</option>
|
||
<option value="abstract">Abstract (text)</option>
|
||
<option value="csv">CSV</option>
|
||
</select>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Save citations to file' panel"
|
||
ref="linksrc=close_save_panel"
|
||
aria-controls="save-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="email-action-panel"
|
||
class="email-action-panel action-panel"
|
||
aria-hidden="true"
|
||
data-recaptcha-script-url="https://www.recaptcha.net/recaptcha/enterprise.js?render=explicit&onload=onloadCaptchaCallback"
|
||
data-recaptcha-enabled="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Email citation
|
||
</h2>
|
||
<form id="email-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/send-email/"
|
||
data-by-search-action="/results-export-email-by-search-data/"
|
||
data-by-ids-action="/send-email/"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post"
|
||
method="post"
|
||
>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="0PgtJS11i67QIAVtPpJYTDFWoh9xjAoihC0ymIunSHUkC11jsIm0nLbAWlRJcbWC">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<span class="action-panel-label">
|
||
Subject:
|
||
</span>
|
||
<span class="email-subject" id="email-subject" aria-label="Email subject">1 selected item: 12077348 - PubMed</span>
|
||
<input type="hidden" name="email-subject" value="1 selected item: 12077348"/>
|
||
<input type="hidden" name="email-subject-hash" value="a938d3fe85d8051d6b2173c3f7432082262a0fd65e9639295748ed80cf641da6"/>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-to" class="action-panel-label required-field-asterisk">
|
||
To:
|
||
</label>
|
||
<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-from" class="action-panel-label">
|
||
From:
|
||
</label>
|
||
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
|
||
</div>
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-citation-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
|
||
<option selected="selected" value="summary">Summary</option>
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="abstract">Abstract</option>
|
||
<option value="abstract-text">Abstract (text)</option>
|
||
|
||
</select>
|
||
</div>
|
||
<div class="include-supplemental-container">
|
||
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
|
||
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="form-field recaptcha ">
|
||
|
||
|
||
|
||
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
|
||
|
||
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="send">
|
||
Send email
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Email citations' panel"
|
||
ref="linksrc=close_email_panel"
|
||
aria-controls="email-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
<input type="hidden" name="email-search-details" value="" />
|
||
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="collections-action-panel"
|
||
class="collections-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-collections-open-panel-enabled="false"
|
||
data-collections-open-panel-url-hash="#open-collections-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to Collections
|
||
</h3>
|
||
|
||
|
||
<form id="collections-action-panel-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-add-to-collection-max-amount="1000"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="0PgtJS11i67QIAVtPpJYTDFWoh9xjAoihC0ymIunSHUkC11jsIm0nLbAWlRJcbWC">
|
||
|
||
|
||
|
||
<div class="choice-group" role="radiogroup">
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_new">
|
||
<label for="collections-action-panel-new">Create a new collection</label>
|
||
</li>
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_existing">
|
||
<label for="collections-action-panel-existing">Add to an existing collection</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
|
||
<div class="controls-wrapper">
|
||
<div class="action-panel-control-wrap new-collections-controls">
|
||
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label>
|
||
<input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-panel-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="save_share"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection">
|
||
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div>
|
||
</div>
|
||
<div class="action-panel-control-wrap existing-collections-controls">
|
||
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label>
|
||
<select id="collections-action-panel-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="save_share"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
|
||
</select>
|
||
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="add">
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="bibliography-action-panel"
|
||
class="bibliography-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-bibliography-open-panel-enabled="false"
|
||
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to My Bibliography
|
||
</h3>
|
||
<form id="bibliography-action-panel-form"
|
||
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-add-to-bibliography-max-amount="100"
|
||
data-add-to-bibliography-batch-size="10"
|
||
data-bibliography-delegates-url="/list-bibliography-delegates/"
|
||
data-add-to-bibliography-url="/add-to-bibliography/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="0PgtJS11i67QIAVtPpJYTDFWoh9xjAoihC0ymIunSHUkC11jsIm0nLbAWlRJcbWC">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap bibliographies-controls">
|
||
<div class="choice-group">
|
||
<ul class="bibliographies-action-add radio-group-items">
|
||
<li>
|
||
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
|
||
<label for="my-bibliography">My Bibliography</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your delegates due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore>
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to bibliography' panel"
|
||
ref="linksrc=close_bibliography_panel"
|
||
aria-controls="bibliography-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="mybib"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
|
||
data-saved-search-open-panel-enabled="false"
|
||
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your saved search
|
||
</h2>
|
||
|
||
<form id="saved-search-action-panel-form"
|
||
class="saved-search-action-panel-form action-panel-content action-form"
|
||
data-create-saved-search-url="/create-saved-search/"
|
||
data-try-search-terms-url="/try-search-term/"
|
||
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="0PgtJS11i67QIAVtPpJYTDFWoh9xjAoihC0ymIunSHUkC11jsIm0nLbAWlRJcbWC">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
|
||
Name of saved search:
|
||
</label>
|
||
<input maxlength="200"
|
||
type="text"
|
||
name="saved-search-name"
|
||
id="saved-search-name"
|
||
class="saved-search-name"
|
||
value=""
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
|
||
Search terms:
|
||
</label>
|
||
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
|
||
</div>
|
||
<div class="test-search-term-wrap">
|
||
<a href="#" class="try-search-term">Test search terms</a>
|
||
</div>
|
||
<div class="choice-group action-panel-extra-margin-top">
|
||
<span class="action-panel-label" id="fieldset-label">
|
||
Would you like email updates of new search results?
