MCID: MNN013
MIFTS: 68

Meningitis malady

Neuronal diseases, Rare diseases, Infectious diseases, Respiratory diseases categories
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Summaries for Meningitis

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Sources:
8Disease Ontology, 34MedlinePlus, 4CDC, 44NINDS, 65Wikipedia, 33MalaCards
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MedlinePlus:34 Meningitis is inflammation of the thin tissue that surrounds the brain and spinal cord, called the meninges. there are several types of meningitis. the most common is viral meningitis, which you get when a virus enters the body through the nose or mouth and travels to the brain. bacterial meningitis is rare, but can be deadly. it usually starts with bacteria that cause a cold-like infection. it can block blood vessels in the brain and lead to stroke and brain damage. it can also harm other organs. pneumococcal infections and meningococcal infections can cause bacterial meningitis. anyone can get meningitis, but it is more common in people whose bodies have trouble fighting infections. meningitis can progress rapidly. you should seek medical care quickly if you have a sudden fever a severe headache a stiff neck early treatment can help prevent serious problems, including death. vaccines can prevent some of the bacterial infections that cause meningitis. parents of adolescents and students living in college dorms should talk to a doctor about the vaccination. nih: national institute of neurological disorders and stroke

MalaCards: Meningitis is related to meningococcal meningitis and aseptic meningitis. An important gene associated with Meningitis is ADA (adenosine deaminase), and among its related pathways are Oxidative Stress and Detoxification of Reactive Oxygen Species. The compounds bucillamine and muramyl dipeptide have been mentioned in the context of this disorder. Affiliated tissues include brain, spinal cord and testes, and related mouse phenotypes are renal/urinary system and tumorigenesis.

Disease Ontology:8 Meningitis is a nervous system infectious disease characterized as an inflammation of the pia-arachnoid meninges. it can be caused by growth of bacteria, fungi, or parasites within the subarachnoid space or by the growth of bacteria or viruses within the meningeal or ependymal cells. meningitis is a diffuse infection caused by a variety of different agents.

CDC:4 Meningitis is a disease caused by the inflammation of the protective membranes covering the brain and spinal cord known as the meninges. The inflammation is usually caused by an infection of the fluid surrounding the brain and spinal cord.

NINDS:44 Meningitis and encephalitis are inflammatory diseases of the membranes that surround the brain and spinal cord and are caused by bacterial or viral infections. Viral meningitis is sometimes called aseptic meningitis to indicate it is not the result of bacterial infection and cannot be treated with antibiotics. Symptoms of encephalitis include sudden fever, headache, vomiting, heightened sensitivity to light, stiff neck and back, confusion and impaired judgment, drowsiness, weak muscles, a clumsy and unsteady gait, and irritability. Symptoms that might require emergency treatment include loss of consciousness, seizures, muscle weakness, or sudden severe dementia.

Wikipedia:65 Meningitis (from Ancient Greek ??????/m more...

Aliases & Classifications for Meningitis

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Sources:
8Disease Ontology, 44NINDS, 10DISEASES, 45Novoseek, 34MedlinePlus, 62UMLS, 35MeSH, 58SNOMED-CT, 27ICD9CM, 40NCIt, 25ICD10
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Related Diseases for Meningitis

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Sources:
17GeneCards, 18GeneDecks
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Diseases in the Viral Meningitis family:

