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In Android a similar feature called "digital wellbeing" has been implemented to keep track of cell phone usage. [85] These apps usually work by doing one of two things: increasing awareness by sending user usage summaries, or notifying the user when he/she has exceeded some user-defined time-limit for each app or app category. ... Journal of Behavioral Addictions . 7 (2): 252–259. doi : 10.1556/2006.7.2018.49 . ... Behaviour & Information Technology . 38 (2): 110–119. doi : 10.1080/0144929X.2018.1515984 . ... A review of the literature". Adicciones . 24 (2): 139–152. PMID 22648317 . ^ Koo HJ, Kwon JH (2014). ... S2CID 148724233 . ^ "iPhone" , Wikipedia , 29 February 2020 , retrieved 2 March 2020 ^ "iPad" , Wikipedia , 20 February 2020 , retrieved 2 March 2020 ^ a b Brody, Jane E. (9 January 2017).
Heredofamilial amyloidosis Specialty Dermatology Heredofamilial amyloidosis is an inherited condition that may be characterized by systemic or localized deposition of amyloid in body tissues. [1] : 522 [2] See also [ edit ] Amyloidosis List of cutaneous conditions References [ edit ] ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology . Saunders Elsevier. ISBN 978-0-7216-2921-6 . ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set . St. Louis: Mosby. ISBN 978-1-4160-2999-1 . v t e Amyloidosis Common amyloid forming proteins AA ATTR Aβ2M AL Aβ / APP AIAPP ACal APro AANF ACys ABri Systemic amyloidosis AL amyloidosis AA amyloidosis Aβ2M/Haemodialysis-associated AGel/Finnish type AA/Familial Mediterranean fever ATTR/Transthyretin-related hereditary Organ-limited amyloidosis Heart AANF/Isolated atrial Brain Familial amyloid neuropathy ACys+ABri/Cerebral amyloid angiopathy Aβ/Alzheimer's disease Kidney AApoA1+AFib+ALys/Familial renal Skin Primary cutaneous amyloidosis Amyloid purpura Endocrine Thyroid ACal/Medullary thyroid cancer Pituitary APro/Prolactinoma Pancreas AIAPP/Insulinoma AIAPP/Diabetes mellitus type 2 This cutaneous condition article is a stub .
Hereditary amyloidosis refers to a group of inherited conditions that make up one of the subtypes of amyloidosis . Hereditary amyloidosis is characterized by the deposit of an abnormal protein called amyloid in multiple organs of the body where it should not be, which causes disruption of organ tissue structure and function. In hereditary amyloidosis, amyloid deposits most often occur in tissues of the heart, kidneys, and nervous system. While symptoms of hereditary amyloidosis may appear in childhood, most individuals do not experience symptoms until adulthood. There are many types of hereditary amyloidosis associated with different gene mutations and abnormal proteins.
Secondary systemic amyloidosis Micrograph of liver amyloidosis, H&E stain Secondary systemic amyloidosis is a condition that involves the adrenal gland , liver , spleen , and kidney as a result of amyloid deposition due to a chronic disease such as Behçet's disease , ulcerative colitis , etc. [1] : 520 [2] See also [ edit ] Amyloidosis Primary systemic amyloidosis List of cutaneous conditions References [ edit ] ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology . Saunders Elsevier. ISBN 978-0-7216-2921-6 . ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set . St. Louis: Mosby. ISBN 978-1-4160-2999-1 . v t e Amyloidosis Common amyloid forming proteins AA ATTR Aβ2M AL Aβ / APP AIAPP ACal APro AANF ACys ABri Systemic amyloidosis AL amyloidosis AA amyloidosis Aβ2M/Haemodialysis-associated AGel/Finnish type AA/Familial Mediterranean fever ATTR/Transthyretin-related hereditary Organ-limited amyloidosis Heart AANF/Isolated atrial Brain Familial amyloid neuropathy ACys+ABri/Cerebral amyloid angiopathy Aβ/Alzheimer's disease Kidney AApoA1+AFib+ALys/Familial renal Skin Primary cutaneous amyloidosis Amyloid purpura Endocrine Thyroid ACal/Medullary thyroid cancer Pituitary APro/Prolactinoma Pancreas AIAPP/Insulinoma AIAPP/Diabetes mellitus type 2 This cutaneous condition article is a stub .
Secondary cutaneous amyloidosis Specialty Dermatology Secondary cutaneous amyloidosis is a skin condition that occurs following PUVA therapy and in benign and malignant cutaneous neoplasms in which deposits of amyloid may be found. [1] : 522 [2] See also [ edit ] Amyloidosis Skin lesion List of cutaneous conditions References [ edit ] ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology . Saunders Elsevier. ISBN 978-0-7216-2921-6 . ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set . St. Louis: Mosby. ISBN 978-1-4160-2999-1 . v t e Amyloidosis Common amyloid forming proteins AA ATTR Aβ2M AL Aβ / APP AIAPP ACal APro AANF ACys ABri Systemic amyloidosis AL amyloidosis AA amyloidosis Aβ2M/Haemodialysis-associated AGel/Finnish type AA/Familial Mediterranean fever ATTR/Transthyretin-related hereditary Organ-limited amyloidosis Heart AANF/Isolated atrial Brain Familial amyloid neuropathy ACys+ABri/Cerebral amyloid angiopathy Aβ/Alzheimer's disease Kidney AApoA1+AFib+ALys/Familial renal Skin Primary cutaneous amyloidosis Amyloid purpura Endocrine Thyroid ACal/Medullary thyroid cancer Pituitary APro/Prolactinoma Pancreas AIAPP/Insulinoma AIAPP/Diabetes mellitus type 2 This cutaneous condition article is a stub .