|
||
</span>
|
||
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
|
||
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
|
||
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
|
||
</li>
|
||
<li>
|
||
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
|
||
<label for="saved-search-alert-no" class="action-panel-label">No</label>
|
||
</li>
|
||
</ul>
|
||
</fieldset>
|
||
</div>
|
||
|
||
<div class="alert-schedule-wrap">
|
||
<div class="action-panel-control-wrap">
|
||
<label class="action-panel-label">
|
||
Email:
|
||
</label>
|
||
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
|
||
</div>
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="saved-search-frequency" class="action-panel-label">
|
||
Frequency:
|
||
</label>
|
||
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
|
||
<option value="monthly">Monthly</option>
|
||
<option value="weekly">Weekly</option>
|
||
<option value="daily">Daily</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-monthly-additional">
|
||
<label for="saved-search-monthly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
|
||
<option value="Sunday">The first Sunday</option>
|
||
<option value="Monday">The first Monday</option>
|
||
<option value="Tuesday">The first Tuesday</option>
|
||
<option value="Wednesday">The first Wednesday</option>
|
||
<option value="Thursday">The first Thursday</option>
|
||
<option value="Friday">The first Friday</option>
|
||
<option value="Saturday">The first Saturday</option>
|
||
<option value="day">The first day</option>
|
||
<option value="weekday">The first weekday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-weekly-additional">
|
||
<label for="saved-search-weekly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
|
||
<option value="Sunday">Sunday</option>
|
||
<option value="Monday">Monday</option>
|
||
<option value="Tuesday">Tuesday</option>
|
||
<option value="Wednesday">Wednesday</option>
|
||
<option value="Thursday">Thursday</option>
|
||
<option value="Friday">Friday</option>
|
||
<option value="Saturday">Saturday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-report" class="action-panel-label">
|
||
Report format:
|
||
</label>
|
||
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
|
||
<option value="DocSum">Summary</option>
|
||
<option value="DocSumText">Summary (text)</option>
|
||
<option value="Abstract">Abstract</option>
|
||
<option value="AbstractText">Abstract (text)</option>
|
||
<option value="MEDLINE">PubMed</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-amount" class="action-panel-label">
|
||
Send at most:
|
||
</label>
|
||
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
|
||
<option value="1">1 item</option>
|
||
<option value="5" selected>5 items</option>
|
||
<option value="10">10 items</option>
|
||
<option value="20">20 items</option>
|
||
<option value="50">50 items</option>
|
||
<option value="100">100 items</option>
|
||
<option value="200">200 items</option>
|
||
</select>
|
||
</div>
|
||
<div>
|
||
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
|
||
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
|
||
Send even when there aren't any new results
|
||
</label>
|
||
</div>
|
||
<div class="action-panel-control-wrap option-text-in-email-wrap">
|
||
<label for="saved-search-email-text" class="action-panel-label">
|
||
Optional text in email:
|
||
</label>
|
||
<textarea name="saved-search-email-text"
|
||
id="saved-search-email-text"
|
||
class="saved-search-email-text"></textarea>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Save
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your saved search' panel"
|
||
ref="linksrc=close_saved_search_panel"
|
||
aria-controls="saved-search-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Create a file for external citation management software
|
||
</h2>
|
||
<form id="citation-manager-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="0PgtJS11i67QIAVtPpJYTDFWoh9xjAoihC0ymIunSHUkC11jsIm0nLbAWlRJcbWC">
|
||
|
||
|
||
|
||
<input name="results-format" type="hidden" value="pubmed"/>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Send citations to citation manager' panel"
