INT209019

Context Info Confidence 0.33 First Reported 2007 Last Reported 2008 Negated 0 Speculated 0 Reported most in Body Documents 12 Total Number 13 Disease Relevance 4.33 Pain Relevance 2.33

transport (Slc11a1) plasma membrane (Slc11a1) lysosome (Slc11a1)

Anatomy Link Frequency bladder 4 plug 2 vesicles 2 urinary bladder 1 Slc11a1 (Mus musculus)

Pain Link Frequency Relevance Heat cytokine 399 100.00 Inflammation 356 99.56 chemokine 99 98.24 Inflammatory stimuli 42 92.88 Inflammatory response 44 68.84 ketamine 2 67.52 anesthesia 2 65.36 Eae 7 61.68 imagery 14 50.76 interstitial cystitis 29 5.00

Disease Link Frequency Relevance Heat INFLAMMATION 442 99.56 Cystitis 23 96.04 Overactive Bladder 138 95.28 Cancer 278 94.00 Bladder Cancer 117 94.00 Hypersensitivity 31 92.88 Sprains And Strains 17 90.24 Injury 21 87.80 Stress Incontinence 2 72.68 Granuloma 46 50.20

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Mice were randomly assigned to either a control group (receiving PBS) or two treatment groups (receiving BCG or rBCG-S1PT).

Localization (receiving) of rBCG

1) Confidence 0.33 Published 2008 Journal J Exp Clin Cancer Res Section Body Doc Link PMC2647907 Disease Relevance 0.60 Pain Relevance 0.13

Mice were randomly assigned to either a control group (receiving PBS) or two treatment groups (receiving BCG or rBCG-S1PT).

Localization (receiving) of BCG

2) Confidence 0.29 Published 2008 Journal J Exp Clin Cancer Res Section Body Doc Link PMC2647907 Disease Relevance 0.60 Pain Relevance 0.13

Others have found that BCG also releases IL-10 from the mouse bladder [37].

Localization (releases) of BCG in bladder

3) Confidence 0.25 Published 2007 Journal BMC Immunol Section Body Doc Link PMC1891101 Disease Relevance 0.59 Pain Relevance 0.37

BCG-induced cytokine release

Localization (release) of BCG associated with cytokine

4) Confidence 0.22 Published 2007 Journal BMC Immunol Section Body Doc Link PMC1891101 Disease Relevance 0.45 Pain Relevance 0.54

Among the cytokines released by BCG, attention has been paid to IL-6 because its urinary levels are correlated with symptom scores in cystitis [50,51] and are reduced by BCG therapy in bladder cancer [52].

Localization (released) of BCG in bladder associated with bladder cancer, cystitis and cytokine

5) Confidence 0.20 Published 2007 Journal BMC Immunol Section Body Doc Link PMC1891101 Disease Relevance 0.43 Pain Relevance 0.49

In this first manuscript, we propose to determine whether the intact mouse urinary bladder takes up BCG, the time-dependent morphological alterations, and urinary cytokine release in response to intravesical BCG.

Localization (release) of BCG in urinary bladder associated with cytokine

6) Confidence 0.19 Published 2007 Journal BMC Immunol Section Body Doc Link PMC1891101 Disease Relevance 0.63 Pain Relevance 0.31

Co-localization of BCG-GFP with LRG47 in the mouse bladder urothelium

Localization (localization) of BCG in bladder

7) Confidence 0.19 Published 2008 Journal BMC Immunol Section Body Doc Link PMC2262873 Disease Relevance 0 Pain Relevance 0

For co-localization of BCG-GFP and LRG47-Rhodamine, pictures were converted to 8-bit gray scale images (fluorescence intensity range: 0 < 255) using Image J software [23] and the analysis was performed with the co-localization-finder plug-in [24].

Localization (localization) of BCG in plug

8) Confidence 0.19 Published 2008 Journal BMC Immunol Section Body Doc Link PMC2262873 Disease Relevance 0 Pain Relevance 0.03

Next, the co-localization of BCG-GFP and LRG47-Rhodamine was performed by converting the Figures 13B and 13C to 8-bit gray scale images (fluorescence intensity range: 0 < 255) using Image J software [23], assigned as red and green channels, and the analysis was performed with the co-localization-finder plug-in [24].

Localization (localization) of BCG in plug

9) Confidence 0.16 Published 2008 Journal BMC Immunol Section Body Doc Link PMC2262873 Disease Relevance 0 Pain Relevance 0

Next, we used fluorescence immunohistochemistry to demonstrate that, in our laboratory conditions, instillation of BCG-GFP does not cause any microscopic extravasation of BCG or cause artifacts, including forcing bacteria into the urothelium.

Localization (extravasation) of BCG

10) Confidence 0.15 Published 2008 Journal BMC Immunol Section Body Doc Link PMC2262873 Disease Relevance 0.15 Pain Relevance 0.03

Although this finding potentially linking BCG to axonal guidance is unique, activation of small GTPases genes by intravesical instillation of BCG into the mouse bladder was just demonstrated by our laboratory [25] and we extended the results into the present work, indicating that acute BCG does co-localize with LRG47 vesicles.

Localization (localize) of BCG in vesicles

11) Confidence 0.15 Published 2008 Journal BMC Immunol Section Body Doc Link PMC2262873 Disease Relevance 0.13 Pain Relevance 0.03

In the merged picture, presented in Figure 13D, it can be appreciated that most of background fluorescence coincides with DAPI staining (blue) whereas the BCG-GFP is co-localized in vesicles positives for LRG-47 (yellow).

Localization (localized) of BCG in vesicles

12) Confidence 0.15 Published 2008 Journal BMC Immunol Section Body Doc Link PMC2262873 Disease Relevance 0 Pain Relevance 0

For this purpose, we used the C57BL/6 mice because our previous work already defined the time-course of bladder inflammation and urinary cytokine release in response to intravesical instillation of BCG, TNF-?

Localization (release) of BCG in bladder associated with inflammation and cytokine

13) Confidence 0.06 Published 2008 Journal BMC Immunol Section Body Doc Link PMC2262873 Disease Relevance 0.75 Pain Relevance 0.27

General Comments

This test has worked.