Disease relevance of ADAMTS2

• Novel types of mutation responsible for the dermatosparactic type of Ehlers-Danlos syndrome (Type VIIC) and common polymorphisms in the ADAMTS2 gene [1].
• The prognostic contribution of intratumour VEGF, the most important factor in tumour-induced angiogenesis, to NPI was evaluated by using flexible modelling in a series of 226 N-primary breast cancer patients in which steroid receptors and cell proliferation were also accounted for [2].
• We studied 20 patients and 20 age-matched control subjects with neuropsychiatric tests (Blessed, Cornell depression and NPI scores) and autonomic tests (Deep breath (HRdb), 30:15 ratio and orthostatic hypotension (Bpoh)) [3].
• A standard clinical protocol including inclusion/exclusion criteria, collection of demographic and medical data, cognitive (Mini Mental State Examination: MMSE), motor (Unified Parkinson's Disease Rating Scale: UPDRS) and neuropsychiatric (Neuropsychiatric Inventory: NPI) examinations, was applied after obtaining informed consent [4].

Psychiatry related information on ADAMTS2

• This article analyzes data from a subgroup of patients (N = 165) with no or minimal delusions and/or hallucinations at baseline as measured by the Neuropsychiatric Inventory-Nursing Home Version (NPI/NH) [5].
• During follow-up, anxious children were more likely to develop new psychiatric disorders (30%), primarily new anxiety disorders (16%), than were NPI children (11% and 2%, respectively), but not psychopathological controls (42% and 10%, respectively) [6].
• RESULTS: On univariate analysis, decreased quality of life was statistically significantly correlated with higher levels of behavioural and psychological disturbance (NPI total score and its agitation, depression, anxiety, disinhibition, and irritability subscales); younger age of the person with dementia; and poorer mental health of the carer [7].
• Follow-up interviews assessed subjects' residential, educational, occupational, and marital status; utilization of mental health services; and psychological status RESULTS: Anxious subjects without histories of depression were less likely than NPI controls to be living independently [8].
• METHOD: This 8-year prospective study compared psychosocial functioning in young adults (mean age 22 years) who had histories of early-onset anxiety disorders, comorbid anxiety and depressive disorders, or no history of psychiatric illness (NPI) [8].

High impact information on ADAMTS2

• The pNPI enzyme is a metalloproteinase containing properdin repeats and a cysteine-rich domain with similarities to the disintegrin domain of reprolysins [9].
• We also demonstrate that, despite similarities in NH2-terminal domain structures, pro-alpha2(V) NH2-terminal globular sequences are not cleaved by ADAMTS-2, the metalloproteinase that cleaves the N-propeptides of the major fibrillar procollagen chains [10].
• Null mutations in procollagen I N-propeptidase (ADAMTS-2) cause dermatosparaxis in cattle and the Ehlers-Danlos syndrome (dermatosparactic type) in humans by preventing proteolytic excision of the N-propeptide of procollagen I [11].
• Although the exons 3-5 or 14-16 encode protein domains that have not been previously recognized as crucial for ADAMTS-2 activity, the aminoprocollagen processing was strongly impaired in vitro and in vivo, providing evidence for the requirement of these domains for proper enzyme function [1].
• Ehlers-Danlos syndrome (EDS) type VIIC, or dermatosparactic type, is a recessively inherited connective tissue disorder characterized, among other symptoms, by an extreme skin fragility resulting from mutations inactivating ADAMTS-2, an enzyme excising the aminopropeptide of procollagens type I, II, and III [1].

Chemical compound and disease context of ADAMTS2

• In the first case, a homozygous nonsense mutation in ADAMTS2 (substitution of a codon for tryptophan by a stopcodon) causes type VIIC Ehlers-Danlos syndrome (EDS) with multiple tooth agenesis and focal dysplastic dentin defects [12].

Biological context of ADAMTS2

• All participants completed NPI I on their first or second postpartum day [13].
• PI (normalized (NPI) for heart rate) and maximum, minimum and average velocities of the uterine artery were recorded and waveforms were qualitatively assessed using Goswamy and Steptoe's waveform classification [14].
• The relationship between age and urodynamic parameters was studied cross-sectionally in a group of 28 women in whom clinically and urodynamically both stress incontinence and detrusor instability were excluded (no proven incontinence, NPI) and in a group, matched for age, with genuine stress incontinence (GSI) [15].
• Presence and severity of psychosis was measured with a modification of the Neuropsychiatric Inventory (NPI; Cummings, J. L., Mega, M., Gray, K., Rosenberg-Thompson, S., Carusi, D. A., & Gorbein, J. (1994). The neuropsychiatric inventory: Comprehensive assessment of psychopathology in dementia. Neurology, 44, 2308-2314) [16].

Anatomical context of ADAMTS2

• The results were related to clinical and pathological parameters, i.e. histological grade, tumor diameter, lymph node involvement, NPI, steroid receptor (estrogen, ER, and progesterone, PgR) expression, and HER2/neu over-expression [17].
• Patients with elevated agitation scores on the NPI have a higher burden of frontal lobe neurofibrillary tangles than patients without agitation [18].

Associations of ADAMTS2 with chemical compounds

• CONCLUSIONS: Nifedipine induces a reversible decrease in NPI and an increase in blood flow velocities in the uterine artery in prematurely menopausal women [14].
• RESULTS: Patients treated with memantine had significantly lower NPI total scores than patients treated with placebo [19].
• METHODS: Based on the Croatian Institute for Health Insurance data for 2003, the number of prescriptions per insured individual (NPI) was calculated for employed and unemployed persons, as well as for different subsets according to the region (Zagreb, Split, Rijeka, Osijek), age, gender, and prescribed drug category [20].
• Compared with placebo, the use of trazodone was not associated with statistically significant benefits for behavioural manifestations as measured by various rating scales (ABID, CERAD-BRSD,CMAI, NPI) [21].

Other interactions of ADAMTS2

• Abnormal dentin structure in two novel gene mutations [COL1A1, Arg134Cys] and [ADAMTS2, Trp795-to-ter] causing rare type I collagen disorders [12].
• We investigated the mRNA expression of ADAM-8, -17, -19, -28, ADAM-TS1, and ADAM-TS2 in paired tissue samples from cancerous and non-cancerous parts of the kidneys of 27 patients with RCC who underwent tumour nephrectomy [22].
• ADAM-8 and ADAM-TS2 over expression as well as decreased hepsin expression were associated with shorter patient survival [23].

Analytical, diagnostic and therapeutic context of ADAMTS2

• Like the animal model dermatosparaxis, EDS type VIIC results from the absence of activity of procollagen I N-proteinase (pNPI), the enzyme that excises the N-propeptide of type I and type II procollagens [9].
• On NPI II a significantly positive change in perception was found for the experimental group, but not for the control group [13].
• Neuropsychiatric symptom profiles differ among dementia syndromes, and the NPI provides a means of assessing neuropsychiatric symptoms that may aid in differential diagnosis [18].
• METHODS: On admission and on discharge, a multidimensional evaluation was performed assessing mental and functional status, BPSD (Neuropsychiatric Inventory, NPI), somatic health status, and pharmacotherapy [24].

References