|
||
ref="linksrc=close_citation_manager_panel"
|
||
aria-controls="citation-manager-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your RSS Feed
|
||
</h2>
|
||
|
||
<form id="rss-action-panel-form"
|
||
class="rss-action-panel-form action-panel-content action-form"
|
||
data-create-rss-feed-url="/create-rss-feed-url/"
|
||
data-search-form-term-value="">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="0PgtJS11i67QIAVtPpJYTDFWoh9xjAoihC0ymIunSHUkC11jsIm0nLbAWlRJcbWC">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="rss-name" class="action-panel-label required-field-asterisk">
|
||
Name of RSS Feed:
|
||
</label>
|
||
<input maxlength="200"
|
||
placeholder="Name"
|
||
type="text"
|
||
name="rss-name"
|
||
id="rss-name"
|
||
class="rss-name"
|
||
value=''
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="rss-limit-wrap">
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="rss-limit" class="action-panel-label">
|
||
Number of items displayed:
|
||
</label>
|
||
<select id="rss-limit" class="no-border-panel-selector rss-limit">
|
||
<option value="5">5</option>
|
||
<option value="10">10</option>
|
||
<option value="15" selected="selected">15</option>
|
||
<option value="20">20</option>
|
||
<option value="50">50</option>
|
||
<option value="100">100</option>
|
||
</select>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Creating..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Create RSS
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your RSS' panel"
|
||
ref="linksrc=close_rss_panel"
|
||
aria-controls="rss-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap rss-link-copy-wrap">
|
||
<label for="rss-link" class="usa-sr-only">RSS Link</label>
|
||
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
|
||
<button
|
||
type="button"
|
||
disabled
|
||
class="rss-link-copy-button disabled"
|
||
data-ga-category="save_share"
|
||
data-ga-action="rss"
|
||
data-ga-label="copy">
|
||
Copy
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="article-page" id="article-page" data-article-pmid="12077348">
|
||
<aside class="page-sidebar">
|
||
<div class="inner-wrap">
|
||
|
||
<div class="full-text-links">
|
||
<div class="full-view">
|
||
<h3 class="title">
|
||
Full text links
|
||
</h3>
|
||
<div class="full-text-links-list">
|
||
<a class="link-item
|
||
|
||
dialog-focus"
|
||
href="https://www.tandfonline.com/doi/10.1128/MCB.22.14.5212-5221.2002?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub 0pubmed"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=4487&itool=Abstract-def&log$=linkouticon&uid=12077348&db=pubmed&nlmid=8109087"
|
||
title="See full text options at Atypon"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="Atypon"
|
||
data-ga-label="12077348"
|
||
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.tandfonline.com-pb-assets-tandf-logos-tf_pubmed_fulltext_icon.png" alt="Atypon full text link"><span class="text">
|
||
|
||
Atypon
|
||
|
||
</span></a><a class="link-item
|
||
pmc
|
||
"
|
||
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/12077348/"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=12077348&db=pubmed&nlmid=8109087"
|
||
title="Free full text at PubMed Central"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="PMC"
|
||
data-ga-label="12077348"
|
||
><span class="text">
|
||
|
||
Free PMC article
|
||
|
||
</span></a>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="short-view">
|
||
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
|
||
Full text links
|
||
</a>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
|
||
aria-label="Open dialog with citation text in different styles"
|
||
data-ga-category="save_share"
|
||
data-ga-action="cite"
|
||
data-ga-label="open"
|
||
data-all-citations-url="/12077348/citations/"
|
||
data-citation-style="nlm"
|
||
data-pubmed-format-link="/12077348/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="12077348" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
|
||
aria-label="Save article in MyNCBI collections."
