Input: Reduced adiponectin expression after high - fat diet is associated with selective up - regulation of ALDH1A1 and further retinoic acid receptor signaling in adipose tissue . Adiponectin is an adipocyte - derived adipokine with potent antidiabetic , anti - inflammatory , and antiatherogenic activity . Long - term , high - fat diet results in gain of body weight , adiposity , further inflammatory - based cardiovascular diseases , and reduced adiponectin secretion . Vitamin A derivatives / retinoids are involved in several of these processes , which mainly take place in white adipose tissue ( WAT ) . In this study , we examined adiponectin expression as a function of dietary high - fat and high - vitamin A conditions in mice . A decrease of adiponectin expression in addition to an up - regulation of aldehyde dehydrogenase A1 ( ALDH1A1 ) , retinoid signaling , and retinoic acid response element signaling was selectively observed in WAT of mice fed a normal - vitamin A , high - fat diet . Reduced adiponectin expression in WAT was also observed in mice fed a high - vitamin A diet . Adipocyte cell culture revealed that endogenous and synthetic retinoic acid receptor ( RAR ) a - and RARg - selective agonists , as well as a synthetic retinoid X receptor agonist , efficiently reduced adiponectin expression , whereas ALDH1A1 expression only increased with RAR agonists . We conclude that reduced adiponectin expression under high - fat dietary conditions is dependent on 1 ) increased ALDH1A1 expression in adipocytes , which does not increase all - trans - retinoic acid levels ; 2 ) further RAR ligand - induced , WAT - selective , increased retinoic acid response element - mediated signaling ; and 3 ) RAR ligand - dependent reduction of adiponectin expression . - Landrier , J . - F . , Kasiri , E . , Karkeni , E . , Mihaly , J . , Beke , G . , Weiss , K . , Lucas , R . , Aydemir , G . , Salles , J . , Walrand , S . , de Lera , A . R . , Ruhl , R . Reduced adiponectin expression after high - fat diet is associated with selective up - regulation of ALDH1A1 and further retinoic acid receptor signaling in adipose tissue .