Bacterial Meningitis Chronic Meningitis
meningitis

Diseases related to Meningitis via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show top 50)    (show all 767)
idRelated DiseaseScoreTop Affiliating Genes
1meningococcal meningitis31.7CFP, MBL2
2aseptic meningitis31.7GUSB, SOD2, ADA
3bacterial meningitis31.5TLR2, CFP, GUSB, SOD2, ADA, IL8
4viral meningitis31.4ADA, IL8, CRP
5encephalitis30.9TLR2, IL1B, CAT
6influenza30.9MBL2, ADA, SOD2
7pneumonia30.7TLR2, IL10, IL8, IL1B, CRP, MBL2
8tuberculosis30.7IL1B, CRP, MBL2, IL10, LYZ, TLR2
9herpes simplex30.6NTF3, SOD2, TLR2
10otitis media30.5TLR2, IL1B, MBL2
11sepsis30.5TLR2, SOD2, IL10, IL8, IL1B, CRP
12bacteremia30.5MBL2, CRP, CAT, GUSB
13arthritis30.5IL8, IL1B
14hepatitis30.5CAT, SOD2, GUSB, TLR2
15leukemia30.4TLR2, GUSB, ADA, LYZ, NTF3, IL1B
16osteomyelitis30.4CRP, CAT
17sarcoma30.3LYZ, ADA, SOD2, GUSB
18systemic lupus erythematosus30.3CRP, IL10, ADA, GUSB, CFP, TLR2
19multiple sclerosis30.2MMP9, IL10, IL1B, MBL2
20melanoma30.2GUSB, SOD2, MMP9, ADA, NTF3, IL10
21malaria30.2TLR2, CFP, IL10
22complement deficiency30.2MBL2, CFP
23adenocarcinoma30.1GUSB, SOD2, MMP9, ADA, NTF3
24behcet's disease30.1ADA, IL8, CRP, MBL2
25kawasaki disease30.1MMP9, CRP, MBL2
26eosinophilia30.1MBL2, IL8, IL10
27peritonitis30.1TLR2, ADA, IL1B, CRP
28glomerulonephritis30.1CFP, IL1B, CAT, MBL2
29lung adenocarcinoma30.0SOD2, MMP9, CAT
30neisseria meningitidis infection30.0TLR2, CFP, MBL2
31sarcoidosis30.0IL1B, LYZ, ADA
32aspergillosis29.9TLR2, MBL2
33chronic granulomatous disease29.9CFP, ADA, CAT
34lymphopenia29.9CAT, IL10, ADA
35cerebral malaria29.9IL1B, IL10
36diabetes mellitus29.8CFP, SOD2, MMP9, IL1B, CAT, CRP
37pancreatitis29.8SOD2, IL10, IL1B, CRP
38mastitis29.8TLR2, LYZ, IL8, IL1B
39rheumatic fever29.7MBL2, CRP
40pulmonary tuberculosis29.7TLR2, GUSB, ADA, IL10, CAT, MBL2
41membranoproliferative glomerulonephritis29.7MBL2, CFP
42familial mediterranean fever29.7IL1B, CRP
43malignant glioma29.7SOD2, MMP9, NTF3, CAT
44septic shock29.7TLR2, CFP, IL10, IL8, IL1B, CRP
45alcoholic liver cirrhosis29.7SOD2, IL8, CAT
46acute pancreatitis29.7IL10, IL8, CRP
47common variable immune deficiency29.6IL10, MBL2
48keratitis29.6MMP9, TLR2
49hyperglycemia29.6TLR2, SOD2, CAT, CRP
50adult respiratory distress syndrome29.6IL8, IL1B

Graphical network of the top 20 diseases related to Meningitis:



Diseases related to meningitis

Symptoms for Meningitis

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Drugs & Therapeutics for Meningitis

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Sources:
42NIH Clinical Center, 6ClinicalTrials, 62UMLS, 41NDF-RT
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Drug clinical trials:

Search ClinicalTrials for Meningitis

Search NIH Clinical Center for Meningitis

Genetic Tests for Meningitis

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Anatomical Context for Meningitis

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33MalaCards
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MalaCards organs/tissues related to Meningitis:

33
Brain, Spinal cord, Testes, T cells, Bone, Pituitary, B cells, Liver, Endothelial, Lung, Skin, Myeloid, Pineal, Breast, Cortex, Bone marrow, Eye, Prostate, Medulla oblongata, Monocytes, Colon, Kidney, Tonsil, Heart, Cervix, Spleen, Temporal lobe, Thyroid, Adrenal gland

Animal Models for Meningitis or affiliated genes

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37MGI
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MGI Mouse Phenotypes related to Meningitis:

37 (show all 14)
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053678.4TLR2, GUSB, SOD2, MMP9, ADA, MBL2
2MP:00020068.1TLR2, SOD2, MMP9, IL10, IL1B, CAT
3MP:00028738.0TLR2, CFP, GUSB, ADA, NTF3, IL10
4MP:00053907.9TLR2, CFP, GUSB, MMP9, ADA, IL10
5MP:00053887.9TLR2, MMP9, ADA, NTF3, IL10
6MP:00053697.8IL10, NTF3, MMP9, SOD2, TLR2
7MP:00053847.7TLR2, GUSB, SOD2, MMP9, ADA, IL10
8MP:00053897.6GUSB, SOD2, MMP9, ADA, NTF3, IL10
9MP:00053977.3TLR2, GUSB, SOD2, MMP9, ADA, IL10
10MP:00053877.1MMP9, SOD2, CFP, TLR2, ADA, IL10
11MP:00053857.0TLR2, CFP, SOD2, MMP9, NTF3, IL10
12MP:00053786.9TLR2, GUSB, SOD2, MMP9, ADA, NTF3
13MP:00107686.4TLR2, CFP, GUSB, SOD2, MMP9, ADA
14MP:00053765.9MBL2, TLR2, CFP, GUSB, SOD2, MMP9

Publications for Meningitis

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52PubMed
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Articles related to Meningitis:

(show top 50)    (show all 4856)
idTitleAuthorsYear
1
Association of treatment for bacterial meningitis with the development of sequelae. (23537920)
2013
2
Aseptic meningitis. (23622323)
2013
3
Lumbar drainage for the treatment of severe bacterial meningitis. (23739926)
2013
4
The elusive diagnosis: recurrent benign lymphocytic meningitis. (24156176)
2013
5
Bacillus Calmette-GuAcrin is a preventive factor in mortality of childhood tuberculous meningitis. (24231588)
2013
6
Eosinophilic meningitis caused by Angiostrongylus cantonensis in an adolescent with mental retardation and pica disorder. (23445744)
2013
7
Cryptococcal meningitis occurring eight years before a diagnosis of lupus was made. (23973401)
2013
8
Recurrent case of ibuprofen-induced aseptic meningitis in mixed connective tissue disease. (23632618)
2013
9
Recurrent meningitis in children. (23894913)
2013
10
Meningeal hemangiopericytoma and solitary fibrous tumors carry the NAB2-STAT6 fusion and can be diagnosed by nuclear expression of STAT6 protein. (23575898)
2013
11
Induction of mouse melioidosis with meningitis by CD11b+ phagocytic cells harboring intracellular B. pseudomallei as a Trojan horse. (23951382)
2013
12
Postoperative meningitis and epidural abscess due to extended-spectrum I^-lactamase-producing Klebsiella pneumoniae: a case report and a review of the literature. (22989843)
2012
13
Effect of vaccines on bacterial meningitis worldwide. (23141619)
2012
14
Treatment of Drug-resistant Pneumococcal Meningitis. (21308542)
2010
15
Etiology of aseptic meningitis, peripheral facial nerve palsy, and a combination of both in children. (19934789)
2010
16
Regulation of activin A synthesis in microglial cells: pathophysiological implications for bacterial meningitis. (19681171)
2010
17
Rhabdoid meningioma presenting with subependymal and diffuse meningeal involvement but no mass lesion. (20800496)
2010
18
Shunting in hydrocephalus due to tuberculous meningitis. Cases presenting with high cerebrospinal fluid proteins in pediatric age. (19546843)
2009
19
Disseminated cryptococcosis with meningitis, peritonitis, and cryptococcemia in a HIV-negative patient with cirrhosis: a case report. (19946481)
2009
20
Tuberculous meningitis presenting with unusual clinical features in Nigerians: Two case reports. (18816394)
2008
21
Bacterial meningitis score is valid in other populations of children. (18571557)
2008
22
Diagnosis of meningococcal meningitis in Brazil by use of PCR. (17366009)
2007
23
Endoscopic third ventriculostomy in prepontine-suprasellar tuberculoma with tuberculous meningitis hydrocephalus: a case report. (17190988)
2007
24
Hospital-based surveillance of meningococcal meningitis in Salvador, Brazil. (17681359)
2007
25
Prophagic DNA fragments in Streptococcus agalactiae strains and association with neonatal meningitis. (16517893)
2006
26
Pretreatment intracerebral and peripheral blood immune responses in Vietnamese adults with tuberculous meningitis: diagnostic value and relationship to disease severity and outcome. (16424233)
2006
27
Pneumococcal meningitis epidemics in Africa. (16912942)
2006
28
The changing epidemiology of pediatric aseptic meningitis in Daejeon, Korea from 1987 to 2003. (16262909)
2005
29
Cytokine profile in cerebrospinal fluid of children with echovirus type 4 meningitis. (14643393)
2003
30
The possible role of cerebrospinal fluid adenosine deaminase activity in the diagnosis of tuberculous meningitis in adults. (11792470)
2002
31
Mild cognitive impairment after viral meningitis in adults. (12021945)
2002
32
Streptococcal meningitis in adults: therapeutic outcomes and prognostic factors. (11532551)
2001
33
Multicenter evaluation of the Amplicor Enterovirus PCR test with cerebrospinal fluid from patients with aseptic meningitis. The European Union Concerted Action on Viral Meningitis and Encephalitis. (9705409)
1998
34
Increased glutamine synthetase immunoreactivity in experimental pneumococcal meningitis. (9083551)
1997
35
Nosocomial bacterial and fungal meningitis in cancer patients. (8564349)
1995
36
Pseudogout mimicking meningitis. (8461939)
1993
37
C-reactive proteins, immunoglobulin profile and mycobacterial antigens in cerebrospinal fluid of patients with pyogenic and tuberculous meningitis. (1293215)
1992
38
Group C streptococcal meningitis with favorable recovery. A case report. (2246567)
1990
39
Tumor necrosis factor alpha/cachectin and interleukin 1 beta initiate meningeal inflammation. (2373990)
1990
40
Molecular epidemiology of neonatal meningitis due to Citrobacter diversus: a study of isolates from hospitals in Maryland. (3734491)
1986
41
Sphenoid sinusitis presenting as chronic meningitis. (3699068)
1986
42
Evaluation of aztreonam in experimental bacterial meningitis and cerebritis. (6362552)
1983
43
Intrafamilial meningococcal meningitis. (7428775)
1980
44
Meningococcal meningitis in northern Ghana: epidemiology and control measures. (889015)
1977
45
An unusual case of meningococcal meningitis. (5539776)
1971
46
Viral meningitis. (13525934)
1958
47
Purulent neonatal meningitis; a study of forty-five cases. (13406691)
1957
48
Meningococcal meningitis. (13296658)
1956
49
Epidemic meningitis and meningococcemia treated with penicillin. (21012527)
1946
50
Lateral Sinus Thrombosis; Serous Meningitis; Recovery. (19977139)
1913