Familial Alzheimer disease is caused by a mutation in one of at least three genes, which code for presenilin 1 , presenilin 2 , and amyloid precursor protein (APP). [6] [7] [8] Other gene mutations are in study. ... Unsourced material may be challenged and removed . ( October 2009 ) ( Learn how and when to remove this template message ) Following cleavage by β-secretase , APP is cleaved by a membrane-bound protein complex called γ-secretase to generate Aβ. [26] Presenilins 1 and 2 are the enzymatic centers of this complex along with nicastrin, Aph1, and PEN-2. Alpha-secretase cleavage of APP, which precludes the production of Aβ, is the most common processing event for APP. 21 allelic mutations have been discovered in the APP gene. ... "YAC fragmentation with repetitive and single-copy sequences: detailed physical mapping of the presenilin 1 gene on chromosome 14". Gene . 229 (1–2): 193–201. doi : 10.1016/S0378-1119(99)00023-2 . ... Nature Medicine . 2 (2): 224–9. doi : 10.1038/nm0296-224 .
Primary cutaneous amyloidosis Other names Primary localized cutaneous amyloidosis [1] Macular amyloidosis, located on the right lumbar region of the back Specialty Dermatology Primary cutaneous amyloidosis is a form of amyloidosis associated with oncostatin M receptor . [2] [3] This type of amyloidosis has been divided into the following types: [4] : 520 Macular amyloidosis is a cutaneous condition characterized by itchy, brown, rippled macules usually located on the interscapular region of the back. [4] : 521 Combined cases of lichen and macular amyloidosis are termed biphasic amyloidosis, and provide support to the theory that these two variants of amyloidosis exist on the same disease spectrum. [5] Lichen amyloidosis is a cutaneous condition characterized by the appearance of occasionally itchy lichenoid papules , typically appearing bilaterally on the shins. [4] : 521 Histopathology of lichen amyloidosis, with subepithelial Congo red -positive deposits Nodular amyloidosis is a rare cutaneous condition characterized by nodules that involve the acral areas. [4] : 521 See also [ edit ] Amyloidosis List of cutaneous conditions References [ edit ] ^ "Primary cutaneous amyloidosis | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program" . rarediseases.info.nih.gov . ... Andrews' Diseases of the Skin: clinical Dermatology . Saunders Elsevier. ISBN 978-0-7216-2921-6 . ^ Lichen amyloidosis of the auricular concha Craig, E. (2006) Dermatology Online Journal 12 (5): 1, University of California, Davis Department of Dermatology External links [ edit ] Classification D ICD - 9-CM : 277.3 OMIM : 105250 MeSH : C562643 DiseasesDB : 29871 v t e Amyloidosis Common amyloid forming proteins AA ATTR Aβ2M AL Aβ / APP AIAPP ACal APro AANF ACys ABri Systemic amyloidosis AL amyloidosis AA amyloidosis Aβ2M/Haemodialysis-associated AGel/Finnish type AA/Familial Mediterranean fever ATTR/Transthyretin-related hereditary Organ-limited amyloidosis Heart AANF/Isolated atrial Brain Familial amyloid neuropathy ACys+ABri/Cerebral amyloid angiopathy Aβ/Alzheimer's disease Kidney AApoA1+AFib+ALys/Familial renal Skin Primary cutaneous amyloidosis Amyloid purpura Endocrine Thyroid ACal/Medullary thyroid cancer Pituitary APro/Prolactinoma Pancreas AIAPP/Insulinoma AIAPP/Diabetes mellitus type 2 This cutaneous condition article is a stub .
Cutaneous amyloidosis refers to a variety of skin diseases characterized histologically by the extracellular accumulation of amyloid deposits in the dermis. Rare forms include lichen amyloidosus, X-linked reticulate pigmentary disorder, primary localized cutaneous nodular amyloidosis, and macular amyloidosis (see these terms).
Lichen amyloidosis is a rare chronic form of cutaneous amyloidosis (see this term), a skin disease characterized by the accumulation of amyloid deposits in the dermis, clinically characterized by the development of pruritic, often pigmented, hyperkeratotic papules on trunk and extremities, especially on the shins, and histologically by the deposition of amyloid or amyloid-like proteins in the papillary dermis.
Primary cutaneous amyloidosis is a form of amyloidosis , a group of conditions in which an abnormal protein (called amyloid) builds up in various organs and tissues throughout the body. In primary cutaneous amyloidosis, specifically, this protein accumulates in the skin. There are three main forms of primary cutaneous amyloidosis: Lichen amyloidosis - multiple itchy, raised spots which are scaly and red/brown in color. This rash generally affects the shins, thighs, feet and forearms. Macular amyloidosis - mild to severely itchy, flat, dusky-brown or greyish colored spots that may come together to form patches of darkened skin. This rash generally appears on the upper back between the shoulder blades, the chest and less commonly, the arms.
Needham Heights, MA, USA: Allyn & Bacon. ISBN 0-205-14164-1 . Das, J.P. (2002). A better look at intelligence. ... Cambridge: Cambridge University Press. pp. 445–476. ISBN 978-0-521-59648-0 . Lay summary (22 July 2013). ... Essentials of Psychological Testing . John Wiley & Sons. ISBN 978-0-471-41978-5 . Lay summary (10 October 2013). Urbina, Susana (2011). "Chapter 2: Tests of Intelligence". In Sternberg, Robert J. ; Kaufman, Scott Barry (eds.). ... Cambridge: Cambridge University Press. pp. 20–38. ISBN 978-0-521-73911-5 . Lay summary (9 February 2012).