adiponectin

retinoic acid receptor

Adiponectin

adipokine

adiponectin

adiponectin

adiponectin

aldehyde dehydrogenase A1

adiponectin

retinoic acid receptor ( RAR ) a

RARg

retinoid X receptor

adiponectin

RAR

adiponectin

RAR

RAR

adiponectin

adiponectin

retinoic acid receptor

inflammatory

adiposity

inflammatory

cardiovascular diseases

Vitamin A

retinoids

vitamin A

retinoic acid

vitamin A

vitamin A

retinoic acid

retinoic acid

mice

mice

mice

retinoic acid receptor

retinoic acid

retinoic acid receptor

retinoic acid

retinoic acid receptor

retinoic acid

retinoid X receptor

retinoic acid

retinoid X receptor

retinoic acid

retinoid X receptor

retinoic acid

RAR

retinoic acid

RAR

retinoic acid

RAR

retinoic acid

RAR

retinoic acid

RAR

retinoic acid

RAR

retinoic acid

RAR

retinoic acid

RAR

retinoic acid

RAR

retinoic acid

retinoic acid receptor

retinoic acid

retinoic acid receptor

retinoic acid

retinoic acid receptor

retinoic acid

RARg

retinoic acid

RARg

retinoic acid

RARg

retinoic acid

retinoic acid receptor ( RAR ) a

retinoic acid

retinoic acid receptor ( RAR ) a

retinoic acid

retinoic acid receptor ( RAR ) a

retinoic acid

retinoic acid receptor

retinoid X receptor

RAR

RAR

RAR

retinoic acid receptor

aldehyde dehydrogenase A1

retinoic acid receptor

aldehyde dehydrogenase A1

retinoid X receptor

aldehyde dehydrogenase A1

RAR

aldehyde dehydrogenase A1

RAR

aldehyde dehydrogenase A1

RAR

aldehyde dehydrogenase A1

retinoic acid receptor

retinoic acid receptor

retinoid X receptor

RAR

RAR

RAR

retinoic acid receptor

retinoic acid receptor

retinoid X receptor

RAR

RAR

RAR

retinoic acid receptor

retinoic acid receptor

retinoid X receptor

RAR

RAR

RAR

retinoic acid receptor

retinoic acid receptor

retinoid X receptor

RAR

RAR

RAR

retinoic acid receptor

RARg

aldehyde dehydrogenase A1

RARg

RARg

RARg

RARg

RARg

retinoic acid receptor ( RAR ) a

aldehyde dehydrogenase A1

retinoic acid receptor ( RAR ) a

retinoic acid receptor ( RAR ) a

retinoic acid receptor ( RAR ) a

retinoic acid receptor ( RAR ) a

retinoic acid receptor ( RAR ) a

Vitamin A

vitamin A

vitamin A

vitamin A

aldehyde dehydrogenase A1

Vitamin A

aldehyde dehydrogenase A1

vitamin A

aldehyde dehydrogenase A1

vitamin A

aldehyde dehydrogenase A1

vitamin A

Vitamin A

vitamin A

vitamin A

vitamin A

Vitamin A

vitamin A

vitamin A

vitamin A

Vitamin A

vitamin A

vitamin A

vitamin A

Vitamin A

vitamin A

vitamin A

vitamin A

retinoic acid receptor

adiponectin

retinoic acid receptor

Adiponectin

retinoic acid receptor

adipokine

retinoic acid receptor

adiponectin

retinoic acid receptor

adiponectin

retinoic acid receptor

adiponectin

retinoic acid receptor

adiponectin

retinoic acid receptor

adiponectin

retinoic acid receptor

adiponectin

retinoic acid receptor

adiponectin

retinoic acid receptor

adiponectin

retinoid X receptor

adiponectin

retinoid X receptor

Adiponectin

retinoid X receptor

adipokine

retinoid X receptor

adiponectin

retinoid X receptor

adiponectin

retinoid X receptor

adiponectin

retinoid X receptor

adiponectin

retinoid X receptor

adiponectin

retinoid X receptor

adiponectin

retinoid X receptor

adiponectin

retinoid X receptor

adiponectin

RAR

adiponectin

RAR

Adiponectin

RAR

adipokine

RAR

adiponectin

RAR

adiponectin

RAR

adiponectin

RAR

adiponectin

RAR

adiponectin

RAR

adiponectin

RAR

adiponectin

RAR

adiponectin

RAR

adiponectin

RAR

Adiponectin

RAR

adipokine

RAR

adiponectin

RAR

adiponectin

RAR

adiponectin

RAR

adiponectin

RAR

adiponectin

RAR

adiponectin

RAR

adiponectin

RAR

adiponectin

RAR

adiponectin

RAR

Adiponectin

RAR

adipokine

RAR

adiponectin

RAR

adiponectin

RAR

adiponectin

RAR

adiponectin

RAR

adiponectin

RAR

adiponectin

RAR

adiponectin

RAR

adiponectin

retinoic acid receptor

adiponectin

retinoic acid receptor

Adiponectin

retinoic acid receptor

adipokine

retinoic acid receptor

adiponectin

retinoic acid receptor

adiponectin

retinoic acid receptor

adiponectin

retinoic acid receptor

adiponectin

retinoic acid receptor

adiponectin

retinoic acid receptor

adiponectin

retinoic acid receptor

adiponectin

retinoic acid receptor

adiponectin

RARg

adiponectin

RARg

Adiponectin

RARg

adipokine

RARg

adiponectin

RARg

adiponectin

RARg

adiponectin

RARg

adiponectin

RARg

adiponectin

RARg

adiponectin

RARg

adiponectin

RARg

adiponectin

retinoic acid receptor ( RAR ) a

adiponectin

retinoic acid receptor ( RAR ) a

Adiponectin

retinoic acid receptor ( RAR ) a

adipokine

retinoic acid receptor ( RAR ) a

adiponectin

retinoic acid receptor ( RAR ) a

adiponectin

retinoic acid receptor ( RAR ) a

adiponectin

retinoic acid receptor ( RAR ) a

adiponectin

retinoic acid receptor ( RAR ) a

adiponectin

retinoic acid receptor ( RAR ) a

adiponectin

retinoic acid receptor ( RAR ) a

adiponectin

retinoic acid receptor ( RAR ) a

adiponectin

adiponectin

inflammatory

adiponectin

inflammatory

Adiponectin

inflammatory

Adiponectin

inflammatory

adipokine

inflammatory

adipokine

inflammatory

adiponectin

inflammatory

adiponectin

inflammatory

adiponectin

inflammatory

adiponectin

inflammatory

adiponectin

inflammatory

adiponectin

inflammatory

adiponectin

inflammatory

adiponectin

inflammatory

adiponectin

inflammatory

adiponectin

inflammatory

adiponectin

inflammatory

adiponectin

inflammatory

adiponectin

inflammatory

adiponectin

inflammatory

adiponectin

inflammatory

adiponectin

inflammatory

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

Adiponectin

retinoic acid

Adiponectin

retinoic acid

Adiponectin

retinoic acid

adipokine

retinoic acid

adipokine

retinoic acid

adipokine

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

retinoic acid

adiponectin

adiponectin

aldehyde dehydrogenase A1

adiponectin

adiponectin

adiponectin

adiponectin

Adiponectin

Adiponectin

aldehyde dehydrogenase A1

Adiponectin

Adiponectin

Adiponectin

Adiponectin

adipokine

adipokine

aldehyde dehydrogenase A1

adipokine

adipokine

adipokine

adipokine

adiponectin

adiponectin

aldehyde dehydrogenase A1

adiponectin

adiponectin

adiponectin

adiponectin

adiponectin

adiponectin

aldehyde dehydrogenase A1

adiponectin

adiponectin

adiponectin

adiponectin

adiponectin

adiponectin

aldehyde dehydrogenase A1

adiponectin

adiponectin

adiponectin

adiponectin

adiponectin

adiponectin

aldehyde dehydrogenase A1

adiponectin

adiponectin

adiponectin

adiponectin

adiponectin

adiponectin

aldehyde dehydrogenase A1

adiponectin

adiponectin

adiponectin

adiponectin

adiponectin

adiponectin

aldehyde dehydrogenase A1

adiponectin

adiponectin

adiponectin

adiponectin

adiponectin

adiponectin

aldehyde dehydrogenase A1

adiponectin

adiponectin

adiponectin

adiponectin

adiponectin

adiponectin

aldehyde dehydrogenase A1

adiponectin

adiponectin

adiponectin

adiponectin

adiponectin

Vitamin A

adiponectin

vitamin A

adiponectin

vitamin A

adiponectin

vitamin A

Adiponectin

Vitamin A

Adiponectin

vitamin A

Adiponectin

vitamin A

Adiponectin

vitamin A

adipokine

Vitamin A

adipokine

vitamin A

adipokine

vitamin A

adipokine

vitamin A

adiponectin

Vitamin A

adiponectin

vitamin A

adiponectin

vitamin A

adiponectin

vitamin A

adiponectin

Vitamin A

adiponectin

vitamin A

adiponectin

vitamin A

adiponectin

vitamin A

adiponectin

Vitamin A

adiponectin

vitamin A

adiponectin

vitamin A

adiponectin

vitamin A

adiponectin

Vitamin A

adiponectin

vitamin A

adiponectin

vitamin A

adiponectin

vitamin A

adiponectin

Vitamin A

adiponectin

vitamin A

adiponectin

vitamin A

adiponectin

vitamin A

adiponectin

Vitamin A

adiponectin

vitamin A

adiponectin

vitamin A

adiponectin

vitamin A

adiponectin

Vitamin A

adiponectin

vitamin A

adiponectin

vitamin A

adiponectin

vitamin A

adiponectin

Vitamin A

adiponectin

vitamin A

adiponectin

vitamin A

adiponectin

vitamin A

retinoic acid

Vitamin A

retinoic acid

vitamin A

retinoic acid

vitamin A

retinoic acid

vitamin A

retinoic acid

Vitamin A

retinoic acid

vitamin A

retinoic acid

vitamin A

retinoic acid

vitamin A

retinoic acid

Vitamin A

retinoic acid

vitamin A

retinoic acid

vitamin A

retinoic acid

vitamin A


Input: Arginase 1 deletion in myeloid cells affects the inflammatory response in allergic asthma , but not lung mechanics , in female mice . BACKGROUND : ( Over - ) expression of arginase may limit local availability of arginine for nitric oxide synthesis . We investigated the significance of arginase1 ( ARG1 ) for the development of airway hyperresponsiveness ( AHR ) and lung inflammation in female mice with ovalbumin ( OVA ) - induced allergic asthma . METHODS : Arg1 was ablated in the lung by crossing Arg1 fl / fl and Tie2Cre tg / - mice . OVA sensitization and challenge were conducted , and AHR to methacholine was determined using the Flexivent system . Changes in gene expression , chemokine and cytokine secretion , plasma IgE , and lung histology were quantified using RT - qPCR , ELISA , and immunohistochemistry , respectively . RESULTS : Arg1 ablation had no influence on the development of OVA - induced AHR , but attenuated OVA - induced increases in expression of Arg2 and Nos2 , Slc7a1 , Slc7a2 , and Slc7a7 ( arginine transporters ) , Il4 , Il5 and Il13 ( TH2 - type cytokines ) , Ccl2 and Ccl11 ( chemokines ) , Ifng ( TH1 - type cytokine ) , Clca3 and Muc5ac ( goblet cell markers ) , and OVA - specific IgE . Pulmonary IL - 10 protein content increased , but IL - 4 , IL - 5 , IL - 13 , TNFalpha and IFNgamma content , and lung histopathology , were not affected . Arg1 elimination also decreased number and tightness of correlations between adaptive changes in lung function and inflammatory parameters in OVA / OVA - treated female mice . OVA / OVA - treated female mice mounted a higher OVA - IgE response than males , but the correlation between lung function and inflammation was lower . Arg1 - deficient OVA / OVA - treated females differed from males in a more pronounced decline of arginine - metabolizing and - transporting genes , higher plasma arginine levels , a smaller OVA - specific IgE response , and no improvement of peripheral lung function . CONCLUSION : Complete ablation of Arg1 in the lung affects mRNA abundance of arginine - transporting and - metabolizing genes , and pro - inflammatory genes , but not methacholine responsiveness or accumulation of inflammatory cells .