Variations for Meningitis

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Expression for genes affiliated with Meningitis

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Sources:
2BioGPS, 15Gene Expression Omnibus DataSets
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Expression patterns in normal tissues for genes affiliated with Meningitis

Search GEO for disease gene expression data for Meningitis.

Pathways for genes affiliated with Meningitis

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Sources:
50PathCards, 38NCBI BioSystems Database, 55Reactome, 51PharmGKB, 53QIAGEN, 60Thomson Reuters, 57SinoBiological, 30KEGG, 54R&D Systems, 12EMD Millipore
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Pathways related to Meningitis according to GeneCards/GeneDecks:

(show all 31)
idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.7SOD2, CAT
2
Show member pathways
9.7CAT, SOD2
39.7CAT, SOD2
49.7MMP9, IL8
5
Show member pathways
Immune response Alternative complement pathway60
Immune response Lectin Induced complement pathway60
Immune response Classic complement pathway60
9.6MBL2, CRP, CFP
69.5IL1B, IL10
79.5IL1B, IL10
89.5IL10, IL1B
99.4IL1B, IL8, TLR2
10
Show member pathways
Transcription NF kB signaling pathway60
Immune response Toll like receptor TLR ligands and common TLR signaling pathway leading to cell proinflammatory response60
9.4TLR2, IL8, IL1B
11
Show member pathways
Immune response Role of TLRs 3 and 4 in cell antiviral response TICAM1 specific signaling pathways60
Immune response IL 1 signaling pathway60
9.4TLR2, IL8, IL1B
129.4TLR2, IL8, IL1B
139.4TLR2, IL8, IL1B
149.3IL1B, IL8, IL10
159.3IL10, IL8, IL1B
169.3IL10, IL8, IL1B
179.3IL1B, IL8, MMP9
18
Show member pathways
PLK2 and PLK4 events38
Polo-like kinase signaling events in the cell cycle38
9.2SOD2, IL10, CAT
199.2IL1B, IL10, TLR2
20
Show member pathways
IL27-mediated signaling events38
9.2TLR2, IL10, IL1B
21
Show member pathways
9.2TLR2, IL10, IL1B
22
Show member pathways
9.1IL1B, IL8, CFP, TLR2
23
Show member pathways
thioredoxin pathway38
9.1SOD2, IL1B, CAT, CRP
248.9IL1B, IL8, IL10, TLR2
258.9IL1B, IL8, IL10, TLR2
26
Show member pathways
8.9IL1B, NTF3, TLR2
27
Show member pathways
8.8IL1B, IL8, IL10, SOD2
28
Show member pathways
8.5NTF3, IL10, IL8, IL1B
29
Show member pathways
8.5NTF3, IL10, IL8, IL1B
30
Show member pathways
Toll-like receptor signaling pathway38
Regulation of toll-like receptor signaling pathway38
8.4TLR2, MMP9, IL10, IL8, IL1B
31
Show member pathways
8.1TLR2, NTF3, IL10, IL8, IL1B