Revesz et al. (2003) reviewed the pathology and genetics of APP-related CAA and discussed the different neuropathologic consequences of different APP mutations. ... Molecular Genetics In 2 patients from presumably unrelated Dutch families with hereditary cerebral hemorrhage with amyloidosis, Levy et al. (1990) identified a glu693-to-gln mutation in the APP gene (E693Q; 104760.0001). ... In 4 affected members of an Italian family with cerebral amyloid angiopathy, Obici et al. (2005) identified a mutation in the APP gene (104760.0019). In 2 brothers from an extensive Iowa kindred with progressive dementia and cerebroarterial amyloidosis, Grabowski et al. (2001) identified a heterozygous mutation in the APP gene (N694D; 104760.0016). ... Human APP mRNA was detected in neurons and neuronal processes, but not in vessel walls. ... Herzig et al. (2006) extended their earlier studies by developing several murine models of APP-related CAA and APP-related parenchymal amyloid deposition.
Etiology HCHWA-D is due to a mutation in the APP gene on chromosome 21q21.2, encoding the beta-amyloid precursor protein. ... Genetic testing reveals a mutation in the APP gene. Differential diagnosis Differential diagnoses include other conditions that could cause intracerebral hemorrhage such as coagulopathies, vasculitis (see these terms), CNS neoplasms, cerebral vascular malformations, ischemic stroke and antecedent trauma.
The Dutch type is the most common, with over 200 affected individuals reported in the scientific literature. Causes Mutations in the APP gene are the most common cause of hereditary cerebral amyloid angiopathy. APP gene mutations cause the Dutch, Italian, Arctic, Iowa, Flemish, and Piedmont types of this condition. ... Familial British and Danish dementia are caused by mutations in the ITM2B gene. The APP gene provides instructions for making a protein called amyloid precursor protein. ... Additionally, the ITM2B protein may be involved in processing the amyloid precursor protein. Mutations in the APP , CST3 , or ITM2B gene lead to the production of proteins that are less stable than normal and that tend to cluster together (aggregate). ... Learn more about the genes associated with Hereditary cerebral amyloid angiopathy APP CST3 ITM2B Inheritance Pattern Hereditary cerebral amyloid angiopathy caused by mutations in the APP , CST3 , or ITM2B gene is inherited in an autosomal dominant pattern , which means one copy of the altered gene in each cell is sufficient to cause the disorder.
Baumbach et al. (1990) reported the first familial cases. Six persons in 2 generations were affected in an autosomal dominant pattern of inheritance. ... Muscle fibers and brain tissue from the 2 disorders, respectively, share abnormal protein accumulation, including beta-amyloid, phosphorylated tau, ubiquitin, ApoE (107741), and presenilin-1 (PSEN1; 104311). The authors discussed the abnormalities of APP processing, the role of abnormal intracellular protein folding, oxidative stress, and the potential role of cholesterol in the pathogenic cascade of IBM. ... To elucidate the possible role of beta-APP mismetabolism in the pathogenesis of IBM, Sugarman et al. (2002) selectively targeted beta-APP overexpression to skeletal muscle in transgenic mice, using the muscle creatine kinase promoter. They reported that older (more than 10 months) transgenic mice exhibited intracellular immunoreactivity to beta-APP and its proteolytic derivatives in skeletal muscle.
Underdiagnosis may be an explanation for the high ethno-geographic variation. Male-to-female ratio is 2:1 on average (0.5 to 6.5:1). Clinical description IBM onset is over 50 years but may also occur earlier, in the 5th decade.
Find sources: "Inclusion body myositis" – news · newspapers · books · scholar · JSTOR ( September 2009 ) ( Learn how and when to remove this template message ) Inclusion body myositis Other names sIBM Specialty Rheumatology Inclusion body myositis ( IBM ) ( / m aɪ oʊ ˈ s aɪ t ɪ s / ) (sometimes called sporadic inclusion body myositis , sIBM ) is the most common inflammatory muscle disease in older adults. [1] The disease is characterized by slowly progressive weakness and wasting of both proximal muscles (closest to the body's midline) and distal muscles (the limbs), most apparent in the finger flexors and knee extensors . [2] IBM is often confused with an entirely different class of diseases, called hereditary inclusion body myopathies (hIBM). [3] [4] The "M" in hIBM is an abbreviation for "myopathy" while the "M" in IBM is an abbreviation for "myositis". ... Death in IBM is sometimes related to malnutrition and respiratory failure. [10] There is no effective treatment for the disease. Contents 1 Signs and symptoms 2 Causes 2.1 Genetics 3 Diagnosis 3.1 Differential diagnosis 3.2 Classification 4 Treatment 5 Other related disorders 6 References 7 External links Signs and symptoms [ edit ] How sIBM affects individuals is quite variable as is the age of onset (which generally varies from the forties upwards). ... "Inclusion-body myositis: a myodegenerative conformational disorder associated with Abeta, protein misfolding, and proteasome inhibition". Neurology . 66 (2 Suppl 1): S39–S48. doi : 10.1212/01.wnl.0000192128.13875.1e . ... "Sporadic inclusion body myositis--diagnosis, pathogenesis and therapeutic strategies" . Nat Clin Pract Neurol . 2 (8): 437–447. doi : 10.1038/ncpneuro0261 . ... External links [ edit ] GeneReview/NIH/UW entry on Inclusion Body Myopathy 2 Classification D ICD - 10 : M60.8 ICD - 9-CM : 359.71 OMIM : 147421 MeSH : D018979 DiseasesDB : 30691 External resources eMedicine : neuro/422 GeneReviews : Inclusion Body Myopathy 2 Orphanet : 611 v t e Systemic connective tissue disorders General Systemic lupus erythematosus Drug-induced SLE Libman–Sacks endocarditis Inflammatory myopathy Myositis Dermatopolymyositis Dermatomyositis / Juvenile dermatomyositis Polymyositis * Inclusion body myositis Scleroderma Systemic scleroderma Progressive systemic sclerosis CREST syndrome Overlap syndrome / Mixed connective tissue disease Other hypersensitivity / autoimmune Sjögren syndrome Other Behçet's disease Polymyalgia rheumatica Eosinophilic fasciitis Eosinophilia–myalgia syndrome fibrillin Marfan syndrome Congenital contractural arachnodactyly v t e Symptoms and conditions relating to muscle Pain Myalgia Fibromyalgia Acute Delayed onset Inflammation Myositis Pyomyositis Destruction Muscle weakness Rhabdomyolysis Muscle atrophy / Amyotrophy Other Myositis ossificans Fibrodysplasia ossificans progressiva Compartment syndrome Anterior Diastasis of muscle Diastasis recti Muscle spasm
Inclusion body myositis (IBM) is a progressive muscle disorder characterized by muscle inflammation, weakness, and atrophy (wasting). It is a type of inflammatory myopathy . IBM develops in adulthood, usually after age 50. The symptoms and rate of progression vary from person to person. The most common symptoms include progressive weakness of the legs, arms, fingers, and wrists. Some people also have weakness of the facial muscles (especially muscles controlling eye closure), or difficulty swallowing (dysphagia). Muscle cramping and pain are uncommon, but have been reported in some people.
Direct sequencing of the gene identified 2 rare, potentially disease-associated nonsynonymous mutations, Q170H (602192.0006) and R181G (602192.0007), in the ADAM10 prodomain. Heterozygosity for these mutations was found in 11 of 16 affected individuals from 7 of 436 AD families (NIMH cohort), as well as in 2 of 5 affected individuals from 2 of 351 additional affected families (NIA cohort). ... Q170H and R181G mutant mice showed significant attenuation of APP processing compared to wildtype, with a decrease in APP-CTF-alpha levels and an increase in sAPP-beta levels, indicating that the mutations attenuated Adam10 alpha-secretase activity on APP. Crossing these Adam10 mutant mice with the Tg2576 AD mouse model showed that the Adam10 mutations increased amyloidogenic APP processing, as manifest by a shift from the alpha-secretase to the amyloidogenic beta-secretase pathway. ... Collectively, these findings suggested that diminished alpha-secretase activity of ADAM10 on APP resulting from mutations in the ADAM10 prodomain can cause AD-related pathology.
Clinical Features Blais et al. (1999) and Adam et al. (2002) reported significantly lower plasma aminopeptidase P (APP) activities in patients with a history of AEACEI. ... Measured genotype analysis strongly suggested that the linkage signal for APP activity at this locus was accounted for predominantly by the SNP association. ... There was a significant association between the -2399A allele and decreased serum APP activity in both men and women, but the APP activity was lower in men regardless of genotype. ... This haplotype was associated with decreased plasma APP activity and decreased luciferase gene expression compared to other haplotypes of these SNPs. Cilia La Corte et al. (2011) concluded that the ATG haplotype of XPNPEP2 is functional and contributes to the development of ACEi-angioedema through a reduction in APP activity.
Type 1 is associated with various other diseases including lymphoproliferative disorders , and autoimmune diseases that may not become apparent until years after the angioedema begins. Type 2 is associated with an autoimmune abnormality in which a person has autoantibodies against a protein in the blood called C1-INH . In some cases, it is hard to distinguish between AAE types 1 and 2. Treatment options depend on the severity of symptoms, the parts of the body affected, and the type of AAE a person has.
Type 1 AAE (see this term) is frequently associated with lymphoproliferative syndromes and accelerated consumption of C1-INH, and with autoimmune diseases that may manifest several years after the initial episodes of angioedema. Type 2 AAE (see this term) is associated with the presence of autoantibodies to the C1-INH that neutralize C1-INH activity and are often associated with dysglobulinemia of unknown origin.
McMenemey et al. (1939) described 4 affected males in 2 generations with pathologic confirmation in one. ... Rovelet-Lecrux et al. (2006) estimated that in their whole cohort of 65 ADEOAD families, the frequency of the APP locus duplication was roughly 8% (5 of 65), which corresponds to half of the contribution of APP missense mutations to ADEOAD. ... Revesz et al. (2003) reviewed the pathology and genetics of APP-related CAA and discussed the different neuropathologic consequences of different APP mutations. ... Israel et al. (2012) reprogrammed primary fibroblasts from 2 patients with familial Alzheimer disease, in both caused by a duplication of the amyloid-beta precursor protein gene (APP; 104760), 2 with sporadic Alzheimer disease, and 2 nondemented control individuals into induced pluripotent stem cell (iPSC) lines. ... The A673V mutation, which corresponds to position 2 of amyloid beta, affected APP processing, resulting in enhanced beta-amyloid production and formation of amyloid fibrils in vitro.
Liu et al. (2007) noted that these 2 loci were in a linkage region spanning 1q21-q31 identified by Zubenko et al. (1998), Hiltunen et al. (2001), Myers et al. (2002), and Blacker et al. (2003). Haplotype analysis showed that the 2 linkage peaks on chromosome 1q21 and 1q25 are explained by different haplotypes, of 15 cM and 21 cM, respectively, segregating in different families.
There are three subtypes of early-onset familial AD which are each associated with changes (mutations) in unique genes: (1) Alzheimer disease, type 1 is caused by mutations in the APP gene (2) Alzheimer disease, type 3 is caused by mutations in the PSEN1 gene (3) Alzheimer disease, type 4 is caused by mutations in the PSEN2 gene.
A 10-cM genomic scan revealed significant allelic association with AD (p less than 0.05) at locations on chromosomes 2, 9, 10, and 12. The location on chromosome 9 yielded a maximum lod score of 5.5.
Using an autosomal dominant model, the maximum 2-point parametric lod score was 3.3 at theta of 0.22 at marker D10S583. ... The findings indicated that SORCS1 can influence APP processing, and Reitz et al. (2011) suggested that variation in the SORCS1 gene may be associated with risk of LOAD. ... Genomewide association analysis using 564 cis-SNPs identified a significant association between rs7910977, located 4.2 kb beyond the 3-prime end of the IDE gene, and 2-fold higher cerebellar expression levels of IDE (p = 2.7 x 10(-8)). ... Ertekin-Taner et al. (2003) identified 2 intronic CTNNA3 SNPs in strong linkage disequilibrium that showed highly significant association with plasma A-beta-42 levels in 10 extended LOAD families. ... The findings indicated a role for calcium signaling in APP (104760) processing and suggested that variations in the CALHM1 gene may influence susceptibility to late-onset AD.
A 10-cM genomic scan revealed significant allelic association with AD (p less than 0.05) at locations on chromosomes 2, 9, 10, and 12. The location on chromosome 12 yielded a maximum lod score of 4.8.
The brain pathology of 5 deceased members of this family, from 2 generations, represented a coexisting beta-amyloid and prion protein (PrP; 176640) pathology. ... Molecular Genetics In 5 deceased members from a Swiss family with early-onset Alzheimer disease with coexisting beta-amyloid and prion protein pathology, Leuba et al. (2000) did not identify mutations in the beta-amyloid precursor protein (104760), presenilin-1 (104311), or presenilin-2 (600759) genes. INHERITANCE - Autosomal dominant NEUROLOGIC Central Nervous System - Alzheimer disease - Seizures - Cerebral cortex with spongiform changes - Neurofibrillary tangles - Beta-amyloid-positive senile plaques - Prion protein-positive senile plaques MISCELLANEOUS - Age of onset 43-64 years ▲ Close
Within this candidate region, 1 gene of particular interest was that encoding cystatin-3 (CST3; 604312), because it is known to be an amyloidogenic protein and is codeposited with the amyloid-beta precursor protein (APP; 104760) in amyloid plaques in the brain of AD patients. Using a covariate-based linkage method, Olson et al. (2001) showed that the APP region on chromosome 21q21 is strongly linked to AD-affected sib pairs of the oldest current age (i.e., age either at last exam or at death) who lacked E4 alleles at the apolipoprotein E (APOE; 107741) locus. ... Two-locus analysis provided evidence of strong epistasis between 20p and the APP region, limited to the oldest age group and to those lacking E4 alleles at the APOE locus. Olson et al. (2002) speculated that high-risk polymorphisms in both regions produce a biologic interaction between these 2 proteins that increases susceptibility to a very late-onset form of AD. ... In addition, they observed association for markers located near the CST3 gene, with P values between 0.002 and 0.08 for 2-locus haplotypes. The results supported the presence of a susceptibility locus for AD in the vicinity of CST3 for very elderly subjects with AD.
A number sign (#) is used with this entry because of the association between late-onset Alzheimer disease-2 (AD2) and the apolipoprotein E (107741) E4 allele. ... The APOE E4 allele was associated with a nearly 2-fold increased risk of AD, a history of stroke (601367) was associated with a 4-fold increase, and a statistical interaction between APOE E4 and stroke was observed. ... Pericak-Vance et al. (1989, 1990) presented evidence for linkage to 2 markers on chromosome 19. When analysis was limited to the affecteds only, a lod score of 2.5 at theta = 0 was obtained for linkage with BCL3 (109560). ... The next highest lod score was to chromosome 5q35, and no linkage was found to chromosomes 9, 10, and 12. Harold et al. (2009) undertook a 2-stage genomewide association study of Alzheimer disease involving 16,000 individuals, which they stated was the most powerful AD GWAS to date. ... Onset was early in 4 other families tested; 2 had chromosome 21 APP (104760) mutations and 2 showed linkage to chromosome 14, thus representing AD1 (104300) and AD3 (607822), respectively.
Etiology EOAD is the consequence of either PSEN1 mutations (69%), APP mutations (13%), or APP duplication (7,5%), and exceptionally of PSEN2 mutations (2%).
A number sign (#) is used with this entry because Alzheimer disease-4 (AD4) is caused by heterozygous mutation in the presenilin-2 gene (PSEN2; 600759) on chromosome 1q42. ... All 5 were descendants of persons who originally lived in 2 small adjacent Volga German villages and shared several surnames known to have been present in the census records of those villages. ... Finckh et al. (2000) reported a family in which 3 sibs with a mutation in the PSEN2 gene (600759.0006) were affected with early-onset AD and 2 sibs with the mutation were not affected. ... Furthermore, the age of onset in this person, 67 years, was greater than 2 standard deviations above the family mean.
About 25% of all Alzheimer disease is familial (more than 2 people in a family have AD). When Alzheimer disease begins before 60 or 65 years of age (early-onset AD) about 60% of the cases are familial (also known as Early-onset familial AD). ... There are three subtypes of early-onset familial AD which are each associated with changes (mutations) in unique genes: (1) Alzheimer disease, type 1 is caused by mutations in the APP gene (2) Alzheimer disease, type 3 is caused by mutations in the PSEN1 gene (3) Alzheimer disease, type 4 is caused by mutations in the PSEN2 gene. The condition known as late-onset familial AD includes only the subtype Alzheimer disease, type 2 and is associated with the APOE *4 allele on chromosome 19.
For a general phenotypic description and a discussion of genetic heterogeneity of Alzheimer disease, see 104300. Mapping Liu et al. (2007) conducted a genome screen of 103 patients with late-onset AD who were ascertained as part of the Genetic Research in Isolated Populations (GRIP) program that was conducted in an isolated population from the southwestern area of the Netherlands. Genealogic information resulted in an extremely large and complex pedigree of 4,645 members. The pedigree was split into 35 subpedigrees to reduce the computational burden of linkage analysis. They found significant evidence of linkage of AD to 3q22-q24 (AD15), in a region of 18 cM from D3S3514 to D3S3626 that reached a maximum hlod of 4.44 at marker D3S1579.
Liu et al. (2007) noted that these 2 loci were in a linkage region spanning 1q21-q31 identified by Zubenko et al. (1998), Hiltunen et al. (2001), Myers et al. (2002), and Blacker et al. (2003). Haplotype analysis showed that the 2 linkage peaks on chromosome 1q21 and 1q25 are explained by different haplotypes, of 15 cM and 21 cM, respectively, segregating in different families.
Although no common disease locus could be found in all families, in 2 families an extended haplotype was identified on chromosome 8q shared by all affected members.
The authors commented on the atypical clinical presentation. Godbolt et al. (2004) reported 2 sibs with early-onset Alzheimer disease confirmed by genetic analysis (104311.0030). ... Matsubara-Tsutsui et al. (2002) reported a Japanese family in which 6 individuals in 2 generations were affected with presenile dementia preceded by spastic gait. ... George-Hyslop et al. (1992), Van Broeckhoven et al. (1992), and Mullan et al. (1992) presented evidence of linkage of early-onset FAD to chromosome 14q. In 2 Belgian families with early-onset autosomal dominant AD, Van Broeckhoven et al. (1987) excluded linkage to the APP locus on chromosome 21q. ... The brothers had onset of progressive dementia and ataxia between ages 29 and 32 years; 2 died at age 32 and the other died at age 36. ... Phenotypic cluster analysis applied to 50 patients at onset and during the first 2 years identified 4 subgroups: 2 with a cognitive onset (58%), including memory loss or disorientation, and 2 with a behavioral onset (42%), including apathy, depression, and executive dysfunction.
For a phenotypic description and a discussion of genetic heterogeneity of Alzheimer disease (AD), see 104300. Mapping In an extended multiplex family, ascertained in a population-based study of early-onset AD in the northern Netherlands, Rademakers et al. (2005) obtained conclusive evidence of linkage of AD with a candidate region of 19.7 cM at 7q36. They identified a shared haplotype at 7q36 between the index family and 3 of 6 multiplex AD-affected families from the same geographic region, which was indicative of a founder effect and defined a priority region of 9.3 cM. Mutation analysis of coding exons of 29 candidate genes identified only an exonic silent mutation in the PAXIP1 gene (608254), 38030G-C in the exon 10 genomic sequence, which affected codon 626. It remained to be determined whether PAXIP1 has a functional role in the expression of AD in the index family or whether another mutation at this locus explained the observed linkage and sharing.
For a phenotypic description and a discussion of genetic heterogeneity of Alzheimer disease (AD), see 104300. Mapping In a systematic survey of the human genome in patients with AD, Zubenko et al. (1998) identified D10S1423, located at 10p13, as a candidate susceptibility locus. The allelic associations in this survey were observed in independent samples of autopsied AD cases and controls from geographically disparate sites (Boston and Pittsburgh). Majores et al. (2000) replicated these findings by identifying an association of the D10S1423 234-bp allele with AD in an ethnically homogeneous group of 397 German AD cases and controls. Zubenko et al. (2001) described a prospective, longitudinal, double-blind assessment of the age-specific risk of AD encountered by 325 asymptomatic first-degree relatives of AD probands who carried the D10S1423 234-bp allele, the APOE E4 allele (107741), or both, after 11.5 years of systematic follow-up.
The hypothesis holds that an amyloid-related mechanism that prunes neuronal connections in the brain in the fast-growth phase of early life may be triggered by ageing-related processes in later life to cause the neuronal withering of Alzheimer's disease. [64] N-APP, a fragment of APP from the peptide's N-terminus , is adjacent to beta-amyloid and is cleaved from APP by one of the same enzymes. N-APP triggers the self-destruct pathway by binding to a neuronal receptor called death receptor 6 (DR6, also known as TNFRSF21 ). [64] DR6 is highly expressed in the human brain regions most affected by Alzheimer's, so it is possible that the N-APP/DR6 pathway might be hijacked in the ageing brain to cause damage. ... Although many older individuals develop some plaques and tangles as a consequence of ageing, the brains of people with AD have a greater number of them in specific brain regions such as the temporal lobe. [100] Lewy bodies are not rare in the brains of people with AD. [101] Biochemistry Main article: Biochemistry of Alzheimer's disease Enzymes act on the APP (amyloid precursor protein) and cut it into fragments. ... A β is a fragment from the larger amyloid precursor protein (APP). APP is a transmembrane protein that penetrates through the neuron's membrane. APP is critical to neuron growth, survival, and post-injury repair. [103] [104] In Alzheimer's disease, gamma secretase and beta secretase act together in a proteolytic process which causes APP to be divided into smaller fragments. [105] One of these fragments gives rise to fibrils of amyloid beta, which then form clumps that deposit outside neurons in dense formations known as senile plaques . [98] [106] AD is also considered a tauopathy due to abnormal aggregation of the tau protein .
Researchers have found that this form of the disorder can result from mutations in the APP , PSEN1 , or PSEN2 genes. When any of these genes is altered, large amounts of a toxic protein fragment called amyloid beta peptide are produced in the brain. ... As a result, people with Down syndrome have three copies of many genes in each cell, including the APP gene, instead of the usual two copies. ... Learn more about the genes associated with Alzheimer disease APOE APP PSEN1 PSEN2 Inheritance Pattern Early-onset familial Alzheimer disease is inherited in an autosomal dominant pattern , which means one copy of an altered gene in each cell is sufficient to cause the disorder.
For example, workers cannot be exposed to a sound level of 95 dB for more than 4 hours per day, or to sounds at 100 dB for more than 2 hours per day. ... Some recent studies suggest that some smartphone applications may be able to measure noise as precisely as a Type 2 SLM. [15] [16] Although most smartphone sound measurement apps are not accurate enough to be used for legally required measurements, the NIOSH Sound Level Meter app met the requirements of IEC 61672/ANSI S1.4 Sound Level Meter Standards (Electroacoustics - Sound Level Meters - Part 3: Periodic Tests). [17] Ototoxic chemical exposure [ edit ] Chemically-induced hearing loss (CIHL) is a potential result of occupational exposures. ... International Journal of Audiology . 42 Suppl 2: 2S17–20. doi : 10.3109/14992020309074639 . ... "Evaluation of smartphone sound measurement applications (apps) using external microphones-A follow-up study" . ... Occupational hearing loss (2nd ed.). New York: M. Dekker. ISBN 978-0-8247-8814-8 . ^ Al-Otaibi ST (June 2000).
The term pustular psoriasis is used for a heterogeneous group of diseases that share pustular skin characteristics. [1] Pustular Psoriasis Severe pustular psoriasis. Contents 1 Signs and symptoms 2 Diagnosis 2.1 Classification 3 Management 4 References 5 External links Signs and symptoms [ edit ] Characteristics may vary according to the subtype of pustular psoriasis. For example, it can be localized, commonly to the hands and feet ( localized pustular psoriasis ), or generalized with widespread patches appearing randomly on any part of the body ( generalized pustular psoriasis ). [2] [3] However, all forms of pustular psoriasis share in common the presence of red and tender blotchy skin covered with pustules . [1] Pustular psoriasis can be localized, commonly to the hands and feet (palmoplantar pustulosis), or generalized with widespread patches occurring randomly on any part of the body. ... This skin eruption is often accompanied by a fever , muscle aches , nausea , and an elevated white blood cell count . [1] Annular pustular psoriasis (APP), a rare form of GPP, is the most common type seen during childhood. [6] APP tends to occur in women more frequently than in men, and is usually less severe than other forms of generalized pustular psoriasis such as impetigo herpetiformis. [6] This form of psoriasis is characterized by ring-shaped plaques with pustules around the edges and yellow crusting. [6] APP most often affects the torso, neck, arms, and legs. [6] Diagnosis [ edit ] Classification [ edit ] Pustular psoriasis is classified into two major forms: localized and generalized pustular psoriasis . [1] Within these two categories there are several variants: Classification of Localized and Generalized Pustular Psoriasis Localized pustular psoriasis Palmoplantar pustulosis (acute and chronic) Acrodermatitis continua (of Hallopeau) Generalized pustular psoriasis (von Zumbusch) acute generalized pustular psoriasis Acute generalized pustular psoriasis of pregnancy ( impetigo herpetiformis ) Infantile and juvenile Subacute circinate and annular Management [ edit ] injection of methotrexate This section is empty. ... "Impetigo herpetiformis". Clinics in Dermatology . 24 (2): 101–104. doi : 10.1016/j.clindermatol.2005.10.009 .
Pustular psoriasis is a rare form of psoriasis that is characterized by widespread pustules and reddish skin. This condition can occur alone or with plaque-type psoriasis . Most cases of pustular psoriasis are thought to be " multifactorial " or associated with the effects of multiple genes in combination with lifestyle and environmental factors. There are several triggers for this conditions including withdrawal from corticosteroids, exposure to various medications and/or infections. Some cases of the generalized form are caused by changes (mutations) in the IL36RN gene and are inherited in an autosomal recessive pattern. In severe cases, hospitalization may be required. Treatment aims to alleviate the associated symptoms and may include certain medications and/or phototherapy.
A Dorling Kindersley Book. p. 199. ISBN 978-0-75-133383-1 . ^ a b Manfred Oehmichen; Roland N. ... American Psychiatric Pub. p. 210. ISBN 978-0-89042-385-1 . ^ Bost C, Pascual O, Honnorat J (2016). ... "Long-term tracking of neurological complications of encephalopathy and myopathy in a patient with nephropathic cystinosis: a case report and review of the literature" . J Med Case Rep . 2 : 235. doi : 10.1186/1752-1947-2-235 . ... Harrison's Neurology in Clinical Medicine (3rd ed.). p. 438. ISBN 978-0-07-181501-7 . ^ Benjamin J. Sadock; Virginia A. ... Further reading [ edit ] The Diagnosis of Stupor and Coma by Plum and Posner, ISBN 0-19-513898-8 , remains one of the best detailed observational references to the condition.
Lippincott Williams & Wilkins. 22 November 2004. p. 318. ISBN 978-0-7817-4586-4 . Retrieved 15 October 2012 . ^ Haas CA, Brown SL, Spirnak JP (April 1999). "Penile fracture and testicular rupture". World J Urol . 17 (2): 101–6. doi : 10.1007/s003450050114 . ... "Penile fracture in Kermanshah, Iran: report of 172 cases". J. Urol . 164 (2): 364–6. doi : 10.1016/s0022-5347(05)67361-2 . ... "The role of ultrasound in the diagnosis of penile fracture" . Sonography . 0 : 15–23. doi : 10.1002/sono.12167 . ... Lippincott Williams & Wilkins. pp. 305–. ISBN 978-0-7817-6275-5 . Retrieved 18 April 2010 .
The drug of choice is typically methamphetamine , known as crystal meth , tina or T , [2] but other drugs are also used, such as mephedrone , GHB , GBL , [3] and alkyl nitrites (known as poppers ). [4] Slamsex is associated with users who inject the drugs. [5] Some studies have found that people participating in such sex parties have a higher probability of acquiring sexually transmitted diseases , including HIV/AIDS , by having unprotected anal sex with large numbers of sexual partners. For this reason, it is considered "a public health priority." [3] Contents 1 Terminology 2 Participants and drugs 3 Risks 4 Statistics 5 History and cultural significance 6 Criticism 7 See also 8 References 9 Further reading 10 External links Terminology [ edit ] The practice is nicknamed "party 'n' play" ("PNP" or "PnP") by some participants. ... In some instances, PNP sessions play a part in the formation of loose social networks that are valued and relied upon by participants. [22] For other men, increasing reliance on hookup apps and websites to arrange sex may result in a sense of isolation that may exacerbate the risk of drug dependence, especially in the context of a lack of other venues for gay socializing and sexual community-formation. [23] A 2014 study found that one of the key reasons for taking drugs before and during sex was to boost sexual confidence and reduce feelings of self-doubt, regarding feelings of "internalised homophobia" from society, concerns about an HIV diagnosis, or "guilt related to having or desiring gay sex". A key self-confidence issue for study participants was "body image", a concern that was heightened by the focus on social networking apps on appearance, because on these apps, there is a focus on idealized male bodies that are "toned and muscular". ... Addict Behav . 29 (1): 89–106. doi : 10.1016/S0306-4603(03)00082-0 . PMID 14667423 . ^ "ChemSex and hepatitis C: a guide for healthcare providers" (PDF) .
A rare X-linked syndromic intellectual disability characterized by a variable clinical picture including developmental delay, mild to moderate intellectual disability, learning difficulties, communication deficits, and behavioral problems (such as aggression, attention deficit, hyperactivity, and autistic features). Personality disorder and psychotic behavior have also been reported.
Fragile XE syndrome is a genetic disorder that impairs thinking ability and cognitive functioning. Most affected individuals have mild intellectual disability. In some people with this condition, cognitive function is described as borderline, which means that it is below average but not low enough to be classified as an intellectual disability. Females are rarely diagnosed with fragile XE syndrome, likely because the signs and symptoms are so mild that the individuals function normally. Learning disabilities are the most common sign of impaired cognitive function in people with fragile XE syndrome. The learning disabilities are likely a result of communication and behavioral problems, including delayed speech, poor writing skills, hyperactivity, and a short attention span.
Slight mental retardation was evident in a male with mosaic genotype. Stettner et al. (2011) reported 2 brothers, aged 10 and 11 years, with mild to moderate mental retardation and behavioral abnormalities. ... Further, FRAXE expansion events were detected in 2 related females known to be cytogenetically positive for a fragile site in Xq27.3-q28. ... Only the propositus was investigated in family 2. All affected individuals lacked a definite phenotype and showed different degrees of mental retardation. ... The 2 FRAXE expansions led to complete methylation at the CCG repeat. ... A second boy reported by Gedeon et al. (1995) had less than 100-kb deletion wholly overlapped by the deletion in the first boy.
Fragile XE syndrome (FRAXE) is a genetic condition associated with mild to borderline intellectual disabilities with physical features differing from person to person. The characteristic features are learning difficulties, often a consequence of communication problems (speech delay, poor writing skills), hyperactivity, and a shortened attention span. Nearly all cases of FRAXE are caused by a specific type of mutation, called a trinucleotide repeat expansion , in the AFF2 gene, which is located on the X chromosome. A trinucleotide repeat expansion occurs when there is an abnormally large number of repeats of a specific sequence of three nucleotides (building block of DNA) within our DNA. The repeating nucleotides in FRAXE syndrome are CCG. When the number of CCG repeats is over 200, people typically have the signs and symptoms seen in FRAXE.
