Talk:Protein C

Effectiveness of APC in treating sepsis

The comment about activated protein c being effective in septic patients with an APACHEII score < 25 is inaccurate. The ADDRESS trial was stopped early because 28day mortality in such patients was worse (not statistically significant) in those receiving activated protein c compared to placebo. Furthermore, subgroup analyses of PROWESS and ENHANCE both support this finding. PROWESS concluded that activated protein c was effective only in those with APACHEII scores > 25, though these results are debatable. A meta-analysis of PROWESS and ADDRESS data by J. Friedrich (NEJM 2006;354(1):94-96.) suggests that activated protein c is ineffective even in those with severe sepsis (i.e. APACHEII score > 25 or multiple organ system failure). As such, many would debate that activated protein c has yet to demonstrate conclusively its worth in sepsis. —The preceding unsigned comment was added by Daleyc78 (talk • contribs) . --Daleyc78 12:59, 13 July 2006 (UTC)

Thrombomodulin?

Isn't protein c activated by thrombomodulin, not thrombin?128.253.178.201 20:48, 13 May 2007 (UTC)brook

Thrombomodulin is a cofactor of thrombin in the activation of protein c. --Franklinjefferson (talk) 01:37, 24 May 2009 (UTC)

WikiProject class rating

This article was automatically assessed because at least one WikiProject had rated the article as start, and the rating on other projects was brought up to start class. BetacommandBot 16:30, 10 November 2007 (UTC)

Citation format

Rmrfstar, thank you for all your hard work in rewriting this article. It is a major improvement!

Below is my reasoning for the citation format that I tried to introduce in this article. Using List-defined references:

... can help separate large reftags with long cite entries from the ordinary text, making it easier to read and to edit.

Many of the references are cited multiple times within the text so that the text and the corresponding citations are already often separated from each other. Moving all the citation templates to the {{reflist}} template makes the document less cluttered and better organized. Also this syntax is compatible with vertical formatting of the templates as I introduced in this edit. So, I don't understand what about this syntax is difficult to read. If anything IMHO, this syntax makes underlying text easier to read and to maintain.

Finally, if you haven't seen this yet, please check out User:Diberri's Wikipedia template filling tool (instructions). Given a PubMed ID, one can quickly produce a full citation that can be copied and pasted into a Wikipedia article. In addition, this tool will add PMID, DOI, and PMC parameters that assist users in quickly finding the full article as well as helping bots such as Citation bot maintain these citations. These citation parameters were included in a previous version of this article but now have been removed. Boghog (talk) 18:36, 13 September 2010 (UTC)

OK, now I know about list-defined references. The problem wasn't that my way was objectively any easier to read. Rather, I was in the middle of working heavily on the article, so every little change seriously confused my thinking. I have no objection to switching conventions; it was just very disconcerting right then. For instance, even the (very reasonable) changes you made to the names of each reference messed me up, as I had not memorised the year of each publication, and I thus couldn't write in-line citations as easily as when the year wasn't included. Also there were little things such as when I would intentionally keep the references inconsistently formatted for a few hours so that I would know which I had already perused. When you came in and standardised them, I had lost track of my progress. What do you say I take a little bit more time filling out the article, and then, when all of the major expansion is done, we make the wikisyntax pretty? Also, I do all of my citations with Zotero, and I have a whole system worked out. When I'm done, we can use that tool to add all of those great blue links... Also, sorry if I sounded snappy on your talk page: I was just very frustrated by having to deal with all of that material and edits I didn't understand. -- Rmrfstar (talk) 03:04, 14 September 2010 (UTC)

OK, no problem. I will hold off further edits until you are finished with your revisions. Cheers. Boghog (talk) 05:06, 14 September 2010 (UTC)

*Phew*. I'm done with the major additions, for now. You're welcome to change the syntax, etc. as you wish. I think I'll put the article up for peer review soon, too... What do you think of that? Let's say I want to get this article to FA status. Where do you think it stands? -- Rmrfstar (talk) 22:10, 16 September 2010 (UTC)