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_button"
|
||
data-collections-open-dialog-enabled="false"
|
||
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F12077348%2F%23open-collections-dialog"
|
||
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
|
||
class="dialog collections-dialog"
|
||
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="0PgtJS11i67QIAVtPpJYTDFWoh9xjAoihC0ymIunSHUkC11jsIm0nLbAWlRJcbWC"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
|
||
id="collections-action-dialog-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
|
||
id="collections-action-dialog-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label><input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-dialog-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label><select id="collections-action-dialog-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="add">
|
||
Add
|
||
</button><button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger"
|
||
title="Open dialog with more actions to take"
|
||
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</a></li></ul></div></div></div><span class="period">. </span><span class="cit">2002 Jul;22(14):5212-21.</span>
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Targeted deletion of both thymidine phosphorylase and uridine phosphorylase and consequent disorders in mice
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Targeted deletion of both thymidine phosphorylase and uridine phosphorylase and consequent disorders in mice
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><sup class="key">1</sup> Department of Cancer Chemotherapy, Institute for Cancer Research, Third Department of Internal Medicin, Kagoshima University, 8-35-1 Sakura-gaoka, Kagoshima 890-8520, Japan.</li>
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Thymidine phosphorylase (TP) regulates intracellular and plasma thymidine levels. TP deficiency is hypothesized to (i) increase levels of thymidine in plasma, (ii) lead to mitochondrial DNA alterations, and (iii) cause mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). In order to elucidate the physiological roles of TP, we generated mice deficient in the TP gene. Although TP activity in the liver was inhibited in these mice, it was fully maintained in the small intestine. Murine uridine phosphorylase (UP), unlike human UP, cleaves thymidine, as well as uridine. We therefore generated TP-UP double-knockout (TP(-/-) UP(-/-)) mice. TP activities were inhibited in TP(-/-) UP(-/-) mice, and the level of thymidine in the plasma of TP(-/-) UP(-/-) mice was higher than for TP(-/-) mice. Unexpectedly, we could not observe alterations of mitochondrial DNA or pathological changes in the muscles of the TP(-/-) UP(-/-) mice, even when these mice were fed thymidine for 7 months. However, we did find hyperintense lesions on magnetic resonance T(2) maps in the brain and axonal edema by electron microscopic study of the brain in TP(-/-) UP(-/-) mice. These findings suggested that the inhibition of TP activity caused the elevation of pyrimidine levels in plasma and consequent axonal swelling in the brains of mice. Since lesions in the brain do not appear to be due to mitochondrial alterations and pathological changes in the muscle were not found, this model will provide further insights into the causes of MNGIE.
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a90/139774/c882a3bbd684/mb1420311001.gif"
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<p> FIG. 1. </p>
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<div class="figure-caption-contents"><p> Targeted disruption of the TP… </p></div>
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<p> FIG. 1. </p>
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<div class="figure-caption-contents"><p> Targeted disruption of the TP gene. (a) Schematic representation of the murine <i> TP… </i> </p></div>
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FIG. 1.
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<div class="figure-caption-contents">Targeted disruption of the TP gene. (a) Schematic representation of the murine <i>TP</i> locus (top), the targeting vector (middle), and the mutated allele (bottom). The closed boxes denote the 10 exons of the <i>TP</i> gene. The targeting vector was designed to replace an exon encoding a portion of the phosphate- or deoxyribose-binding site (top [K or L]) with a neomycin resistance gene. The position of the 3′-flanking probe used for Southern blot analysis is indicated. Positions of the PCR primers for the wild-type allele (TPf and TPr) and the mutant allele (TPf and neo) are also shown. S, n, N, A, and C represent the <i>Spe</i>I, <i>Nhe</i>I, <i>Nde</i>I, <i>Afl</i>II, and <i>Cla</i>I sites, respectively. (b) Southern blot analysis of wild-type and mutant ES cell DNA. Genomic DNA from wild-type (+/+) and TP<sup>+/−</sup> (+/−) ES cell clones were digested with <i>Nhe</i>I (left) or <i>Nde</i>I (right) and hybridized with the 3′-flanking probe. The 10-kb wild-type fragment (WT) and the 15-kb mutant fragment (MT) obtained after <i>Nhe</i>I digestion are indicated on the left. The wild-type allele produced an 8.5-kb <i>Nde</i>I digestion product, whereas the mutant allele gave rise to an 11-kb hybridizing product (right). (c) PCR analysis of mouse tail DNA from the wild-type allele (+/+), heterozygous <i>TP</i>-null allele (+/−), and homozygous <i>TP</i>-null allele (−/−). Oligonucleotides TPf and TPr (see panel a) were used as primers for the upstream and downstream disruption sites, respectively. Oligonucleotides TPf and Neo were used as primers for the knockout allele. The amplified PCR products were analyzed on 1% agarose gels to separate the 640-bp wild-type (WT) and 400-bp <i>TP</i>-null (Null) targeted allele fragments. (d) Reverse transcription-PCR analysis of TP mRNA in the livers of wild-type mice (+/+), TP<sup>+/−</sup> (+/−) mice, and TP<sup>−/−</sup> (−/−) mice. The total RNA was isolated from the liver and reverse transcribed. The resulting cDNA was used for PCR analysis with specific primers for <i>TP</i> and for the murine glyceraldehyde-3-phosphate dehydrogenase (<i>G3PDH</i>) gene. A 300-bp band is amplified by the TP-specific primers (<i>TP</i>), and a 950-bp band represents mRNA for <i>G3PDH</i>.</div>
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data-image-alt="FIG. 2."