Arginase 1

arginase

ovalbumin

OVA

OVA

IgE

OVA

OVA

arginine transporters

TH2 - type cytokines

chemokines

Ifng

TH1 - type cytokine

OVA

IgE

IL - 10

IL - 4

IL - 5

IL - 13

TNFalpha

IFNgamma

OVA

OVA

OVA

OVA

OVA

IgE

OVA

OVA

OVA

IgE

inflammatory

asthma

lung inflammation

asthma

inflammatory

inflammation

inflammatory

inflammatory

mice

mice

mice

mice

mice

nitric oxide

methacholine

methacholine

ovalbumin

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

ovalbumin

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

ovalbumin

Ifng

ovalbumin

TH1 - type cytokine

ovalbumin

IFNgamma

OVA

Ifng

OVA

TH1 - type cytokine

OVA

IFNgamma

OVA

Ifng

OVA

TH1 - type cytokine

OVA

IFNgamma

OVA

Ifng

OVA

TH1 - type cytokine

OVA

IFNgamma

OVA

Ifng

OVA

TH1 - type cytokine

OVA

IFNgamma

OVA

Ifng

OVA

TH1 - type cytokine

OVA

IFNgamma

OVA

Ifng

OVA

TH1 - type cytokine

OVA

IFNgamma

OVA

Ifng

OVA

TH1 - type cytokine

OVA

IFNgamma

OVA

Ifng

OVA

TH1 - type cytokine

OVA

IFNgamma

OVA

Ifng

OVA

TH1 - type cytokine

OVA

IFNgamma

OVA

Ifng

OVA

TH1 - type cytokine

OVA

IFNgamma

OVA

Ifng

OVA

TH1 - type cytokine

OVA

IFNgamma

OVA

Ifng

OVA

TH1 - type cytokine

OVA

IFNgamma

OVA

Ifng

OVA

TH1 - type cytokine

OVA

IFNgamma

ovalbumin

ovalbumin

chemokines

OVA

OVA

chemokines

OVA

OVA

chemokines

OVA

OVA

chemokines

OVA

OVA

chemokines

OVA

OVA

chemokines

OVA

OVA

chemokines

OVA

OVA

chemokines

OVA

OVA

chemokines

OVA

OVA

chemokines

OVA

OVA

chemokines

OVA

OVA

chemokines

OVA

OVA

chemokines

OVA

OVA

chemokines

ovalbumin

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

ovalbumin

ovalbumin

TH2 - type cytokines

ovalbumin

IL - 13

OVA

OVA

TH2 - type cytokines

OVA

IL - 13

OVA

OVA

TH2 - type cytokines

OVA

IL - 13

OVA

OVA

TH2 - type cytokines

OVA

IL - 13

OVA

OVA

TH2 - type cytokines

OVA

IL - 13

OVA

OVA

TH2 - type cytokines

OVA

IL - 13

OVA

OVA

TH2 - type cytokines

OVA

IL - 13

OVA

OVA

TH2 - type cytokines

OVA

IL - 13

OVA

OVA

TH2 - type cytokines

OVA

IL - 13

OVA

OVA

TH2 - type cytokines

OVA

IL - 13

OVA

OVA

TH2 - type cytokines

OVA

IL - 13

OVA

OVA

TH2 - type cytokines

OVA

IL - 13

OVA

OVA

TH2 - type cytokines

OVA

IL - 13

OVA

OVA

TH2 - type cytokines

OVA

IL - 13

ovalbumin

ovalbumin

IL - 5

OVA

OVA

IL - 5

OVA

OVA

IL - 5

OVA

OVA

IL - 5

OVA

OVA

IL - 5

OVA

OVA

IL - 5

OVA

OVA

IL - 5

OVA

OVA

IL - 5

OVA

OVA

IL - 5

OVA

OVA

IL - 5

OVA

OVA

IL - 5

OVA

OVA

IL - 5

OVA

OVA

IL - 5

OVA

OVA

IL - 5

ovalbumin

ovalbumin

IL - 4

OVA

OVA

IL - 4

OVA

OVA

IL - 4

OVA

OVA

IL - 4

OVA

OVA

IL - 4

OVA

OVA

IL - 4

OVA

OVA

IL - 4

OVA

OVA

IL - 4

OVA

OVA

IL - 4

OVA

OVA

IL - 4

OVA

OVA

IL - 4

OVA

OVA

IL - 4

OVA

OVA

IL - 4

OVA

OVA

IL - 4

ovalbumin

ovalbumin

arginine transporters

OVA

OVA

arginine transporters

OVA

OVA

arginine transporters

OVA

OVA

arginine transporters

OVA

OVA

arginine transporters

OVA

OVA

arginine transporters

OVA

OVA

arginine transporters

OVA

OVA

arginine transporters

OVA

OVA

arginine transporters

OVA

OVA

arginine transporters

OVA

OVA

arginine transporters

OVA

OVA

arginine transporters

OVA

OVA

arginine transporters

OVA

OVA

arginine transporters

ovalbumin

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

ovalbumin

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

ovalbumin

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

ovalbumin

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

IgE

ovalbumin

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

ovalbumin

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

ovalbumin

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

ovalbumin

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

IgE

OVA

Arginase 1

ovalbumin

Arginase 1

OVA

Arginase 1

OVA

Arginase 1

OVA

Arginase 1

OVA

Arginase 1

OVA

Arginase 1

OVA

Arginase 1

OVA

Arginase 1

OVA

Arginase 1

OVA

Arginase 1

OVA

Arginase 1

OVA

Arginase 1

OVA

Arginase 1

OVA

arginase

ovalbumin

arginase

OVA

arginase

OVA

arginase

OVA

arginase

OVA

arginase

OVA

arginase

OVA

arginase

OVA

arginase

OVA

arginase

OVA

arginase

OVA

arginase

OVA

arginase

OVA

arginase

OVA

ovalbumin

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

ovalbumin

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

ovalbumin

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

ovalbumin

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

ovalbumin

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

ovalbumin

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

ovalbumin

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

ovalbumin

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

OVA

Arginase 1

IgE

Arginase 1

IgE

Arginase 1

IgE

Arginase 1

IgE

arginase

IgE

arginase

IgE

arginase

IgE

arginase

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

IgE

Arginase 1

arginase

Arginase 1

arginase

Arginase 1

Ifng

Arginase 1

TH1 - type cytokine

Arginase 1

IFNgamma

arginase

Ifng

arginase

TH1 - type cytokine

arginase

IFNgamma

Ifng

TH1 - type cytokine

IFNgamma

Ifng

TH1 - type cytokine

IFNgamma

Ifng

TH1 - type cytokine

IFNgamma

Ifng

TH1 - type cytokine

IFNgamma

Ifng

TH1 - type cytokine

IFNgamma

Ifng

TH1 - type cytokine

IFNgamma

Ifng

TH1 - type cytokine

IFNgamma

Ifng

TH1 - type cytokine

IFNgamma

Arginase 1

Arginase 1

chemokines

arginase

arginase

chemokines

chemokines

chemokines

chemokines

chemokines

chemokines

chemokines

chemokines

chemokines

Arginase 1

arginase

Arginase 1

Arginase 1

TH2 - type cytokines

Arginase 1

IL - 13

arginase

arginase

TH2 - type cytokines

arginase

IL - 13

TH2 - type cytokines

IL - 13

TH2 - type cytokines

IL - 13

TH2 - type cytokines

IL - 13

TH2 - type cytokines

IL - 13

TH2 - type cytokines

IL - 13

TH2 - type cytokines

IL - 13

TH2 - type cytokines

IL - 13

TH2 - type cytokines

IL - 13

Arginase 1

Arginase 1

IL - 5

arginase

arginase

IL - 5

IL - 5

IL - 5

IL - 5

IL - 5

IL - 5

IL - 5

IL - 5

IL - 5

Arginase 1

Arginase 1

IL - 4

arginase

arginase

IL - 4

IL - 4

IL - 4

IL - 4

IL - 4

IL - 4

IL - 4

IL - 4

IL - 4

Arginase 1

Arginase 1

arginine transporters

arginase

arginase

arginine transporters

arginine transporters

arginine transporters

arginine transporters

arginine transporters

arginine transporters

arginine transporters

arginine transporters

arginine transporters

Arginase 1

arginase

Arginase 1

arginase

Arginase 1

arginase

Arginase 1

arginase

Arginase 1

nitric oxide

arginase

nitric oxide

nitric oxide

nitric oxide

nitric oxide

nitric oxide

nitric oxide

nitric oxide

nitric oxide

nitric oxide

Arginase 1

asthma

Arginase 1

asthma

arginase

asthma

arginase

asthma

asthma

asthma

asthma

asthma

asthma

asthma

asthma

asthma

asthma

asthma

asthma

asthma

asthma

asthma

asthma

asthma

Arginase 1

inflammatory

Arginase 1

inflammatory

Arginase 1

inflammation

Arginase 1

inflammatory

Arginase 1

inflammatory

arginase

inflammatory

arginase

inflammatory

arginase

inflammation

arginase

inflammatory

arginase

inflammatory

inflammatory

inflammatory

inflammation

inflammatory

inflammatory

inflammatory

inflammatory

inflammation

inflammatory

inflammatory

inflammatory

inflammatory

inflammation

inflammatory

inflammatory

inflammatory

inflammatory

inflammation

inflammatory

inflammatory

inflammatory

inflammatory

inflammation

inflammatory

inflammatory

inflammatory

inflammatory

inflammation

inflammatory

inflammatory

inflammatory

inflammatory

inflammation

inflammatory

inflammatory

inflammatory

inflammatory

inflammation

inflammatory

inflammatory

Arginase 1

IL - 10

arginase

IL - 10

IL - 10

IL - 10

IL - 10

IL - 10

IL - 10

IL - 10

IL - 10

IL - 10


Input: Cerebrospinal fluid penetration of high - dose daptomycin in suspected Staphylococcus aureus meningitis . OBJECTIVE : To report a case of methicillin - sensitive Staphylococcus aureus ( MSSA ) bacteremia with suspected MSSA meningitis treated with high - dose daptomycin assessed with concurrent serum and cerebrospinal fluid ( CSF ) concentrations . CASE SUMMARY : A 54 - year - old male presented to the emergency department with generalized weakness and presumed health - care - associated pneumonia shown on chest radiograph . Treatment was empirically initiated with vancomycin , levofloxacin , and piperacillin / tazobactam . Blood cultures revealed S . aureus susceptible to oxacillin . Empiric antibiotic treatment was narrowed to nafcillin on day 4 . On day 8 , the patient developed acute renal failure ( serum creatinine 1 . 9 mg / dL , increased from 1 . 2 mg / dL the previous day and 0 . 8 mg / dL on admission ) . The patient ' s Glasgow Coma Score was 3 , with normal findings shown on computed tomography scan of the head 72 hours following an episode of cardiac arrest on day 10 . The patient experienced relapsing MSSA bacteremia on day 9 , increasing the suspicion for a central nervous system ( CNS ) infection . Nafcillin was discontinued and daptomycin 9 mg / kg daily was initiated for suspected meningitis and was continued until the patient ' s death on day 16 . Daptomycin serum and CSF trough concentrations were 11 . 21 ug / mL and 0 . 52 ug / mL , respectively , prior to the third dose . Lumbar puncture results were inconclusive and no further blood cultures were positive for MSSA . Creatine kinase levels were normal prior to daptomycin therapy and were not reassessed . DISCUSSION : Daptomycin was initiated in our patient secondary to possible nafcillin - induced acute interstitial nephritis and relapsing bacteremia . At a dose of 9 mg / kg , resultant penetration of 5 % was higher than in previous reports , more consistent with inflamed meninges . CONCLUSIONS : High - dose daptomycin may be an alternative option for MSSA bacteremia with or without a CNS source in patients who have failed or cannot tolerate standard therapy . Further clinical evaluation in patients with confirmed meningitis is warranted .

daptomycin

methicillin

daptomycin

vancomycin

levofloxacin

piperacillin / tazobactam

oxacillin

antibiotic

nafcillin

creatinine

Nafcillin

daptomycin

Daptomycin

daptomycin

Daptomycin

nafcillin

daptomycin

Staphylococcus aureus

Staphylococcus aureus

S . aureus

patient

patient

patient

patient

patient

patients

patients

meningitis

bacteremia

meningitis

weakness

pneumonia

acute renal failure

Coma

cardiac arrest

bacteremia

central nervous system ( CNS ) infection

meningitis

death

interstitial nephritis

bacteremia

bacteremia

meningitis

Creatine kinase

antibiotic

pneumonia

daptomycin

interstitial nephritis

daptomycin

interstitial nephritis

daptomycin

interstitial nephritis

Daptomycin

interstitial nephritis

daptomycin

interstitial nephritis

Daptomycin

interstitial nephritis

daptomycin

interstitial nephritis

daptomycin

bacteremia

daptomycin

bacteremia

daptomycin

bacteremia

daptomycin

bacteremia

daptomycin

bacteremia

daptomycin

bacteremia

daptomycin

bacteremia

daptomycin

bacteremia

daptomycin

bacteremia

daptomycin

bacteremia

daptomycin

bacteremia

daptomycin

bacteremia

Daptomycin

bacteremia

Daptomycin

bacteremia

Daptomycin

bacteremia

Daptomycin

bacteremia

daptomycin

bacteremia

daptomycin

bacteremia

daptomycin

bacteremia

daptomycin

bacteremia

Daptomycin

bacteremia

Daptomycin

bacteremia

Daptomycin

bacteremia

Daptomycin

bacteremia

daptomycin

bacteremia

daptomycin

bacteremia

daptomycin

bacteremia

daptomycin

bacteremia

daptomycin

meningitis

daptomycin

meningitis

daptomycin

meningitis

daptomycin

meningitis

daptomycin

meningitis

daptomycin

meningitis

daptomycin

meningitis

daptomycin

meningitis

daptomycin

meningitis

daptomycin

meningitis

daptomycin

meningitis

daptomycin

meningitis

Daptomycin

meningitis

Daptomycin

meningitis

Daptomycin

meningitis

Daptomycin

meningitis

daptomycin

meningitis

daptomycin

meningitis

daptomycin

meningitis

daptomycin

meningitis

Daptomycin

meningitis

Daptomycin

meningitis

Daptomycin

meningitis

Daptomycin

meningitis

daptomycin

meningitis

daptomycin

meningitis

daptomycin

meningitis

daptomycin

meningitis

pneumonia

piperacillin / tazobactam

pneumonia

levofloxacin

pneumonia

vancomycin

weakness

piperacillin / tazobactam

weakness

levofloxacin

weakness

vancomycin

nafcillin

interstitial nephritis

Nafcillin

interstitial nephritis

nafcillin

interstitial nephritis

nafcillin

bacteremia

nafcillin

bacteremia

nafcillin

bacteremia

nafcillin

bacteremia

Nafcillin

bacteremia

Nafcillin

bacteremia

Nafcillin

bacteremia

Nafcillin

bacteremia

nafcillin

bacteremia

nafcillin

bacteremia

nafcillin

bacteremia

nafcillin

bacteremia

acute renal failure

creatinine

methicillin

bacteremia

methicillin

bacteremia

methicillin

bacteremia

methicillin

bacteremia

levofloxacin

piperacillin / tazobactam

vancomycin

piperacillin / tazobactam

vancomycin

levofloxacin


Input: Lack of association of C - C chemokine receptor 5 DD32 deletion status with rheumatoid arthritis , systemic lupus erythematosus , lupus nephritis , and disease severity . OBJECTIVE : C - C chemokine receptor 5 ( CCR5 ) plays an important role in inflammation . A 32 base - pair ( DD32 ) deletion in the CCR5 gene leads to a nonfunctional receptor . This deletion has been reported to have a protective effect on the development and progression of several autoimmune diseases . We investigated whether the DD32 deletion is associated with disease susceptibility in a population of patients with rheumatoid arthritis ( RA ) , systemic lupus erythematosus ( SLE ) , and lupus nephritis ( LN ) ; and whether it is associated with disease severity . METHODS : DNA samples from 405 RA patients , 97 SLE patients , 113 LN patients , and 431 healthy controls were genotyped for the CCR5 DD32 deletion . Differences in genotype frequencies were tested between patients and controls . Association of genotypes with disease severity was analyzed . RESULTS : Genotype frequencies of each group were in Hardy - Weinberg equilibrium . The genotype frequencies of patients did not differ significantly from controls ( CCR5 / DD32 , DD32 / DD32 : RA 18 . 3 % and 1 . 2 % , respectively ; SLE 17 . 5 % and 2 . 1 % ; LN 13 . 3 % and 1 . 8 % ; controls 20 . 0 % and 2 . 8 % ) . However , there was a trend for lower DD32 deletion allele frequency in LN patients compared to controls ( p = 0 . 08 ) . There was no significant association between the CCR5 status and disease severity in RA , SLE , or LN . CONCLUSION : Although an association with LN cannot be excluded , the CCR5 DD32 deletion does not seem to be a disease susceptibility genotype for RA , SLE , or LN . No significant effect of the DD32 deletion on disease severity was demonstrated .