You have done an incredible job of improving and expanding this article. Excellent work! I think it may be close to FA status, but I think it would be better to start with a GA review (edit conflict: as I see that you have already initiated). Cheers. Boghog (talk) 18:45, 17 September 2010 (UTC)

Thank you very much. I'm glad you think so. Thanks for your contributions also. I can be pretty sloppy with wikilinking. And thanks for dealing with my quirks of personality; I'm very much used to working alone. -- Rmrfstar (talk) 18:59, 17 September 2010 (UTC)

GA Review

This review is transcluded from Talk:Protein C/GA1. The edit link for this section can be used to add comments to the review.

Reviewer: Sasata (talk) 17:50, 27 November 2010 (UTC)

Hi, I've signed up for the review. I read the comments on the talk page that this was headed for FAC? If so, I can gear my commentary for that (which won't, of course, affect the GA assessment). Anyway, I'll have some notes up in a few days. Sasata (talk) 17:50, 27 November 2010 (UTC)

Comments, questions and suggestions from 1st read-through for prose/jargon/MOS compliance. Sasata (talk) 07:09, 2 December 2010 (UTC)

• according to WP:lead, the lead is to be a summary of the article, and there should not be any information here that's not also in the main article text (like, for example, the alternate name blood coagulation factor). Also, there shouldn't really be any need to cite info here if it's already cited later in the article. Lead citations are typically reserved for quotations, or for controversial statements that you think might be challenged, but I don't see that applying here (except for perhaps the final two sentences about the drug effects of drotrecogin).

The lead is not *just* a summary; it is also an introduction. And while it should not include lots of important information not found in the article proper, I think alternative names for the protein are actually very appropriate for the first line, yet they would be silly and redundant anywhere else. With regard to citations in the lede, I don't think there is a true consensus across Wikipedia, and I don't see a reason why the lede shouldn't be cited exactly like the rest of the article. If, for example, someone wants to know the source of a particular statement, he shouldn't have to find its repeat in the rest of the article before seeing said source.

Fair enough. Sasata (talk) 06:37, 2 January 2011 (UTC)

• suggest linking permeability to vascular permeability

Done.

• "…in humans and other animals." In the article I can't see reference to animals other than humans and rodents, so is "mammals" more accurate?.

It's hard to say, because the proteins may be different in different species. I think vaguer is better, because "mammals" is exclusive, while "animals" is much less so.

According to HomoloGene: 37288, protein C is found in at least one bird, Gallus gallus (chickens), hence "animals" is more accurate than "mammals". (Note: the HomoloGene link is found in the Identifiers/External IDs section of the protein infobox).

• link serine, residue (but perhaps reword to avoid consecutive links), active site, leukocyte

Done.

• the EC number is a bit of jargon that shouldn't be in the lead… remember the lead should be friendly and inviting, readable by a "bright high school student"; save the nitty gritty details for later

Right. I just took it out. It's in the infobox anyway.

• should insert a non-breaking space in "protein C" throughout article to prevent unsightly line wraps; also between numbers and units later on

Done.

• "However, recent studies question the drug's overall benefit" How recent? "Recent" is a word to be avoided, as it is vague and becomes outdated.

Replaced with "Later studies". This should satisfy, I think.

• from the figure caption: "Tertiary structure of Gla-domainless human activated protein C" Gla-domainless is heavy jargon, I doubt few average readers will know the three-letter codes for amino acids… would it be so bad if it was just left out (interested readers will click the image for more details, although I see the image description is somewhat lacking)

Hmm. The problem is that I'd have to modify the info box directly, and it could theoretically be used in another (more technical) article.

A link to Gla domain has been added to the figure caption.

• "Protein C's anticoagulant role in the human body was first noted by Seegers et al. in 1960" Sounds like a seminal paper… why not cite it?

Now cited.

