INT174653

Context Info Confidence 0.70 First Reported 2003 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 15 Total Number 16 Disease Relevance 12.06 Pain Relevance 1.93

cytosol (MEFV) cytoskeleton (MEFV) nucleus (MEFV) intracellular (MEFV) cytoplasm (MEFV)

Anatomy Link Frequency blood 1 arm 1 alimentary canal 1 SH3 1 neutrophils 1 MEFV (Homo sapiens)

Pain Link Frequency Relevance Heat Inflammation 576 100.00 Bile 8 100.00 Inflammatory stimuli 2 99.36 Inflammatory mediators 2 99.28 Pain 52 90.68 Arthritis 22 90.52 abdominal pain 22 88.12 Inflammatory response 10 51.36 cva 6 5.00 Angina 4 5.00

Disease Link Frequency Relevance Heat Fever 904 100.00 INFLAMMATION 590 100.00 Disease 362 100.00 Familial Mediterranean Fever 132 100.00 Convulsion 4 99.50 Pleurisy 6 98.64 Synovitis 6 98.08 Peritonitis 42 97.64 Diarrhoea 24 97.58 Vomiting 20 97.30

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Unsurprisingly, pyrin is found in large quantities in neutrophils and released in response to inflammatory stimuli.

Localization (released) of pyrin in neutrophils associated with inflammatory stimuli

1) Confidence 0.70 Published 2003 Journal BMC Nephrol Section Body Doc Link PMC194618 Disease Relevance 1.27 Pain Relevance 0.32

This region might also be a PEST phosphatase interaction surface, since pyrin and PEST phosphatase are thought to bind to the same region of PSTPIP1 and the PAPA mutations increase affinity for pyrin while decreasing affinity for PEST phophatases [5].

Localization (phosphatase) of pyrin

2) Confidence 0.69 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

Finally, we demonstrate that pyrin can recruit PSTPIP1 into aggregations (specks) of ASC, another pyrin binding protein.

Localization (recruit) of pyrin

3) Confidence 0.69 Published 2009 Journal PLoS ONE Section Abstract Doc Link PMC2702820 Disease Relevance 0.67 Pain Relevance 0.03

It was not possible to simultaneously image both pyrin and PSTPIP1 in human cells since both primary antibodies were generated in rabbits.

Localization (image) of pyrin

4) Confidence 0.69 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

The gene locus responsible for FMF was identified in 1992 and localized to the short arm of chromosome 16.

Localization (localized) of FMF in arm associated with fever

5) Confidence 0.65 Published 2003 Journal BMC Nephrol Section Abstract Doc Link PMC194618 Disease Relevance 1.63 Pain Relevance 0.13

In this case, pyrin is localized in 100% of specks, but PSTPIP1 is never localized in specks (Figure 9Q–S).

Localization (localized) of pyrin

6) Confidence 0.64 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.07 Pain Relevance 0

This is totally the reverse in other cases, as Southeastern Turkey, where the presence of a MEFV mutation is obligatory to diagnose FMF.

Localization (diagnose) of FMF associated with familial mediterranean fever and fever

7) Confidence 0.63 Published 2010 Journal The Open Rheumatology Journal Section Body Doc Link PMC2825617 Disease Relevance 1.07 Pain Relevance 0

415 of 1100 patients suspected as FMF were diagnosed as having FMF according to Yalc?

Localization (suspected) of FMF associated with familial mediterranean fever

8) Confidence 0.63 Published 2010 Journal The Open Rheumatology Journal Section Body Doc Link PMC2825617 Disease Relevance 1.09 Pain Relevance 0.22

We found that the PAPA-causing mutations, A230T and E250Q (Figure 6S–X), were reticularized by pyrin in a manner similar to that seen with wildtype PSTPIP1.

Localization (reticularized) of pyrin

9) Confidence 0.60 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.16 Pain Relevance 0

Figure 4F–H shows that the filaments formed by PSTPIP1(-SH3) effectively recruited full length pyrin.

Localization (recruited) of pyrin in SH3

10) Confidence 0.60 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0 Pain Relevance 0

If this is the case, then pyrin and ASC should only co-localize in the presence of PSTPIP1.

Localization (localize) of pyrin

11) Confidence 0.56 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.05 Pain Relevance 0

In this case, pyrin is localized in 100% of specks, but PSTPIP1 is never localized in specks (Figure 9Q–S).

Localization (localized) of pyrin

12) Confidence 0.56 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2702820 Disease Relevance 0.08 Pain Relevance 0

He now argued that puerperal fever could take any one of a number of different forms, which he organized into a complex classification, and that some of these were caused by inflammation—usually brought on by a plethora.83

Localization (take) of puerperal fever associated with inflammation and fever

13) Confidence 0.09 Published 2005 Journal Medical History Section Body Doc Link PMC1088248 Disease Relevance 1.41 Pain Relevance 0.28

In his Essays on the puerperal fever and on puerperal convulsions of 1768, he argued that puerperal fever began as an inflammatory condition, but progressed to a putrid disease after “some days”.

Localization (disease) of puerperal fever associated with convulsion, inflammation, disease and fever

14) Confidence 0.09 Published 2005 Journal Medical History Section Body Doc Link PMC1088248 Disease Relevance 1.49 Pain Relevance 0.12

Butter saw all fevers as disorders of the “first passages” (that is, the alimentary canal)102 whilst Walsh argued that puerperal fever was essentially a “synochus”—a disease of debility rather than excitability or inflammation.103

Localization (disease) of puerperal fever in alimentary canal associated with inflammation, disease and fever

15) Confidence 0.09 Published 2005 Journal Medical History Section Body Doc Link PMC1088248 Disease Relevance 1.96 Pain Relevance 0.46

As pressure was released from the aorta, the main arteries and the small abdominal vessels, blood would “rush into those vessels with a force superior to their resistance, and by putting them violently on the stretch, may occasion pain, inflammation and fever”.56 This occurred most readily in the omentum and intestines where the blood vessels were “numerous and most yielding”.57 Along with the local inflammation of the abdominal viscera, the diversion of a large volume of blood into the lower abdomen caused deficiency elsewhere, particularly in the heart and brain, which was rapidly followed by an over-compensation and the pooling of blood in these organs once more, accompanied by “anxiety and oppression at the breast and praecordia”.58 The “cold fit” which followed was caused by a draining of blood from the extremities, and the vomiting and diarrhoea which may accompany this were the result of a pooling of blood in the “vena portae ventralis”, leading to the excessive secretion of bile.59 Leake's description of the effects of puerperal fever offers a vivid account of mechanistic and hydraulic movements of blood within the circulatory system, redolent of an almost tidal sense of blood washing rapidly into and out of the small vessels, creating alternately heat and cold, pain and relaxation.

Localization (secretion) of puerperal fever in blood associated with pain, bile, diarrhoea, inflammation, vomiting, anxiety disorder and fever

16) Confidence 0.09 Published 2005 Journal Medical History Section Body Doc Link PMC1088248 Disease Relevance 1.12 Pain Relevance 0.37

General Comments

This test has worked.