C - C chemokine receptor 5

C - C chemokine receptor 5

DD32 deletion

32 base - pair ( DD32 ) deletion

DD32 deletion

DD32 deletion

DD32 deletion

DD32 deletion

DD32 deletion

rheumatoid arthritis

systemic lupus erythematosus

lupus nephritis

inflammation

autoimmune diseases

rheumatoid arthritis

RA

systemic lupus erythematosus

SLE

lupus nephritis

LN

RA

SLE

LN

RA

SLE

LN

LN

RA

SLE

LN

LN

RA

SLE

LN

patients

patients

patients

patients

patients

patients

patients

C - C chemokine receptor 5

inflammation

C - C chemokine receptor 5

inflammation

inflammation

inflammation

inflammation

inflammation

inflammation

inflammation

C - C chemokine receptor 5

autoimmune diseases

C - C chemokine receptor 5

autoimmune diseases

autoimmune diseases

autoimmune diseases

autoimmune diseases

autoimmune diseases

autoimmune diseases

autoimmune diseases

DD32 deletion

autoimmune diseases

32 base - pair ( DD32 ) deletion

autoimmune diseases

DD32 deletion

autoimmune diseases

DD32 deletion

autoimmune diseases

autoimmune diseases

autoimmune diseases

autoimmune diseases

DD32 deletion

autoimmune diseases

DD32 deletion

autoimmune diseases

DD32 deletion

autoimmune diseases


Input: Context - and cell - dependent effects of Delta - like 4 targeting in the bone marrow microenvironment . Delta - like 4 ( Dll4 ) is a ligand of the Notch pathway family which has been widely studied in the context of tumor angiogenesis , its blockade shown to result in non - productive angiogenesis and halted tumor growth . As Dll4 inhibitors enter the clinic , there is an emerging need to understand their side effects , namely the systemic consequences of Dll4 : Notch blockade in tissues other than tumors . The present study focused on the effects of systemic anti - Dll4 targeting in the bone marrow ( BM ) microenvironment . Here we show that Dll4 blockade with monoclonal antibodies perturbs the BM vascular niche of sub - lethally irradiated mice , resulting in increased CD31 ( + ) , VE - Cadherin ( + ) and c - kit ( + ) vessel density , and also increased megakaryocytes , whereas CD105 ( + ) , VEGFR3 ( + ) , SMA ( + ) and lectin ( + ) vessel density remained unaltered . We investigated also the expression of angiocrine genes upon Dll4 treatment in vivo , and demonstrate that IGFbp2 , IGFbp3 , Angpt2 , Dll4 , DHH and VEGF - A are upregulated , while FGF1 and CSF2 are reduced . In vitro treatment of endothelial cells with anti - Dll4 reduced Akt phosphorylation while maintaining similar levels of Erk 1 / 2 phosphorylation . Besides its effects in the BM vascular niche , anti - Dll4 treatment perturbed hematopoiesis , as evidenced by increased myeloid ( CD11b ( + ) ) , decreased B ( B220 ( + ) ) and T ( CD3 ( + ) ) lymphoid BM content of treated mice , with a corresponding increase in myeloid circulating cells . Moreover , anti - Dll4 treatment also increased the number of CFU - M and - G colonies in methylcellulose assays , independently of Notch1 . Finally , anti - Dll4 treatment of donor BM improved the hematopoietic recovery of lethally irradiated recipients in a transplant setting . Together , our data reveals the hematopoietic ( BM ) effects of systemic anti - Dll4 treatment result from qualitative vascular changes and also direct hematopoietic cell modulation , which may be favorable in a transplant setting .

Delta - like 4

Delta - like 4

Notch

Notch

VE - Cadherin

c - kit

SMA

lectin

DHH

VEGF - A

Akt

Erk 1 / 2

tumor

tumor

tumors

mice

mice

Delta - like 4

Delta - like 4

Delta - like 4

Delta - like 4

Delta - like 4

Delta - like 4

Delta - like 4

Delta - like 4

Delta - like 4

VEGF - A

Delta - like 4

VEGF - A

VEGF - A

VEGF - A

VEGF - A

VEGF - A

VEGF - A

VEGF - A

VEGF - A

VEGF - A

VEGF - A

VEGF - A

VEGF - A

VEGF - A

Delta - like 4

DHH

Delta - like 4

DHH

DHH

DHH

DHH

DHH

DHH

DHH

DHH

DHH

DHH

DHH

DHH

DHH

Delta - like 4

Delta - like 4

Delta - like 4

Delta - like 4

Delta - like 4

Delta - like 4

Delta - like 4

Delta - like 4

Delta - like 4

Akt

Delta - like 4

Akt

Akt

Akt

Akt

Akt

Akt

Akt

Akt

Akt

Akt

Akt

Akt

Akt

Delta - like 4

tumor

Delta - like 4

tumor

Delta - like 4

tumors

Delta - like 4

tumor

Delta - like 4

tumor

Delta - like 4

tumors

tumor

tumor

tumors

tumor

tumor

tumors

tumor

tumor

tumors

tumor

tumor

tumors

tumor

tumor

tumors

tumor

tumor

tumors

tumor

tumor

tumors

tumor

tumor

tumors

tumor

tumor

tumors

tumor

tumor

tumors

tumor

tumor

tumors

tumor

tumor

tumors

Delta - like 4

Notch

Delta - like 4

Notch

Delta - like 4

Delta - like 4

Notch

Delta - like 4

Notch

Delta - like 4

Notch

Notch

Notch

Notch

Notch

Notch

Notch

Notch

Notch

Notch

Notch

Notch

Notch

Notch

Notch

Notch

Notch

Notch

Notch

Notch

Notch

Notch

Notch

Notch

Delta - like 4

c - kit

Delta - like 4

c - kit

c - kit

c - kit

c - kit

c - kit

c - kit

c - kit

c - kit

c - kit

c - kit

c - kit

c - kit

c - kit

Delta - like 4

VE - Cadherin

Delta - like 4

VE - Cadherin

VE - Cadherin

VE - Cadherin

VE - Cadherin

VE - Cadherin

VE - Cadherin

VE - Cadherin

VE - Cadherin

VE - Cadherin

VE - Cadherin

VE - Cadherin

VE - Cadherin

VE - Cadherin

Delta - like 4

Delta - like 4


Input: Role of angiotensin II type 1a receptor in renal injury induced by deoxycorticosterone acetate - salt hypertension . The aim of this study was to investigate the in vivo role of angiotensin II type 1a ( AT1a ) receptor in renal damage as a result of hypertension by using transgenic mice with AT1a receptor gene disruption . Transgenic mice that express human liver - type fatty acid binding protein ( L - FABP ) with or without disruption of the AT1a receptor gene ( L - FABP ( + / - ) AT1a ( - / - ) , and L - FABP ( + / - ) AT1a ( + / + ) , respectively ) were used with urinary L - FABP as an indicator of tubulointerstitial damage . Those female mice were administered subcutaneously deoxycorticosterone acetate ( DOCA ) - salt tablets plus drinking water that contained 1 % saline for 28 d after uninephrectomy . In L - FABP ( + / - ) AT1a ( + / + ) mice that received DOCA - salt treatment , hypertension was induced and slight expansion of glomerular area , glomerular sclerosis , and tubulointerstitial damage were observed . In L - FABP ( + / - ) AT1a ( - / - ) mice that received DOCA - salt treatment , hypertension was similarly induced and the degree of glomerular damage was significantly more severe than in L - FABP ( + / - ) AT1a ( + / + ) - DOCA mice . Urinary L - FABP levels were significantly higher in L - FABP ( + / - ) AT1a ( - / - ) - DOCA mice compared with those in L - FABP ( + / - ) AT1a ( + / + ) - DOCA mice . Hydralazine treatment significantly attenuated renal damage that was found in L - FABP ( + / - ) AT1a ( - / - ) - DOCA mice along with a reduction in blood pressure . In summary , activation of the AT1a receptor may contribute to maintenance of the glomerular structure against hypertensive renal damage . - Hisamichi , M . , Kamijo - Ikemori , A . , Sugaya , T . , Ichikawa , D . , Natsuki , T . , Hoshino , S . , Kimura , K . , Shibagaki , Y . Role of angiotensin II type 1a receptor in renal injury induced by deoxycorticosterone acetate - salt hypertension .

angiotensin II type 1a receptor

angiotensin II type 1a ( AT1a ) receptor

AT1a receptor

liver - type fatty acid binding protein

L - FABP

AT1a receptor

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

AT1a receptor

angiotensin II type 1a receptor

renal injury

hypertension

renal damage

hypertension

tubulointerstitial damage

hypertension

glomerular sclerosis

tubulointerstitial damage

hypertension

glomerular damage

renal damage

hypertensive renal damage

renal injury

hypertension

deoxycorticosterone acetate

deoxycorticosterone acetate

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

Hydralazine

DOCA

deoxycorticosterone acetate

mice

mice

human

mice

mice

mice

mice

mice

mice

mice

Hydralazine

renal injury

Hydralazine

renal damage

Hydralazine

tubulointerstitial damage

Hydralazine

glomerular sclerosis

Hydralazine

tubulointerstitial damage

Hydralazine

glomerular damage

Hydralazine

renal damage

Hydralazine

hypertensive renal damage

Hydralazine

renal injury

liver - type fatty acid binding protein

angiotensin II type 1a receptor

liver - type fatty acid binding protein

angiotensin II type 1a ( AT1a ) receptor

liver - type fatty acid binding protein

AT1a receptor

liver - type fatty acid binding protein

AT1a receptor

liver - type fatty acid binding protein

liver - type fatty acid binding protein

liver - type fatty acid binding protein

liver - type fatty acid binding protein

liver - type fatty acid binding protein

liver - type fatty acid binding protein

liver - type fatty acid binding protein

liver - type fatty acid binding protein

liver - type fatty acid binding protein

AT1a receptor

liver - type fatty acid binding protein

angiotensin II type 1a receptor

L - FABP

angiotensin II type 1a receptor

L - FABP

angiotensin II type 1a ( AT1a ) receptor

L - FABP

AT1a receptor

L - FABP

AT1a receptor

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

AT1a receptor

L - FABP

angiotensin II type 1a receptor

L - FABP

angiotensin II type 1a receptor

L - FABP

angiotensin II type 1a ( AT1a ) receptor

L - FABP

AT1a receptor

L - FABP

AT1a receptor

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

AT1a receptor

L - FABP

angiotensin II type 1a receptor

L - FABP

angiotensin II type 1a receptor

L - FABP

angiotensin II type 1a ( AT1a ) receptor

L - FABP

AT1a receptor

L - FABP

AT1a receptor

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

AT1a receptor

L - FABP

angiotensin II type 1a receptor

L - FABP

angiotensin II type 1a receptor

L - FABP

angiotensin II type 1a ( AT1a ) receptor

L - FABP

AT1a receptor

L - FABP

AT1a receptor

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

AT1a receptor

L - FABP

angiotensin II type 1a receptor

L - FABP

angiotensin II type 1a receptor

L - FABP

angiotensin II type 1a ( AT1a ) receptor

L - FABP

AT1a receptor

L - FABP

AT1a receptor

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

AT1a receptor

L - FABP

angiotensin II type 1a receptor

L - FABP

angiotensin II type 1a receptor

L - FABP

angiotensin II type 1a ( AT1a ) receptor

L - FABP

AT1a receptor

L - FABP

AT1a receptor

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

AT1a receptor

L - FABP

angiotensin II type 1a receptor

L - FABP

angiotensin II type 1a receptor

L - FABP

angiotensin II type 1a ( AT1a ) receptor

L - FABP

AT1a receptor

L - FABP

AT1a receptor

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

AT1a receptor

L - FABP

angiotensin II type 1a receptor

L - FABP

angiotensin II type 1a receptor

L - FABP

angiotensin II type 1a ( AT1a ) receptor

L - FABP

AT1a receptor

L - FABP

AT1a receptor

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

AT1a receptor

L - FABP

angiotensin II type 1a receptor

L - FABP

angiotensin II type 1a receptor

L - FABP

angiotensin II type 1a ( AT1a ) receptor

L - FABP

AT1a receptor

L - FABP

AT1a receptor

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

AT1a receptor

L - FABP

angiotensin II type 1a receptor

L - FABP

angiotensin II type 1a receptor

L - FABP

angiotensin II type 1a ( AT1a ) receptor

L - FABP

AT1a receptor

L - FABP

AT1a receptor

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

AT1a receptor

L - FABP

angiotensin II type 1a receptor

L - FABP

angiotensin II type 1a receptor

L - FABP

angiotensin II type 1a ( AT1a ) receptor

L - FABP

AT1a receptor

L - FABP

AT1a receptor

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

L - FABP

AT1a receptor

L - FABP

angiotensin II type 1a receptor

liver - type fatty acid binding protein

renal injury

liver - type fatty acid binding protein

renal damage

liver - type fatty acid binding protein

tubulointerstitial damage

liver - type fatty acid binding protein

glomerular sclerosis

liver - type fatty acid binding protein

tubulointerstitial damage

liver - type fatty acid binding protein

glomerular damage

liver - type fatty acid binding protein

renal damage

liver - type fatty acid binding protein

hypertensive renal damage

liver - type fatty acid binding protein

renal injury

L - FABP

renal injury

L - FABP

renal damage

L - FABP

tubulointerstitial damage

L - FABP

glomerular sclerosis

L - FABP

tubulointerstitial damage

L - FABP

glomerular damage

L - FABP

renal damage

L - FABP

hypertensive renal damage

L - FABP

renal injury

L - FABP

renal injury

L - FABP

renal damage

L - FABP

tubulointerstitial damage

L - FABP

glomerular sclerosis

L - FABP

tubulointerstitial damage

L - FABP

glomerular damage

L - FABP

renal damage

L - FABP

hypertensive renal damage

L - FABP

renal injury

L - FABP

renal injury

L - FABP

renal damage

L - FABP

tubulointerstitial damage

L - FABP

glomerular sclerosis

L - FABP

tubulointerstitial damage

L - FABP

glomerular damage

L - FABP

renal damage

L - FABP

hypertensive renal damage

L - FABP

renal injury

L - FABP

renal injury

L - FABP

renal damage

L - FABP

tubulointerstitial damage

L - FABP

glomerular sclerosis

L - FABP

tubulointerstitial damage

L - FABP

glomerular damage

L - FABP

renal damage

L - FABP

hypertensive renal damage

L - FABP

renal injury

L - FABP

renal injury

L - FABP

renal damage

L - FABP

tubulointerstitial damage

L - FABP

glomerular sclerosis

L - FABP

tubulointerstitial damage

L - FABP

glomerular damage

L - FABP

renal damage

L - FABP

hypertensive renal damage

L - FABP

renal injury

L - FABP

renal injury

L - FABP

renal damage

L - FABP

tubulointerstitial damage

L - FABP

glomerular sclerosis

L - FABP

tubulointerstitial damage

L - FABP

glomerular damage

L - FABP

renal damage

L - FABP

hypertensive renal damage

L - FABP

renal injury

L - FABP

renal injury

L - FABP

renal damage

L - FABP

tubulointerstitial damage

L - FABP

glomerular sclerosis

L - FABP

tubulointerstitial damage

L - FABP

glomerular damage

L - FABP

renal damage

L - FABP

hypertensive renal damage

L - FABP

renal injury

L - FABP

renal injury

L - FABP

renal damage

L - FABP

tubulointerstitial damage

L - FABP

glomerular sclerosis

L - FABP

tubulointerstitial damage

L - FABP

glomerular damage

L - FABP

renal damage

L - FABP

hypertensive renal damage

L - FABP

renal injury

L - FABP

renal injury

L - FABP

renal damage

L - FABP

tubulointerstitial damage

L - FABP

glomerular sclerosis

L - FABP

tubulointerstitial damage

L - FABP

glomerular damage

L - FABP

renal damage

L - FABP

hypertensive renal damage

L - FABP

renal injury

L - FABP

renal injury

L - FABP

renal damage

L - FABP

tubulointerstitial damage

L - FABP

glomerular sclerosis

L - FABP

tubulointerstitial damage

L - FABP

glomerular damage

L - FABP

renal damage

L - FABP

hypertensive renal damage

L - FABP

renal injury

L - FABP

renal injury

L - FABP

renal damage

L - FABP

tubulointerstitial damage

L - FABP

glomerular sclerosis

L - FABP

tubulointerstitial damage

L - FABP

glomerular damage

L - FABP

renal damage

L - FABP

hypertensive renal damage

L - FABP

renal injury

angiotensin II type 1a receptor

renal injury

angiotensin II type 1a receptor

renal damage

angiotensin II type 1a receptor

tubulointerstitial damage

angiotensin II type 1a receptor

glomerular sclerosis

angiotensin II type 1a receptor

tubulointerstitial damage

angiotensin II type 1a receptor

glomerular damage

angiotensin II type 1a receptor

renal damage

angiotensin II type 1a receptor

hypertensive renal damage

angiotensin II type 1a receptor

renal injury

angiotensin II type 1a ( AT1a ) receptor

renal injury

angiotensin II type 1a ( AT1a ) receptor

renal damage

angiotensin II type 1a ( AT1a ) receptor

tubulointerstitial damage

angiotensin II type 1a ( AT1a ) receptor

glomerular sclerosis

angiotensin II type 1a ( AT1a ) receptor

tubulointerstitial damage

angiotensin II type 1a ( AT1a ) receptor

glomerular damage

angiotensin II type 1a ( AT1a ) receptor

renal damage

angiotensin II type 1a ( AT1a ) receptor

hypertensive renal damage

angiotensin II type 1a ( AT1a ) receptor

renal injury

AT1a receptor

renal injury

AT1a receptor

renal damage

AT1a receptor

tubulointerstitial damage

AT1a receptor

glomerular sclerosis

AT1a receptor

tubulointerstitial damage

AT1a receptor

glomerular damage

AT1a receptor

renal damage

AT1a receptor

hypertensive renal damage

AT1a receptor

renal injury

AT1a receptor

renal injury

AT1a receptor

renal damage

AT1a receptor

tubulointerstitial damage

AT1a receptor

glomerular sclerosis

AT1a receptor

tubulointerstitial damage

AT1a receptor

glomerular damage

AT1a receptor

renal damage

AT1a receptor

hypertensive renal damage

AT1a receptor

renal injury

renal injury

renal damage

tubulointerstitial damage

glomerular sclerosis

tubulointerstitial damage

glomerular damage

renal damage

hypertensive renal damage

renal injury

renal injury

renal damage

tubulointerstitial damage

glomerular sclerosis

tubulointerstitial damage

glomerular damage

renal damage

hypertensive renal damage

renal injury

renal injury

renal damage

tubulointerstitial damage

glomerular sclerosis

tubulointerstitial damage

glomerular damage

renal damage

hypertensive renal damage

renal injury

renal injury

renal damage

tubulointerstitial damage

glomerular sclerosis

tubulointerstitial damage

glomerular damage

renal damage

hypertensive renal damage

renal injury

renal injury

renal damage

tubulointerstitial damage

glomerular sclerosis

tubulointerstitial damage

glomerular damage

renal damage

hypertensive renal damage

renal injury

renal injury

renal damage

tubulointerstitial damage

glomerular sclerosis

tubulointerstitial damage

glomerular damage

renal damage

hypertensive renal damage

renal injury

renal injury

renal damage

tubulointerstitial damage

glomerular sclerosis

tubulointerstitial damage

glomerular damage

renal damage

hypertensive renal damage

renal injury

renal injury

renal damage

tubulointerstitial damage

glomerular sclerosis

tubulointerstitial damage

glomerular damage