• "In 1982, a family study by Griffin et al." clarify "family study"
• "cDNA cloning of protein C was first performed in 1984 by Beckmann et al." link cDNA cloning, and reword the unnecessary passive voice
• "In 1987 a seminal experiment was performed (Taylor et al.)" Seems inelegant to use passive voice and give author parenthetically.
• coagulopathy should be linked here rather than (or in addition to) several sections later
• I'll just mention a couple more examples of passive voice that could easily be reworded to make the prose stronger, and leave you to go through the rest of the article to fix similar instances.

• "In 1994, the relatively common genetic mutation which produces Factor VLeiden was noted (Bertina et al.)."
• "Two years later, Gla-domainless APC was imaged"

• please clarify the Gla-domainless APC somewhere; was it not crystallizable with the Gla domain?

I more precisely defined what Gla-domainless APC is and explained why the Gla-domain was removed from the protein in this edit.

• "Beginning with the PROWESS clinical trial of 2001" Seems odd that this PROWESS is mentioned here but not explained until later… I'm stuck wondering what it means, not knowing I have to wait until later to find out.

Citation to the first mention of the PROWESS trial has been added. In addition, what PROWESS stands for (recombinant Human Activated PROtein C Worldwide Evaluation in Severe Sepsis) has been added to the citation.

• "protein C activates PAR-1" acronyms should be spelled out on first usage (other instances throughout article, e.g. IL-1β, TNF-α, GAG domain)

Done

• link glycoprotein; I think being a glycoprotein is a lead-worthy fact

Done.

• prothrombin should be linked here, not later; link Factor VII, Factor IX, etc.

Done

• add citation for end of 1st paragraph of "Synthesis, structure and activation" section
• "and EPRC speeds up activation" -> EPCR

Done.

• phospholipids not linked at 1st occurrence

Done.

• link cytoprotection

Done.

• "Concentration of protein C increases until six months" missing initial "The"?

Yup.

• "are the specific chemical reactions which control the level of expression" which->that

Good.

• "Which function protein C performs depends on whether or not APC remains bound to EPCR after it is activated. The anticoagulative effects of APC occur when it does not." should combine these with a semicolon, I think (else second sentence is grammatically dubious)

Done.

• link up/downregulation, anticoagulation

Done. I linked the first use of "anticoagulant" not in the lede. Is there somewhere specific you think it should be wikilinked again?

Nope, good now. Sasata (talk)

• "These proteins which APC inactivates" which->that (which generally follows a comma)

Sure.

• "APC has anti-inflammatory effects on endothelial cells (cells on the interior surface of blood vessels) and leukocytes (white blood cells)." Don't think the parenthetical glosses are required here, we've been told already.

Sure.

• link endotoxin

Done.

• "Around 5% of APC resistance are not associated" are->is?

"5%" means "5 for every 100": that's a plural subject.

• link autoantibody

Done.

• "functions.[4]:33Studies " needs a space

Done.

• "Drotrecogin alfa-activated is a recombinant form" recombinant DNA is linked twice in this sentence.

Done.

• "It is marketed as Xigris by Eli Lilly and Company." In the lead, it was "Eli Lilly and Co." (should be consistent)

Done.

• link randomized, double-blind, placebo-controlled, confidence interval, ng

Done.

• "infusion related" hyphenate

Done.

• For FAC (not important for GA), you'll want to make sure that the display of journal titles is consistently abbreviated (e.g., there's a Journal of Biological Chemistry in there now, and a Semin Vasc Med that doesn't have periods); also, clean up (remove) the empty template parameters as well. Otherwise, the refs look fine. Sasata (talk) 06:46, 2 January 2011 (UTC)

Done

After the above comments are addressed, I'll read through the article again and check citation/sources more carefully. Sasata (talk) 07:09, 2 December 2010 (UTC)

Hi and thanks for the review. I am indeed considering WP:FAC. -- Rmrfstar (talk) 15:22, 7 December 2010 (UTC)