Compounds for genes affiliated with Meningitis

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Sources:
45Novoseek, 29IUPHAR, 51PharmGKB, 11DrugBank, 61Tocris Bioscience, 24HMDB, 3BitterDB
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Compounds related to Meningitis according to GeneCards/GeneDecks:

(show top 50)    (show all 192)
idCompoundScoreTop Affiliating Genes
1bucillamine459.8IL1B, CRP, CAT
2muramyl dipeptide45 2910.6IL8, IL1B, TLR2
3echinacea459.6IL10, IL1B, IL8
4bifidobacterium459.6TLR2, GUSB, IL10
53-amino-1,2,4-triazole459.5CAT, SOD2, GUSB
6hbd2459.5IL1B, IL8, TLR2
7ulinastatin459.4IL8, IL10, GUSB
8etanercept45 51 1111.4IL10, CRP, IL1B, IL8
9diphenyleneiodonium459.3CAT, SOD2, IL8, IL1B
10gabexate mesilate459.3MMP9, IL10, CRP, IL8
11toxin-1459.3IL1B, IL8, IL10
12mip 1alpha459.3IL8, IL10, IL1B
13polyinosinic-polycytidylic acid459.3TLR2, IL8, IL10, IL1B
14il 10459.2IL10, IL1B, TLR2, IL8
15betacarotene459.1CRP, CAT, IL10, SOD2
16azithromycin45 1110.1CRP, IL8, IL10
17ribavirin45 51 1111.1ADA, MBL2, MMP9, IL10
188-isoprostane459.1IL10, CAT, MMP9, CRP, IL8
19polymyxin b459.0IL8, IL1B, IL10, MBL2, TLR2
20ivig459.0IL1B, IL10, MMP9, CRP
21lipoteichoic acid459.0IL10, TLR2, IL8, IL1B, MBL2
22peptidoglycan45 2910.0TLR2, IL10, IL8, IL1B, MBL2
23endotoxin459.0TLR2, IL10, IL1B, IL8, CRP
24leukotriene b445 61 2410.9GUSB, TLR2, IL1B, MMP9, IL8
25pdtc458.9SOD2, MMP9, IL8, CAT, IL1B
26simvastatin45 51 61 29 24 1113.9MMP9, TLR2, IL8, IL10, CRP
27neopterin458.9MBL2, ADA, IL1B, IL10, CRP, IL8
28curcumin458.9CAT, IL1B, SOD2, MMP9, IL8
29ccl345 299.8IL1B, IL8, IL10, MMP9, TLR2
304-hydroxynonenal45 249.8SOD2, IL10, GUSB, CAT
31cyclophosphamide45 51 1110.8MMP9, IL10, CRP, MBL2, SOD2
32n acetylcysteine458.7CAT, SOD2, MMP9, IL8, IL1B, CRP
33creatinine458.6GUSB, MBL2, CRP, SOD2, MMP9, ADA
34lactate458.5IL8, GUSB, CAT, ADA, MMP9, CRP
35methotrexate51 45 1110.5IL1B, IL10, ADA, MMP9, SOD2, CRP
36rantes458.4IL10, MMP9, TLR2, MBL2, IL1B, IL8
37cyclosporin a45 29 6110.4TLR2, SOD2, MMP9, IL10, ADA, IL8
38pge2458.3MMP9, GUSB, TLR2, IL1B, IL8, IL10
39sb 20358045 619.3IL1B, CAT, CRP, MMP9, IL10, TLR2
40genistein45 29 61 3 24 1113.0IL1B, NTF3, MMP9, SOD2, GUSB, IL8
41histamine45 29 249.9IL1B, IL8, GUSB, IL10, ADA, TLR2
42dexamethasone45 51 29 1110.8MMP9, SOD2, TLR2, ADA, IL10, IL1B
43actinomycin d457.8CAT, IL1B, IL8, NTF3, MMP9, SOD2
44ly294002457.6MMP9, SOD2, NTF3, CRP, IL1B, IL8
45aspartate457.4ADA, NTF3, IL10, MMP9, SOD2, GUSB
46nitric oxide45 24 119.4IL10, IL8, MBL2, CAT, IL1B, TLR2
47superoxide45 248.3CAT, IL1B, IL8, NTF3, SOD2, GUSB
48cysteine457.3MBL2, TLR2, CAT, SOD2, MMP9, NTF3
49cycloheximide457.0TLR2, SOD2, NTF3, IL10, IL1B, CAT
50vegf456.7MBL2, TLR2, SOD2, MMP9, ADA, NTF3