renal damage

hypertensive renal damage

renal injury

AT1a receptor

renal injury

AT1a receptor

renal damage

AT1a receptor

tubulointerstitial damage

AT1a receptor

glomerular sclerosis

AT1a receptor

tubulointerstitial damage

AT1a receptor

glomerular damage

AT1a receptor

renal damage

AT1a receptor

hypertensive renal damage

AT1a receptor

renal injury

angiotensin II type 1a receptor

renal injury

angiotensin II type 1a receptor

renal damage

angiotensin II type 1a receptor

tubulointerstitial damage

angiotensin II type 1a receptor

glomerular sclerosis

angiotensin II type 1a receptor

tubulointerstitial damage

angiotensin II type 1a receptor

glomerular damage

angiotensin II type 1a receptor

renal damage

angiotensin II type 1a receptor

hypertensive renal damage

angiotensin II type 1a receptor

renal injury

deoxycorticosterone acetate

liver - type fatty acid binding protein

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

liver - type fatty acid binding protein

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

DOCA

liver - type fatty acid binding protein

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

liver - type fatty acid binding protein

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

liver - type fatty acid binding protein

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

liver - type fatty acid binding protein

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

liver - type fatty acid binding protein

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

liver - type fatty acid binding protein

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

liver - type fatty acid binding protein

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

DOCA

L - FABP

deoxycorticosterone acetate

liver - type fatty acid binding protein

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

L - FABP

deoxycorticosterone acetate

angiotensin II type 1a receptor

deoxycorticosterone acetate

angiotensin II type 1a ( AT1a ) receptor

deoxycorticosterone acetate

AT1a receptor

deoxycorticosterone acetate

AT1a receptor

deoxycorticosterone acetate

deoxycorticosterone acetate

deoxycorticosterone acetate

deoxycorticosterone acetate

deoxycorticosterone acetate

deoxycorticosterone acetate

deoxycorticosterone acetate

deoxycorticosterone acetate

deoxycorticosterone acetate

AT1a receptor

deoxycorticosterone acetate

angiotensin II type 1a receptor

deoxycorticosterone acetate

angiotensin II type 1a receptor

deoxycorticosterone acetate

angiotensin II type 1a ( AT1a ) receptor

deoxycorticosterone acetate

AT1a receptor

deoxycorticosterone acetate

AT1a receptor

deoxycorticosterone acetate

deoxycorticosterone acetate

deoxycorticosterone acetate

deoxycorticosterone acetate

deoxycorticosterone acetate

deoxycorticosterone acetate

deoxycorticosterone acetate

deoxycorticosterone acetate

deoxycorticosterone acetate

AT1a receptor

deoxycorticosterone acetate

angiotensin II type 1a receptor

DOCA

angiotensin II type 1a receptor

DOCA

angiotensin II type 1a ( AT1a ) receptor

DOCA

AT1a receptor

DOCA

AT1a receptor

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

AT1a receptor

DOCA

angiotensin II type 1a receptor

DOCA

angiotensin II type 1a receptor

DOCA

angiotensin II type 1a ( AT1a ) receptor

DOCA

AT1a receptor

DOCA

AT1a receptor

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

AT1a receptor

DOCA

angiotensin II type 1a receptor

DOCA

angiotensin II type 1a receptor

DOCA

angiotensin II type 1a ( AT1a ) receptor

DOCA

AT1a receptor

DOCA

AT1a receptor

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

AT1a receptor

DOCA

angiotensin II type 1a receptor

DOCA

angiotensin II type 1a receptor

DOCA

angiotensin II type 1a ( AT1a ) receptor

DOCA

AT1a receptor

DOCA

AT1a receptor

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

AT1a receptor

DOCA

angiotensin II type 1a receptor

DOCA

angiotensin II type 1a receptor

DOCA

angiotensin II type 1a ( AT1a ) receptor

DOCA

AT1a receptor

DOCA

AT1a receptor

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

AT1a receptor

DOCA

angiotensin II type 1a receptor

DOCA

angiotensin II type 1a receptor

DOCA

angiotensin II type 1a ( AT1a ) receptor

DOCA

AT1a receptor

DOCA

AT1a receptor

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

AT1a receptor

DOCA

angiotensin II type 1a receptor

DOCA

angiotensin II type 1a receptor

DOCA

angiotensin II type 1a ( AT1a ) receptor

DOCA

AT1a receptor

DOCA

AT1a receptor

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

DOCA

AT1a receptor

DOCA

angiotensin II type 1a receptor

deoxycorticosterone acetate

angiotensin II type 1a receptor

deoxycorticosterone acetate

angiotensin II type 1a ( AT1a ) receptor

deoxycorticosterone acetate

AT1a receptor

deoxycorticosterone acetate

AT1a receptor

deoxycorticosterone acetate

deoxycorticosterone acetate

deoxycorticosterone acetate

deoxycorticosterone acetate

deoxycorticosterone acetate

deoxycorticosterone acetate

deoxycorticosterone acetate

deoxycorticosterone acetate

deoxycorticosterone acetate

AT1a receptor

deoxycorticosterone acetate

angiotensin II type 1a receptor

deoxycorticosterone acetate

hypertension

deoxycorticosterone acetate

hypertension

deoxycorticosterone acetate

hypertension

deoxycorticosterone acetate

hypertension

deoxycorticosterone acetate

hypertensive renal damage

deoxycorticosterone acetate

hypertension

deoxycorticosterone acetate

hypertension

deoxycorticosterone acetate

hypertension

deoxycorticosterone acetate

hypertension

deoxycorticosterone acetate

hypertension

deoxycorticosterone acetate

hypertensive renal damage

deoxycorticosterone acetate

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertensive renal damage

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertensive renal damage

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertensive renal damage

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertensive renal damage

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertensive renal damage

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertensive renal damage

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertensive renal damage

DOCA

hypertension

deoxycorticosterone acetate

hypertension

deoxycorticosterone acetate

hypertension

deoxycorticosterone acetate

hypertension

deoxycorticosterone acetate

hypertension

deoxycorticosterone acetate

hypertensive renal damage

deoxycorticosterone acetate

hypertension

renal injury

deoxycorticosterone acetate

renal injury

deoxycorticosterone acetate

renal injury

DOCA

renal injury

DOCA

renal injury

DOCA

renal injury

DOCA

renal injury

DOCA

renal injury

DOCA

renal injury

DOCA

renal injury

deoxycorticosterone acetate

renal damage

deoxycorticosterone acetate

renal damage

deoxycorticosterone acetate

renal damage

DOCA

renal damage

DOCA

renal damage

DOCA

renal damage

DOCA

renal damage

DOCA

renal damage

DOCA

renal damage

DOCA

renal damage

deoxycorticosterone acetate

tubulointerstitial damage

deoxycorticosterone acetate

tubulointerstitial damage

deoxycorticosterone acetate

tubulointerstitial damage

DOCA

tubulointerstitial damage

DOCA

tubulointerstitial damage

DOCA

tubulointerstitial damage

DOCA

tubulointerstitial damage

DOCA

tubulointerstitial damage

DOCA

tubulointerstitial damage

DOCA

tubulointerstitial damage

deoxycorticosterone acetate

glomerular sclerosis

deoxycorticosterone acetate

glomerular sclerosis

deoxycorticosterone acetate

glomerular sclerosis

DOCA

glomerular sclerosis

DOCA

glomerular sclerosis

DOCA

glomerular sclerosis

DOCA

glomerular sclerosis

DOCA

glomerular sclerosis

DOCA

glomerular sclerosis

DOCA

glomerular sclerosis

deoxycorticosterone acetate

tubulointerstitial damage

deoxycorticosterone acetate

tubulointerstitial damage

deoxycorticosterone acetate

tubulointerstitial damage

DOCA

tubulointerstitial damage

DOCA

tubulointerstitial damage

DOCA

tubulointerstitial damage

DOCA

tubulointerstitial damage

DOCA

tubulointerstitial damage

DOCA

tubulointerstitial damage

DOCA

tubulointerstitial damage

deoxycorticosterone acetate

glomerular damage

deoxycorticosterone acetate

glomerular damage

deoxycorticosterone acetate

glomerular damage

DOCA

glomerular damage

DOCA

glomerular damage

DOCA

glomerular damage

DOCA

glomerular damage

DOCA

glomerular damage

DOCA

glomerular damage

DOCA

glomerular damage

deoxycorticosterone acetate

renal damage

deoxycorticosterone acetate

renal damage

deoxycorticosterone acetate

renal damage

DOCA

renal damage

DOCA

renal damage

DOCA

renal damage

DOCA

renal damage

DOCA

renal damage

DOCA

renal damage

DOCA

renal damage

deoxycorticosterone acetate

hypertensive renal damage

deoxycorticosterone acetate

hypertensive renal damage

deoxycorticosterone acetate

hypertensive renal damage

DOCA

hypertensive renal damage

DOCA

hypertensive renal damage

DOCA

hypertensive renal damage

DOCA

hypertensive renal damage

DOCA

hypertensive renal damage

DOCA

hypertensive renal damage

DOCA

hypertensive renal damage

deoxycorticosterone acetate

renal injury

deoxycorticosterone acetate

renal injury

deoxycorticosterone acetate

renal injury

DOCA

renal injury

DOCA

renal injury

DOCA

renal injury

DOCA

renal injury

DOCA

renal injury

DOCA

renal injury

DOCA

renal injury

deoxycorticosterone acetate


Input: PTPN22 Is a Critical Regulator of Fcg Receptor - Mediated Neutrophil Activation . Neutrophils act as a first line of defense against bacterial and fungal infections , but they are also important effectors of acute and chronic inflammation . Genome - wide association studies have established that the gene encoding the protein tyrosine phosphatase nonreceptor 22 ( PTPN22 ) makes an important contribution to susceptibility to autoimmune disease , notably rheumatoid arthritis . Although PTPN22 is most highly expressed in neutrophils , its function in these cells remains poorly characterized . We show in this article that neutrophil effector functions , including adhesion , production of reactive oxygen species , and degranulation induced by immobilized immune complexes , were reduced in Ptpn22 ( - / - ) neutrophils . Tyrosine phosphorylation of Lyn and Syk was altered in Ptpn22 ( - / - ) neutrophils . On stimulation with immobilized immune complexes , Ptpn22 ( - / - ) neutrophils manifested reduced activation of key signaling intermediates . Ptpn22 ( - / - ) mice were protected from immune complex - mediated arthritis , induced by the transfer of arthritogenic serum . In contrast , in vivo neutrophil recruitment following thioglycollate - induced peritonitis and in vitro chemotaxis were not affected by lack of PTPN22 . Our data suggest an important role for PTPN22 - dependent dephosphorylation events , which are required to enable full FcgR - induced activation , pointing to an important role for this molecule in neutrophil function .

Fcg Receptor

protein tyrosine phosphatase nonreceptor 22

Lyn

Syk

FcgR

fungal infections

acute and chronic inflammation

autoimmune disease

rheumatoid arthritis

arthritis

peritonitis

reactive oxygen species

thioglycollate

mice

thioglycollate

peritonitis

Syk

Syk

protein tyrosine phosphatase nonreceptor 22

Syk

Syk

Syk

Syk

Syk

Syk

Syk

Syk

Lyn

Lyn

protein tyrosine phosphatase nonreceptor 22

Lyn

Lyn

Lyn

Lyn

Lyn

Lyn

Lyn

Lyn

rheumatoid arthritis

protein tyrosine phosphatase nonreceptor 22

rheumatoid arthritis

rheumatoid arthritis

rheumatoid arthritis

rheumatoid arthritis

rheumatoid arthritis

rheumatoid arthritis

rheumatoid arthritis

rheumatoid arthritis

rheumatoid arthritis

autoimmune disease

protein tyrosine phosphatase nonreceptor 22

autoimmune disease

autoimmune disease

autoimmune disease

autoimmune disease

autoimmune disease

autoimmune disease

autoimmune disease

autoimmune disease

autoimmune disease

arthritis

protein tyrosine phosphatase nonreceptor 22

arthritis

arthritis

arthritis

arthritis

arthritis

arthritis

arthritis

arthritis

arthritis

Fcg Receptor

FcgR

protein tyrosine phosphatase nonreceptor 22

Fcg Receptor

protein tyrosine phosphatase nonreceptor 22

FcgR

Fcg Receptor

FcgR

Fcg Receptor

FcgR

Fcg Receptor

FcgR

Fcg Receptor

FcgR

Fcg Receptor

FcgR

Fcg Receptor

FcgR

Fcg Receptor

FcgR

Fcg Receptor

FcgR

reactive oxygen species

protein tyrosine phosphatase nonreceptor 22

reactive oxygen species

reactive oxygen species

reactive oxygen species

reactive oxygen species

reactive oxygen species

reactive oxygen species

reactive oxygen species

reactive oxygen species

reactive oxygen species


Input: Four novel mutations in the thiazide - sensitive Na - Cl co - transporter gene in Japanese patients with Gitelman ' s syndrome . BACKGROUND : Gitelman ' s syndrome ( GS ) is an autosomal recessive disorder resulting from inactivating mutations in the thiazide - sensitive Na - Cl co - transporter ( NCCT ) gene . To date , almost 90 mutations have been identified . It is possible that there is a population - specific distribution of mutations . In this study , we analysed mutations in the NCCT gene of seven Japanese patients with GS . METHODS : Peripheral blood mononuclear cells were isolated from patients with GS , their family members and healthy control subjects . A mutation analysis of the NCCT gene was performed completely by direct automated sequencing of polymerase chain reaction - amplified DNA products . In patients with a deletion or splice site mutation , we undertook cDNA sequence analysis . RESULTS : We identified nine mutations . Five of them [ c . 185C > T ( Thr60Met ) , c . 1712C > T ( Ala569Val ) , c . 1930C > T ( Arg642Cys ) , c . 2552T > A ( Leu849His ) and c . 1932delC ] have been reported in Japanese patients , but not in GS patients from other ethnic groups . The remaining four mutations [ c . 7A > T ( Met1Leu ) , c . 1181_1186 + 20del26 , c . 1811_1812delAT and IVS16 + 1G > A ] were novel . In cDNA derived from a patient with c . 1181_1186 + 20del26 , a deletion of exon 9 and a frameshift at the start of exon 10 were observed . In cDNA derived from patients with IVS16 + 1G > A , an additional 96 bp insertion between exons 16 and 17 was observed . Six out of seven patients were compound heterozygotes , and the remaining one carried a single heterozygous mutation . CONCLUSIONS : We found four novel mutations in the NCCT gene in seven Japanese patients with GS . Moreover , our study suggests that the distribution of mutations in the NCCT gene in Japanese GS patients potentially differs from that in other populations .

thiazide

thiazide

Na - Cl co - transporter

Na - Cl co - transporter

NCCT

NCCT

NCCT

NCCT

NCCT

patients

patients

patients

patients

patients

patients

patient

patients

patients

patients

patients

Gitelman ' s syndrome

Gitelman ' s syndrome

GS

autosomal recessive disorder

GS

GS

GS

GS

GS

c . 185C > T

c . 1712C > T

c . 1930C > T

c . 2552T > A

c . 1932delC

c . 7A > T

c . 1181_1186 + 20del26

c . 1811_1812delAT

IVS16 + 1G > A

c . 1181_1186 + 20del26

IVS16 + 1G > A

96 bp insertion

thiazide

Na - Cl co - transporter

thiazide

Na - Cl co - transporter

thiazide

NCCT

thiazide

NCCT

thiazide

NCCT

thiazide

NCCT

thiazide

NCCT

thiazide

Na - Cl co - transporter

thiazide

Na - Cl co - transporter

thiazide

NCCT

thiazide

NCCT

thiazide

NCCT

thiazide

NCCT

thiazide

NCCT

c . 1932delC

Gitelman ' s syndrome

c . 1932delC

Gitelman ' s syndrome

c . 1932delC

GS

c . 1932delC

GS

c . 1932delC

GS

c . 1932delC

GS

c . 1932delC

GS

c . 1932delC

GS

c . 2552T > A

Gitelman ' s syndrome

c . 2552T > A

Gitelman ' s syndrome

c . 2552T > A

GS

c . 2552T > A

GS

c . 2552T > A

GS

c . 2552T > A

GS

c . 2552T > A

GS

c . 2552T > A

GS

Gitelman ' s syndrome

Gitelman ' s syndrome

GS

GS

GS

GS

GS

GS

c . 1930C > T

Gitelman ' s syndrome

c . 1930C > T

Gitelman ' s syndrome

c . 1930C > T

GS

c . 1930C > T

GS

c . 1930C > T

GS

c . 1930C > T

GS

c . 1930C > T

GS

c . 1930C > T

GS

Gitelman ' s syndrome

Gitelman ' s syndrome

GS

GS

GS

GS

GS

GS

c . 1712C > T

Gitelman ' s syndrome

c . 1712C > T

Gitelman ' s syndrome

c . 1712C > T

GS

c . 1712C > T

GS

c . 1712C > T

GS

c . 1712C > T

GS

c . 1712C > T

GS

c . 1712C > T

GS

Gitelman ' s syndrome

Gitelman ' s syndrome

GS

GS

GS

GS

GS

GS

Gitelman ' s syndrome

96 bp insertion

Gitelman ' s syndrome

96 bp insertion

GS

96 bp insertion

GS

96 bp insertion

GS

96 bp insertion

GS

96 bp insertion

GS

96 bp insertion

GS

96 bp insertion

Gitelman ' s syndrome

IVS16 + 1G > A

Gitelman ' s syndrome

IVS16 + 1G > A

Gitelman ' s syndrome

IVS16 + 1G > A

Gitelman ' s syndrome

IVS16 + 1G > A

GS

IVS16 + 1G > A

GS

IVS16 + 1G > A

GS

IVS16 + 1G > A

GS

IVS16 + 1G > A

GS

IVS16 + 1G > A

GS

IVS16 + 1G > A

GS

IVS16 + 1G > A

GS

IVS16 + 1G > A

GS

IVS16 + 1G > A

GS

IVS16 + 1G > A

GS

IVS16 + 1G > A

GS

IVS16 + 1G > A

Gitelman ' s syndrome

c . 1811_1812delAT

Gitelman ' s syndrome

c . 1811_1812delAT

GS

c . 1811_1812delAT

GS

c . 1811_1812delAT

GS

c . 1811_1812delAT

GS

c . 1811_1812delAT

GS

c . 1811_1812delAT

GS

c . 1811_1812delAT

Gitelman ' s syndrome

c . 1181_1186 + 20del26

Gitelman ' s syndrome

c . 1181_1186 + 20del26

Gitelman ' s syndrome

c . 1181_1186 + 20del26

Gitelman ' s syndrome

c . 1181_1186 + 20del26

GS

c . 1181_1186 + 20del26

GS

c . 1181_1186 + 20del26

GS

c . 1181_1186 + 20del26

GS

c . 1181_1186 + 20del26

GS

c . 1181_1186 + 20del26

GS

c . 1181_1186 + 20del26

GS

c . 1181_1186 + 20del26

GS

c . 1181_1186 + 20del26

GS

c . 1181_1186 + 20del26

GS

c . 1181_1186 + 20del26

GS

c . 1181_1186 + 20del26

GS

c . 1181_1186 + 20del26

Gitelman ' s syndrome

Gitelman ' s syndrome

GS

GS

GS

GS

GS

GS

Gitelman ' s syndrome

c . 7A > T

Gitelman ' s syndrome

c . 7A > T

GS

c . 7A > T

GS

c . 7A > T

GS

c . 7A > T

GS

c . 7A > T

GS

c . 7A > T

GS

c . 7A > T

c . 185C > T

Gitelman ' s syndrome

c . 185C > T

Gitelman ' s syndrome

c . 185C > T

GS

c . 185C > T

GS

c . 185C > T

GS

c . 185C > T

GS

c . 185C > T

GS

c . 185C > T

GS

Gitelman ' s syndrome

Gitelman ' s syndrome

GS

GS

GS

GS

GS

GS

Na - Cl co - transporter

Gitelman ' s syndrome

Na - Cl co - transporter

Gitelman ' s syndrome

Na - Cl co - transporter

GS

Na - Cl co - transporter

GS

Na - Cl co - transporter

GS

Na - Cl co - transporter

GS

Na - Cl co - transporter

GS

Na - Cl co - transporter

GS

Na - Cl co - transporter

Gitelman ' s syndrome

Na - Cl co - transporter

Gitelman ' s syndrome

Na - Cl co - transporter

GS

Na - Cl co - transporter

GS

Na - Cl co - transporter

GS

Na - Cl co - transporter

GS

Na - Cl co - transporter

GS

Na - Cl co - transporter

GS

NCCT

Gitelman ' s syndrome

NCCT

Gitelman ' s syndrome

NCCT

GS

NCCT

GS

NCCT

GS

NCCT

GS

NCCT

GS

NCCT

GS

NCCT

Gitelman ' s syndrome

NCCT

Gitelman ' s syndrome

NCCT

GS

NCCT

GS

NCCT

GS

NCCT

GS

NCCT

GS

NCCT

GS

NCCT

Gitelman ' s syndrome

NCCT

Gitelman ' s syndrome

NCCT

GS

NCCT

GS

NCCT

GS

NCCT

GS

NCCT

GS

NCCT

GS

NCCT

Gitelman ' s syndrome

NCCT

Gitelman ' s syndrome

NCCT

GS

NCCT

GS

NCCT

GS

NCCT

GS

NCCT

GS

NCCT

GS

NCCT

Gitelman ' s syndrome

NCCT

Gitelman ' s syndrome

NCCT

GS

NCCT

GS

NCCT

GS

NCCT

GS

NCCT

GS

NCCT

GS


Input: Regulatory network of inflammation downstream of proteinase - activated receptors . BACKGROUND : Protease - activated receptors ( PAR ) are present in the urinary bladder , and their expression is altered in response to inflammation . PARs are a unique class of G protein - coupled that carry their own ligands , which remain cryptic until unmasked by proteolytic cleavage . Although the canonical signal transduction pathway downstream of PAR activation and coupling with various G proteins is known and leads to the rapid transcription of genes involved in inflammation , the effect of PAR activation on the downstream transcriptome is unknown . We have shown that intravesical administration of PAR - activating peptides leads to an inflammatory reaction characterized by edema and granulocyte infiltration . Moreover , the inflammatory response to intravesical instillation of known pro - inflammatory stimuli such as E . coli lipopolysaccharide ( LPS ) , substance P ( SP ) , and antigen was strongly attenuated by PAR1 - and to a lesser extent by PAR2 - deficiency . RESULTS : Here , cDNA array experiments determined inflammatory genes whose expression is dependent on PAR1 activation . For this purpose , we compared the alteration in gene expression in wild type and PAR1 - / - mice induced by classical pro - inflammatory stimuli ( LPS , SP , and antigen ) . 75 transcripts were considered to be dependent on PAR - 1 activation and further annotated in silico by Ingenuity Pathways Analysis ( IPA ) and gene ontology ( GO ) . Selected transcripts were target validated by quantitative PCR ( Q - PCR ) . Among PAR1 - dependent transcripts , the following have been implicated in the inflammatory process : b2m , ccl7 , cd200 , cd63 , cdbpd , cfl1 , dusp1 , fkbp1a , fth1 , hspb1 , marcksl1 , mmp2 , myo5a , nfkbia , pax1 , plaur , ppia , ptpn1 , ptprcap , s100a10 , sim2 , and tnfaip2 . However , a balanced response to signals of injury requires a transient cellular activation of a panel of genes together with inhibitory systems that temper the overwhelming inflammation . In this context , the activation of genes such as dusp1 and nfkbia seems to counter - balance the inflammatory response to PAR activation by limiting prolonged activation of p38 MAPK and increased cytokine production . In contrast , transcripts such as arf6 and dcnt1 that are involved in the mechanism of PAR re - sensitization would tend to perpetuate the inflammatory reaction in response to common pro - inflammatory stimuli . CONCLUSION : The combination of cDNA array results and genomic networks reveals an overriding participation of PAR1 in bladder inflammation , provides a working model for the involvement of downstream signaling , and evokes testable hypotheses regarding the transcriptome downstream of PAR1 activation . It remains to be determined whether or not mechanisms targeting PAR1 gene silencing or PAR1 blockade will ameliorate the clinical manifestation of cystitis .

inflammation

inflammation

inflammation

inflammatory

edema

inflammatory

inflammatory

inflammatory

inflammatory

inflammatory

inflammation

inflammatory

inflammatory

inflammatory

bladder inflammation

cystitis

proteinase - activated receptors

Protease - activated receptors

PAR

PARs

PAR

PAR

PAR

PAR - 1

cdbpd

nfkbia

plaur

ppia

ptprcap

nfkbia

PAR

p38 MAPK

PAR

E . coli

mice

lipopolysaccharide

LPS

substance P

SP

LPS

SP

proteinase - activated receptors

Protease - activated receptors

PAR

PARs

PAR

PAR

PAR

PAR

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PAR - 1

proteinase - activated receptors

Protease - activated receptors

PAR

PARs

PAR

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PAR - 1

nfkbia

p38 MAPK

nfkbia

p38 MAPK

nfkbia

proteinase - activated receptors

nfkbia

Protease - activated receptors

nfkbia

PAR

nfkbia

PARs

nfkbia

PAR

nfkbia

PAR

nfkbia

PAR

nfkbia

nfkbia

PAR

nfkbia

PAR

nfkbia

proteinase - activated receptors

nfkbia

Protease - activated receptors

nfkbia

PAR

nfkbia

PARs

nfkbia

PAR

nfkbia

PAR

nfkbia

PAR

nfkbia

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PAR

nfkbia

PAR

p38 MAPK

p38 MAPK

proteinase - activated receptors

Protease - activated receptors

PAR

PARs

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PAR

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proteinase - activated receptors

Protease - activated receptors

PAR

PARs

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proteinase - activated receptors

edema

Protease - activated receptors

edema

PAR

edema

PARs

edema

PAR

edema

PAR

edema

PAR

edema

edema

PAR

edema

PAR

edema

proteinase - activated receptors

p38 MAPK

Protease - activated receptors

p38 MAPK

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edema

edema

edema

PAR - 1

edema

edema

edema

edema

edema

edema

proteinase - activated receptors

bladder inflammation

proteinase - activated receptors

cystitis

Protease - activated receptors

bladder inflammation

Protease - activated receptors

cystitis

PAR

bladder inflammation

PAR

cystitis

PARs

bladder inflammation

PARs

cystitis

PAR

bladder inflammation

PAR

cystitis

PAR

bladder inflammation

PAR

cystitis

PAR

bladder inflammation

PAR

cystitis

bladder inflammation

cystitis

bladder inflammation

cystitis

bladder inflammation

cystitis

PAR - 1

bladder inflammation

PAR - 1

cystitis

bladder inflammation

cystitis

PAR

bladder inflammation

PAR

cystitis

PAR

bladder inflammation

PAR

cystitis

bladder inflammation

cystitis

bladder inflammation

cystitis

bladder inflammation

cystitis

bladder inflammation

cystitis

p38 MAPK

p38 MAPK

p38 MAPK

PAR - 1

p38 MAPK

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proteinase - activated receptors

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proteinase - activated receptors

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proteinase - activated receptors

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proteinase - activated receptors

ptprcap

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ptprcap

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proteinase - activated receptors

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proteinase - activated receptors

ppia

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proteinase - activated receptors

plaur

Protease - activated receptors

plaur

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plaur

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plaur

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plaur

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proteinase - activated receptors

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proteinase - activated receptors

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proteinase - activated receptors

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proteinase - activated receptors

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proteinase - activated receptors

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proteinase - activated receptors

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proteinase - activated receptors

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proteinase - activated receptors

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inflammation

inflammation

inflammation

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inflammatory

inflammatory

inflammatory

inflammatory

inflammatory

inflammation

inflammatory

inflammatory

inflammatory

inflammation

inflammation

inflammation

inflammatory

inflammatory

inflammatory

inflammatory

inflammatory

inflammatory

inflammation

inflammatory

inflammatory

inflammatory

inflammation

p38 MAPK

inflammation

p38 MAPK

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p38 MAPK

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p38 MAPK

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p38 MAPK

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p38 MAPK

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p38 MAPK

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p38 MAPK

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p38 MAPK

inflammation

p38 MAPK

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p38 MAPK

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p38 MAPK

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inflammation

inflammation

inflammation

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inflammatory

inflammation

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ptprcap

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ptprcap

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ptprcap

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ptprcap

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ptprcap

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ptprcap

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inflammation

inflammation

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ppia

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plaur

inflammation

plaur

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plaur

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plaur

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plaur

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plaur

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plaur

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plaur

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inflammatory

plaur

inflammatory

plaur

inflammation

inflammation

inflammation

inflammatory

inflammatory

inflammatory

inflammatory

inflammatory

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inflammation

inflammatory

inflammatory

inflammatory

inflammation

nfkbia

inflammation

nfkbia

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nfkbia

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proteinase - activated receptors

inflammation

Protease - activated receptors

inflammation

PAR

inflammation

PARs

inflammation

PAR

inflammation

PAR

inflammation

PAR

inflammation

inflammation

PAR

inflammation

PAR

inflammation

proteinase - activated receptors

inflammation

Protease - activated receptors

inflammation

PAR

inflammation

PARs

inflammation

PAR

inflammation

PAR

inflammation

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inflammation

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inflammation

PAR

inflammation

proteinase - activated receptors

inflammation

Protease - activated receptors

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PAR

inflammation

PAR

inflammation

PAR

inflammation

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PAR

inflammation

PAR

inflammatory

proteinase - activated receptors

inflammatory

Protease - activated receptors

inflammatory

PAR

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PARs

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PAR

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proteinase - activated receptors

inflammatory

Protease - activated receptors

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PAR

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PAR

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proteinase - activated receptors

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Protease - activated receptors

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PAR

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PAR

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proteinase - activated receptors

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Protease - activated receptors

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PAR

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proteinase - activated receptors

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Protease - activated receptors

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proteinase - activated receptors

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Protease - activated receptors

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PAR

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inflammation

proteinase - activated receptors

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Protease - activated receptors

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proteinase - activated receptors

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Protease - activated receptors

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PAR

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proteinase - activated receptors

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proteinase - activated receptors

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PAR

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PAR

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PAR

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PAR

inflammation

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PAR - 1

inflammation

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PAR - 1

inflammation

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PAR - 1

inflammation

inflammation

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PAR - 1

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PAR - 1

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PAR - 1

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PAR - 1

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proteinase - activated receptors

substance P

proteinase - activated receptors

SP

proteinase - activated receptors

SP

Protease - activated receptors

substance P

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proteinase - activated receptors

lipopolysaccharide

proteinase - activated receptors

LPS

proteinase - activated receptors

LPS

Protease - activated receptors

lipopolysaccharide

Protease - activated receptors

LPS

Protease - activated receptors

LPS

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lipopolysaccharide

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lipopolysaccharide

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lipopolysaccharide

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lipopolysaccharide

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lipopolysaccharide

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inflammatory

LPS


Input: Caffeine challenge test in panic disorder and depression with panic attacks . Our aim was to observe if patients with panic disorder ( PD ) and patients with major depression with panic attacks ( MDP ) ( Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria ) respond in a similar way to the induction of panic attacks by an oral caffeine challenge test . We randomly selected 29 patients with PD , 27 with MDP , 25 with major depression without panic attacks ( MD ) , and 28 healthy volunteers . The patients had no psychotropic drug for at least a 4 - week period . In a randomized double - blind experiment performed in 2 occasions 7 days apart , 480 mg caffeine and a caffeine - free ( placebo ) solution were administered in a coffee form and anxiety scales were applied before and after each test . A total of 58 . 6 % ( n = 17 ) of patients with PD , 44 . 4 % ( n = 12 ) of patients with MDP , 12 . 0 % ( n = 3 ) of patients with MD , and 7 . 1 % ( n = 2 ) of control subjects had a panic attack after the 480 - mg caffeine challenge test ( chi ( 2 ) ( 3 ) = 16 . 22 , P = . 001 ) . The patients with PD and MDP were more sensitive to caffeine than were patients with MD and healthy volunteers . No panic attack was observed after the caffeine - free solution intake . The patients with MD had a lower heart rate response to the test than all the other groups ( 2 - way analysis of variance , group by time interaction with Greenhouse - Geisser correction : F ( 3 , 762 ) = 2 . 85 , P = . 026 ) . Our data suggest that there is an association between panic attacks , no matter if associated with PD or MDP , and hyperreactivity to an oral caffeine challenge test .

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