I don't think there's any need to keep this in GAR limbo any longer, my remaining suggestions are minor and I'll sure they'll be dealt with on the workup to FAC. I spot-checked a few citations and everything seemed ok; all images have appropriate licenses; all other GA criteria are met or exceeded. Thank you for an excellent contribution to Wikipedia, and good luck with the FAC! Sasata (talk) 01:41, 4 January 2011 (UTC)

Residue numbering

There is currently some inconsistency in the residue numbering in the "synthesis, structure and activation" section. The numbering in the first paragraph is based on the full length protein that includes the N-terminal signal peptide. The numbering in the second paragraph is reset so that the new N-terminus produced after cleavage of the signal peptide is now designated residue #1. I think is would be less confusing if a consistent numbering scheme based on the full length protein is used throughout (see the "sequence annotation" section of UniProt entry P04070 and File:Protein_C_1D_schematic.png). For example, the catalytic triad of the serine protease would be changed from 211, 257, and 360 to 253, 299, and 402. Does anyone have an objection if I make this change? Boghog (talk) 18:21, 2 January 2011 (UTC)

I have no objection. Indeed, I support the change. -- Rmrfstar (talk) 15:50, 3 January 2011 (UTC)

 Done Thanks for your support! I have gone ahead and made the change. Boghog (talk) 21:15, 3 January 2011 (UTC)

Reference page numbering

Should we consider changing the {{rp}} numbers to the page of the article, rather than the journal? At the moment having a four digit number after a reference tag looks rather ugly. For example, for the first citation in the article, I would suggest changing 6822 > 1 and for the one after the first use of reference 4, 35 would be changed to 3. This would still allow the reader to easily find the information on the page if they wanted to but would make the article a little prettier. SmartSE (talk) 16:25, 5 January 2011 (UTC)

I am guilty of changing the page number in the other direction (e.g., 1 > 6822) based on the idea that if someone went back to the source, it would be quicker to find the exact page if the full page number were specified. When I made this change, there were not so many in-line citations that specified page numbers and I agree that it now may have gotten out of hand. In an attempt to improve the aesthetics of the article, I have added page number parameters to the {{rp}} templates in this edit so that page number are now surrounded by parenthesis. Does this look any better? Boghog (talk) 16:39, 5 January 2011 (UTC)

I must say, I think it looked better with the colons. I'm also inclined to believe that using the page of the journal is better; because then we don't have to count ourselves (and make errors). It's easier to use (as Boghog notes). It's also more standard (the convention being used universally by the journals themselves). -- Rmrfstar (talk) 19:49, 5 January 2011 (UTC)

I don't have any strong opinions one way or the other on whether the parentheses around the page numbers improves the aesthetics so I have taken them back out. In case anyone is coming late to this discussion and is curious how they look, a version that includes the parentheses may be found here.. Boghog (talk) 09:11, 8 January 2011 (UTC)

This review not reflected

Martí-Carvajal, AJ (2011 Apr 13). "Human recombinant activated protein C for severe sepsis". Cochrane database of systematic reviews (Online) (4): CD004388. PMID 21491390. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help) Doc James (talk · contribs · email) 14:21, 30 August 2011 (UTC)

how can protein C be an autoprothrombin if it's an anticoagulant and thrombin is procoagulant?

the article indicates that it is an autoprothrombin, but that is incorrect. Protein C is by nature an anticoagulant, so it can't be a prothrombin since thrombin is a procoagulant. The rest of article states that it functions as a natural anticoagulant, which is correct, but it doesn't mention it's primary roll with PAI-1 (plasminogen activating inhibitor-1). It inhibits PAI-1 which disinhibits tPA which allows dissolution of a formed clot.71.61.221.173 (talk) 01:45, 1 May 2013 (UTC)

Engineering APC for other clinical uses

Blood doi:10.1182/blood-2015-02-355974 JFW | T@lk 09:41, 8 May 2015 (UTC)

and 3K3A-APC "being developed to treat stroke patients could also prevent Alzheimer's disease." Stroke drug may also prevent Alzheimer's disease, study says 2019 - Rod57 (talk) 12:12, 23 September 2019 (UTC)