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|
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id="article-image-1"
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a90/139774/4cce4a3ca88e/mb1420311002.gif"
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alt="FIG. 2." />
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<p> FIG. 2. </p>
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<div class="figure-caption-contents"><p> Generation of mice with targeted… </p></div>
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<div class="figure-caption-contents"><p> Generation of mice with targeted deletions of both TP and UP. (a) Levels… </p></div>
|
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|
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<div class="figure-caption-contents">Generation of mice with targeted deletions of both TP and UP. (a) Levels of F<sub>3</sub>dThd in plasma in mice after administration of F<sub>3</sub>dThd. F<sub>3</sub>dThd (100 mg/kg) was administered orally to TP<sup>+/+</sup> and TP<sup>−/−</sup> mice. The concentration of F<sub>3</sub>dThd in plasma was determined as described previously (7). Statistical significance was determined by using the Student's <i>t</i> test (mean ± the standard error; <i>n</i> = 3). (b) TP activity in various tissues from wild-type, TP<sup>−/−</sup>, UP<sup>−/−</sup>, and TP<sup>−/−</sup> UP<sup>−/−</sup> mice. The rate of conversion of thymidine to thymine was measured radiometrically as described previously (6). TP activity is expressed as nanomoles of thymidine catalyzed to thymine per minute per milligram of protein. Tissues were collected from three 2-month-old mice. (c) PCR analysis of mouse tail DNA from animals with the following six phenotypes: wild-type allele (TP<sup>+/+</sup> UP<sup>+/+</sup>), heterozygous <i>TP</i>-null allele (TP<sup>+/−</sup> UP<sup>+/+</sup>), homozygous <i>TP</i>-null allele (TP<sup>−/−</sup> UP<sup>+/+</sup>), heterozygous <i>UP</i>-null allele (TP<sup>+/+</sup> UP<sup>+/−</sup>), homozygous <i>UP</i>-null allele (TP<sup>+/+</sup>UP<sup>−/−</sup>), heterozygous <i>TP</i> or <i>UP</i> allele (TP<sup>+/−</sup> UP<sup>+/−</sup>), and homozygous <i>TP</i>- and <i>UP</i>-null allele (TP<sup>−/−</sup> UP<sup>−/−</sup>). The sizes of the amplified PCR products were 210 bp for UP wild type, 640 bp for TP wild type, 313 bp for the UP targeted allele, and 400 bp for the TP targeted allele fragments. (d) Five female mice at 5 months of age were injected intraperitoneally with pentobarbital. The time during which postural reflex was lost was measured.</div>
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data-image-width="759"
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data-image-height="320"
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data-image-alt="FIG. 3."
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data-pmc-id="PMC139774"
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data-figure-id="f3">
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<img class="figure-thumb" itemprop="thumbnail"
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id="article-image-2"
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a90/139774/0c3070939ed6/mb1420311003.gif"
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alt="FIG. 3." />
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<strong class="figure-label">
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<p> FIG. 3. </p>
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<div class="figure-caption-contents"><p> Elevated concentrations of thymidine in… </p></div>
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<strong class="figure-label">
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<p> FIG. 3. </p>
|
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</strong>
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<div class="figure-caption-contents"><p> Elevated concentrations of thymidine in the plasma and brains of TP <sup> −/− </sup> UP… </p></div>
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<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
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<strong class="figure-label">
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FIG. 3.
|
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</strong>
|
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|
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<div class="figure-caption-contents">Elevated concentrations of thymidine in the plasma and brains of TP<sup>−/−</sup> UP<sup>−/−</sup> mice. (a) Concentrations of pyrimidine nucleosides in the plasma of wild-type, TP<sup>−/−</sup>, and TP<sup>−/−</sup> UP<sup>−/−</sup> mice. Blood was collected from five mice at the age of 2 months and centrifuged to obtain the plasma. An aliquot (0.2 ml) of mouse plasma was applied to a high-pressure liquid chromatography column. The concentrations of thymidine, uridine, and cytidine in plasma were then measured. (b) Concentrations of thymidine in the plasma and brains of wild-type mice, TP<sup>−/−</sup> UP<sup>−/−</sup> mice, and thymidine-fed mice (indicated as “wild-type+” and “TP<sup>−/−</sup> UP<sup>−/−</sup>+”).</div>
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<a class="figure-link"
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|
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itemprop="contentUrl"
|
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aria-describedby="figure-caption-3"
|
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role="button"
|
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data-image-width="776"
|
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data-image-height="518"
|
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data-image-alt="FIG. 4."
|
||
data-pmc-id="PMC139774"
|
||
data-figure-id="f4">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-3"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a90/139774/aa38c40d8a4c/mb1420311004.gif"
|
||
alt="FIG. 4." />
|
||
</a>
|
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|
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<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="776">
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<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="518">
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|
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|
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|
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|
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|
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|
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|
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|
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<strong class="figure-label">
|
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<p> FIG. 4. </p>
|
||
</strong>
|
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|
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|
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|
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<div class="figure-caption-contents"><p> Lack of significant features of… </p></div>
|
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|
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|
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|
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|
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|
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|
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|
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<strong class="figure-label">
|
||
<p> FIG. 4. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Lack of significant features of MNGIE in the muscles of TP <sup> −/− </sup> UP… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
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|
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<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
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|
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|
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|
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|
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<strong class="figure-label">
|
||
FIG. 4.
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">Lack of significant features of MNGIE in the muscles of TP<sup>−/−</sup> UP<sup>−/−</sup> mice. The morphology of serial sections of muscles from 12-month-old wild-type (TP<sup>+/+</sup>) mice (a and b) and TP<sup>−/−</sup> mice (c and d) and 10-month-old TP<sup>−/−</sup> UP<sup>−/−</sup> mice (e and f) and thymidine-fed TP<sup>−/−</sup> UP<sup>−/−</sup> mice (g and h) was examined. Histochemical staining of soleus muscle or EDL sections was done with modified Gomori trichrome (GT; shown in panels b, d, f, and h), and histochemical staining was done to detect COX (shown in panels a, c, e, and g). (i) COX activities in the lysates of leg muscles and livers from three 2-month-old wild-type and TP<sup>−/−</sup> mice were measured. (j and k) Southern blot (j) and PCR (k) analyses of mtDNA. The total DNAs from the muscles of wild-type mice (lanes 1 and 2), TP<sup>−/−</sup> UP<sup>−/−</sup> mice (lanes 3 and 4), and thymidine-fed (dThd+) mice (wild type, lanes 5 and 6; TP<sup>−/−</sup> UP<sup>−/−</sup>, lanes 7 and 8) were tested to measure the amount of mtDNA.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item "
|
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|
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|
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data-slide-index="4"
|
||
data-label-slug="fig-5">
|
||
<a class="figure-link"
|
||
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|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-4"
|
||
role="button"
|
||
data-image-width="731"
|
||
data-image-height="963"
|
||
data-image-alt="FIG. 5."
|
||
data-pmc-id="PMC139774"
|
||
data-figure-id="f5">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-4"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a90/139774/1f81ad5312ca/mb1420311005.gif"
|
||
alt="FIG. 5." />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="731">
|
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|
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|
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|
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|
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|
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|
||
|
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|
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|
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|
||
<strong class="figure-label">
|
||
<p> FIG. 5. </p>
|
||
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|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Abnormalities of the brains as… </p></div>
|
||
|
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|
||
|
||
|
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|
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|
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|
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
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|
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|
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|
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|
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|
||
|
||
<strong class="figure-label">
|
||
<p> FIG. 5. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Abnormalities of the brains as shown by MRI and electron micrographic studies. In… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
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<figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
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|
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|
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|
||
|
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|
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|
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<strong class="figure-label">
|
||
FIG. 5.
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">Abnormalities of the brains as shown by MRI and electron micrographic studies. In the magnetic resonance images, the T<sub>2</sub> maps at 9.4 T at the level of lateral ventricles in wild-type (a) and TP<sup>−/−</sup> UP<sup>−/−</sup> (b and c) mice are shown. The gray scale for T<sub>2</sub> maps ranges from 0 to 80 ms. (d to f) Light microscopic sections of the brains from the wild-type and TP<sup>−/−</sup> UP<sup>−/−</sup> mice brain were examined by toluidine blue (TB) staining. (g to i) Ultrastructures of myelinated fibers as viewed by electron microscopy (EM). The enlarged myelinated fibers were conspicuous in TP<sup>−/−</sup> UP<sup>−/−</sup> mouse brains (see panels e, f, h, and i). Magnification, ×2,000. (j and k) Southern blot (j) and PCR (k) analyses of mtDNA. The total DNAs from the muscles of wild-type mice (lanes 1 and 2), TP<sup>−/−</sup> UP <sup>−/−</sup> mice (lanes 3 and 4), and thymidine-fed (dThd<sup>+</sup>) mice (wild type, lanes 5 and 6; TP<sup>−/−</sup> UP<sup>−/−</sup>, lanes 7 and 8) were tested to measure the amount of mtDNA.</div>
|
||
|
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|
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|
||
|
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</figcaption>
|
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|
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|
||
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|
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data-label-slug="fig-6">
|
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|
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|
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itemprop="contentUrl"
|
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aria-describedby="figure-caption-5"
|
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role="button"
|
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data-image-width="800"
|
||
data-image-height="343"
|
||
data-image-alt="FIG. 6."
|
||
data-pmc-id="PMC139774"
|
||
data-figure-id="f6">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-5"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a90/139774/b588aba3fb9c/mb1420311006.gif"
|
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alt="FIG. 6." />
|
||
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|
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|
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<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="800">
|
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|
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|
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|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIG. 6. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> The <i> TP </i> gene overlaps with… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
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|
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
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|
||
|
||
|
||
|
||
|
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<strong class="figure-label">
|
||
<p> FIG. 6. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> The <i> TP </i> gene overlaps with the <i> SCO2 </i> gene. (a) Chromosomal positions of the… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
FIG. 6.
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">The <i>TP</i> gene overlaps with the <i>SCO2</i> gene. (a) Chromosomal positions of the human <i>TP</i> (NM_001953) and human <i>SCO2</i> (XM_017992) genes. The best match of these genes determined by a BLAST search against the human genome sequence was a chromosome 22 working draft sequence segment (HS22_11683). The <i>TP</i> gene lies between positions 45508430 and 45504150, and the <i>SCO2</i> gene lies between positions 45503950 and 45501950 within chromosome 22q13.33. (b) Schematic diagram of the mouse <i>TP</i> and <i>SCO2</i> gene structures. Schematic representation of the murine <i>TP</i> gene (top), <i>TP</i> cDNA (middle), and murine <i>SCO2</i> cDNA (bottom). The coding regions of both cDNAs are shown as black boxes, and noncoding regions are shown as white boxes. The cDNA sequence of <i>SCO2</i> shares exons 9 and 10 of <i>TP</i>, indicated as white boxes (noncoding region) and a black box (coding region). In addition to these sequences, <i>SCO2</i> cDNA has a unique sequence in the 5′-noncoding region as indicated by a gray box.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
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|
||
|
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</figure>
|
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|
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</div>
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Carrozzo, R., M. Hirano, B. Fromenty, C. Casali, F. M. Santorelli, E. Bonilla, S. DiMauro, E. A. Schon, and A. F. Miranda. 1998. Multiple mtDNA deletions features in autosomal dominant and recessive diseases suggest distinct pathogeneses. Neurology 50:99-106.
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Mice"
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aria-expanded="false"
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Mice
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</button><div id="keyword-actions-mesh-terms-7"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
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aria-label="Dropdown menu for keyword Mice"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Mice%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Mice%22%5BMeSH%5D&sort=date&sort_order=desc"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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Mice, Knockout
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aria-label="Dropdown menu for keyword Mice, Knockout"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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Phenotype
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</button><div id="keyword-actions-mesh-terms-12"
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|
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Thymidine Phosphorylase / genetics
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Thymidine Phosphorylase / physiology
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Uridine Phosphorylase / deficiency*
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Search in PubMed
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