GO Terms for genes affiliated with Meningitis

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16Gene Ontology
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Cellular components related to Meningitis according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1extracellular regionGO:0055767.0MMP9, LYZ, NTF3, IL8, IL1B, CRP
2extracellular spaceGO:0056156.7MBL2, CFP, MMP9, ADA, LYZ, IL10

Biological processes related to Meningitis according to GeneCards/GeneDecks:

(show all 23)
idNameGO IDScoreTop Affiliating Genes
1response to vitamin EGO:03319710.2CAT, ADA
2opsonizationGO:00822810.2CRP, MBL2
3embryonic digestive tract developmentGO:04856610.1IL8, ADA
4response to molecule of bacterial originGO:00223710.0IL8, IL10
5response to hyperoxiaGO:05509310.0CAT, SOD2
6defense response to Gram-positive bacteriumGO:0508309.8MBL2, CRP, TLR2
7positive regulation of NF-kappaB import into nucleusGO:0423469.8TLR2, IL1B
8negative regulation of interleukin-12 productionGO:0326959.8IL10, TLR2
9positive regulation of interleukin-8 productionGO:0327579.8IL1B, TLR2
10lipopolysaccharide-mediated signaling pathwayGO:0316639.7IL1B, TLR2
11positive regulation of cytokine secretionGO:0507159.6IL10, TLR2
12positive regulation of NF-kappaB transcription factor activityGO:0510929.6TLR2, IL1B, CAT
13negative regulation of growth of symbiont in hostGO:0441309.6MBL2, IL10, TLR2
14induction of positive chemotaxisGO:0509309.6IL8, NTF3
15positive regulation of nitric oxide biosynthetic processGO:0454299.6IL1B, SOD2, TLR2
16embryo implantationGO:0075669.5IL1B, MMP9
17immune responseGO:0069559.4IL1B, IL8, CFP, TLR2
18response to activityGO:0148239.4SOD2, IL10
19negative regulation of cell proliferationGO:0082859.2TLR2, SOD2, IL8, IL1B
20response to hypoxiaGO:0016669.2TLR2, SOD2, ADA, CAT, CRP
21defense response to bacteriumGO:0427429.0CFP, LYZ, IL10, MBL2
22cell-cell signalingGO:0072678.4IL1B, IL10, NTF3
23inflammatory responseGO:0069548.4CRP, IL1B, IL8, IL10, LYZ, TLR2

Products for genes affiliated with Meningitis

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  • Antibodies
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Sources for Meningitis

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4CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
29IUPHAR
30KEGG
35MeSH
36MESH via Orphanet
37MGI
40NCIt
41NDF-RT
44NINDS
45Novoseek
47OMIM
48OMIM via Orphanet
52PubMed
53QIAGEN
59SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet